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Sample records for resembled anaplastic oligodendroglioma

  1. Low-grade and anaplastic oligodendroglioma.

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

    2016-01-01

    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. PMID:26948366

  2. MicroRNA expression profiling in recurrent anaplastic oligodendroglioma treated with postoperative radiotherapy

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    Giwon Kim; Edmond Changkyun Park; Chung Heon Ryu; Sin-Soo Jeon; Seung Il Kim; Hong-Seok Jang; Gun-Hwa Kim; Byung-Ock Choi

    2011-01-01

    In anaplastic oligodendroglioma (AO), genetic alternation was associated with clinical outcome. We explored radiation-associated up or downregulation of microRNAs (miRNAs) in AO by comparing miRNA expression profiles in newly-diagnosed AO to recurrent AO treated with postoperative radiotherapy. We identified that 23 miRNAs were upregulated and 42 miRNAs were downregulated in recurrent AO compared with newly-diagnosed AO. Especially, the expression of MiR-124, miR-128, miR-139-5p, miR-153, miR...

  3. Pleomorphic xanthoastrocytoma and oligodendroglioma: collision of 2 morphologically and genetically distinct anaplastic components.

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    Hattab, Eyas M; Martin, Sarah E; Shapiro, Scott A; Cheng, Liang

    2011-06-01

    With the exception of oligoastrocytoma, mixed gliomas are rarely encountered, and the astrocytic component of mixed oligoastrocytoma is almost always fibrillary and diffusely infiltrative. Pleomorphic xanthoastrocytoma (PXA) has occasionally been described in conjunction with ganglioglioma, as well as in 1 case of oligodendroglioma. In this latter case, described by Perry et al., 1p/19q codeletions were not detected. The authors report on a 25-year-old woman with a combined PXA/oligodendroglioma in which concurrent 1p/19q codeletions were detected in the oligodendroglial component only. The patient presented with a 1-month history of headaches. Neuroimaging revealed a heterogeneous left temporal mass with focal enhancement, cystic changes, hemorrhage, and left-to-right midline shift. The patient underwent a craniotomy and gross-total resection. Pathological examination revealed a glial tumor composed of 2 apparently distinct components. The largest component exhibited a prominent fascicular, reticulin-rich, spindle cell arrangement admixed with areas of highly pleomorphic cells, with bizarre cytological features reminiscent of PXA. A smaller component was composed of cellular sheets and lobules of oligodendroglial cells. Both components were characterized by anaplastic features. Dual-color fluorescence in situ hybridization for 1p/19q codeletions was performed. Only the oligodendroglial component showed the combined 1p/19q deletions. This case represents the first instance in which PXA has been reported in conjunction with an oligodendroglioma exhibiting the "molecular signature" characteristic of oligodendroglial neoplasms. The different genetic alterations seen in the 2 components of this neoplasm argue in favor of a "collision tumor" rather than a mixed glioma of the same genotype. PMID:21214337

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

    International Nuclear Information System (INIS)

    Purpose: Radiation Therapy Oncology Group 9402 compared procarbazine, lomustine, and vincristine (PCV) chemotherapy plus radiation therapy (PCV + RT) vs. RT alone for anaplastic oligodendroglioma. Here we report longitudinal changes in cognition and quality of life, effects of patient factors and treatments on cognition, quality of life and survival, and prognostic implications of cognition and quality of life. Methods and Materials: Cognition was assessed by Mini Mental Status Examination (MMSE) and quality of life by Brain-Quality of Life (B-QOL). Scores were analyzed for survivors and within 5 years of death. Shared parameter models evaluated MMSE/B-QOL with survival. Results: For survivors, MMSE and B-QOL scores were similar longitudinally and between treatments. For those who died, MMSE scores remained stable initially, whereas B-QOL slowly declined; both declined rapidly in the last year of life and similarly between arms. In the aggregate, scores decreased over time (p = 0.0413 for MMSE; p = 0.0016 for B-QOL) and were superior with age <50 years (p < 0.001 for MMSE; p = 0.0554 for B-QOL) and Karnofsky Performance Score (KPS) 80-100 (p < 0.001). Younger age and higher KPS were associated with longer survival. After adjusting for patient factors and drop-out, survival was longer after PCV + RT (HR = 0.66, 95% CI = 0.49-0.9, p = 0.0084; HR = 0.74, 95% CI = 0.54-1.01, p = 0.0592) in models with MMSE and B-QOL. In addition, there were no differences in MMSE and B-QOL scores between arms (p = 0.4752 and p = 0.2767, respectively); higher scores predicted longer survival. Conclusion: MMSE and B-QOL scores held steady in the upper range in both arms for survivors. Younger, fitter patients had better MMSE and B-QOL and longer survival.

  5. Infratentorial oligodendrogliomas: Imaging findings in six patients

    International Nuclear Information System (INIS)

    Background: Oligodendrogliomas are primarily supratentorial tumors. However, infrequently, they can also arise from infratentorial structures. There are only limited numbers of radiological articles on the specific imaging findings of this entity. Purpose: To investigate the imaging findings of infratentorial oligodendrogliomas. Material and Methods: We retrospectively reviewed the magnetic resonance imaging (MRI) findings and clinical records of six patients with pathologically proven infratentorial oligodendrogliomas between December 1994 and April 2008. Tumor location, circumscription, signal intensity (SI), enhancement pattern, the presence of restricted diffusion, and the change of the relative cerebral blood volume (rCBV) on MRI were evaluated. Results: In total, six patients (three male, three female; mean age 65 years, range 51-75 years) were included. The pathology revealed anaplastic oligodendrogliomas in all six patients. The location was cerebellum in four patients, medulla in one patient, and fourth ventricle and tegmentum in one patient. Three of them were of the infiltrative type, and the other three of the mass-forming type. The solid component of the tumors showed high SI (n=6) on FLAIR and T2-weighted images, and low (n=5) or iso (n=1) SI on T1-weighted images. All infiltrative lesions showed multifocal patchy enhancement, and mass-forming lesions showed heterogeneous enhancement (n=2) and diffuse homogeneous enhancement (n=1). Three patients had restricted diffusion, and one had leptomeningeal seeding. There was markedly increased rCBV on perfusion-weighted image (PWI) in one patient. Calcification or hemorrhage was not found. Tumor progression after operation, radiation therapy, gamma-knife surgery, or chemotherapy developed in five patients. Conclusion: Although infratentorial oligodendrogliomas did not show characteristic imaging findings, there was a tendency toward multifocal heterogeneous enhancement and absent or mild mass effect of infiltrative lesions. Infratentorial oligodendrogliomas may be more malignant than supratentorial oligodendrogliomas

  6. Clinical management of grade III oligodendroglioma

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    Simonetti G

    2015-07-01

    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, molecular markers, treatments toxicity

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

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

    2009-01-01

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

  8. Brain scanning in oligodendrogliomas

    International Nuclear Information System (INIS)

    Thirty-six brain scans and biopsies from 34 patients with histologically verified oligodendrogliomas were evaluated. Twenty-nine of the 36 scans were positive (80.6 percent) but the abnormal uptake produced by these neoplasms had no distinguishing features. The levels of endothelial proliferation-vascularity, necrosis, and mitoses were significantly different between the positive and negative scans. In the oligodendrogliomas, the relationship between histologic malignancy, detectability on scan, and prognosis remains unresolved. (U.S.)

  9. Clinical management of grade III oligodendroglioma

    International Nuclear Information System (INIS)

    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

  10. Pediatric brainstem oligodendroglioma

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    Sandeep Mohindra

    2012-01-01

    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.

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

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    Del Bigio Marc R

    2003-12-01

    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.

  12. Radiation and chemotherapy improve outcome in oligodendroglioma

    International Nuclear Information System (INIS)

    Purpose: Oligodendroglioma is a rare central nervous system tumor which may occur in pure or mixed histology. This scarcity results in difficulty in defining optimal management, mainly due to a lack of outcome analysis. Results are further complicated because the reported series include patients treated before megavoltage radiation or computed tomographic (CT) scan development. This makes extrapolation of outcome difficult to apply to modern-era patients. We report results obtained by current treatment and evaluation. Methods and Materials: Outcome of all 38 patients (age 5-70 years) pathologically diagnosed between 1975 and 1993 were reviewed. Pure lesions were seen in 14 cases, of which three were anaplastic. The remainder had mixed tumors, of which sic contained anaplastic astrocytic elements. Each patient had undergone maximal debulking surgery, but all remained with residual disease on postoperative CT. Results: For nonanaplastic lesions, no local failure was seen in any patient receiving postoperative radiation (60 Gy) and chemotherapy (vincristine, procarbazine, and carmustine). Follow-up ranged from 28 to 240 months (median 125; N = 6). No postoperative therapy or chemotherapy alone resulted in local failure in all nine patients at risk [time to failure (TTF): 2-40 months; median 25]. Radiation alone in doses of 50 Gy at 2 Gy per day resulted in all six patients failing (TTF: 12-52 months; median 36). Achieving 60 Gy at 2 Gy a day allowed five of eight patients to remain disease free (disease-free survival: 24-160 months; median 66), with three failing at 26, 40, and 60 months. All lesions containing anaplastic elements underwent post-operative radiation therapy (60 Gy) and chemotherapy, with five of nine patients alive and well (median disease-free survival: 48 months; range 28-120). Conclusion: The combination of radiation and chemotherapy increases local control of oligodendroglioma whether they contain pure, mixed, or anaplastic histology. Radiation alone may offer good local control as long as 60 Gy is delivered. Chemotherapy alone appears to delay TTF and may be useful for pediatric patients

  13. A Malignant Oligarchy: Progenitors Govern the Behavior of Oligodendrogliomas

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    Pei, Yanxin; Wechsler-Reya, Robert J.

    2010-01-01

    Recent studies have suggested that brain tumors arise from neural stem cells, and are maintained by stem-like tumor-initiating cells (TICs). In this issue of Cancer Cell Persson et al. report that oligodendrogliomas, unlike malignant astrocytomas, originate from – and are propagated by – cells that resemble oligodendrocyte progenitors.

  14. Management of oligodendroglioma

    International Nuclear Information System (INIS)

    This paper reports on oligodendrogliomas which are rare intracranial tumors. While surgical resection (S) is the mainstay of treatment, radiation therapy (RT) remains controversial. To define its role and to delineate failure patterns and prognostic factors, a review of the UCLA experience and the literature was undertaken. Forty-nine cases of oligodendrogliomas were treated at UCLA between 1957 and 1990. Age, race, gender, CT findings, location, grade, histology, calcification, S ± RT, and RT fields and dose were evaluated for prognostic relevance by means of x2 and log-rank tests. At 5, 10, and 15 years, actuarial survival was 61%, 41%, and 24%, respectively. Ten patients were free of disease. Failure pattern was overwhelmingly local; in 97%, failure was only local. Analysis for prognostic factors showed age less than 40 years, low grade, calcification, and evaluation with CT to be significant. Trend toward improved 5-year survival with postoperative RT was noted. With stratification for subtotal resection, this improvement was significant. Furthermore, meta-analysis demonstrated survival advantage with S plus RT

  15. Psoriatic Arthritis during Treatment with Bevacizumab for Anaplastic Oligodendroglioma.

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    Graceffa, D; Maiani, E; Pace, A; Solivetti, F M; Elia, F; De Mutiis, C; Bonifati, C

    2012-01-01

    Bevacizumab is a recombinant humanised monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The drug, alone or in combination with other anticancer agents, has been shown to be effective against several types of neoplasms. We report a case of a woman with a history of severe psoriasis who developed psoriatic arthritis during a course of bevacizumab, which was administered for a malignant glioma. PMID:23243547

  16. Psoriatic Arthritis during Treatment with Bevacizumab for Anaplastic Oligodendroglioma

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    Graceffa, D.; E. Maiani; De Pace, A; Solivetti, F. M.; F. Elia; de Mutiis, C.; C. Bonifati

    2012-01-01

    Bevacizumab is a recombinant humanised monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The drug, alone or in combination with other anticancer agents, has been shown to be effective against several types of neoplasms. We report a case of a woman with a history of severe psoriasis who developed psoriatic arthritis during a course of bevacizumab, which was administered for a malignant glioma.

  17. Characteristic CT signs in oligodendrogliomas

    International Nuclear Information System (INIS)

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

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

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    Levidou Georgia

    2010-09-01

    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.

  19. Oligodendroglioma presenting as chronic mania

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    SAHA, Rahul; JAKHAR, Kiran

    2015-01-01

    Summary Oligodendrogliomas may present with a variety of psychological symptoms but it only rarely presents with mania. The patient described in this case report is a 55-year-old man with a three year history of progressive mania who was initially diagnosed as chronic mania but a subsequent MRI identified a brain tumor. This report highlights the importance of considering differential organic diagnosis when patients present with atypical presentations of psychiatric disorders. A brain tumor should be considered and brain imaging studies conducted for patients with a late age of onset who do not respond to appropriate medication.     PMID:26300601

  20. CT evaluation of intracranial oligodendrogliomas

    International Nuclear Information System (INIS)

    Intracranial oligodendrogliomas show relatively low incidence among the intracranial tumors and difficult to differentiation with the other brain tumors. CT plays an important role in the diagnosis of these lesions. Authors reviewed the 16 cases of pathologically proven oligodendrogliomas at Korea University Medical Center for recent 7 years and the results were as follows; 1. They showed biphasic age distribution, one peak in 2nd decade and another in 5th decade. 2. 14 cases (88%) located supratentorially and frequent in frontal lobe of the patient age over 20 (6/8), frequent in parietal lobe below 20 (4/6). 3. Generally the tumors composed of solid portion but they almost always had some cystic or degenerative portion. 4. The diameter of the tumors varied from 2.5 cm to 8 cm. 5. The tumor calcification on CT scans were found in 14 cases and appearances were; 1) large irregular nodular calcifications; 5 cases 2) small nodular calcification; 4 cases 3) scattered stippled calcifications; 4 cases 4) shell like incomplete circular calcifications; 2 cases 6.14 cases (88%) showed contrast enhancement, irregular enhancement in 5 cases, diffuse enhancement in 4 case and ring like enhancement pattern in 5 cases

  1. Recurrent Oligodendroglioma Treated with Acupuncture and Pharmacopuncture.

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

    2015-06-01

    Acupuncture and pharmacopuncture have been shown to be effective in tumor treatment. However, their effectiveness for treating oligodendroglioma has not been reported yet. The purpose of this study was to provide an initial report on the effectiveness of acupuncture and pharmacopuncture for the treatment of an oligodendroglioma by presenting a case that was treated successfully. A 54-year-old man, who had experienced intracranial hemorrhage, was diagnosed with recurrent oligodendroglioma. His expected survival period was 3-6 months. The patient received daily acupuncture and weekly pharmacopuncture of mountain ginseng and bee venom. After treatment for 18 months, the tumor size was decreased markedly on brain magnetic resonance imaging, and severe seizures had disappeared. In this case, a combination of acupuncture and pharmacopuncture was shown to be effective for the treatment of recurrent oligodendroglioma. PMID:26100069

  2. Concordant cerebral oligodendroglioma in identical twins.

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    Roelvink, N C; Kamphorst, W.; Lindhout, D.; Ponssen, H

    1986-01-01

    A case of concordant oligodendroglioma in monozygotic twins is reported. The twins were also concordant for uterine leiomyoma and one twin partner had fibroadenoma and lipoma of the breast and myelofibrosis. As very few cases of concordant glioma in monozygotic twins have been published and no such cases in dizygotic twins, a genetic influence in the aetiology of glioma can only be suggested.

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

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    Jae Kyung Myung

    2014-12-01

    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.

  4. 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)

    2015-11-15

    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.)

  5. Anaplastic pleomorphic xanthoastrocytoma.

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    Bayindir, C; Balak, N; Karasu, A; Kasaroğlu, D

    1997-01-01

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

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

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    A. Derakhshanfar

    2010-05-01

    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.

  7. Anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Sixteen consecutive patients with anaplastic carcinoma of the thyroid were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin and debulking surgery. The radiotherapy was preoperatively administered to a target dose of 30 Gy in 3 weeks, and postoperatively to an additional dose of 16 Gy in 1.5 weeks. Radiotherapy was administered twice daily, 5 days a week, with a target dose of 1 Gy per fraction and with a minimum interval of 6 hours. A dose of 20 mg doxorubicin was administered intravenously 1 to 2 hours before the first radiotherapy session every week. Debulking surgery was feasible in 9 patients. Local complete remission was achieved in 5 patients and 3 of these are still alive disease-free at 10, 30, and 30 months respectively after diagnosis. Only 6 patients succumbed to a local failure. This combination regimen was well tolerated despite the patients' high age and advanced disease. (orig.)

  8. Anaplastic meningioma: case report

    Directory of Open Access Journals (Sweden)

    Falavigna Asdrubal

    2001-01-01

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

  9. Meningioma anaplásico Anaplastic meningioma

    Directory of Open Access Journals (Sweden)

    Arlines Alina Piña Tornés

    2013-03-01

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

  10. Meningioma anaplásico / Anaplastic meningioma

    Scientific Electronic Library Online (English)

    Arlines Alina, Piña Tornés; Fernando, Mendoza Montero; Francisco José, Oliva Pontón.

    2013-03-01

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

  11. ANAPLASTIC THYROID CARCINOMA

    Directory of Open Access Journals (Sweden)

    AugustoTaccaliti

    2012-07-01

    Full Text Available Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs, papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC is estimated to comprise 1-2% of thyroid malignancies and it accounts for 14% to 39% of thyroid cancer deaths. The annual incidence of ATC is about 1-2 cases/million, with the overall incidence being higher in Europe (and area of endemic goiter than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85–100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6 months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery or adjuvant (after surgery therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include antiangiogenetic drugs, multi-kinase inhibitor drugs.

  12. Oligodendroglioma occurring after radiation therapy for pituitary adenoma

    International Nuclear Information System (INIS)

    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. (author)

  13. Extraneural metastases in anaplastic ependymoma

    Directory of Open Access Journals (Sweden)

    Kumar Pavan

    2007-01-01

    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.

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

    Science.gov (United States)

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

    2015-10-01

    We present a 41-year-old man who experienced alien limb syndrome as a complication of treatment for recurrent Grade III oligodendroglioma of the right parietal lobe. Alien limb syndrome is a rare phenomenon in which a limb performs involuntary actions and the affected individual feels a sense of estrangement towards the limb. It occurs most commonly as a result of corticobasal syndrome, though a variety of other etiologies have been reported. It is rarely associated with focal lesions, such as stroke or tumors. PMID:26094559

  15. Outcome of oligodendroglioma treatment in the era of modern neuroimaging

    International Nuclear Information System (INIS)

    Purpose/Objective: The benefit of routine postoperative radiotherapy for low grade oligodendroglioma remains controversial. Most published series include many patients treated before the availability of CT or MRI scans which allow early diagnosis, guide surgery, detect residual disease, improve radiotherapy, and detect asymptomatic recurrences. The purpose of this analysis is to determine whether observation rather than radiation continues to be an appropriate option for selected patients with the availability of modern neuroimaging. Materials and Methods: 58 patients (age 2-67 years, 6 pts. =2 poor prognostic factor (p=.04). Results: Two and five year actuarial freedom from local progression was 93 +/- 4% and 75% +/- 8% whereas 2 and 5 year overall survival was 94% +/- 3% and 80% +/- 7%. Despite the imbalance of prognostic factors, there was no significant difference whether or not postoperative RT was given. With RT, 2 and 4 year actuarial freedom from progression was 94% +/- 4% and 78% +/- 8%, whereas without RT it was 94% +/- 6% at 2 and 4 years. Similarly, 2 and 4 year actuarial survival was 94% +/- 4% and 78% +/- 8% with RT and was 91% +/- 8% without RT. (5(10)) recurrences were detected radiologically without new or progressive clinical symptoms. Conclusion: These data support the hypothesis that, in the era of modern neuroimaging, the initial observation of good risk patients and immediate irradiation of poor risk patients is an appropriate treatment approach which results in good medium term control and survival for low grade oligodendroglioma patients. A policy of treatment vs. observation based on selected prognostic factors will be tested prospectively in an intergroup trial for low grade glioma histologies

  16. Anaplastic lymphoma kinase-positive primary cutaneous anaplastic large cell lymphoma- Is it a new variant?

    Directory of Open Access Journals (Sweden)

    Muthu Sendhil Kumaran

    2012-01-01

    Full Text Available Anaplastic large cell cutaneous lymphomas are clinically and pathologically heterogeneous, CD30 + (Ki-1 lymphoproliferative disorders. The importance of anaplastic lymphoma kinase (ALK positivity is well known in the prognosis of primary systemic anaplastic large cell cutaneous lymphomas; however, the same in primary cutaneous anaplastic large cell cutaneous lymphomas is not much clear. Herein we report a 65-year-old male with an 18-month history of minimally pruritic localized nodulo-plaque lesion over lower back. Histology revealed cutaneous large cell lymphoma and immunohistochemical staining showed positivity for CD30, CD3 and ALK. The role of ALK positivity in pcALCL is discussed in this article.

  17. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    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.

  18. Does facial resemblance enhance cooperation?

    Science.gov (United States)

    Giang, Trang; Bell, Raoul; Buchner, Axel

    2012-01-01

    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. PMID:23094095

  19. Pleomorphic xanthoastrocytoma with anaplastic features

    Directory of Open Access Journals (Sweden)

    Cheng ZHI

    2015-08-01

    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 necrosis. The differential diagnosis from glioblastoma multiforme and gaint cell glioblastoma should be paid attention, as all of them contain variable numbers of pleomorphic astrocytes, in order to avoid overtreatment. DOI: 10.3969/j.issn.1672?6731.2015.08.010

  20. Role of endothelin B receptor in oligodendroglioma proliferation and survival: In vitro and in vivo evidence.

    Science.gov (United States)

    Wan, Xin; Zhang, Longbo; Jiang, Bing

    2014-01-01

    In this study, the role of the endothelin B receptor (ETBR) in oligodendroglioma cell proliferation and survival was investigated in vitro and in vivo. The overexpression and knockdown of ETBR was conducted in Hs683 human oligodendroglioma cells, and cell proliferation and activation (phosphorylation) of extracellular signal-regulated kinase (ERK) were measured in vitro. An orthotopic xenograft oligodendroglioma mouse model was established. Mouse survival times and immunohistochemical Ki67 staining in the xenografts were examined. In vitro experiments demonstrated that the overexpression of ETBR significantly enhanced the proliferation of oligodendroglioma cells and the activation of ERK compared with the controls, which was eliminated by the selective ETBR inhibitor BQ788 and ERK-specific inhibitor U0126, but not selective endothelin A receptor inhibitor BQ123. By contrast, the knockdown of endogenous ETBR markedly decreased oligodendroglioma cell proliferation and the activation of ERK compared with the controls. Overexpression of ETBR significantly increased immunohistochemical Ki67 staining in the Hs683 cell orthotopic xenograft and decreased animal survival. By contrast, knockdown of ETBR significantly decreased Ki67 staining and increased mouse survival times. Intratumoral injection of BQ788, but not BQ123, significantly decreased Ki67 staining and prolonged mouse survival times. In conclusion, ETBR was demonstrated to mediate the proliferation of oligodendroglioma cells according to an ERK-dependent mechanism. Using an orthotopic xenograft oligodendroglioma mouse model, it was demonstrated in vivo that ETBR promotes oligodendroglioma proliferation and that the selective ETBR antagonist effectively inhibits the proliferation of oligodendroglioma cells and prolongs survival times. This study provides a novel insight into the role of ETBR in oligodendroglioma proliferation and survival, and provides the first in vivo evidence that ETBR-specific antagonists are a potential therapeutic alternative for oligodendrogliomas. PMID:24145738

  1. Oligodendroglioma of the ciliary body: a unique case report and the review of literature

    International Nuclear Information System (INIS)

    To date, there is no report in the international literature of an oligodendroglioma of the ciliary body, nor is there an analysis of the possible origins of this lesion. Here we report on a 52-year-old man admitted to our hospital with a ciliary body tumor revealed by clinical examination and ultrasound, computed tomography and magnetic resonance imaging studies. Following enucleation, pathological and immunohistochemical analyses were performed. Postoperative histopathological staining results included OLIGO-2(+) and GFAP(-), leading to a pathological diagnosis of oligodendroglioma of the ciliary body in the right eye (WHO grade II). Since malignant gliomas derive from transformed neural stem cells, the presence of oligodendroglioma in the ciliary body supports the hypothesis that gliomas can occur wherever neural stem cells exist. Tumors of the ciliary body derived from oligodendrocytes are difficult to diagnose; pathological analyses are essential

  2. Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report

    Science.gov (United States)

    Yuh, Woon Tak; Park, Sung-Hye

    2015-01-01

    Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas. PMID:26512274

  3. Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report.

    Science.gov (United States)

    Yuh, Woon Tak; Chung, Chun Kee; Park, Sung-Hye

    2015-09-01

    Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas. PMID:26512274

  4. ETV/Pea3 family transcription factor-encoding genes are overexpressed in CIC-mutant oligodendrogliomas.

    Science.gov (United States)

    Padul, Vijay; Epari, Sridhar; Moiyadi, Aliasgar; Shetty, Prakash; Shirsat, Neelam Vishwanath

    2015-12-01

    Oligodendrogliomas with combined loss of chromosome arms 1p and 19q are known to be particularly sensitive to chemotherapy, and the CIC gene located on 19q is known to be mutated in over 50% of the 1p/19q codeleted oligodendrogliomas. However, the role of CIC in the oligodendroglioma pathogenesis is not known. Exome sequencing of 11 oligodendroglial tumors identified 9 tumors with combined loss of 1p and 19q. Somatic mutations were found in the CIC and FUBP1 genes. Recurrent somatic mutations were also identified in the Notch signaling pathway genes NOTCH1 and MAML3, the chromatin modifying gene ARID1A and in KRAS. Comparison of the transcriptome profiles of CIC-mutant and CIC-wild type oligodendrogliomas from the study cohort as well as 65 1p/19q codeleted oligodendrogliomas from the TCGA cohort identified genes encoding the ETV transcription factor family to be significantly upregulated in the CIC-mutant tumors. Upregulation of a number of negative regulators of the receptor tyrosine kinase signaling pathway like Sprouty and SPRED family members in the CIC-mutant oligodendrogliomas is likely due to the constitutive activation of the pathway resulting from inactive CIC protein. Higher expression of the oncogenic ETV transcription factors in the CIC-mutant oligodendrogliomas may make these tumors more aggressive than the CIC-wild type tumors. © 2015 Wiley Periodicals, Inc. PMID:26357005

  5. GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas

    Science.gov (United States)

    Moro-Rodríguez, Ernesto; Figols, Javier; Alvira, Mariano; Uranga-Ocio, José A; García-Poblete, Eduardo

    2008-01-01

    Objective This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. Study design Surgical specimens from 24 patients with oligodendrogliomas during the period 1981–2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor), diameters (max, mean and min.), radius (max. and min.) margination, ratio of perimeter-area, roundness and sizes (length and width). In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. Results Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 ?m2 vs. GIII 43.45 ?m2 p-value = 0.02), aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03), axis minor (GII 6.66 ?m vs. GIII 6.01 ?m p-value = 0.003), diameter minor (GII 5.93 ?m vs. GIII 5.27 ?m p-value = 0.002), radius minor (GII 2.64 ?m vs. GIII 2.25 ?m p-value = 0,003), perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04), size width (GII 6.60 ?m vs. GIII 5.96 ?m p-value = 0,003), and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05) were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01) and the intensity of alpha1a-AR (p-value = 0.01) were statistically significant in predicting survival. Conclusion These results suggest that some nuclear morphometrical features and the GFAP and alpha1a-AR immunofluorescence staining may be useful parameters for predicting survival in oligodendrogliomas. PMID:18673515

  6. Synchronous multicentric pleomorphic xanthoastrocytoma with anaplastic features

    OpenAIRE

    Kavita Mardi; R.C. Thakur

    2012-01-01

    Pleomorphic xanthoastrocytoma (PXA) has been considered an astrocytic tumor with a relatively favorable prognosis. However, PXA cases having several recurrent patterns with poor prognosis have been reported in recent years, and a new concept of "PXA with anaplastic features" has been proposed. The present case was of a 55-year-old male who presented with weakness and numbness of right upper and lower limbs since 3 months along with difficulty in walking as well as difficulty in speaking since...

  7. Breast implants and anaplastic large cell lymphoma

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Friis, Søren; Bautz, Andrea; Bendix, Knud; Sørensen, Henrik Toft; d'Amore, Francesco

    2013-01-01

    Background:A potential link between breast implants and anaplastic large cell lymphoma (ALCL) has been suggested. Methods:We examined lymphoma occurrence in a nationwide cohort of 19,885 Danish women who underwent breast implant surgery during 1973-2010. Standardized incidence ratios, with 95% confidence intervals (CI), for ALCL and lymphoma overall associated with breast implantation were calculated. Results:: During 179,246 person-years of follow-up, we observed 31 cases of lymphoma among coho...

  8. Extensive Growth of an Anaplastic Meningioma

    Science.gov (United States)

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

    2013-01-01

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

  9. Synchronous multicentric pleomorphic xanthoastrocytoma with anaplastic features

    Directory of Open Access Journals (Sweden)

    Kavita Mardi

    2012-01-01

    Full Text Available Pleomorphic xanthoastrocytoma (PXA has been considered an astrocytic tumor with a relatively favorable prognosis. However, PXA cases having several recurrent patterns with poor prognosis have been reported in recent years, and a new concept of "PXA with anaplastic features" has been proposed. The present case was of a 55-year-old male who presented with weakness and numbness of right upper and lower limbs since 3 months along with difficulty in walking as well as difficulty in speaking since then. He also complained of headache since 9 months. The magnetic resonance imaging study revealed two nodular, homogeneously enhancing lesions, approximately 1 cm in size in the right cerebral hemisphere. Clinical and radiological examinations were suggestive of a metastatic neoplasm. A right frontal craniotomy was performed for excisional biopsy of both lesions. Histopathological findings showed that the tumor was PXA with strong pleomorphism, xanthomatous changes, extensive areas of tumor necrosis, and increased mitotic activity. From these findings, the histopathological diagnosis "PXA with anaplastic features" was given. Synchronous multicentric PXA presents unique challenges in that gross total resection would impose significant surgical morbidity; histological homogeneity among the lesions cannot be confirmed; and the well-described potential for anaplastic transformation may be increased with multiple lesions. The optimal treatment for patients with this rare and challenging diagnosis awaits further study.

  10. Primary multicentric anaplastic pleomorphic xanthoastrocytoma with atypical features.

    Science.gov (United States)

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

    2013-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Fuller Gregory N

    2005-09-01

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

  12. Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.

    Science.gov (United States)

    Vaquero, J; Zurita, M; Morales, C; Coca, S

    2001-06-01

    The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma. PMID:11478061

  13. Varied Persistent Life Cycles of Borna Disease Virus in a Human Oligodendroglioma Cell Line

    OpenAIRE

    Ibrahim, Madiha S.; Watanabe, Makiko; Palacios, J. Alejandro; Kamitani, Wataru; Komoto,Satoshi; Kobayashi, Takeshi; Tomonaga, Keizo; Ikuta, Kazuyoshi

    2002-01-01

    Borna disease virus (BDV) establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures. In an attempt to characterize the life cycle of BDV in persistently infected cultured cells, we developed 30 clones by single-cell cloning from a human oligodendroglioma (OL) cell line after infection with BDV. According to the percentage of cells expressing the BDV major proteins, p40 (nucleoprotein) and p24 (phosphoprotein), the clones were c...

  14. Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction.

    OpenAIRE

    Ross, C. W.; Schlegelmilch, J. A.; Grogan, T M; Weiss, L.M.; Schnitzer, B; Hanson, C. A.

    1992-01-01

    Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic simil...

  15. Prognostic value of perfusion MR imaging in patients with oligodendroglioma: a survival study

    International Nuclear Information System (INIS)

    Objective: The purpose of this study was to evaluate retrospectively whether cerebral blood volume measurement based on pretreatment perfusion MRI is a prognostic bio-marker for survival in patients with oligodendroglioma or mixed oligo-astrocytoma. Patients and methods: Between 1998 and 2004, 54 patients (23 females and 31 males), aged 21-73 years, with oligodendroglioma (or mixed tumour) were examined prior to beginning treatment with dynamic susceptibility-weighted contrast (DSC) perfusion MRI during gadolinium first-pass. The relative cerebral blood volume (rCBV) was calculated by dividing the measurement within the tumour by the measurement of the normal-appearing contralateral region. Patients were classified in two groups, grade A and grade B, according to the Saint-Anne Hospital classification and followed-up clinically and by means of MRI until their death or for a minimum of 5 years. Patients were also classified in grade II and grade III-IV, according to the World Health Organisation (WHO) classification, and were analysed with the same methods. Age, sex, treatment, tumour grade, contrast agent uptake, and rCBV were tested using survival curves with Kaplan-Meier's method, and their differences were analysed using the log-rank test. Results: In this population, median survival was 3 years. A rCBV threshold value of 2.2 was validated as a prognostic factor, for survival in these patients with oligodendrogliomas. Age, sex, contrast uptake, and maximum rCBV were found to be prognostic factors in univariate analysis. Multivariate analysis revealed that tumour grade (grade A/grade B), rCBV, age, and sex were prognostic factors independent of the other factors. The tumour grade according to the WHO classification (II versus III-IV) was also detected as an independent prognostic factor. Conclusion: Pretreatment rCBV measured by DSC perfusion MRI was found to be a prognostic factor for survival in patients with oligodendroglioma or mixed tumour, by using the Saint-Anne Hospital classification, which separate the IIB from the IIA. (authors)

  16. A 16-gene signature distinguishes anaplastic astrocytoma from glioblastoma.

    Science.gov (United States)

    Rao, Soumya Alige Mahabala; Srinivasan, Sujaya; Patric, Irene Rosita Pia; Hegde, Alangar Sathyaranjandas; Chandramouli, Bangalore Ashwathnarayanara; Arimappamagan, Arivazhagan; Santosh, Vani; Kondaiah, Paturu; Rao, Manchanahalli R Sathyanarayana; Somasundaram, Kumaravel

    2014-01-01

    Anaplastic astrocytoma (AA; Grade III) and glioblastoma (GBM; Grade IV) are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM) and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT) pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma. PMID:24475040

  17. AT-57LONG-TERM CLINICAL RESULTS OF EXTENSIVE TUMOR REMOVAL FOLLOWED BY ACNU-BASED CHEMORADIOTHERAPY FOR 147 ANAPLASTIC GLIOMAS

    Science.gov (United States)

    Takayuki, Yasuda; Masayuki, Nitta; Takashi, Maruyama; Taichi, Saito; Satoko, Ikuta; Yoshikazu, Okada; Hiroshi, Iseki; Yoshihiro, Muragaki

    2014-01-01

    INTRODUCTION: Recent randomized trials showed that highly extent of resection (EOR) and PCV chemoradiotherapy had therapeutic long-term efficacy to anaplastic glioma (AG). From 2000, we have consistently enforced extensive removal and ACNU-based chemoradiotherapy for AG. We report retrospective clinical results of a single institution. METHODS: We reviewed 147 cases of primary AG between 2000 and 2011 (Male : Female = 94:53, average age; 43.9 year-old). 69 were anaplastic astrocytoma (41%), 43 were anaplastic oligoastrocytoma (29%), and 44 were anaplastic oligodendroglioma (30%). The intraoperative MRI was performed in 133 cases (90%), and awake surgery was performed in 58 cases (39%). Gross-total removal was 46 (31%), partial removal was 89 (61%), and biopsy was 12 (8%) (average; 83%, median; 95%). After resection, 60 Gy radiotherapy and ACNU or PAV chemotherapy were performed. The average Mib-1 index was 15%. The mean observation periods were 57 months and 95% follow-up rate. RESULTS: Overall survival (OS) wasn't reached median. The 3y-OS was 82%, 5y-OSs was 72%, and 10y-OS was 66%. There was no statistical significance among AA, AOA, AO (5y-OS; 64%, 79%, 77%). The each 5 years survival rate of gross-total resection, partial resection, and biopsy were 83%, 70%, 39%, and there was statistical significance (P = 0.0024). Extent of resection (EOR) correlated OS in AA (P = 0.02) but not in oligodendroglial subtypes (P = 0.6). Statistical significant factors were EOR (P = 0.0024) and Mib-1 index (P = 0.013). The significant factors in multi variable analysis were EOR (more than 95% or not, HR 2.5) and Mib-1 index (more than 13% or not, HR 2.3). The median PFS was 8.3, and 5y-PFS was 59%,and 10y-PFS was 45%. CONCLUSION: Our long-term clinical results of AG treated with extensive resection and ACNU-based chemoradiotherapy were better than previous reports. The EOR contributed better prognosis especially for AA.

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

    Directory of Open Access Journals (Sweden)

    Marcelo E. Corti

    2004-08-01

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

  19. Intraventricular pleomorphic xanthoastrocytoma with anaplastic features.

    Science.gov (United States)

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

    2010-08-01

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

  20. Anaplastic large cell lymphoma, ALK-negative.

    Science.gov (United States)

    Ferreri, Andrés J M; Govi, Silvia; Pileri, Stefano A; Savage, Kerry J

    2013-02-01

    Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-negative (ALCL-ALK-) is a provisional entity in the WHO 2008 Classification that represents 2-3% of NHL and 12% of T-cell NHL. No particular risk factor has been clearly identified for ALCL, but a recent study showed an odds ratio of 18 for ALCL associated with breast implants. Usually, the architecture of involved organs is eroded by solid, cohesive sheets of neoplastic cells, with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and classical Hodgkin lymphoma being the main differential diagnoses. In this regard, staining for PAX5 and CD30 is useful. Translocations involving ALK are absent, TCR genes are clonally rearranged. CGH and GEP studies suggest a tendency of ALCL-ALK- to differ both from PTCL-NOS and from ALCL-ALK+. Patients with ALCL-ALK- are usually adults with a median age of 54-61 years, and a male-to-female ratio of 0.9. At presentation, ALCL-ALK- is often in III-IV stage, with B symptoms, high International Prognostic Index score, high lactate dehydrogenase serum levels, and an aggressive course. ALCL-ALK- presents with lymph node involvement in ?50% of cases; extranodal spread (20%) is less common. Staging work-up for ALCL-ALK- is similar to that routinely used for nodal NHL. Overall prognosis is poor, with a 5-year OS of 30-49%, which is significantly worse when compared to OS reported in patients with ALCL-ALK+ (5-year: 70-86%). Patients with systemic ALCL exhibit a significantly better survival compared with patients with PTCL-NOS, with a 5-year OS of 51% and 32%, respectively. Age, PIT scoring system, ?2-microglobulin, and bone marrow infiltration are the main prognostic factors. The expression of proteins involved in the regulation of apoptosis (caspase 3, Bcl-2, PI9) and of CD56 is related to clinical outcome. ALCL-ALK- is generally responsive to doxorubicin-containing chemotherapy, but relapses are frequent. CHOP is the most commonly used regimen to treat systemic ALCL with complete remission rates of 56%, and a 10-year DFS of 28%. Encouraging results have been reported with more intensive chemotherapy regimens. The addition of etoposide improved outcome. Alemtuxumab-CHOP regimen was associated with excellent remission rate but increased toxicity. The role of high-dose chemotherapy supported by ASCT has not been investigated in a trial of exclusively ALCL patients. When used in first remission, it was associated with a 5-year PFS of 64%. High-dose chemotherapy with ASCT is the standard therapeutic option for patients with relapsed or refractory disease. The role of allogeneic transplantation in patients with relapsed/refractory ALCL remains to be defined but there are data to support the contention that a graft-versus-lymphoma effect does exist. Myeloablative conditioning has been associated with 5-year PFS and OS of 40% and 41%, respectively, but a 5-year TRM of 33% was reported. Allo-SCT can be an option for relapsed/refractory ALCL in younger patients, preferably in the setting of a clinical trial. Pralatrexate, anti-CD30 monoclonal antibodies, brentuximab vedotin (SGN-35) in particular, (131)I-anti-CD45 radioantibody, yttrium-anti-CD25 radioimmunoconjugates, histone deacetylase inhibitors, bortezomib, gemcitabine, vorinostat, lenalidomide, and their combinations represent the most appealing chemotherapy and/or targeted agents to be investigated in future trials. PMID:22789917

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

    Directory of Open Access Journals (Sweden)

    Christopher Mulligan, MBBS

    2014-10-01

    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.

  2. Galectin 1 Proangiogenic and Promigratory Effects in the Hs683 Oligodendroglioma Model Are Partly Mediated through the Control of BEX2 Expression1

    OpenAIRE

    Mercier, Marie Le; Fortin, Shannon; Mathieu, Véronique; Roland, Isabelle; Spiegl-Kreinecker, Sabine; Haibe-Kains, Benjamin; Bontempi, Gianluca; Decaestecker, Christine; Berger, Walter; Lefranc, Florence; Kiss, Robert

    2009-01-01

    We have previously reported that galectin 1 (Gal-1) plays important biological roles in astroglial as well as in oligodendroglial cancer cells. As an oligodendroglioma model, we make use of the Hs683 cell line that has been previously extensively characterized at cell biology, molecular biology, and genetic levels. Galectin 1 has been shown to be involved in Hs683 oligodendroglioma chemoresistance, neoangiogenesis, and migration. Down-regulating Gal-1 expression in Hs683 cells through targete...

  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

    2010-01-01

    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. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    Directory of Open Access Journals (Sweden)

    Biersack Hans-Jürgen

    2011-08-01

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

  5. Spinal imaging in intracranial primary pleomorphic xanthoastrocytoma with anaplastic features.

    Science.gov (United States)

    Nern, Christian; Hench, Jürgen; Fischmann, Arne

    2012-09-01

    We present a patient with an intracranial primary pleomorphic xanthoastrocytoma (PXA) with anaplastic features that recurred repeatedly after surgery. Late in the course, radiological follow-up revealed an unresectable spinal tumor. Very few patients with PXA associated with a spinal tumor have been reported. Earlier detection of the spinal lesion would have potentially improved the therapeutic options for the patient. PMID:22789631

  6. Lhx3 is required to maintain cancer cell development of high-grade oligodendroglioma.

    Science.gov (United States)

    Liu, Hongliang; Liu, Wei; Zhu, Bin; Xu, Qiang; Ni, Xiaowei; Yu, Ji

    2015-01-01

    The LHX genes play a substantial role in an amount of adorning processes. Potential roles of LHXs have been accepted and approved in an assortment of neoplastic tissues as bump suppressors or promoters depending on bump cachet and types. The aim of this abstraction was to investigate the action role of LHXs in the animal High-grade Oligodendroglioma (HG-OT). The gene announcement changes of LHXs in HG-OT tissues compared with non-cancerous colorectal tissues were detected using application real-time quantitative about-face transcriptase-polymerase alternation acknowledgment (QRT-PCR) assay and immunohistochemistry. And we articulate the gene LHX3 that was decidedly up-regulated in HG-OT by QRT-PCR assay and immunohistochemistry. Furthermore, it was obvious that LHX3 responds to blight corpuscle admeasurement in vitro and LHX3 announcement activated with animated ?-catenin levels in HG-OT and ?-catenin action was appropriate for LHX3's oncogenic effects.  Mechanistically, LHX3 facilitates TCF4 to bind to ?-catenin and facilitates LHX3/TCF4/?-catenin circuitous and trans-active it's after ambition gene. LHX3 mutations that agitate the LHX3-?-catenin alternation partially anticipate its action in bump cells. All in all, LHX3 is a frequently activated bump apostle that actuates Wnt/?-catenin signaling in blight beef of HG-OT. PMID:25399296

  7. Hot-spot selection and evaluation methods for whole slice images of meningiomas and oligodendrogliomas.

    Science.gov (United States)

    Swiderska, Zaneta; Markiewicz, Tomasz; Grala, Bartlomiej; Slodkowska, Janina

    2015-08-01

    The paper presents a combined method for an automatic hot-spot areas selection based on penalty factor in the whole slide images to support the pathomorphological diagnostic procedure. The studied slides represent the meningiomas and oligodendrogliomas tumor on the basis of the Ki-67/MIB-1 immunohistochemical reaction. It allows determining the tumor proliferation index as well as gives an indication to the medical treatment and prognosis. The combined method based on mathematical morphology, thresholding, texture analysis and classification is proposed and verified. The presented algorithm includes building a specimen map, elimination of hemorrhages from them, two methods for detection of hot-spot fields with respect to an introduced penalty factor. Furthermore, we propose localization concordance measure to evaluation localization of hot spot selection by the algorithms in respect to the expert's results. Thus, the results of the influence of the penalty factor are presented and discussed. It was found that the best results are obtained for 0.2 value of them. They confirm effectiveness of applied approach. PMID:26737721

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

    Science.gov (United States)

    2015-06-03

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

  9. Anaplastic cerebral hemangiopericytoma: Rare variant of a rare disease

    Directory of Open Access Journals (Sweden)

    Purnima Thakur

    2015-01-01

    Full Text Available Intracranial hemangiopericytoma (HPC is a rare tumor of central nervous system, anaplastic type (grade 3 being the rarest. HPC closely mimics meningiomas in clinical and radiological features, thus, its diagnosis and treatment is a challenge. We report a rare case of histopathologically diagnosed anaplastic HPC of frontal lobe of the brain. A lady in her 60?s presented with neurological signs of impaired memory, headache, decreased vision and slurring of speech that gradually progressed to aphasia over a period of 2 months. A space occupying lesion was identified on magnetic resonance imaging in the left frontal region. Left frontal craniotomy and Simpson grade 1 excision of the tumor was done. Postoperative radiotherapy was administered in view of positive margins on histopathological specimen. We describe the clinical, radiological, and histological features of this tumor, its outcome on completion of treatment and on subsequent follow-up along with a review of the literature.

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

    Science.gov (United States)

    2015-10-19

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

  11. DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

    OpenAIRE

    Martínez, Ramón; Carmona, F. J.; Vizoso, Miguel; Rohde, Veit; Kirsch, Matthias; Schackert, Gabriele; Ropero, Santiago; Paulus, Werner; Barrantes, Alonso; Gomez, Antonio; Esteller, Manel

    2014-01-01

    Background Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients. Methods Using a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue ...

  12. Pleomorphic xanthoastrocytoma with anaplastic features: A case report

    OpenAIRE

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

    2014-01-01

    Pleomorphic xanthoastrocytoma has been considered as an astrocytic tumor with relatively favorable prognosis. It corresponds to WHO Grade-II neoplasm. Recently, several patterns with relatively poor prognosis have been recorded and a new concept of "PXA with anaplastic features" has been proposed. The present case is about a 9-year-old girl who presented with symptoms of recurrent headache, seizures and poor academic performance. MRI revealed left fronto-parietal irregular enhancing mass lesi...

  13. Pathobiology of ALK-negative anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Stefano A. Pileri

    2011-06-01

    Full Text Available The authors revise the concept of ALK-negative 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 as well as the phenotypic, molecular and clinical characteristics. Finally, the biological rationale for possible innovative targeted therapies is presented.

  14. DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma

    International Nuclear Information System (INIS)

    Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients. Using a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue (n = 10) and glioblastoma (n = 87) samples. DNA methylation levels were further confirmed on independent samples by pyrosequencing of the promoter sequences. Increasing DNA promoter hypermethylation events were observed in anaplastic PXA as compared with grade II samples. We further validated differential hypermethylation of CD81, HCK, HOXA5, ASCL2 and TES on anaplastic PXA and grade II tumors. Moreover, these epigenetic alterations overlap those described in glioblastoma patients, suggesting common mechanisms of tumorigenesis. Even taking into consideration the small size of our patient populations, our data strongly suggest that epigenome-wide profiling of PXA is a valuable tool to identify methylated genes, which may play a role in the malignant progression of PXA. These methylation alterations may provide useful biomarkers for decision-making in those patients with low-grade PXA displaying a high risk of malignant transformation

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

    OpenAIRE

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

    2002-01-01

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

  16. Clinicopathological and immunohistochemical analysis of anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    To study the clinicopathological and immunohistochemical features of Anaplastic Large Cell Lymphoma (ALCL). Study Design: The study design was cross sectional descriptive study. Place and Duration of Study: The study was conducted in Armed forces institute of pathology. The duration of study was two years from 1st Jan 2010 to 31st Dec 2011. Material and Methods: A total of twenty five consecutive biopsy proven cases of anaplastic large cell lymphoma (ALCL) were selected through non probability, consecutive sampling. The inclusion criteria was, all newly diagnosed patients of ALCL having sufficient tumour material in paraffin embedded tissue blocks with appropriate clinical information regarding age, gender and anatomic location. The exclusion criteria included all poorly fixed specimen. The clinical information regarding age, gender and location was noted. All the cases were evaluated on Haematoxylin and Eosin (H and E). Cases were subjected to Immunohistochemistry (IHC) using CD45 (LCA), CD3, CD 45 RO, CD 15, CD20, CD 30, ALK, EMA, Cytokeratin and classified according to WHO classification of lymphoid neoplasm. Results: Twenty five cases of anaplastic large cell lymphoma were reported during this time period. Out of 25 cases, 22(88%) were ALCL ALK positive, 2(8%) were ALCL ALK negative and 1(4%) case was cutaneous ALCL. The male to female ratio was 2.5:1. The age range was between 6 years and 70 years with majority of cases in third decade. Seventy six percent were nodal and rest were extranodal. The cervical lymph nodes were the commonest nodal group involved making 15(60 %) cases followed by 3 (12%) cases of axillary lymph nodes. The histopathological appearance showed complete effacement of architecture in 17 (68 %) of cases followed by sinusoidal distribution in 6(24 %) cases while partial effacement of architecture in 2 (8%) of cases. All the cases were positive for CD30 while 23 (92%) cases for CD3, 22 (88 %) cases for ALK and 19 (76%) cases positive for EMA. ALK negative lymphomas were 3(12%) cases. Conclusion: Anaplastic large cell lymphoma is more common in males and young adults. Nodal involvement is more common. Majority of cases show complete effacement of architecture. All cases are CD 30 positive. Most of cases are anaplastic lymphoma kinase antigen positive. (author)

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

    Science.gov (United States)

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

    2015-02-01

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

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

    DEFF Research Database (Denmark)

    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie; Shen, Yulei; Dabrowska, Magdalena Julia; Dybkær, Karen; Lim, Megan S; Piva, Roberto; Barreca, Antonella; Pellegrino, Elisa; Spaccarotella, Elisa; Lachel, Cynthia M; Kucuk, Can; Jiang, Chun-Sun; Hu, Xiaozhou; Bhagavathi, Sharathkumar; Greiner, Timothy C; Weisenburger, Dennis D; Aoun, Patricia; Perkins, Sherrie L; Gao, Z.; McKeithan, Timothy W; Inghirami, Giorgio; Chan, Wing C

    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...

  19. 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)

    2014-01-01

    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.

  20. Pleomorphic xanthoastrocytoma with anaplastic features: A case report

    Directory of Open Access Journals (Sweden)

    Sadiya Niamathullah

    2014-01-01

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

  1. Pleomorphic xanthoastrocytoma with anaplastic features: a case report.

    Science.gov (United States)

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

    2014-01-01

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

  2. Recurrent Systemic Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant-Associated Lesion.

    Science.gov (United States)

    Zimmerman, Amanda; Locke, Frederick L; Emole, Josephine; Rosa, Marilin; Horna, Pedro; Hoover, Susan; Dayicioglu, Deniz

    2015-07-01

    A woman aged 48 years presented with fevers, chills, weight loss, and night sweats. She had significant lymphadenopathy of the left neck as well as the left axilla. Her history was significant for bilateral breast augmentation with textured silicone implants more than 25 years ago. Excisional biopsy of a cervical lymph node revealed large, atypical cells positive for CD4 and CD30 and negative for Epstein-Barr virus-encoded ribonucleic acid, CD2, CD3, CD5, CD7, CD8, CD15, CD20, pan-keratin, S100, anaplastic lymphoma kinase (ALK), and paired box 5. These findings were consistent with Ann Arbor stage IIIB ALK-anaplastic large cell lymphoma (ALCL). The patient was started on 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone. She initially had no signs or symptoms of breast involvement; however, after developing seroma during the clinical course, the patient underwent capsulectomy and removal of the intact, textured silicone implants. Pathological evaluation demonstrated ALK-ALCL in the left breast capsule with cells displaying a significant degree of pleomorphism with binucleated forms and numerous mitoses. Fluorescence in situ hybridization confirmed the tumor was negative for t(2;5). She presented 8 weeks later showing evidence of recurrent systemic disease. PMID:26351895

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

    Science.gov (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

    2016-01-01

    The benefit of postoperative chemotherapy for anaplastic ependymoma remains unknown. We report two pediatric patients with refractory anaplastic ependymoma treated with temozolomide (TMZ). We did not detect O(6) -methylguanine-DNA methyltransferase (MGMT) promoter methylation in tumor samples; however, MGMT protein expression was low. With TMZ treatment, one patient had a 7-month complete remission; the other, stable disease for 15 months. Three other patients did not respond to TMZ; two had high and one low MGMT expression, and two showed no MGMT promoter methylation. These findings suggest that TMZ may be effective for pediatric refractory anaplastic ependymoma with low MGMT protein expression. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. PMID:26305586

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

    Directory of Open Access Journals (Sweden)

    GiorgioInghirami

    2012-05-01

    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.

  5. Steroid Dermatitis Resembling Rosacea: A Clinical Evaluation of 75 Patients

    OpenAIRE

    Hameed, Ammar F.

    2013-01-01

    Background. The use of topical steroids on the skin of the face should be carefully evaluated by the dermatologist; however, its misuse still occurs producing dermatological problem resembling rosacea. Objectives. To report the different clinical manifestations of steroid dermatitis resembling rosacea and to discover causes behind abusing topical steroids on the face. Methods. In this prospective observational study, 75 patients with steroid dermatitis resembling rosacea who had history of to...

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

    Directory of Open Access Journals (Sweden)

    Ganguly R

    2010-04-01

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

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

    Science.gov (United States)

    2015-03-02

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

  8. Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation

    OpenAIRE

    Koga, Tomoyuki; MORITA, Akio; Maruyama, Keisuke; TANAKA, Minoru; Ino, Yasushi; Shibahara, Junji; Louis, David N.; Reifenberger, Guido; Itami, Jun; Hara, Ryusuke; Saito, Nobuhito; Todo, Tomoki

    2009-01-01

    Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain. Some PXAs are accompanied by anaplastic features and are difficult to manage because of frequent recurrences that lead to early death. No previous reports have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy for this disease. We report a case of PXA with anaplastic features treated with stereotactic irradiation (STI) that resulted in long-term control of repeatedly recurring nodules throu...

  9. Critical appraisal of clinicopathological features of anaplastic carcinoma small intestine – A rare case report

    OpenAIRE

    VANDANA PURI

    2012-01-01

    Anaplastic carcinoma is an extremely rare variant of small intestine adenocarcinoma with only an occasional case having been reported in literature to date. We report a case of 46 year old male who presented with an endophytic tumor in ileum extending through full thickness of intestinal wall, with invasion into mesenteric fat. Microscopically, the tumor showed a biphasic growth pattern unlike conventional adenocarcinoma. The present case discusses the histomorphology of anaplastic c...

  10. Small cell anaplastic carcinoma of the prostate: a clinical, pathological and immunohistological study of 27 patients.

    Science.gov (United States)

    Oesterling, J E; Hauzeur, C G; Farrow, G M

    1992-03-01

    Because small cell anaplastic carcinoma of the prostate is an uncommon tumor, it has remained a poorly defined entity. To elucidate further the clinical, pathological and immunohistochemical characteristics of this cancer the 27 patients who presented to the Mayo Clinic from 1960 to 1990 were reviewed. Of these patients 18 (67%) presented with pure small cell anaplastic carcinoma, and 9 (33%) were diagnosed with small cell anaplastic carcinoma and adenocarcinoma of the prostate. Twenty-six patients (96%) had either stage C or D disease at the time of diagnosis. Two patients presented with a paraneoplastic syndrome, including 1 man with inappropriate antidiuretic hormone secretion and 1 who suffered from thyroxine intoxication. Of 24 men with long-term followup 22 (92%) died of small cell anaplastic carcinoma of the prostate despite antiandrogen therapy and the remaining 2 are alive with active, progressive disease. The median survival time following diagnosis was 17.1 months (range 2 to 90 months). All tumors with tissue available for immunohistochemical staining reacted positive for neuron-specific enolase, indicating that small cell anaplastic carcinoma of the prostate is most likely a neuroendocrine neoplasm. No tumor stained positive for either prostatic acid phosphatase or prostate specific antigen. Pathologically, small cell anaplastic carcinoma of the prostate appears to be similar to oat cell carcinoma of the lung. This series of 27 patients emphasizes that small cell anaplastic carcinoma of the prostate is highly malignant, is frequently of advanced stage at presentation, responds poorly to antiandrogen therapy and has a poor prognosis. PMID:1311395

  11. Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase.

    Science.gov (United States)

    Gingrich, Diane E; Lisko, Joseph G; Curry, Matthew A; Cheng, Mangeng; Quail, Matthew; Lu, Lihui; Wan, Weihua; Albom, Mark S; Angeles, Thelma S; Aimone, Lisa D; Haltiwanger, R Curtis; Wells-Knecht, Kevin; Ott, Gregory R; Ghose, Arup K; Ator, Mark A; Ruggeri, Bruce; Dorsey, Bruce D

    2012-05-24

    Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhibitor crizotinib. Through a series of targeted modifications on an ALK inhibitor diaminopyrimidine scaffold, our research group has driven improvements in ALK potency, kinase selectivity, and overall pharmaceutical properties. Optimization of this scaffold has led to the identification of a potent and efficacious inhibitor of ALK, 25b. A striking feature of 25b over previously described ALK inhibitors is its >600-fold selectivity over insulin receptor (IR), a closely related kinase family member. Most importantly, 25b exhibited dose proportional escalation in rat compared to compound 3 which suffered dose limiting absorption preventing further advancement. Compound 25b exhibited significant in vivo antitumor efficacy when dosed orally in an ALK-positive ALCL tumor xenograft model in SCID mice, warranting further assessment in advanced preclinical models. PMID:22564207

  12. Pulmonary Anaplastic Large Cell Lymphoma - a Rare Case

    Directory of Open Access Journals (Sweden)

    Züleyha Bingöl

    2009-03-01

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

  13. Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC. 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy. The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress. The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases

  14. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    International Nuclear Information System (INIS)

    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. 18F-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)

  15. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-04-01

    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).

  16. Anaplastic Lymphoma Kinase (ALK) Signaling in Lung Cancer.

    Science.gov (United States)

    Ou, Sai-Hong Ignatius; Shirai, Keisuke

    2016-01-01

    Chromosomal rearrangement in the anaplastic lymphoma kinase (ALK) gene was identified as an oncogenic driver in non-small cell lung cancer (NSCLC) in 2007. A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al. Oncologist 17:1351-1375, 2012). Knowledge gained from treating ALK-rearranged NSCLC patients including the presenting clinicopathologic characteristics, methods of detecting ALK-rearranged NSCLC, pattern of relapse and acquired resistance mechanisms while on crizotinib, and the clinical activities of more potent ALK inhibitors has led us to a detailed and ever expanding knowledge of the ALK signaling pathway in lung cancer but also raising many more questions that remained to be answered in the future. This book chapter will provide a concise summary of the importance of ALK signaling pathway in lung cancer. Understanding the ALK signaling pathway in lung cancer will likely provide the roadmap to the management of major epithelial malignancies driven by receptor tyrosine kinase rearrangement. PMID:26667344

  17. Results of combined treatment of anaplastic thyroid carcinoma (ATC)

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis. We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin. Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months. Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging

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

    International Nuclear Information System (INIS)

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

  19. Combined chemotherapy and irradiation in anaplastic thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Pejčić Ivica

    2003-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

    We describe the first patient, to our knowledge, with anaplastic pleomorphic xanthoastrocytoma (PXA) with spinal leptomeningeal spread at the time of diagnosis and present a review of the literature. PXA is a tumor that typically has an indolent course but occasionally, when anaplastic features are present, behaves in a more aggressive manner. We found that PXA with spinal leptomeningeal spread at the time of diagnosis confers a worse prognosis. Craniospinal imaging should be obtained at time of diagnosis of PXA and the presence of leptomeningeal spread may be indicative of a more aggressive disease process. PMID:25934112

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

    Science.gov (United States)

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

    2015-01-01

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

  2. CYTOLOGICAL DIAGNOSIS OF A RARE CASE OF ANAPLASTIC CARCINOMA OF THYROID IN A YOUNG WOMAN

    Directory of Open Access Journals (Sweden)

    Neha

    2014-04-01

    Full Text Available Anaplastic carcinoma is a rare tumor of thyroid accounting for 5 to 14% of all the thyroid neoplasms. Mean age of presentation is 5th to 6th decade. We report a case of 39-year-old woman presenting with complains of dyspnea, dysphagia and an anterior neck swelling. FNAC smears revealed both bizarre spindle cells and squamoid cells in cluster and sheets, also dispersed singly with wide areas of necrosis. The present case highlights a rare presentation of anaplastic carcinoma thyroid in a young woman and illustrates the role of cytology in giving an accurate diagnosis.

  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

    Science.gov (United States)

    2016-01-07

    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. Conodont bioapatite resembles vertebrate enamel by XRD properties

    OpenAIRE

    Jüri Nemliher; Toivo Kallaste

    2012-01-01

    XRD properties of Phanerozoic conodont apatite material were studied. It was found out that in terms of crystallinity the apatite resembles the enamel tissue of modern vertebrates. In terms of crystal lattice, apatite of conodonts is independent of taxa on the one hand and of chemistry of the surrounding rock type on the other hand.

  5. Polioencephalomyelopathy in a mixed breed dog resembling Leigh's disease.

    Science.gov (United States)

    Chai, Orit; Milgram, Joshua; Shamir, Merav H; Brenner, Ori

    2015-01-01

    A 14-month-old mixed-breed dog was presented with acute onset of exercise intolerance that quickly progressed to quadriparesis. Gross and microscopic autopsy findings indicated a type of degenerative polioencephalomyelopathy resembling subacute necrotizing encephalomyelopathy in dogs or Leigh's disease in humans. This syndrome has previously been reported only in purebred dogs. PMID:25565716

  6. 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

    2012-11-01

    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

  7. Anaplastic Thyroid Carcinoma or Thyroid Metastasis from Cholangiocarcinoma? A Case Report

    Directory of Open Access Journals (Sweden)

    Lidia Ionescu

    2014-05-01

    Full Text Available Anaplastic thyroid carcinoma presents as an extremely localy invasive neck mass while metastases in the thyroid are most commonly described as small, indolent, solitary nodules usually originating from kidney, breast, lungs and skin tumors. We report the case of a 74-year old male patient illustrating the difficulties of differential diagnosis between an anaplastic thyroid carcinoma and a thyroid metastasis of a peripheral cholangiocarcinoma in a cirrhotic patient diagnosed and operated for a locally advanced thyroid tumor. The history, clinical and imagistical features strongly pleaded for the diagnosis of anaplastic thyroid carcinoma presumably with liver metastases, also supported by the rapid recurrence following total thyroidectomy. Immunohistochemical tests showed a malignant carcinomatous proliferation with anaplastic prophile. Positive immunochemical staining for cytokeratin AE1/AE3, CK7 and negative CK20, AFP, CD15, CD30, CD5, TTF1 and thyroglobulin directed the possible diagnosis toward a secondary thyroid tumor from a peripheral cholangiocarcinoma. Immunohistochemical tests showed a malignant carcinomatous proliferation with anaplastic prophile. Positive immunochemical staining for cytokeratin AE1/AE3, CK7 and negative CK20, AFP, CD15, CD30, CD5, TTF1 and thyroglobulin directed the possible diagnosis toward a secondary thyroid tumor from a peripheral cholangiocarcinoma. A CT-guided percutaneous hepatic punction biopsy was planned but the patient presented an ischemic stroke with fatal outcome. In conclusion, in spite of surgical treatment the rapid recurrent thyroid cancer either primary or metastatic had a poor prognosis with fatal outcome mainly in the presence liver cirrhosis and cardio-vascular co-morbidities.

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

    Directory of Open Access Journals (Sweden)

    Nicholas M Kelly

    2005-07-01

    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 glioma cells, and the other group of genes is expressed primarily in neoplastic astrocytes but not in neoplastic oligodendrocytes. Differential protein expression of these two groups of genes in ODG and OAC may be related to the cellular origins and the histological features of the neoplastic cells.

  9. VPS35 Parkinson's disease phenotype resembles the sporadic disease.

    Science.gov (United States)

    Struhal, Walter; Presslauer, Stefan; Spielberger, Sabine; Zimprich, Alexander; Auff, Eduard; Bruecke, Thomas; Poewe, Werner; Ransmayr, Gerhard

    2014-07-01

    Recently a new autosomal dominant Parkinson's disease mutation (p.Asp620Asn) in the VPS35 gene was discovered. The clinical features of 14 PD patients with this mutation from three Austrian families were evaluated. Age at disease-onset appears lower and depression was more common in Austrian patients compared to sporadic PD patients. However, we were unable to identify a specific clinical maker of VPS35 patients, who otherwise resemble sporadic PD patients. PMID:24557499

  10. Carbonaceous objects resembling nannobacteria in the Allende meteorite

    Science.gov (United States)

    Folk, Robert L.; Lynch, F. Leo

    1998-07-01

    The carbon in Allende consists of balls ranging form 30 to 150 nm in diameter.Most are spheres, but some ovoid to worm- like forms occur. Grape-like clumps and rosary-like chains are the most dramatic mimics of terrestrial bacterial colonies. We propose that the carbon balls in Allende represent roasted corpses of nanobacteria because of their resemblance to nanobacteria on earth.

  11. expresses surface proteins that closely resemble those from

    OpenAIRE

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

    2009-01-01

    is a commensal of dogs that is implicated in the pathogenesis of canine pyoderma. This study aimed to determine if expresses surface proteins resembling those from and to characterise them. strain 326 was shown to adhere strongly to purified fibrinogen, fibronectin and cytokeratin 10. It adhered to the ?-chain of fibrinogen which, along with binding to cytokeratin 10, is the hallmark of clumping factor B of , a surface protein that is in part responsible for colonization of the human nares. L...

  12. Lingual Tuberculosis Clinically Resembling as a Neoplasm - A Case Report

    Directory of Open Access Journals (Sweden)

    Smita S. Shete

    2013-07-01

    Full Text Available Lingual tuberculosis is a very rare case in theareas where tuberculosis is endemic. There arediagnostic difficulties in patients presentingwith non healing ulcer over the tongue due tovariety of clinical appearances, most of whichmay clinically resemble malignant lingual neo-plasm. Here we report a case of lingual nonhealing ulcer in a 40 years male which was clini-cally diagnosed as malignant ulcer but histopa-thology and ZN staining confirmed the diagno-sis of lingual tuberculosis.

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

    Science.gov (United States)

    2016-01-11

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

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

    Science.gov (United States)

    Geller, James I

    2016-01-01

    'High risk' renal tumors of childhood generally includes anaplastic Wilms tumor, rhabdoid tumor, and metastatic renal sarcomas and carcinomas. In this review, the epidemiology, biology, treatment and prognosis of anaplastic Wilms tumor and rhabdoid tumor are presented. Future directions related to management of such cancers are discussed, with insights provided into possible clinical trials in development that consider integration of novel targeted therapies. PMID:26612481

  15. Multiple oligodendroglioma with pseudoprogression

    Directory of Open Access Journals (Sweden)

    Junko Matsuyama

    2012-01-01

    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.

  16. Sequence of retrovirus provirus resembles that of bacterial transposable elements

    Science.gov (United States)

    Shimotohno, Kunitada; Mizutani, Satoshi; Temin, Howard M.

    1980-06-01

    The nucleotide sequences of the terminal regions of an infectious integrated retrovirus cloned in the modified ? phage cloning vector Charon 4A have been elucidated. There is a 569-base pair direct repeat at both ends of the viral DNA. The cell-virus junctions at each end consist of a 5-base pair direct repeat of cell DNA next to a 3-base pair inverted repeat of viral DNA. This structure resembles that of a transposable element and is consistent with the protovirus hypothesis that retroviruses evolved from the cell genome.

  17. Anaplastic large-cell lymphoma presenting as a nasopharyngeal mass and cervical lymphadenopathy.

    Science.gov (United States)

    Dion, Gregory R; Packer, Mark D

    2015-06-01

    Cervical lymphadenopathy in adults has a broad differential diagnosis, including bacterial and viral infections, Kikuchi-Fujimoto disease, systemic lupus erythematosus, and various neoplasms. Many of its etiologies share similar symptomatology and presentations, which complicates the diagnosis. A thorough history and a comprehensive physical examination, to include nasopharyngoscopy and imaging as indicated by the specific case, are key to determining the origin of the lymphadenopathy and to avoid a missed or delayed diagnosis. Based on our review of the literature, we present the second reported case of anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma presenting in an adult with an obstructing adenoid/nasopharyngeal mass and lymphadenopathy. The mass, which occurred in a 19-year-old woman of Asian descent, caused nasal airway obstruction in the setting of cervical lymphadenopathy that was initially ascribed to mononucleosis. PMID:26053987

  18. Anaplastic large cell lymphoma associated with breast implant: a case report.

    Science.gov (United States)

    Rajabiani, Afsaneh; Arab, Hosein; Emami, Abolhasan; Manafi, Ali; Bazzaz, Navid; Saffar, Hiva

    2012-01-01

    Primary breast lymphoma represents less than 1% of all primary breast malignancies and most primary breast lymphomas are of B-Cell origin. The association of anaplastic lymphoma kinase (ALK) negative anaplastic large cell lymphoma (ALCL), a very rare form of primary breast lymphoma, with silicone-filled breast implants has been suggested and several case reports supported this proposal, especially in Western countries. Here we describe one of the first cases of primary breast ALK-negative ALCL in association with saline-filled silicone breast implants evaluated in Iran, where the rising number of breast reconstructive and aesthetic surgeries would commit both surgical pathologists and plastic surgeons to be familiar with this entity. PMID:25734044

  19. Endobronchial ALK-Positive Anaplastic Large Cell Lymphoma Presenting Massive Hemoptysis

    Science.gov (United States)

    Kim, Hee Kyung; Kim, Bo Hye; Kim, Sae Ahm; Shin, Jae Kyoung; Song, Ji-Hyun; Kwon, Ah-Young; Kim, Jung-Hyun; Kim, Eun-Kyung; Lee, Ji-Hyun; Kim, Gwaung-Il

    2015-01-01

    Primary anaplastic large cell lymphoma (ALCL) of the lung is highly aggressive and quite rare. We report here a case of anaplastic lymphoma kinase-positive endobronchial ALCL, that was initially thought to be primary lung cancer. A 68-year-old woman presented with hemoptysis, dyspnea, and upper respiratory symptoms persisting since 1 month. The hemoptysis and and bronchial obstruction lead to respiratory failure, prompting emergency radiotherapy and steroid treatment based on the probable diagnosis of lung cancer, although a biopsy did not confirm malignancy. Following treatment, her symptoms resolved completely. Chest computed tomography scan performed 8 months later showed increased and enlarged intra-abdominal lymph nodes, suggesting lymphoma. At that time, a lymph node biopsy was recommended, but the patient refused and was lost to follow up. Sixteen months later, the patient revisited the emergency department, complaining of persistent abdominal pain since several months. A laparoscopic intra-abdominal lymph node biopsy confirmed a diagnosis of ALCL. PMID:26508931

  20. Resemblance operations and conceptual complexity in animal metaphors

    Directory of Open Access Journals (Sweden)

    Aneider Iza Ervitia

    2012-07-01

    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.

  1. RESEMBLANCE OPERATIONS AND CONCEPTUAL COMPLEXY IN ANIMAL METAPHORS

    Directory of Open Access Journals (Sweden)

    Aneider Iza Ervitia

    2012-07-01

    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.

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

    OpenAIRE

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

    2004-01-01

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

  3. Spinal cord compression caused by anaplastic large cell lymphoma in an HIV infected individual.

    Science.gov (United States)

    Kumar, Susheel; Wanchu, Ajay; Sharma, Aman; Mukherjee, Kanchan; Radotra, B D; Gupta, Vivek; Singh, Surjit

    2010-01-01

    Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV) infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL) is a distinct type of non-Hodgkin's lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual. PMID:21119283

  4. Spinal cord compression caused by anaplastic large cell lymphoma in an HIV infected individual

    Directory of Open Access Journals (Sweden)

    Kumar Susheel

    2010-01-01

    Full Text Available Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL is a distinct type of non-Hodgkin?s lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual.

  5. Spinal cord compression caused by anaplastic large cell lymphoma in an HIV infected individual

    OpenAIRE

    Kumar Susheel; Wanchu Ajay; Sharma Aman; Mukherjee Kanchan; Radotra B; Gupta Vivek; Singh Surjit

    2010-01-01

    Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV) infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL) is a distinct type of non-Hodgkin?s lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual.

  6. An Evolutionary Conserved Role for Anaplastic Lymphoma Kinase in Behavioral Responses to Ethanol

    OpenAIRE

    Lasek, Amy W.; Lim, Jana; Kliethermes, Christopher L; Berger, Karen H.; Joslyn, Geoff; Brush, Gerry; Xue, Liquan; Robertson, Margaret; Moore, Monica S.; Vranizan, Karen; Morris, Stephan W; Schuckit, Marc A; White, Raymond L.; Heberlein, Ulrike

    2011-01-01

    Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk exp...

  7. Mutations in Rb1 pathway-related genes are associated with poor prognosis in Anaplastic Astrocytomas

    OpenAIRE

    Bäcklund, L M; Nilsson, B R; Liu, L.; Ichimura, K; Collins, V. P.

    2005-01-01

    Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most common and most malignant type of adult CNS tumour. Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value. The survival data on 37 carefully sampled AA was correlated with the results of a detailed analysis of...

  8. Long-term control of disseminated pleomorphic xanthoastrocytoma with anaplastic features by means of stereotactic irradiation.

    Science.gov (United States)

    Koga, Tomoyuki; Morita, Akio; Maruyama, Keisuke; Tanaka, Minoru; Ino, Yasushi; Shibahara, Junji; Louis, David N; Reifenberger, Guido; Itami, Jun; Hara, Ryusuke; Saito, Nobuhito; Todo, Tomoki

    2009-08-01

    Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm of the brain. Some PXAs are accompanied by anaplastic features and are difficult to manage because of frequent recurrences that lead to early death. No previous reports have demonstrated consistent efficacy of adjuvant radiotherapy or chemotherapy for this disease. We report a case of PXA with anaplastic features treated with stereotactic irradiation (STI) that resulted in long-term control of repeatedly recurring nodules throughout the neuraxis. A 47-year-old woman presented with an epileptic seizure due to a large tumor in the right frontal lobe. The tumor was resected and diagnosed as PXA with anaplastic features. Sixteen months later, a relapse at the primary site was noted and treated with stereotactic radiosurgery using Gamma Knife. Two years later, the patient developed a tumor nodule in the cervical spinal cord that histologically corresponded to a small-cell glioma with high cellularity and prominent MIB-1 (mindbomb homolog 1) labeling. In the following months, multiple nodular lesions appeared throughout the CNS, and STI was performed six times for eight intracranial lesions using Gamma Knife and twice using a linear accelerator, for three spinal cord lesions in total. All lesions treated with STI were well controlled, and the patient was free from symptomatic progression for 50 months. However, diffuse dissemination along the craniospinal axis eventually progressed, and she died 66 months after initial diagnosis. Autopsy showed that the nodules remained well demarcated from the surrounding nervous system tissue. STI may be an effective therapeutic tool for controlling nodular dissemination of PXA with anaplastic features. PMID:19164434

  9. [Hemophagocytic lymphohistiocytosis associated with a lymphohistiocytic pattern anaplastic large cell lymphoma: a case report].

    Science.gov (United States)

    Sizaret, Damien; Lecointre, Claire; Kerdraon, Rémy; Bléchet, Claire; Bonneau, Carole; Alexis, Magda; Camus, François; Michenet, Patrick

    2013-08-01

    We report the case of a 16-year-old girl with an anaplastic large cell lymphoma of lymphohistiocytic pattern revealed by a hemophagocytic syndrome. Histologically, the lymphomatous population was concealed by clusters of histiocytes. Immunohistochemical study allowed the diagnosis. The combination of these two entities is rarely described and may be a source of delay in diagnosis of a life-threatening condition. PMID:23954124

  10. A Time-Resolved Luminescence Biosensor Assay for Anaplastic Lymphoma Kinase (ALK) Activity†

    Science.gov (United States)

    Cui, Wei; Parker, Laurie L.

    2014-01-01

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

  11. Identification of Oncogenic Point Mutations and Hyperphosphorylation of Anaplastic Lymphoma Kinase in Lung Cancer12

    OpenAIRE

    Wang, Yi-Wei; Tu, Pang-Hsien; Lin, Kuen-Tyng; Lin, Shu-Chen; Ko, Jenq-Yuh; Jou, Yuh-Shan

    2011-01-01

    The oncogenic property of anaplastic lymphoma kinase (ALK) plays an essential role in the pathogenesis of various cancers and serves as an important therapeutic target. In this study, we identified frequent intragenic loss of heterozygosity and six novel driver mutations within ALK in lung adenocarcinomas. Overexpression of H694R or E1384K mutant ALK leads to hyperphosphorylation of ALK, and activation of its downstream mediators STAT3, AKT, and ERK resulted in enhanced cell proliferation, co...

  12. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma?

    OpenAIRE

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

    2008-01-01

    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....

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

    Science.gov (United States)

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

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) is a common subtype of the heterogeneous group of peripheral T-cell lymphomas, which is characterized by large pleomorphic cells with strong expression of CD30. Translocations involving ALK, the anaplastic lymphoma kinase gene, are associated with a favorable clinical outcome. Such ALK-positive ALCLs are usually responsive to a multidrug chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). However, there is no general consensus on the optimal therapy for relapsed or refractory ALCL. We report the case of a 24-year-old male suffering from ALK-positive ALCL with an uncommon manifestation of only extranodal disease in the gastric cardia region that showed primary refractoriness to standard CHOP chemotherapy. A combination therapy consisting of the anti-CD30 drug conjugate, brentuximab vedotin, and classical lymphoma salvage regimen DHAP (cisplatin, high-dose cytarabine and dexamethasone) was administered. Following two treatment cycles in 21-day intervals, the lymphoma showed considerable regression based on imaging diagnostics and no evidence of vital lymphoma in a subsequent biopsy. We did not observe any increase in toxicity; in particular, polyneuropathy and febrile neutropenia were not observed. In summary, we report that the antibody-drug conjugate brentuximab vedotin and a classical regimen used for aggressive lymphoma, DHAP, could be combined as salvage therapy in a case of refractory ALK-positive ALCL. Phase I/II studies will be required for safety and efficacy analysis. PMID:25018638

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

    Directory of Open Access Journals (Sweden)

    Emoto Mie

    2002-10-01

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

  15. PERCEPTUAL RESEMBLANCE OF FACIAL IMAGES: A NEAR SET APPROACH

    Directory of Open Access Journals (Sweden)

    A.MUSTAFI

    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

  16. A case of cervical radiation radiculopathy resembling motor neuron disease

    International Nuclear Information System (INIS)

    A 67-year-old man developed slowly progressive muscular weakness in the bilateral upper extremities (C5-7 regions) without signs of sensory deficit following the cervical radiation therapy (70.5 Gy) for right laryngeal cancer 4 years before. These clinical signs resembled those of lower motor neuron disease. MRI with gadolinium-DTPA, however, showed enhancement in the bilateral C5 and C6 anterior roots, suggesting the cervical radiculopathy due to radiotherapy. It is known that radiation to the spinal cord can lead to ''selective anterior horn cell injury''. This is the first case report of the cervical radiation radiculopathy, which, if without MRI, might be classified into selective anterior horn cell injury. Suggestion is made for the hypothesis that the spinal motoneuron loss in radiation myelopathy would be caused by retrograde degeneration due to anterior root damages. (author)

  17. Skin adnexal neoplasm closely resembling adenomatoid tumor: a unique occurrence.

    Science.gov (United States)

    Crippa, S; Di Bella, C; Faravelli, A

    2006-04-01

    We describe a primary skin neoplasm located in the left chest wall that closely resembled adenomatoid tumor of male and female genital tract. It occurred in a 52-year-old woman who had undergone a left quadrantectomy with regional lymphadenectomy for invasive ductal carcinoma of the breast 7 years previously. The tumor involved the dermis and subcutaneous tissue and measured 0.7 cm in greatest diameter. Immunohistochemical evaluation showed strong positivity for cytokeratin pool and negativity for CD31, calretinin, WT-180, and for estrogen and progesterone receptors. We are unaware of a previous description of this morphologic pattern in a primary skin tumor, which we have interpreted as of skin adnexal and specifically of eccrine sweat gland origin. PMID:16703184

  18. A case of cervical radiation radiculopathy resembling motor neuron disease

    Energy Technology Data Exchange (ETDEWEB)

    Mitsunaga, Yoshihiro; Yoshimura, Takeo; Hara, Hideo; Yamada, Takeshi; Kira, Jun-ichi; Kobayashi, Takuro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1998-05-01

    A 67-year-old man developed slowly progressive muscular weakness in the bilateral upper extremities (C5-7 regions) without signs of sensory deficit following the cervical radiation therapy (70.5 Gy) for right laryngeal cancer 4 years before. These clinical signs resembled those of lower motor neuron disease. MRI with gadolinium-DTPA, however, showed enhancement in the bilateral C5 and C6 anterior roots, suggesting the cervical radiculopathy due to radiotherapy. It is known that radiation to the spinal cord can lead to ``selective anterior horn cell injury``. This is the first case report of the cervical radiation radiculopathy, which, if without MRI, might be classified into selective anterior horn cell injury. Suggestion is made for the hypothesis that the spinal motoneuron loss in radiation myelopathy would be caused by retrograde degeneration due to anterior root damages. (author)

  19. Autonomously Moving Colloidal Objects that Resemble Living Matter

    Directory of Open Access Journals (Sweden)

    Youichi Morimune

    2010-11-01

    Full Text Available The design of autonomously moving objects that resemble living matter is an excellent research topic that may develop into various applications of functional motion. Autonomous motion can demonstrate numerous significant characteristics such as transduction of chemical potential into work without heat, chemosensitive motion, chemotactic and phototactic motions, and pulse-like motion with periodicities responding to the chemical environment. Sustainable motion can be realized with an open system that exchanges heat and matter across its interface. Hence the autonomously moving object has a colloidal scale with a large specific area. This article reviews several examples of systems with such characteristics that have been studied, focusing on chemical systems containing amphiphilic molecules.

  20. IRAS sources associated with nebulosities resembling Herbig-Haro objects

    International Nuclear Information System (INIS)

    The IRAS Survey has been used to search 22 nebulosities resembling Herbig-Haro objects for evidence of newly forming stars. Half the peculiar nebulae are found to have associated IRAS sources. From a study of the energy distributions, obtained from JHKL photometry and IRAS flux densities, the physical characteristics of the sources have been derived. The IRAS sources 04073 + 3800(GY 10), 05173-0555(GY 14), and 05439 + 3035(GY 18) have been identified as possible low-mass protostars, while the sources 03134 + 5958(GY 5) and 21004 + 7811(GY 21) are T Tauri stars with nebular disks and surrounding dust envelopes of residual infall. Finally, the IRAS source 04591-0856, associated with the nebula GY 13, could be in an evolutionary stage intermediate between a protostar in the pure infall phase and that of an obscured T Tauri. 26 references

  1. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2015-07-27

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

  2. Neurogenesis in Aplysia californica resembles nervous system formation in vertebrates

    International Nuclear Information System (INIS)

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

  3. Menisectomized miniature Vietnamese pigs develop articular cartilage pathology resembling osteoarthritis.

    Science.gov (United States)

    Cruz, Raymundo; Ramírez, Carmen; Rojas, Oscar I; Casas-Mejía, Oscar; Kouri, Juan B; Vega-López, Marco A

    2015-11-01

    Animal models have been used to understand the basic biology of osteoarthritis (OA) and have helped to identify new candidate biomarkers for the early diagnosis and treatment of this condition. Small animals cannot sufficiently mimic human diseases; therefore, large animal models are needed. Pigs have been used as models for human diseases because they are similar to humans in terms of their anatomy, physiology and genome. Hence, we analyzed articular cartilage and synovial membrane pathology in miniature Vietnamese pigs after a unilateral partial menisectomy and 20-day exercise regimen to determine if the pigs developed pathological characteristics similar to human OA. Histological and protein expression analysis of articular cartilage from menisectomized pigs revealed the following pathologic changes resembling OA: fibrillation, fissures, chondrocyte cluster formation, decrease in proteoglycan content and upregulation of the OA-associated proteins MMP-3, MMP-13, procaspase-3 and IL-1?. Moreover, histological analysis of synovial membrane revealed mild synovitis, characterized by hyperplasia, cell infiltration and neoangiogenesis. Pathological changes were not observed in the contralateral joints or the joints of sham-operated pigs. Further studies are required to validate such an OA model; however, our results can encourage the use of pigs to study early stages of OA physiopathology. Based on their similarities to humans, pigs may be useful for preclinical studies to identify new candidate biomarkers and novel treatments for OA. PMID:26296921

  4. Facial Resemblance to Emotions: Group Differences, Impression Effects, and Race Stereotypes

    OpenAIRE

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

    2010-01-01

    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...

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

    Science.gov (United States)

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

    2004-01-01

    Background Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. Methods In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. Results A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 ?M, 7 fold at 100 ?M). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 ?M) and earlier exposure time (24 h). Conclusion These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours. PMID:15363094

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

    Directory of Open Access Journals (Sweden)

    Rotiroti Domenicoantonio

    2004-09-01

    Full Text Available Abstract Background Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. Methods In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio. Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. Results A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 ?M, 7 fold at 100 ?M. When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 ?M and earlier exposure time (24 h. Conclusion These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free for the treatment of anaplastic human thyroid tumours.

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

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

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

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

    International Nuclear Information System (INIS)

    Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index. In this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/ 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content. A cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 ?M, 7 fold at 100 ?M). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 ?M) and earlier exposure time (24 h). These findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Balamurugan S

    2009-01-01

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

  11. Treatment of primary cutaneous anaplastic large cell lymphoma with superficial X-rays

    Directory of Open Access Journals (Sweden)

    Malene E. Jepsen

    2015-03-01

    Full Text Available The optimal radiation schedule for primary cutaneous anaplastic lymphoma (PCALCL has not been investigated. We report here satisfactory outcomes of low-dose (16-20 Gy, 3-5 fractions, superficial X-ray radiation (40-50 kV in a series of 10 patients with PCALCL. Only 1 patient developed a local relapse during the median observation time of 25 months; complete remission was recorded in the other patients. This observation indicates that superficial, low dose X-ray therapy may provide a cost-effective alternative to the traditional 35-45 Gy schedules.

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

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2011-01-01

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

  13. Aggressive Multimodal Approach for Anaplastic Thyroid Cancer and Long-Term Survival

    OpenAIRE

    Nasir Hussain; Usman Mustafa; Su Hyeon Jung; Gilman, Alan D

    2013-01-01

    Anaplastic thyroid cancer (ATC) comprises 1-2% of all thyroid cancers and is one of the most aggressive cancers with a median survival rate of around four months. The average 5-year survival rate has been reported to be around 3.6%. In this paper, we have discussed management and prognostic variables of a patient with ATC who has survived for more than 5 years. A 59-year-old female was referred to our facility for an elective thyroid and parathyroidectomy for concerns of thyroid papillary can...

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

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2015-12-01

    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.

  15. Anaplastic small cell (oat cell) carcinoma of the tonsils: report of two cases.

    Science.gov (United States)

    Heimann, R; Dehou, M F; Lentrebecq, B; Faverly, D; Simonet, M L; Dor, P; Chanoine, F

    1989-01-01

    Two cases of anaplastic small cell (oat cell) carcinoma of the tonsils are presented. In the first, cervical metastases preceded the manifestation of the primary tumour by 2 years. In case 2 the tonsillar carcinoma was accompanied by a bronchial tumour of the same histological type and by cervical and axillary metastases. Positive Grimelius stain, positive immunohistochemical staining for chromogranin A and neurone-specific enolase and the presence, in case 1, of membrane-bound granules indicate that these tumours display many similarities with neuroendocrine carcinomas even if they originate from pluripotential ductal cells of tonsillar minor salivary glands and not from Kulchitsky-like cells. PMID:2466759

  16. Predator-Resembling Aversive Conditioning for Managing Habituated Wildlife

    Directory of Open Access Journals (Sweden)

    Colleen Cassady St. Clair

    2005-06-01

    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 hyperabundant and habituated urban wildlife.

  17. Gait analysis in a mouse model resembling Leigh disease.

    Science.gov (United States)

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

    2016-01-01

    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. PMID:26363424

  18. Facial resemblance to emotions: group differences, impression effects, and race stereotypes.

    Science.gov (United States)

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

    2010-02-01

    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. PMID:20085393

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

    Directory of Open Access Journals (Sweden)

    Gladys Iglesias Díaz

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Chen X

    2013-12-01

    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

  1. RNASET2--an autoantigen in anaplastic large cell lymphoma identified by protein array analysis.

    Science.gov (United States)

    Patel, Suketu; Chen, Hong; Monti, Laura; Gould, Edith; Haralambieva, Eugenia; Schmid, Jasmin; Toomey, David; Woessmann, Wilhelm; Roncador, Giovanna; Hatton, Chris S R; Liggins, Amanda P; Taramelli, Roberto; Banham, Alison H; Acquati, Francesco; Murphy, Derek; Pulford, Karen

    2012-09-18

    Characterising tumour-associated antigens (TAAs) not only represents an important approach to the identification of new diagnostic/prognostic markers, but can also provide information on disease processes and additional potential therapeutic targets. Preliminary screening of a protein macroarray, containing more than 12,000 different proteins, with sera from anaplastic lymphoma kinase (ALK)-negative and ALK-positive anaplastic large cell lymphoma (ALCL) patients identified ribonuclease and tumour suppressor protein Ribonuclease T2 (RNASET2), phosphatase lipid phosphate phosphatase-related protein type 3 (LPPR3) and apoptotic adaptor molecule Fas-associating protein (FADD) as ALK-negative ALCL-associated TAAs. Further validation of these observations was confirmed using the ALCL sera in reverse ELISAs. The circulating anti-RNASET2 autoantibodies present in ALCL patients' sera also recognised eukaryotically expressed RNASET2 protein. RNASET2 expression was then investigated in normal tissues and in lymphomas to explore its clinical potential. RNASET2 protein and mRNA levels showed highest expression in the spleen, leucocytes and pancreas. RNASET2 protein expression was not restricted to ALK-negative ALCL (81%), being expressed in ALK-positive ALCL (65%) as well as in a number of other lymphomas. The immunological recognition of RNASET2, its expression in ALCL and other lymphomas together with its known tumourigenic properties suggest that further studies on this autoantigen are warranted. PMID:22732457

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Gibson, C J; Parry, N M A; Jakowski, R M; Eshar, D

    2008-11-01

    A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100. PMID:18984799

  4. Peripheral T-cell lymphoma, NOS, and anaplastic large cell lymphoma.

    Science.gov (United States)

    Beaven, Anne W; Diehl, Louis F

    2015-12-01

    Peripheral T-cell lymphomas (PTCL), with the exception of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), have a very poor prognosis. Although current first line chemotherapy continues to be a CHOP-like (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen there is now data suggesting that the addition of etoposide in younger patients improves outcomes. Even for those patients who do have a response to therapy, the risk of relapse remains quite high. Although autologous transplant in first remission is often used, its role as consolidation therapy in first remission remains unclear and may preferentially benefit low-risk patients. In the relapsed setting, major advances have occurred with Food and Drug Administration (FDA) approval of 4 new agents (pralatrexate, romidepsin, belinostat, brentuximab vedotin) for relapsed/refractory PTCL since 2009. These 4 drugs represent the first agents ever approved specifically for this indication. Unfortunately, with the exception of ALCL for which brentuximab vedotin will likely substantially change our approach to treatment, there are still many patients for whom available drugs will not be effective, and it is for these patients that further advances are urgently needed. PMID:26637771

  5. 18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase

    International Nuclear Information System (INIS)

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

  6. {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)

    2013-12-15

    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.

  7. PI3K/AKT pathway alterations are associated with clinically aggressive and histologically anaplastic subsets of pilocytic astrocytoma

    OpenAIRE

    Rodriguez, Erika F; Scheithauer, Bernd W.; Giannini, Caterina; Rynearson, Amanda; Cen, Ling; Hoesley, Bridget; Gilmer-Flynn, Heather; Sarkaria, Jann N; Jenkins, Sarah; Long, Jin; Rodriguez, Fausto J.

    2010-01-01

    Pilocytic astrocytomas (PA) are well-differentiated gliomas having a favorable prognosis when compared with other diffuse or infiltrative astrocytomas. Molecular genetic abnormalities and activation of signaling pathways associated with clinically aggressive PA and histologically anaplastic PA have not been adequately studied. We performed molecular genetic, gene expression, and immunohistochemical studies using three PA subsets, including conventional PA (n = 43), clinically aggressive/recur...

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

    Science.gov (United States)

    Bai, Lei; Sehgal, Amita

    2015-11-01

    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. PMID:26536237

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

    DEFF Research Database (Denmark)

    Pedersen, Martin B; Danielsen, Allan V; Hamilton-Dutoit, Stephen J; Bendix, Knud; Nørgaard, Peter; Møller, Michael B; Steiniche, Torben; d'Amore, Francesco

    2014-01-01

    AIMS: Macrophage infiltration has been associated with prognosis in several cancers, including lymphoma, but has not been assessed systematically in anaplastic large cell lymphoma (ALCL). The aim of the study was to correlate expression of the macrophage-associated antigens CD68 and CD163 with pre......-therapeutic parameters and outcome in a cohort of treatment-naive ALCL patients. METHODS AND RESULTS: Pre-therapeutic tumour specimens from 52 patients with ALCL were included in a tissue microarray. The intratumoral macrophage content was assessed by immunohistochemical staining for CD68 and CD163, and quantified using......-free survival in ALK-negative patients (P < 0.001). CONCLUSIONS: A high content of intratumoral CD68- and/or CD163-positive macrophages correlates with an adverse outcome in ALK-negative ALCL....

  10. Congenital primary cutaneous anaplastic large-cell lymphoma: a case report.

    Science.gov (United States)

    Seo, An Na; Lee, Seok-Jong; Choi, Yoon Hyuk; Chung, Ho Yun; Huh, Jooryung; Yoon, Ghil Suk

    2015-05-01

    Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is the second most common type of primary cutaneous T-cell lymphoma. The median age of onset of C-ALCL is 60 years. Presented here is a case of congenital CD30-positive (CD30(+)) primary C-ALCL in a 10-day-old neonate who presented with a large erythematous indurative plaque in the right postauricular area. A systemic workup of the patient excluded other potential causes. The neonate was treated with wide excision, but chemotherapy or radiation therapy was not administered, as the patient's parents did not consent to such treatment. The patient has been monitored for 30 months after excision and there has been no disease recurrence. C-ALCL rarely occurs in children, and to the best of our knowledge, this is the first reported case of a neonate with congenital primary C-ALCL. PMID:25365497

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

    Science.gov (United States)

    Lai, Chao-Ming; Horowitz, Sandra

    2013-08-01

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

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

    Science.gov (United States)

    Bai, Lei; Sehgal, Amita

    2015-01-01

    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. PMID:26536237

  13. Small cell anaplastic carcinoma of primary lung tumor in a miniature schnauzer dog

    International Nuclear Information System (INIS)

    A seven-year-old male, an intact miniature Schnauzer dog with history of vomiting, abdominal distention, anorexia, and dyspnea was referred for further evaluation and treatment. Thoracic radiographs showed the well marginated solitary mass with soft density in the right caudal lung field, and abdominal radiographs showed signs of ascites, such as abdominal distention and moderate serosal detail loss. On ultrasonograph and computed tomograph, it was observed that the mass compressed the caudal vena cava (CVC) and adhered to the heart. Exploratory thoracotomy was performed, and then it was showed that mass adhered heart, CVC, and diaphragm. The mass was fully rejected although adhered part of CVC could not be completely rejected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma

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

    Directory of Open Access Journals (Sweden)

    Swaroop Revannasiddaiah

    2015-01-01

    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.

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

    DEFF Research Database (Denmark)

    Liu, Cuiling; Iqbal, Javeed

    2013-01-01

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

  16. Diversity of Genomic Breakpoints in TFG-ALK Translocations in Anaplastic Large Cell Lymphomas

    Science.gov (United States)

    Hernández, Luis; Beà, Sílvia; Bellosillo, Beatriz; Pinyol, Magda; Falini, Brunangelo; Carbone, Antonino; Ott, German; Rosenwald, Andreas; Fernández, Alberto; Pulford, Karen; Mason, David; Morris, Stephan W.; Santos, Eugenio; Campo, Elias

    2002-01-01

    Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5? TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALKS) and 97 kd (TFG-ALKL), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALKXL), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-?. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK. PMID:11943732

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

    Scientific Electronic Library Online (English)

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

    2012-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Fernando Peixoto Ferraz de Campos

    2013-10-01

    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.

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

    International Nuclear Information System (INIS)

    Purpose: To analyze a prospective protocol combining surgery, chemotherapy (CT), and hyperfractionated accelerated radiotherapy (RT) in anaplastic thyroid carcinoma. Methods and materials: Thirty anaplastic thyroid carcinoma patients (mean age, 59 years) were treated during 1990-2000. Tumor extended beyond the capsule gland in 26 patients, with tracheal extension in 8. Lymph node metastases were present in 18 patients and lung metastases in 6. Surgery was performed before RT-CT in 20 patients and afterwards in 4. Two cycles of doxorubicin (60 mg/m2) and cisplatin (120 mg/m2) were delivered before RT and four cycles after RT. RT consisted of two daily fractions of 1.25 Gy, 5 days per week to a total dose of 40 Gy to the cervical lymph node areas and the superior mediastinum. Results: Acute toxicity (World Health Organization criteria) was Grade 3 or 4 pharyngoesophagitis in 10 patients; Grade 4 neutropenia in 21, with infection in 13; and Grade 3 or 4 anemia and thrombopenia in 8 and 4, respectively. At the end of the treatment, a complete local response was observed in 19 patients. With a median follow-up of 45 months (range, 12-78 months), 7 patients were alive in complete remission, of whom 6 had initially received a complete tumor resection. Overall survival rate at 3 years was 27% (95% confidence interval 10-44%) and median survival 10 months. In multivariate analysis, tracheal extension and macroscopic complete tumor resection were significant factors in overall survival. Death was related to local progression in 5% of patients, to distant metastases in 68%, and to both in 27%. Conclusions: Main toxicity was hematologic. High long-term survival was obtained when RT-CT was given after complete surgery. This protocol avoided local tumor progression, and death was mainly caused by distant metastases

  20. Prognostic significance and therapeutic potential of the activation of anaplastic lymphoma kinase/protein kinase B/mammalian target of rapamycin signaling pathway in anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway has been demonstrated to be involved in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated tumorigenesis in anaplastic large cell lymphoma (ALCL) and correlated with unfavorable outcome in certain types of other cancers. However, the prognostic value of AKT/mTOR activation in ALCL remains to be fully elucidated. In the present study, we aim to address this question from a clinical perspective by comparing the expressions of the AKT/mTOR signaling molecules in ALCL patients and exploring the therapeutic significance of targeting the AKT/mTOR pathway in ALCL. A cohort of 103 patients with ALCL was enrolled in the study. Expression of ALK fusion proteins and the AKT/mTOR signaling phosphoproteins was studied by immunohistochemical (IHC) staining. The pathogenic role of ALK fusion proteins and the therapeutic significance of targeting the ATK/mTOR signaling pathway were further investigated in vitro study with an ALK + ALCL cell line and the NPM-ALK transformed BaF3 cells. ALK expression was detected in 60% of ALCLs, of which 79% exhibited the presence of NPM-ALK, whereas the remaining 21% expressed variant-ALK fusions. Phosphorylation of AKT, mTOR, 4E-binding protein-1 (4E-BP1), and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in 76%, 80%, 91%, and 93% of ALCL patients, respectively. Both phospho-AKT (p-AKT) and p-mTOR were correlated to ALK expression, and p-mTOR was closely correlated to p-AKT. Both p-4E-BP1 and p-p70S6K1 were correlated to p-mTOR, but were not correlated to the expression of ALK and p-AKT. Clinically, ALK + ALCL occurred more commonly in younger patients, and ALK + ALCL patients had a much better prognosis than ALK-ALCL cases. However, expression of p-AKT, p-mTOR, p-4E-BP1, or p-p70S6K1 did not have an impact on the clinical outcome. Overexpression of NPM-ALK in a nonmalignant murine pro-B lymphoid cell line, BaF3, induced the cells to become cytokine-independent and resistant to glucocorticoids (GCs). Targeting AKT/mTOR inhibited growth and triggered the apoptotic cell death of ALK + ALCL cells and NPM-ALK transformed BaF3 cells, and also reversed GC resistance induced by overexpression of NPM-ALK. Overexpression of ALK due to chromosomal translocations is seen in the majority of ALCL patients and endows them with a much better prognosis. The AKT/mTOR signaling pathway is highly activated in ALK + ALCL patients and targeting the AKT/mTOR signaling pathway might confer a great therapeutic potential in ALCL

  1. 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; Spang-Thomsen, M; Hirsch, F R; Hansen, M; Nissen, N I

    1980-01-01

    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 and a...... newly developed procedure for storing aspirates at -80 degrees. Thirty-eight different metastases in 30 consecutive patients with small-cell anaplastic carcinoma of the lung were examined with a total of 273 fine-needle aspirations. The results on ploidy are reported in this paper. The degree of...... of the detection limit set by the methodology used and the restricted number of samples studied in each patient indicate that the true occurrence of clonal heterogeneity in small-cell carcinoma of the lung may be much higher....

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

    OpenAIRE

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

    2014-01-01

    This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations i...

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

    OpenAIRE

    Akiba, Jun; Kawahara, Akihiko; Abe, Hideyuki; Azuma, Koichi; Yamaguchi, Tomohiko; TAIRA, TOMOKI; FUKUMITSU, CHIHIRO; TAKASE, YORIHIKO; YASUMOTO, MAKIKO; UMENO, YUMI; Todoroki, Keita; Kurita, Takashi; YAMAGUCHI, RIN; Kage, Masayoshi; YANO, HIROHISA

    2014-01-01

    Rearrangements of anaplastic lymphoma kinase (ALK) have been recently identified in non-small cell lung carcinomas. Previous studies have revealed characteristic features, including adenocarcinoma histology and mucin production, in ALK-positive lung carcinoma. The present study evaluated immunohistochemistry (IHC) in ALK-positive lung carcinoma using two different antibodies, clone 5A4 and D5F3, and compared the results. On the basis of the aforementioned characteristic features, out of 359 p...

  4. An unusual case of primary anaplastic large cell central nervous system lymphoma: an 8-year success story

    OpenAIRE

    Vivekanandan, Sindu; Dickinson, Peter; Bessell, Eric; O'Connor, Simon

    2011-01-01

    Primary central nervous system anaplastic large cell lymphoma (PCNS ALCL) is rare, with only three adult patients reported. We describe a patient with PCNS ALCL with the longest follow-up period so far reported. The patient was successfully treated with chemotherapy and radiotherapy. The patient is well, independent and in full-time employment and has no residual neurological deficit. He has normal mental status, has a full head of hair and has fathered a healthy child.

  5. GE-04MGMT METHYLATION IS A POSITIVE PROGNOSTIC MARKER IN PATIENTS WITH ANAPLASTIC ASTROCYTOMA TREATED WITH CONCURRENT TEMOZOLOMIDE AND RADIATION

    OpenAIRE

    Blumenthal, Deborah; BOKSTEIN, FELIX; Zelikovitsh, Bracha; Mordechai, Anat; Lossos, Alexander; Taliansky, Alisa; Zach, Lior; Tzuk-Shina, Tzahallah; Lavon, Iris

    2014-01-01

    BACKGROUND: Concurrent radiation (RT) and temozolomide (TMZ) has been accepted as standard first-line therapy for glioblastoma since publication of results of the phase III EORTC/NCIC trial in 2005. In the same NEJM issue, data were presented which showed the prognostic significance of MGMT methylation status in these patients. Trials for first-line treatment of anaplastic (grade III) glioma are currently underway, but until these trials complete accrual and mature, the role of concurrent che...

  6. Cytotoxic activity of the histone deacetylase inhibitor panobinostat (LBH589) in anaplastic thyroid cancer in vitro and in vivo.

    OpenAIRE

    BOSCO, Ornella; CATALANO, MARIA GRAZIELLA; BUSSOLATI, Benedetta; BOCCUZZI, Giuseppe; GRANGE, CRISTINA; PUGLIESE, MARIATERESA; GARGANTINI, ELEONORA; POLI, ROBERTA; ASIOLI, Sofia

    2012-01-01

    Anaplastic thyroid carcinoma (ATC) has a rapidly fatal clinical course, being resistant to multimodal treatments. Microtubules, ?/? tubulin heterodimers, are crucial in cell signaling, division and mitosis and are among the most successful targets for anticancer therapy. Panobinostat (LBH589) is a potent deacetylase inhibitor acting both on histones and nonhistonic proteins, including ?-tubulin. In vitro LBH589, evaluated in three ATC cell lines (BHT-101, CAL-62 and 8305C), resulted in impair...

  7. Resveratrol Induces Differentiation Markers Expression in Anaplastic Thyroid Carcinoma via Activation of Notch1 Signaling and Suppresses Cell Growth

    OpenAIRE

    Yu, Xiao-Min; Jaskula-Sztul, Renata; Ahmed, Kamal; Harrison, April D.; Kunnimalaiyaan, Muthusamy; Chen, Herbert

    2013-01-01

    Anaplastic thyroid carcinoma (ATC) is an extremely aggressive malignancy with undifferentiated features, for which conventional treatments, including radioactive iodine ablation, are usually not effective. Recent evidence suggests that the Notch1 pathway is important in the regulation of thyroid cancer cell growth and expression of thyrocyte differentiation markers. However, drug development targeting Notch1 signaling in ATC remains largely underexplored. Previously, we have identified resver...

  8. Restricted expression of oncofetal fibronectin mRNA in thyroid papillary and anaplastic carcinoma: an in situ hybridization study.

    OpenAIRE

    Takano, T.; Matsuzuka, F.; Miyauchi, A; Yokozawa, T.; Liu, G.; Morita, S.; Kuma, K.; Amino, N

    1998-01-01

    Restricted expression of oncofetal fibronectin mRNA in the tissues of thyroid papillary and anaplastic carcinoma has recently been shown by both Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Oncofetal fibronectin mRNA can be a target of gene diagnosis and targeted gene therapy, provided it is expressed in all cancer cells in the tissues. To investigate this criterion in thyroid cancer tissues, we measured their expression of oncofetal fibronectin mRNA us...

  9. Selective Therapeutic Targeting of the Anaplastic Lymphoma Kinase With Liposomal siRNA Induces Apoptosis and Inhibits Angiogenesis in Neuroblastoma

    OpenAIRE

    Chiara,, Ghislieri; Cinzia,, Barbieri; Daniela; Domenico; Fabio; Gabriella; Laura; Michele,, Freppaz; Mirco; Monica; Patrizia; Roberta,, Parolisi; Roberto,, Bono; Theresa M

    2011-01-01

    The anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is involved in the pathogenesis of different types of human cancers, including neuroblastoma (NB). In NB, ALK overexpression, or point mutations, are associated with poor prognosis and advanced stage disease. Inhibition of ALK kinase activity by small-molecule inhibitors in lung cancers carrying ALK translocations has shown therapeutic potential. However, secondary mutations may occur that, generate tumor resistance to AL...

  10. Sunitinib Malate plus Lomustine for Patients with Temozolomide-refractory Recurrent Anaplastic or Low-grade Glioma.

    Science.gov (United States)

    Duerinck, Johnny; Du Four, Stephanie; Sander, Wilhelm; Van Binst, Anne-Marie; Everaert, Hendrik; Michotte, Alex; Hau, Peter; Neyns, Bart

    2015-10-01

    Tyrosine kinase signaling through the vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor- ? (PDGFR-?) and KIT cell surface receptors mediates neo-angiogenesis and contributes to cancer cell survival in recurrent anaplastic and low-grade glioma. Thirteen patients with temozolomide-refractory recurrent anaplastic or low-grade glioma were treated with sunitinib malate, a small-molecule tyrosine kinase inhibitor of the VEGFR, PDGFR, and KIT receptors, in combination with lomustine. The most frequent grade 3 and 4 adverse events were fatigue, thrombocytopenia, neutropenia and lymphopenia. The best objective tumor response by Response Assessment in Neuro-Oncology (RANO) criteria was one complete response, one unconfirmed partial response and three cases of stable disease. The median progression-free survival was 1.8 months (95% confidence interval=1.0-2.7 months) with 6-month progression-free survival of 15% (95% confidence interval=0-35%). The median overall survival was 6.7 months (95% confidence interval=0.7-12 months). The investigated combination regimen of sunitinib and lomustine is well-tolerated but insufficiently active to warrant further investigation in an unselected population of patients with temozolomide-refractory recurrent anaplastic and low-grade glioma. PMID:26408725

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wang Yan-Fang

    2012-07-01

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

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

    International Nuclear Information System (INIS)

    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 Na125I. 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 studies will have to concentrate on the possible expression of enzymatically active proteins or the transfer of multiple genes involved in iodide trapping. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    2001-05-01

    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 studies will have to concentrate on the possible expression of enzymatically active proteins or the transfer of multiple genes involved in iodide trapping. (orig.)

  15. Older Adults' Trait Impressions of Faces Are Sensitive to Subtle Resemblance to Emotions

    OpenAIRE

    Franklin, Robert G.; Zebrowitz, Leslie A.

    2013-01-01

    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 locati...

  16. Pathogenicity of a fungus resembling Wangiella dermatitidis isolated from edible mushrooms.

    OpenAIRE

    Kazanas, N.

    1986-01-01

    A fungus resembling the human pathogen Wangiella dermatitidis (Kano) McGinnis, a dematiaceous hyphomycete, was recovered from imported desiccated "black fungus" mushrooms (Auricularia polytrichia (Mont.) Sacc.), a food item popular in Far Eastern cuisine. Except for its conidia, which are mostly reniform to allantoid rather than ovoid as is characteristic for W. dermatitidis, and the undecided mode of conidiogenesis, the isolate closely resembles W. dermatitidis in gross and microscopic morph...

  17. Familial resemblance for executive functions in families of schizophrenic and bipolar patients.

    OpenAIRE

    Szöke, Andrei; Schürhoff, Franck; Golmard, Jean-Louis; Alter, Caroline; Roy, Isabelle; Méary, Alexandre; Etain, Bruno; Bellivier, Frank; Leboyer, Marion

    2006-01-01

    Executive dysfunctions are considered to be putative markers of familial/genetic vulnerability to both schizophrenia and bipolar disorder. However, familial resemblance must be demonstrated before executive functions are used as a potential endophenotype. The aim of this study was to investigate familial resemblance for executive functions in families of schizophrenic and bipolar subjects. We assessed executive functions by means of two tests - the Wisconsin Card Sorting Test (WCST) and the T...

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

    Directory of Open Access Journals (Sweden)

    Zilan Song

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rajan Vaithianathan

    2014-01-01

    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.

  20. An evolutionary conserved role for anaplastic lymphoma kinase in behavioral responses to ethanol.

    Science.gov (United States)

    Lasek, Amy W; Lim, Jana; Kliethermes, Christopher L; Berger, Karen H; Joslyn, Geoff; Brush, Gerry; Xue, Liquan; Robertson, Margaret; Moore, Monica S; Vranizan, Karen; Morris, Stephan W; Schuckit, Marc A; White, Raymond L; Heberlein, Ulrike

    2011-01-01

    Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies containing transposon insertions in dAlk demonstrate increased resistance to the sedating effect of ethanol. Database analyses revealed that Alk expression levels in the brains of recombinant inbred mice are negatively correlated with ethanol-induced ataxia and ethanol consumption. We therefore tested Alk gene knockout mice and found that they sedate longer in response to high doses of ethanol and consume more ethanol than wild-type mice. Finally, sequencing of human ALK led to the discovery of four polymorphisms associated with a low level of response to ethanol, an intermediate phenotype that is predictive of future alcohol use disorders (AUDs). These results suggest that Alk plays an evolutionary conserved role in ethanol-related behaviors. Moreover, ALK may be a novel candidate gene conferring risk for AUDs as well as a potential target for pharmacological intervention. PMID:21799923

  1. Aggressive Multimodal Approach for Anaplastic Thyroid Cancer and Long-Term Survival

    Science.gov (United States)

    Hussain, Nasir; Mustafa, Usman; Jung, Su Hyeon; Gilman, Alan D.

    2013-01-01

    Anaplastic thyroid cancer (ATC) comprises 1-2% of all thyroid cancers and is one of the most aggressive cancers with a median survival rate of around four months. The average 5-year survival rate has been reported to be around 3.6%. In this paper, we have discussed management and prognostic variables of a patient with ATC who has survived for more than 5 years. A 59-year-old female was referred to our facility for an elective thyroid and parathyroidectomy for concerns of thyroid papillary cancer and hyperparathyroidism. At the time of surgery, the tumor mass had invaded the muscular layer of esophagus; radicle thyroidectomy parathyroidectomy along with removal of muscle layer of esophagus was performed, and diagnosis of ATC was made. The patient was treated with chemoradiation with a good treatment response and no recurrence of tumor for two and a half years until PET/CT followed by wedge biopsy of lung confirmed ATC recurrence. The patient was treated with another course of radiation treatment with a good treatment response. Since then, the patient has been following in our outpatient oncology clinic and has no evidence of tumor recurrence. Aggressive multimodal approach of combining radicle surgery with chemoradiation treatment in select patients of ATC with no distant metastasis helps improve prognosis. PMID:23533874

  2. Large cell anaplastic medulloblastoma metastatic to the scalp: tumor and derived stem-like cells features

    International Nuclear Information System (INIS)

    Extraneural metastases (ENM) rarely occur in medulloblastoma (MBL) patients and only few cases of subcutaneous localizations have been described. ENM indicate an aggressive disease associated with a worse prognosis. The characterization of metastatic tumours might be useful to understand their pathogenesis and to identify the most appropriate therapeutic strategies. We present the case of a child with Large Cell Anaplastic (LC/A) MBL, who developed multiple subcutaneous metastases in the scalp area after a ventriculo-peritoneal shunting procedure. The disease rapidly progressed and the child died despite chemotherapy and primary tumour surgical debulking. We molecularly classified the tumour as a group 3 MBL; in addition, we derived stem-like cells (SLC) from a metastatic lesion. Primary tumour, metastases and SLC were further analysed, particularly focusing on features linked to the cutaneous dissemination. Indeed, molecules involved in angiogenesis, cell invasion and epidermal growth factor signalling resulted highly expressed. The present report describes a very rare case of subcutaneous metastatic MBL. The tumour, metastases and SLC have been clinically, pathologically and molecularly characterized. Our case is an example of multidisciplinary approach aiming to characterize MBL aggressive behaviour

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

    Directory of Open Access Journals (Sweden)

    Arai Hajime

    2007-08-01

    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.

  4. Flavonoid Fraction of Citrus reticulata Juice Reduces Proliferation and Migration of Anaplastic Thyroid Carcinoma Cells.

    Science.gov (United States)

    Celano, Marilena; Maggisano, Valentina; De Rose, Roberta Francesca; Bulotta, Stefania; Maiuolo, Jessica; Navarra, Michele; Russo, Diego

    2015-01-01

    Effects of flavonoids extracted from Citrus reticulata (mandarin) juice on proliferation and migration of 3 human anaplastic thyroid carcinoma (ATC) cell lines were evaluated. Flavonoid components of Mandarin juice extract (MJe) were analyzed by uHPLC. Proliferation of CAL-62, C-643, and 8505C cells, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced by MJe in a concentration- and time-dependent way, with maximal effect elicited at 0.5 mg/ml concentration after 48 h. Cytofluorimetric analysis showed a block in the G2/M phase of the cell cycle, accompanied by low cell mortality owed to autophagic death. The extract caused also a reduction of cell migration, associated with decreased activity of the metalloproteinase MMP-2. These findings demonstrate that the flavonoid fraction of mandarin juice exerts in vitro antiproliferative effects on ATC cells, associated with a reduction of migration, suggesting for such a functional food a potential use as adjuvant in the treatment of thyroid cancer. PMID:26365817

  5. A bone metastases model of anaplastic thyroid carcinoma in athymic nude mice

    International Nuclear Information System (INIS)

    Anaplastic thyroid carcinoma (ATC), an aggressive form of thyroid cancer, represents less than 2% of all thyroid cancers. The survival of patients with ATC remains low especially when accompanied with bone metastasis. This study aims to establish a reproducible animal model of bone metastasis of ATC which may be useful for further research on novel treatment strategy. Eight 6-8 week old female athymic nude mice were randomly selected. ATC cell line ARO cells were injected into the left ventricular cavity of each mouse respectively. Each mouse was imaged using a dedicated small-animal PET/CT scanner after successful injection of [18F]-FDG under deep anesthesia. Pathological examination was carried out to confirm the bone metastases of ATC. Histopathology established ATC bone metastases in five nude mice’s tibia. Similarly, PET image displayed significantly increased radioactivity (P<0.01) in the established bone metastasis compared with the control normal tibia. Both micro-PET/CT and histomorphometric measurement confirmed the bone metastases model of ATC in nude mice by left ventricular cavity injection of ARO cell line. The bone metastases model of ATC will thus facilitate the understanding of its pathogenesis and aid in the development of novel therapies.

  6. ALK-positive anaplastic large cell lymphoma with an unusual alveolar growth pattern

    Science.gov (United States)

    Yu, Guohua; Gao, Zifen; Huang, Xin

    2014-01-01

    Anaplastic large cell lymphoma (ALCL) possesses a broad morphological spectrum. Currently, we present a case of ALK-positive ALCL presenting with an alveolar growth pattern in a 22-year-old Chinese female. This patient complained of a progressively enlarged mass in the right axillary region for 6 months. Excisional biopsy revealed a well-developed alveolar structure with nests of dyscohesive tumor cells separated by delicate fibrovascular septae. The large pleomorphic cells have irregular nuclei with prominent nucleoli and fine chromatin and abundant pale cytoplasm. The neoplasm stained positively for CD2, CD3?, CD30, ALK1, EMA and cytotoxic molecules (TIA1 and Granzyme B). Cytogenetic study via interphase Fluorescence in-Situ Hybridization disclosed the rearrangement involving ALK gene. The patient received 6 cycles of CHOP chemotherapy and achieved complete remission. She is alive in good condition up to the present. Our case is biologically similar to the conventional ALK-positive ALCLs and may just represent an unusual morphological appearance. PMID:25674293

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

    Science.gov (United States)

    YOKOYAMA, NORIKO; MILLER, W. TODD

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Li MA

    2014-12-01

    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. Mutation-Independent Activation of the Anaplastic Lymphoma Kinase in Neuroblastoma.

    Science.gov (United States)

    Regairaz, Marie; Munier, Fabienne; Sartelet, Hervé; Castaing, Marine; Marty, Virginie; Renauleaud, Céline; Doux, Camille; Delbé, Jean; Courty, José; Fabre, Monique; Ohta, Shigeru; Viehl, Philippe; Michiels, Stefan; Valteau-Couanet, Dominique; Vassal, Gilles

    2016-02-01

    Activating mutations of anaplastic lymphoma kinase (ALK) have been identified as important players in neuroblastoma development. Our goal was to evaluate the significance of overall ALK activation in neuroblastoma. Expression of phosphorylated ALK, ALK, and its putative ligands, pleiotrophin and midkine, was screened in 289 neuroblastomas and 56 paired normal tissues. ALK was expressed in 99% of tumors and phosphorylated in 48% of cases. Pleiotrophin and midkine were expressed in 58% and 79% of tumors, respectively. ALK activation was significantly higher in tumors than in paired normal tissues, together with ALK and midkine expression. ALK activation was largely independent of mutations and correlated with midkine expression in tumors. ALK activation in tumors was associated with favorable features, including a younger age at diagnosis, hyperdiploidy, and detection by mass screening. Antitumor activity of the ALK inhibitor TAE684 was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. TAE684 was cytotoxic in vitro in all cell lines, especially those harboring an ALK mutation. TAE684 efficiently inhibited ALK phosphorylation in vivo in both F1174I and R1275Q xenografts but demonstrated antitumor activity only against the R1275Q xenograft. In conclusion, ALK activation occurs frequently during neuroblastoma oncogenesis, mainly through mutation-independent mechanisms. However, ALK activation is not associated with a poor outcome and is not always a driver of cell proliferation and/or survival in neuroblastoma. PMID:26687816

  10. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine in anaplastic large cell lymphoma.

    Science.gov (United States)

    Hassler, Melanie R; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

    2012-11-01

    DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16(INK4A) after drug administration and senescence associated ?-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

  11. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2?-deoxycytidine in anaplastic large cell lymphoma

    Science.gov (United States)

    Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

    2012-01-01

    DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2?-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated ?-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

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

    Directory of Open Access Journals (Sweden)

    Dehghani Mehdi

    2006-01-01

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

  13. 18F FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly Diagnosed or Recurrent Gliomas

    Science.gov (United States)

    2015-05-22

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2015-11-01

    Astrocytoma is the most common childhood brain tumor. Anaplastic astrocytoma (AA) are high grade gliomas (HGG), found very rarely in pediatric patients. AA mainly results from a dedifferentiation of a low grade astrocytoma. Clinical features of supra-tentorial tumors vary according to their anatomic location, biologic aggressiveness and age of the patient. They can be either completely asymptomatic or present with signs of raised intracranial pressure, seizures (about 40% of cases), behavior changes, speech disorders, declining school performance, or hemiparesis. There have been published adult cases of brain tumor misdiagnosed as viral encephalitis. Due to variety of clinical presentations, diagnosis of AA can be challenging. Here we report a case of a 13 year old girl who presented with clinical features suggestive of viral encephalitis, such as fever, headache, dizziness, and first seizure with postictal sleep and prolonged drowsiness. However, her brain MRI findings were consistent with long standing mass effect from the underlying intracranial contents and that coupled with her history of unusual taste led to further investigations and the diagnosis of the AA. In retrospect, this presentation could have been a temporal epileptic aura. High grade astrocytomas are particularly difficult to treat with a two-year survival rates range from 10% to 30%. The treatment is multimodal with gross total surgical resection of the tumor, followed by radiotherapy with or without nitrosourea-containing chemotherapy regimen. Recent promising results seen with the use of temozolamide in adults has not been yet demonstrated in the pediatric patients. The extent of tumor resection remains the most significant indicator of survival and early recognition of this tumor is essential. This case report emphasizes the fact that mass lesions in the temporal lobe, including high-grade astrocytoma, should be considered in the differential diagnosis of suspected herpes simplex encephalitis, especially those not responding to therapy. Remodeling of the calvarium adjacent to an intracranial lesion suggests a long standing process. PMID:26272584

  16. {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)

    2010-12-15

    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.)

  17. Construction of a natural phage antibody library of human anaplastic thyroid carcinoma.

    Science.gov (United States)

    Xi, J M; Pang, H; Hu, X L; Wang, Z J

    2015-01-01

    The objective of this study was to identify and construct a human natural phage single-chain antibody (scFv) library of human anaplastic thyroid carcinoma (ATC) using phage display technology. Total RNA was extracted from lymphatic tissue near an ATC and used to amplify variable heavy chain (VH) and variable light chain (VL) fragments with added linker sequences using reverse transcription-polymerase chain reaction (RT-PCR). After purification, the VH and VL amplicons were used to produce scFv fragments with added SfiI and NotI restriction enzyme recognition sites using splicing-overlap-extension PCR. Following digestion, the scFv gene was cloned in the pCANTAB-5E plasmid, and the recombinant phagemids were transformed into the susceptible Escherichia coli TG1 strain. After infection by the helper phage M13K07, a human ATC phage antibody library was successfully constructed. Clear 28 S and 18 S bands could be seen in the total RNA from the library, and the sizes of the VH, VL, and scFv genes contained therein were approximately 370, 350, and 750 bp, respectively. In addition, the conversion efficiency as measured by the pUC19 standard plasmid was 10(8) CFU/?g, and the positive insert ratio was 86.4% (19/22). These results demonstrated the successful construction of a human ATC scFv antibody gene library, and might provide the experimental basis for the further screening and identification of a phage single-chain antibody with ATC cell-specificity. PMID:26345766

  18. The Emphasis of Tumor Suppressor Genes and Oncogenes in Diagnosis and Prognosis of Anaplastic Brain Tumors

    Directory of Open Access Journals (Sweden)

    Ç???r Biray AVCI

    2011-12-01

    Full Text Available The aim of the study is to the determine the profiles of tumor suppressor genes and oncogenes which cause brain tumor, establishing the association between the prognosis of cancer and the quantitation of genetic and epigenetic changes, and bringing a molecular approach to definite diagnosis. For this purpose, explant cell cultures are performed from the anaplastic brain tumor tissues of the cases. The expression analysis of the tumor suppressor genes (p53, RB1, PTEN, MGMT, RUNX3, DMBT1, PIKE and oncogenes (EGFR, PIK3CA, MDM2, Olig2, GSTT1, COX–2 and hTERT were determined by comparing the expression of GAPDH housekeeping gene using real-time online RT-PCR. The promoter regions of all the tumor suppressor genes' hypermethylation and also methylated and unmethylated copy numbers were determined with Q-PCR by using methylation specific primer and probes and the quantitation was carried out by comparing with each other. A significant difference was determined among the oncogenes; EGFR and hTERT gene expressions in patient tumor group. hTERT gene expression showed a significant difference with tumor grades. DMBT1 gene expression showed a significant difference with tumor grades. A prominent decrease was found in the aberration of tumor suppressor gene copy number in the glioma group. Gene copy number and gene expression of GSTT1 gene showed a significant correlation. RB1 and MGMT promoter methylation showed a significant difference in tumor patient group. Over expression of PIK3CA, EGFR and COX-2 among oncogenes and loss of copy number of PTEN, RB1 and RUNX3 among tumor suppressor genes found associated with short survival.

  19. Anaplastic PXA in adults: case series with clinicopathologic and molecular features

    Science.gov (United States)

    Schmidt, Yao; Kleinschmidt-DeMasters, B.K.; Aisner, Dara L.; Lillehei, Kevin O.; Damek, Denise

    2015-01-01

    Background Pleomorphic xanthoastrocytomas with anaplastic features (PXA-As) are rare tumors about which little is known regarding clinicopathological and molecular features. Several studies have identified BRAF V600E mutations in PXA-As, but the percentage with mutation may differ between adult and pediatric examples, and limited information exists about immunohistochemistry for IDH1 (isocitrate dehydrogenase 1). Design: 10 cases of adult PXA-As seen at our institution since 2000 were assessed for BRAF V600E mutation by polymerase chain reaction testing (PCR) and IDH1 by immunohistochemistry. Results Patients ranged in age from 18-68 years; 4 PXA-As affected temporal lobe and 2 were cystic. Four patients underwent gross total resection; and 9/10 received cranial irradiation and/or adjuvant chemotherapy. Five survived less than 5 years, although 2/5 died from non-tumor causes. Four long-term survivors are alive at 7.5, 9.8, 11.4, and 11.9 years post-diagnosis. 2 of 4 long term survivors had BRAF V600E mutation: patients were ages 18 and 28 years. A 48-year old male without BRAF mutation survives at 9.8 years, even with thalamic location; conversely a 68-year-old female with temporal lobe tumor and BRAF mutation survived 1.9 years after diagnosis. All tumors were IDH1 immunonegative. Conclusion This case series details clinicopathological features of a subset of rare PXA-As in adults. BRAF V600E mutation was identified in 50% of these cases. PMID:23096133

  20. Pleomorphic xanthoastrocytoma with anaplastic features: one case report and review of literature

    Directory of Open Access Journals (Sweden)

    Cui-yun SUN

    2014-12-01

    Full Text Available Objective To investigate the clinicopathological features of pleomorphic xanthoastrocytoma with anaplastic features (PXA-A.  Methods The clinical manifestations, imaging, histopathological features, and immunophenotype were analyzed in one case of PXA-A, and relevant literatures were reviewed. Results The patient was a 58-year-old woman. MRI examination revealed a parenchyma mass with irregularly long T1 and long T2 signal in right temporal lobe and basal ganglia region. The border was clear and peritumoral edema was inconspicuous. The mesocephalon and right ventricle were compressed, and the midline was shifted to left. Enhanced MRI showed multiple flaky and nodular enhancement. Histologically, tumor cells showed remarkable cellular pleomorphism, and they were composed of mononuclear cells, multinuclear giant tumor cells, frothy tumor cells and spindle cells. Eosinophilic granular bodies and intranuclear inclusions were seen. Tumor cells in partial regions were intensively arranged, with obvious atypia. Immunohistochemical analysis showed immunoreactivity of the cells to glial fibrillary acidic protein (GFAP, Vimentin (Vim, S-100 protein (S-100, neuronal nuclei (NeuN and P53. The cells showed a negative reaction for synaptophysin (Syn, chromogranin A (CgA, neurofilament protein (NF, CD34 and isocitrate dehydrogenase 1 (IDH1. The Ki-67 label index was 8.20% .  Conclusions PXA-A is a rare tumor. The imaging features can offer a few diagnostic cues. However, a definite diagnosis depends on the histological and immunohistochemical features. doi: 10.3969/j.issn.1672-6731.2014.12.013

  1. Morphologic Features of ALK-negative Anaplastic Large Cell Lymphomas With DUSP22 Rearrangements.

    Science.gov (United States)

    King, Rebecca L; Dao, Linda N; McPhail, Ellen D; Jaffe, Elaine S; Said, Jonathan; Swerdlow, Steven H; Sattler, Christopher A; Ketterling, Rhett P; Sidhu, Jagmohan S; Hsi, Eric D; Karikehalli, Shridevi; Jiang, Liuyan; Gibson, Sarah E; Ondrejka, Sarah L; Nicolae, Alina; Macon, William R; Dasari, Surendra; Parrilla Castellar, Edgardo; Feldman, Andrew L

    2016-01-01

    Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P=0.039), less likely to have pleomorphic cells (23% vs. 49%; P=0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P<0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study. PMID:26379151

  2. From similitude to success: The effects of facial resemblance on perceptions of team effectiveness.

    Science.gov (United States)

    Wang, Ze; He, Xin; Liu, Fan

    2016-03-01

    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. (PsycINFO Database Record PMID:26752512

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

    Scientific Electronic Library Online (English)

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

    2013-12-01

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

  4. Diversity of Genomic Breakpoints in TFG-ALK Translocations in Anaplastic Large Cell Lymphomas : Identification of a New TFG-ALKXL Chimeric Gene with Transforming Activity

    OpenAIRE

    Hernández, Luis; Beà, Sílvia; Bellosillo, Beatriz; Pinyol, Magda; Falini, Brunangelo; Carbone, Antonino; Ott, German; Rosenwald, Andreas; Fernández, Alberto; Pulford, Karen; Mason, David,; Morris, Stephan W.; Santos, Eugenio; CAMPO, ELIAS

    2002-01-01

    Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gen...

  5. 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.

    Science.gov (United States)

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

    2016-03-01

    A 3-year-old boy with sickle cell anemia (SCA) presented with progressive daily emesis and was found to have an anaplastic ependymoma. Radiation therapy and chemotherapy are usually employed after subtotal resections of anaplastic ependymomas, although the benefits from chemotherapy are unclear. To mitigate the risks of adjuvant treatment in this patient at risk for SCA-associated vasculopathy, renal impairment, and other end-organ damage, proton beam irradiation without chemotherapy was chosen. Scheduled packed red blood cell transfusions were instituted to maintain sickle hemoglobin levels less than 30%. This case highlights treatment complexities for malignant brain tumors in patients predisposed to treatment-related adverse effects. PMID:26488903

  6. Pneumonia and empyema infection associated with a Bacillus species that resembles B. alvei.

    OpenAIRE

    Coudron, P E; Payne, J. M.; Markowitz, S. M.

    1991-01-01

    An organism resembling Bacillus alvei was isolated from the lung and pleural fluid of an immunocompetent patient. The isolate differed from the type strain of B. alvei in its ability to reduce nitrate and its inability to produce dihydroxyacetone and acetylmethylcarbinol. The isolate was resistant to ciprofloxacin and showed intermediate susceptibility to vancomycin.

  7. Canine sterile neutrophilic dermatitis (resembling Sweet’s syndrome) in a Dachshund

    OpenAIRE

    Gains, Malcolm J.; Morency, Andréanne; Sauvé, Frédéric; Blais, Marie-Claude; Bongrand, Yannick

    2010-01-01

    A 6-year-old Dachshund was presented with a 2-day history of lethargy, anorexia and cutaneous erythema, edema, and multifocal erythematous papules affecting the ventral abdomen, axillae, and groin. Microscopic examination revealed a sterile neutrophilic dermatitis resembling Sweet’s syndrome; however, extracutaneous lesions were not present. The condition responded rapidly to corticosteroid therapy.

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

    DEFF Research Database (Denmark)

    Sun, S; Karemore, Gopal Raghunath; Chernoff, Konstantin; Karssemeijer, N; Nielsen, Mads

    PURPOSE Mammographic density is a well established breast cancer risk factor. Texture analysis in terms of the Mammographoc Texture Resemblance (MTR) marker has recently shown to add to risk segregation. Hitherto only single view MTR analysis has been performed. Standard mammography examinations ...

  9. Mammographic Texture Resemblance generalizes as an independent risk factor of breast cancer

    DEFF Research Database (Denmark)

    Chernoff, Konstantin; Christopher, S G; Karemore, Gopal Raghunath; Karssemeijer, N; Nielsen, Mads; Vachon, C M

    PURPOSE Breast density has been established as a risk factor of breast cancer in numerous studies. Mammographic Texture Resemblance (MTR) has shown to be a density independent risk factor, but only on a single study. We examine if the statistics of the texture recorded in one study generalize as ...

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

    DEFF Research Database (Denmark)

    Nielsen, Mads; Vachon, Celine M.; Scott, Christopher G.; Chernoff, Konstantin; Karemore, Gopal; Karssemeijer, Nico; Lillholm, Martin; Karsdal, Morten

    2014-01-01

    INTRODUCTION:Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast d...

  11. Polioencephalomyelopathy in a mixed breed dog resembling Leigh’s disease

    OpenAIRE

    Chai, Orit; Milgram, Joshua; Shamir, Merav H.; Brenner, Ori

    2015-01-01

    A 14-month-old mixed-breed dog was presented with acute onset of exercise intolerance that quickly progressed to quadriparesis. Gross and microscopic autopsy findings indicated a type of degenerative polioencephalomyelopathy resembling subacute necrotizing encephalomyelopathy in dogs or Leigh’s disease in humans. This syndrome has previously been reported only in purebred dogs.

  12. Polioencephalomyelopathy in a mixed breed dog resembling Leigh’s disease

    Science.gov (United States)

    Chai, Orit; Milgram, Joshua; Shamir, Merav H.; Brenner, Ori

    2015-01-01

    A 14-month-old mixed-breed dog was presented with acute onset of exercise intolerance that quickly progressed to quadriparesis. Gross and microscopic autopsy findings indicated a type of degenerative polioencephalomyelopathy resembling subacute necrotizing encephalomyelopathy in dogs or Leigh’s disease in humans. This syndrome has previously been reported only in purebred dogs. PMID:25565716

  13. A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

    Science.gov (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

    2015-06-01

    Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and 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. PMID:25533804

  14. Well-differentiated and anaplastic astroblastoma in the same patient: a case report and review of the literature.

    Science.gov (United States)

    Samkari, Alaa; Hmoud, Mohammed; Al-Mehdar, Abeer; Abdullah, Shaker

    2015-01-01

    Astroblastoma is a rare brain tumor occurring in children and adults, rarely in the elderly. It constitutes up to 3% of all brain tumors. We report a case of a 14-year-old girl who presented with recurrent seizures and minimal right hemiparesis. Magnetic resonance imaging (MRI) revealed a left fronto-parietal brain tumor. It was managed with subtotal resection in a local hospital. Subsequently, she was referred to Princess Nora Oncology Center for further characterization and management. Pathology slide revision revealed well-differentiated astroblastoma. Upon follow up, the patient had multiple recurrences of the same tumor and emergence of a new lesion at the area of Sylvian fissure. Excision of the emerging tumor revealed anaplastic astroblastoma. Astroblastoma is a glial tumor that predominantly affects females. Its clinical progression is unpredictable, with high recurrence rate. Surgical intervention is considered the mainstay of treatment, while radiotherapy and chemotherapy effectiveness is debatable. To our knowledge, this is the first reported case of well-differentiated and anaplastic astroblastoma as two separate neoplastic lesions in the same patient with its clinical, radiological, and pathological features. PMID:26227256

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

    Science.gov (United States)

    Akaishi, Junko; Onda, Masamitsu; Okamoto, Junichi; Miyamoto, Shizuyo; Nagahama, Mitsuji; Ito, Kouichi; Yoshida, Akira; Shimizu, Kazuo

    2006-01-01

    Background Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis. One of these genes, transcription elongation factor A (SII)-like 4 (TCEAL4), encodes a member of the transcription elongation factor A (SII)-like gene family. The detailed function of TCEAL4 has not been described nor has any association between this gene and human cancers been reported previously. Methods To investigate the role of TCEAL4 in ATC carcinogenesis, we examined expression levels of TCEAL4 in ACLs as well as in other types of thyroid cancers and normal human tissue. Results Expression of TCEAL4 was down-regulated in all 11 ACLs as compared to either normal thyroid tissues or papillary and follicular thyroid cancerous tissues. TCEAL4 was expressed ubiquitously in all normal human tissues tested. Conclusion To our knowledge, this is the first report of altered TCEAL4 expression in human cancers. We suggest that loss of TCEAL4 expression might be associated with development of ATC from DTC. Further functional studies are required. PMID:17076909

  16. Genomic profiling reveals different genetic aberrations in systemic ALK-positive and ALK-negative anaplastic large cell lymphomas.

    Science.gov (United States)

    Salaverria, Itziar; Beà, Silvia; Lopez-Guillermo, Armando; Lespinet, Virginia; Pinyol, Magda; Burkhardt, Birgit; Lamant, Laurence; Zettl, Andreas; Horsman, Doug; Gascoyne, Randy; Ott, German; Siebert, Reiner; Delsol, Georges; Campo, Elias

    2008-03-01

    Anaplastic large cell lymphoma (ALCL) is a T/null-cell neoplasm characterized by chromosomal translocations involving the anaplastic lymphoma kinase (ALK) gene (ALK). Tumours with similar morphology and phenotype but negative for ALK have been also recognized. The secondary chromosomal imbalances of these lymphomas are not well known. We have examined 74 ALCL, 43 ALK-positive and 31 ALK-negative, cases by comparative genomic hybridization (CGH), and locus-specific alterations for TP53 and ATM were examined by fluorescence in situ hybridization and real-time quantitative polymerase chain reaction. Chromosomal imbalances were detected in 25 (58%) ALK-positive and 20 (65%) ALK-negative ALCL. ALK-positive ALCL with NPM-ALK or other ALK variant translocations showed a similar profile of secondary genetic alterations. Gains of 17p and 17q24-qter and losses of 4q13-q21, and 11q14 were associated with ALK-positive cases (P = 0.05), whereas gains of 1q and 6p21 were more frequent in ALK-negative tumours (P = 0.03). Gains of chromosome 7 and 6q and 13q losses were seen in both types of tumours. ALCL-negative tumours had a significantly worse prognosis than ALK-positive. However no specific chromosomal alterations were associated with survival. In conclusion, ALK-positive and negative ALCL have different secondary genomic aberrations, suggesting they correspond to different genetic entities. PMID:18275429

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

    Science.gov (United States)

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

    2015-10-01

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

  18. Atypical and anaplastic meningiomas. Does the new WHO-classification of brain tumours affect the indication for postoperative irradiation?

    International Nuclear Information System (INIS)

    We retrospectively analysed 13 patients (pts.) treated at the University of Tuebingen from 1985 to 1993 to evaluate the results of radiation therapy (XRT) given as an adjuvant to totally or subtotally resected meningiomas. The overall survival was 38% at five years with a probability of relapse of 50% at this time. Reclassification of the tumours according to the new WHO-classification of brain tumours revealed 10 grade-II-tumours (atypical menmgioma) and 3 grade-III-tumours (anaplastic meningioma). Radiotherapy failed in all 3 pts. with macroscopically incomplete resection (Simpson' s grade IV), who died with relapse between 4 and 51 months after radiotherapy. 5 out of 10 pts. with grade-II-tumours relapsed. All 3 pts. with grade-III-tumours died with relapse between 6 and 21 months after XRT. Morbidity was seen in 2 pts. after irradiation with 60 GY (ICRU dose specification). Complete surgical exstirpation offers the best possibility of tumour control. Grade-III-tumours should be irradiated whatever the extent of the primary surgery was. Our results might indicate a possible indication for XRT in pts. with atypical grade-II-tumours especially when radical surgery must be in doubt. Prospective multicentric trials are warranted to prove the prognostic value of the new WHO-classification for atypical and anaplastic meningiomas and to define the ultimate role of radiotherapy in this setting. (author)

  19. The effect of 17-AAG on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of 17-allylamino-17-demethoxy geldanamycin (17-AAG) on iodine uptake kinetics of NIS-transfected anaplastic thyroid cancer (ATC) cells. Methods: Lipofection was used to transfect the recombinant plasmid, namely pcDNA3.1-NIS, into FRO cells (ATC cell line). A stable cell line NIS-FRO was obtained by G418 resistance selection. 125I was added into the medium, and influx and efflux experiments were performed. Different time-radioactivity curves were drawn, and further analysis was performed between the non-transfected cells (the control group) and NIS-FRO cells treated with 1 ?mol/L 17-AAG for 24 h. Student's t-test was used to analyze the data. Results: The iodine uptake ability of the NIS-FRO cells was significantly higher than that of the FRO cells (about 10.68 times, t=45.329, P<0.001). However, 125I out-flowed rapidly when removed from the medium, and the retention rate of 125I in the NIS-FRO cells was only 10.5% of the initial amount after 30 rin. After treatment with 1 ?mol/L 17-AAG for 24 h, the 125I uptake ability of NIS-FRO cells further increased. During the 20-60 min incubation with 125I, the iodine uptake ability of 17-AAG treated NIS-FRO cells increased significantly with radioactive counts of 31771.8- 54815.5 per minute,which was much higher than that of the control group (24020.3-41293.8 per minute; t=3.096, 4.275, 3.055, 4.292 and 5.496, respectively, all P<0.05). The iodine uptake ability increased about 24.8%-35.5%. Furthermore, 5-30 min after removing the medium, the retention rates of 125I in the 17-AAG treated NIS-FRO cells were significantly increased compared with those of the control group (32.7%-85.2% vs 10.5%-56.8%; t=22.801, 13.096, 19.631, 38.205, 43.519, 29.322, respectively, all P<0.01), and 125I efflux was reduced. After 30 min,125I retention rate of the treatment group was 32.7%, which was 3.1 times higher than that of the control group. Conclusion: The iodine uptake ability can be enhanced in stable NIS-transfected ATC cells after treatment with 17-AAG, and iodine efflux can be significantly delayed. (authors)

  20. Inhibition of Src with AZD0530 Reveals the Src-Focal Adhesion Kinase Complex as a Novel Therapeutic Target in Papillary and Anaplastic Thyroid Cancer

    OpenAIRE

    Schweppe, Rebecca E; Kerege, Anna A.; French, Jena D.; Sharma, Vibha; Grzywa, Rachel L.; Haugen, Bryan R.

    2009-01-01

    Context: Focal adhesion kinase (FAK) and Src are overexpressed and activated in many cancers and have been associated with tumor progression. The role of the Src-FAK complex has not been characterized in papillary and anaplastic thyroid cancer (PTC and ATC).

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

    Science.gov (United States)

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

    2014-04-01

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

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

    OpenAIRE

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

    2014-01-01

    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 w...

  3. Generalized Resemblance Theory of Evidence: a Proposal for Precision/Personalized Evidence-Based Medicine

    OpenAIRE

    Beigy, Maani

    2015-01-01

    Precision medicine emerges as the most important contemporary paradigm shift of medical practice but has several challenges in evidence formation and implementation for clinical practice. Precision/Personalized evidence-based medicine (pEBM) requires theoretical support for decision making and information management. This study aims to provide the required methodological framework. Generalized Resemblance Theory of Evidence mainly rests upon Generalized Theory of Uncertainty which manages inf...

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

    OpenAIRE

    Pellegrini Ronald; Kaczorowski David; López-Candales Angel

    2005-01-01

    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 Pres...

  5. Captive fledgling American kestrels prefer to play with objects resembling natural prey

    OpenAIRE

    Negro, Juan J.; Bustamante, Javier; Milward, Jane; Bird, David M.

    1996-01-01

    Object play may be a mechanism by which young predators acquire skills in manipulating prey, as well as physical strength and endurance. It has also been proposed that fledgling raptors play with live or dead prey if available, but would play with surrogates such as sticks or grass if not. Different objects were offered to captive fledgling American kestrels, Falco sparverius, to test whether they prefer to play with objects resembling prey. Individuals were divided into two groups: ...

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

    OpenAIRE

    Stafleu, A.

    1994-01-01

    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 and attitudes towards the consumption of 20 foods was developed for which Fishbein and Ajzen's theory of reasoned action was used as a framework. In addition, an attitude scale was developed towards ...

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

    OpenAIRE

    2009-01-01

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

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

    OpenAIRE

    Nielsen, Mads; Vachon, Celine M.; Scott, Christopher G.; Chernoff, Konstantin; Karemore, Gopal; Karssemeijer, Nico; Lillholm, Martin; Karsdal, Morten

    2014-01-01

    INTRODUCTION:Breast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population.METHODS:Texture patterns were recorded in digitalized pre-diagnosis (3.7years) film mammograms of a nested case-control study with...

  9. Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans)

    OpenAIRE

    Gozalo, Alfonso S; Rosenberg, Helene F.; Elkins, William R.; Montoya, Enrique J; Weller, Richard E

    2009-01-01

    In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with...

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

    Science.gov (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.

  11. Anaplastic plasmacytomas: relationships to normal memory B cells and plasma cell neoplasms of immunodeficient and autoimmune mice.

    Science.gov (United States)

    Qi, Chen-Feng; Shin, Dong-Mi; Li, Zhaoyang; Wang, Hongsheng; Feng, Jianxum; Hartley, Janet W; Fredrickson, Torgny N; Kovalchuk, Alexander L; Morse, Herbert C

    2010-05-01

    Anaplastic plasmacytomas (APCTs) from NFS.V(+) congenic mice and pristane-induced plasmacytic PCTs from BALB/c mice were previously shown to be histologically and molecularly distinct subsets of plasma cell neoplasms (PCNs). Here we extended these comparisons, contrasting primary APCTs and PCTs by gene expression profiling in relation to the expression profiles of normal naïve, germinal centre, and memory B cells and plasma cells. We also sequenced immunoglobulin genes from APCT and APCT-derived cell lines and defined surface phenotypes and chromosomal features of the cell lines by flow cytometry and by spectral karyotyping and fluorescence in situ hybridization. The results indicate that APCTs share many features with normal memory cells and the plasma cell-related neoplasms (PLs) of FASL-deficient mice, suggesting that APCTs and PLs are related and that both derive from memory B cells. Published in 2010 by John Wiley & Sons, Ltd. PMID:20217872

  12. Large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation: A case report of a rare tumor

    Directory of Open Access Journals (Sweden)

    Amany A. Fathaddin

    2014-01-01

    Full Text Available Medulloblastoma is an embryonal neuroepithelial tumor of the cerebellum and is the most common malignant central nervous system tumor in children. Different histological variants and patterns have been described. The classic variant represents the majority of cases. This report describes a rare case of large cell/anaplastic medulloblastoma with myogenic, melanotic and neuronal differentiation arising in the cerebellum of a 3-year-old boy who presented with headache and vomiting. Magnetic resonance imaging demonstrated a heterogeneously enhanced lesion in the fourth ventricle. Surgical resection of the tumor was accomplished, but a residual tumor was left behind because of the involvement of the brainstem. Postoperatively, the patient received chemotherapy and radiotherapy. Currently, 20 months after treatment, the patient has survived without further progression. Pathological examination revealed a high grade primitive neuronal tumor with foci of myogenic features, melanin containing epithelial elements and ganglion-like cells, which were confirmed by immunohistochemistry.

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

    Directory of Open Access Journals (Sweden)

    Zu Youli

    2011-01-01

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

  14. Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma.

    Science.gov (United States)

    Tort, F; Pinyol, M; Pulford, K; Roncador, G; Hernandez, L; Nayach, I; Kluin-Nelemans, H C; Kluin, P; Touriol, C; Delsol, G; Mason, D; Campo, E

    2001-03-01

    The majority of anaplastic large cell lymphomas (ALCL) are associated with chromosomal abnormalities affecting the anaplastic lymphoma kinase (ALK) gene which result in the expression of hybrid ALK fusion proteins in the tumor cells. In most of these tumors, the hybrid gene comprises the 5' region of nucleophosmin (NPM) fused in frame to the 3' portion of ALK, resulting in the expression of the chimeric oncogenic tyrosine kinase NPM-ALK. However, other variant rearrangements have been described in which ALK fuses to a partner other than NPM. Here we have identified the moesin (MSN) gene at Xq11-12 as a new partner of ALK in a case of ALCL which exhibited a distinctive membrane-restricted pattern of ALK labeling. The hybrid MSN-ALK protein had a molecular weight of 125 kd and contained an active tyrosine kinase domain. The unique membrane staining pattern of ALK is presumed to reflect association of moesin with cell membrane proteins. In contrast to other translocations involving the ALK gene, the ALK breakpoint in this case occurred within the exonic sequence coding for the juxtamembrane portion of ALK. Identification of the genomic breakpoint confirmed the in-frame fusion of the whole MSN intron 10 to a 17 bp shorter juxtamembrane exon of ALK. The breakpoint in der(2) chromosome showed a deletion, including 30 bp of ALK and 36 bp of MSN genes. These findings indicate that MSN may act as an alternative fusion partner for activation of ALK in ALCL and provide further evidence that oncogenic activation of ALK may occur at different intracellular locations. PMID:11310834

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

    Science.gov (United States)

    Valkonen, Janne K; Mappes, Johanna

    2014-12-01

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

  16. Expression of human butyrylcholinesterase with an engineered glycosylation profile resembling the plasma-derived orthologue

    OpenAIRE

    Schneider, Jeannine D; Castilho, Alexandra; Neumann, Laura; Altmann, Friedrich; Loos, Andreas; Kannan, Latha; Mor, Tsafrir S.; Steinkellner, Herta

    2013-01-01

    Human butyrylcholinesterase (BChE) is considered a candidate bioscavenger of nerve agents for use in pre- and post-exposure treatment. The presence and functional necessity of complex N-glycans (i.e. sialylated structures) is a challenging issue in respect to its recombinant expression. We aim to produce recombinant BChE (rBChE) in plants with a glycosylation profile that largely resembles the plasma-derived counterpart. rBChE was transiently co-expressed in the model plant Nicotiana benthami...

  17. HyperPeer : Searching for resemblance in a P2P network

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Suzuki, Shinichi; Shibata, Masahiko; Gonda, Kenji; KANKE, YASUYUKI; ASHIZAWA, MAI; UJIIE, DAISUKE; SUZUSHINO, SEIKO; NAKANO, KEIICHI; Fukushima, Toshihiko; Sakurai, Kenichi; Tomita, Ryouichi; KUMAMOTO, KENSUKE; Takenoshita, Seiichi

    2013-01-01

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

  20. 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

    2013-05-01

    Full Text Available BACKGROUND 131I is usually employed for the therapy of hyperfunctioning thyroid diseases. This ?-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-?, 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-?1 e TNF-? can, rather than inhibit, induce anaplastic thyroid cancer cells to grow.

  1. Anaplastic Thyroid Cancer: The Addition of Systemic Chemotherapy to Radiotherapy Led to an Observed Improvement in Survival—A Single Centre Experience and Review of the Literature

    OpenAIRE

    Natalie M. Lowe; Sean Loughran; Slevin, Nicholas J.; Yap, Beng K

    2014-01-01

    Introduction. Anaplastic thyroid carcinoma (ATC) is rare yet accounts for up to 50% of all thyroid cancer deaths. This study reviews outcomes of patients with confirmed ATC referred to a tertiary oncology centre plus reviews the literature to explore how poor outcomes may be improved. Materials and Methods. The management and outcomes of 20 patients with ATC were reviewed. Results. Median age at diagnosis was 69.5 years. 19 patients died due to ATC, 40% of whom died from asphyxiation. Median ...

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

    Science.gov (United States)

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

    2005-09-01

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

  3. Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: Results of the prospective German brain tumor trials HIT-SKK 87 and 92

    International Nuclear Information System (INIS)

    Background and purpose: To evaluate the outcome of very young children with anaplastic ependymoma after delayed or omitted radiotherapy (RT). Materials and methods: Children under age of 3 years with anaplastic ependymoma were enrolled in the HIT-SKK 87 trial from 1987. After surgery, low-risk patients (R0, M0) received maintenance chemotherapy until elective RT at age of three. In high-risk patients (R+, M+) intensive induction chemotherapy was followed by maintenance chemotherapy and subsequently delayed RT. If there was, progression radiotherapy started immediately. In the HIT-SKK 92, trial MTX-based chemotherapy was applied. RT was administered in non-responders only. Results: Thirty-four children with anaplastic ependymoma were eligible (age 1.0-33.0 months). All children received chemotherapy. In 13 children, no RT was administered. Preventive RT after chemotherapy was given in nine, and salvage RT in 12 children. OS and PFS rates after 3-year were 55.9 and 27.3%, respectively. Twenty-five children relapsed. Positive impact on survival was observed in children with higher age, M0-stage, complete resection, and treatment with radiotherapy. Without RT only 3/13, children survived. Conclusion: Delaying RT jeopardizes survival even after intensive chemotherapy. Predominant site of failure is the primary tumor site. RT of the neuraxis should be omitted in localized disease

  4. A case of Scabies with Lesions Resembling Perforating Folliculitis and Uremic Pruritus

    Directory of Open Access Journals (Sweden)

    Hülya Akgün

    2010-10-01

    Full Text Available Scabies is an infestation caused by Sarcoptes scabiei and characterised by polymorphous lesions that may include burrows, papules, pustules, crusts and excoriations. Several pruritic diseases may be confused with scabies. Herein, we present a case of scabies with lesions resembling perforating folliculitis diagnosed on the basis of both clinical and histopathological view. A 72-year-old man with type 2 diabetes mellitus and receiving hemodialysis for ten years due to end-stage renal disease was admitted to our dermatology department with a 6-month history of severe pruritus. Based on the results of skin biopsy revealing Sarcoptes scabiei in the epidermis, the patient was diagnosed as scabies and was successfully treated with 5% permethrin. This case is presented to emphasize that scabies should be considered in the differential diagnosis in cases of chronic pruritus.

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

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    Gaurav Garg

    2011-01-01

    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.

  6. Pathological features of proteinuric nephropathy resembling Alport syndrome in a young Pyrenean Mountain dog.

    Science.gov (United States)

    Sugahara, Go; Naito, Ichiro; Miyagawa, Yuichi; Komiyama, Takaaki; Takemura, Naoyuki; Kobayashi, Ryosuke; Mineshige, Takayuki; Kamiie, Junichi; Shirota, Kinji

    2015-10-01

    The renal biopsy tissue from a 9-month-old, male Pyrenean Mountain dog with renal disorder and severe proteinuria was examined. Ultrastructural examination revealed multilaminar splitting and fragmentation of the glomerular basement membrane (GBM) and diffuse podocyte foot process effacement. Immunofluorescent staining for ?(IV) chains revealed presence of ?5(IV) and complete absence of ?3(IV) and ?4(IV) chains in the GBM. Immunohistochemistry also revealed decreased and altered expression of nephrin and podocin in the glomeruli compared with normal canine glomeruli. These results suggested that the glomerular disease of the present case might be consistent with canine hereditary nephropathy resembling human Alport syndrome caused by genetic defect of type IV collagen, and indicated possible contribution of podocyte injury to severe proteinuria in this case. PMID:25892536

  7. Clostridial myonecrosis clinically resembling black quarter in an Indian elephant (Elephas maximus).

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    Rahman, H; Chakraborty, A; Rahman, T; Sharma, R; Shome, B R; Shakuntala, I

    2009-12-01

    An Indian elephant (Elephas maximus) which died of acute fatal myonecrosis was examined to determine the aetiology of the infection. The causative organism was identified as Clostridium perfringens type A. Out of five genes encoding for major toxins (cpa, cpb, etx, iA, and cpe genes) the isolate was found to harbour the cpa gene only, as tested by multiplex polymerase chain reaction. It flanks a 324 base pair segment in the cpa gene, indicating the presence of the alpha toxin gene. The organism was sensitive to amikacin, ampicillin, enrofloxacin, gentamicin and norfloxacin but was resistant to bacitracin, oxytetracycline and tetracycline. The acute malignant nature of the myonecrosis and presence of the alpha toxin gene in the isolate suggested that the myonecrosis, although clinically resembling that caused by C. chauvoei in cases of black quarter, was caused by C. perfringens type A. PMID:20462165

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

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chul Hi; Kim, Ha Na; Byun, Sung Su; Ha, Seung Yeon [Gachon University of Medicine and Science, Incheon (Korea, Republic of)

    2009-04-15

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

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

    DEFF Research Database (Denmark)

    Nielsen, Mads; Vachon, Celine M.

    2014-01-01

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

  10. Rules and Resemblance: Their Changing Balance in the Category Learning of Humans (Homo sapiens) and Monkeys (Macaca mulatta)

    OpenAIRE

    Couchman, Justin J.; Coutinho, Mariana V. C.; SMITH, J. DAVID

    2010-01-01

    In an early dissociation between intentional and incidental category learning, Kemler Nelson (1984) gave participants a categorization task that could be performed by responding either to a single-dimensional rule or to overall family resemblance. Humans learning intentionally deliberately adopted rule-based strategies; humans learning incidentally adopted family-resemblance strategies. The present authors replicated Kemler Nelson’s human experiment and found a similar dissociation. They also...

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2014-11-01

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

  13. Esophagitis resulting from treatment with crizotinib for anaplastic lymphoma kinase rearrangement-positive lung adenocarcinoma: A case report.

    Science.gov (United States)

    Takakuwa, Osamu; Oguri, Tetsuya; Yokoyama, Midori; Hijikata, Hisatoshi; Uemura, Takehiro; Ohkubo, Hirotsugu; Maeno, Ken; Niimi, Akio

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed type of cancer and is a leading cause of cancer-related mortality worldwide. Treatment is currently focused on individualization according to the molecular profile of the disease. Here we present the case of a 41-year-old patient who presented with multiple pulmonary nodules, a left pleural effusion and an ovarian tumor. Adenocarcinoma of the lung was diagnosed from pathological examination of the pleural effusion and the surgically resected ovarian tumor, and chemotherapy was initiated. Relapse was experienced following third-line chemotherapy with pemetrexed and anaplastic lymphoma kinase (ALK)-positive adenocarcinoma was diagnosed using a specimen from the resected ovarian tumor. Subsequently, crizotinib therapy was initiated. Eight days later the patient developed severe nausea and vomiting and esophagitis was diagnosed by gastrointestinal endoscopic examination. Following the interruption of crizotinib treatment by treatment with a proton pump inhibitor (PPI), crizotinib treatment was re-initiated and was effective for a minimum of 6 months. Clinicians should be aware that treatment with crizotinib may result in severe esophagitis. PMID:24649319

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

    Directory of Open Access Journals (Sweden)

    Iwama E

    2014-03-01

    Full Text Available Eiji Iwama,1,2 Isamu Okamoto,3 Taishi Harada,2 Koichi Takayama,2 Yoichi Nakanishi2,3 1Department of Comprehensive Clinical Oncology, Faculty of Medical Sciences, Kyushu University, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan Abstract: The fusion of echinoderm microtubule-associated protein-like 4 with anaplastic lymphoma kinase (ALK was identified as a transforming gene for lung cancer in 2007. This genetic rearrangement accounts for 2%–5% of non-small-cell lung cancer (NSCLC cases, occurring predominantly in younger individuals with adenocarcinoma who are never- or light smokers. A small-molecule tyrosine-kinase inhibitor of ALK, crizotinib, was rapidly approved by the US Food and Drug Administration on the basis of its pronounced clinical activity in patients with ALK rearrangement-positive NSCLC. Next-generation ALK inhibitors, such as alectinib, LDK378, and AP26113, are also being developed in ongoing clinical trials. In addition, the improvement and validation of methods for the detection of ALK rearrangement in NSCLC patients will be key to the optimal clinical use of ALK inhibitors. We here summarize recent progress in the development of new ALK inhibitors and in the molecular diagnosis of ALK rearrangement-positive NSCLC. Keywords: ALK, rearrangement, NSCLC, ALK inhibitor, targeted therapy, diagnosis

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

    Science.gov (United States)

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

    2015-04-01

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

  16. Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: A critical re-evaluation including uniform pathologic review

    International Nuclear Information System (INIS)

    Background and purpose: Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy. The potential for pathologic misclassification complicates interpretation of published data. One standard treatment option for locoregionally advanced disease is weekly low-dose doxorubicin with concurrent radiation therapy, and was previously developed at our institution. We evaluated our more recent experience with this approach, which included pathologic confirmation of all cases. Materials and methods: A retrospective review was performed on patients identified through the Memorial Sloan-Kettering Cancer Center (MSKCC) Cancer Database. Inclusion criteria: pathologically confirmed ATC; locoregional disease encompassable within a radiation portal; treatment with curative intent at MSKCC with planned weekly doxorubicin (10 mg/m2) and concurrent radiation. Principle outcomes assessed were locoregional progression-free survival (LR-PFS) and overall survival (OS). Results: Thirty-seven patients were included. Median radiotherapy dose was 57.6 Gy, and was ⩾50 Gy in 29 (78%), administered through hyperfractionated or once-daily schedules. One-year outcomes were LR-PFS, 45%; OS, 28%. Conclusion: The prognosis of patients with ATC remains grim and our current results appear inferior to those reported previously by our institution. More accurate histologic diagnoses and patient selection in the present series compared to the prior one may be responsible in part. Better therapy is desperately needed for this aggressive disease.

  17. Melanoma maligno anaplásico em um eqüino Anaplastic malignant melanoma in a horse

    Directory of Open Access Journals (Sweden)

    Daniel Ricardo Rissi

    2008-10-01

    Full Text Available Descreve-se um caso de melanoma maligno anaplásico em uma égua Crioula, tordilha, com 10 anos de idade, com histórico clínico de apatia, perda de peso progressiva, febre, anorexia e dispnéia. Múltiplas massas pigmentadas e não-pigmentadas, bem delimitadas ou infiltrativas, foram observadas no tecido subcutâneo e em vários órgãos. Histologicamente o neoplasma era composto de populações de células fusiformes, redondas ou poliédricas e, menos freqüentemente, de células multinucleadas e "células em anel de sinete". O diagnóstico foi realizado com base nos achados clinicopatológicos e confirmado pela microscopia eletrônica de transmissão.A case of anaplastic malignant melanoma in a 10-year-old gray mare is described. Clinical signs included depression, progressive weight loss, fever, anorexia, and dyspnea. Multiple circumscribed or infiltrative, pigmented, and non-pigmented tumors were observed in subcutaneous tissue and in several organs. Histological examination revealed a marked variation in neoplastic cell population, which was composed by spindle, round, polyhedrical, and less frequently, multinucleated or signet ring cells. The diagnostic was based up on clinical and pathological findings, and confirmed by transmission electronic microscopy.

  18. TiO2 nanofibers resembling 'yellow bristle grass' in morphology by a soft chemical transformation.

    Science.gov (United States)

    Nandan, Sandeep; Deepak, T G; Nair, Shantikumar V; Nair, A Sreekumaran

    2015-05-28

    We synthesized a uniquely shaped one-dimensional (1-D) TiO2 nanostructure having the morphology of yellow bristle grass with high surface area by the titanate route under mild reaction conditions. The electrospun TiO2-SiO2 composite nanofibers upon treatment with concentrated NaOH at 80 °C under ambient pressure for 24 h resulted in sodium titanate (Na2Ti3O7) nanostructures. The Na2Ti3O7 nanostructures have an overall 1-D fibrous morphology but the highly porous fiber surfaces were decorated with layered thorn-like features (a morphology resembling that of yellow bristle grass) resulting in high surface area (113 m(2) g(-1)) and porosity. The Na2Ti3O7 nanostructures were converted into TiO2 nanostructures of the same morphology by acidification (0.1 N HCl) followed by low temperature sintering (110 °C) processes. Dye-sensitized solar cells (DSCs) constructed out of the material (cells of area 0.20 cm(2) and thickness 12 ?m) showed a power conversion efficiency (?) of 8.02% in comparison with commercial P-25 TiO2 (? = 6.1%). PMID:25923133

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

    Directory of Open Access Journals (Sweden)

    Nitrini Ricardo

    2001-01-01

    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.

  20. Mouse limbs expressing only the Gli3 repressor resemble those of Sonic hedgehog mutants.

    Science.gov (United States)

    Cao, Ting; Wang, Chengbing; Yang, Mei; Wu, Chuanqing; Wang, Baolin

    2013-07-15

    Anterioposterior vertebrate limb patterning is controlled by opposing action between Sonic Hedgehog (Shh) and the Gli3 transcriptional repressor. Unexpectedly, Gli3(?699) mutant mice, which are thought to express only a Gli3 repressor and not the full-length activator, exhibit limb phenotypes inconsistent with those of Shh mutant mice. Therefore, it remains debatable whether Shh patterns the anterioposterior limb primarily by inhibiting generation of the Gli3 repressor. However, one caveat is that Gli3(?699) may not be as potent as the natural form of Gli3 repressor because of the nature of the mutant allele. In the present study, we created a conditional Gli3 mutant allele that exclusively expresses Gli3 repressor in the presence of Cre recombinase. Using this mutant, we show that the phenotypes of mouse limbs expressing only the Gli3 repressor exhibit no or single digit, resembling those of Shh mutant limbs. Consistent with the limb phenotypes, the expression of genes dependent on Shh signaling is also inhibited in both mutants. This inhibition by the Gli3 repressor is independent of Shh. Thus, our study clarifies the current controversy and provides important genetic evidence to support the hypothesis that Shh patterns the anterioposterior limb primarily through the inhibition of Gli3 repressor formation. PMID:23644062

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

    Directory of Open Access Journals (Sweden)

    Pellegrini Ronald

    2005-10-01

    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.

  2. Granular cell ameloblastoma: case report of a particular ameloblastoma histologically resembling oncocytoma.

    Science.gov (United States)

    Matsushita, Yuki; Fujita, Shuichi; Kawasaki, Goro; Hirota, Yoshinosuke; Rokutanda, Satoshi; Yamashita, Kentaro; Yanamoto, Souichi; Ikeda, Tohru; Umeda, Masahiro

    2015-01-01

    Granular cell ameloblastoma is classified as a histological subtype of solid/multicystic ameloblastoma. Usual granular cell ameloblastoma is histologically characterized by granular changes of stellate-like cells located in the inner portion of the epithelial follicles. Here we report a case of another type of granular cell ameloblastoma, showing predominant anastomosing double-stranded trabeculae of granular cells. This type of granular cell ameloblastoma is extremely rare, and the World Health Organization classification does not contain the entity. We tentatively termed it 'anastomosing granular cell ameloblastoma' in this report. The present case suggests the importance of differential diagnosis because the histology of 'anastomosing granular cell ameloblastoma' resembles that of salivary gland oncocytoma rather than that of usual granular cell ameloblastoma. The trabeculae observed in our case continued to the peripheral cells of a small amount of epithelial sheets of plexiform ameloblastoma, and the tumor cells were positive for CK19, which is regarded as an immunohistochemical marker of odontogenic epithelium. Similar to usual granular cell ameloblastoma, the tumor cells had CD68-positive granules. For precise diagnosis of this condition, immunohistochemistry using CK19 and CD68, as well as detailed histological observation, are recommended. PMID:25421074

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

    International Nuclear Information System (INIS)

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

  4. Tilting marks: Observations on tool marks resembling trace fossils and their morphological varieties

    Science.gov (United States)

    Wetzel, Andreas

    2013-04-01

    Tilting marks, defined here as linear tool marks having transverse ornamentation, are produced in shallow water when the oscillatory action of waves of short wavelength tilt grounded objects rhythmically in such a way that they move and push sediment aside. These tool marks can resemble trace fossils, particularly if they are bilaterally symmetrical. Even asymmetrical objects can produce symmetrical tilting marks because the shape of the mark only depends on the geometry of the ground-touching part of the object, which may be partially floating. Objects of either soft or hard consistency, such as jellyfish or wood, respectively, can produce tilting marks. Tilting marks are normally produced linearly parallel or at an angle to the direction of wave propagation and do not show sharp bends or curves. Tilting marks can be formed on plane beds as well as rippled surfaces. Tilting marks can be distinguished from trace fossils by taking into account the geometry (symmetry), the direction of movement, and the mainly linear course and the internal pattern.

  5. Inherited multicentric osteolysis with arthritis: a variant resembling Torg syndrome in a Saudi family.

    Science.gov (United States)

    Al Aqeel, A; Al Sewairi, W; Edress, B; Gorlin, R J; Desnick, R J; Martignetti, J A

    2000-07-01

    The autosomal recessive multicentric osteolytic disorders of childhood-Torg, Winchester, and François syndromes-predominantly affect the carpal, tarsal, and interphalangeal joints, and their progressive bone loss and crippling arthritic deformities mimic severe juvenile rheumatoid arthritis. In a consanguineous Saudi Arabian family two affected sibs with facial anomalies and short stature displayed a distal arthropathy of the metacarpal, metatarsal, and interphalangeal joints starting in the first few months of life that eventually progressed to the proximal joints and resulted in crippling ankylosis and severe generalized osteopenia. Facial changes included proptosis, a narrow nasal bridge, bulbous nose, and micrognathia. In addition, they had large, painful fibrocollagenous palmar and plantar pads and mild body hirsutism. Affected individuals were of normal intelligence and had normal renal function. Routine hematologic, chemistry, and rheumatoid studies were within normal limits. Histologic examination of bone marrow and an interphalangeal joint biopsy were not informative. The autosomal recessive inheritance, clinical, and radiologic characteristics of the affected sibs suggested that they had a form of multicentric osteolysis most closely resembling the Torg syndrome, but with a unique facial appearance, fibrocollagenous pads, and body hirsutism not noted in the original description of the syndrome. PMID:10861676

  6. Source misattributions and false recognition errors: examining the role of perceptual resemblance and imagery generation processes.

    Science.gov (United States)

    Foley, Mary Ann; Bays, Rebecca Brooke; Foy, Jeffrey; Woodfield, Mila

    2015-01-01

    In three experiments, we examine the extent to which participants' memory errors are affected by the perceptual features of an encoding series and imagery generation processes. Perceptual features were examined by manipulating the features associated with individual items as well as the relationships among items. An encoding instruction manipulation was included to examine the effects of explicit requests to generate images. In all three experiments, participants falsely claimed to have seen pictures of items presented as words, committing picture misattribution errors. These misattribution errors were exaggerated when the perceptual resemblance between pictures and images was relatively high (Experiment 1) and when explicit requests to generate images were omitted from encoding instructions (Experiments 1 and 2). When perceptual cues made the thematic relationships among items salient, the level and pattern of misattribution errors were also affected (Experiments 2 and 3). Results address alternative views about the nature of internal representations resulting in misattribution errors and refute the idea that these errors reflect only participants' general impressions or beliefs about what was seen. PMID:24931435

  7. Multisystemic eosinophilia resembling hypereosinophilic syndrome in a colony-bred owl monkey (Aotus vociferans).

    Science.gov (United States)

    Gozalo, Alfonso S; Rosenberg, Helene F; Elkins, William R; Montoya, Enrique J; Weller, Richard E

    2009-05-01

    In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID:19476722

  8. A uterine tumor resembling ovarian sex cord tumor associated with tamoxifen treatment: a case report and literature review.

    Science.gov (United States)

    Gutierrez-Pecharroman, Ana; Tirado-Zambrana, Pernilla; Pascual, Alejandro; Rubio-Marin, Dolores; García-Cosío, Mónica; Moratalla-Bartolomé, Enrique; Palacios, José

    2014-03-01

    Uterine tumors resembling ovarian sex cord tumors are rare neoplasms of unknown etiology that are classified as distinct from endometrial stromal tumors on the basis of their morphologic, molecular, and behavioral characteristics. These neoplasms have a variable immunophenotype, sometimes coexpressing epithelial, myoid, and sex cord markers. To date, only 2 cases of uterine tumors resembling ovarian sex cord tumors associated with tamoxifen use have been reported. Here, we report the case of a 49-year-old woman who had been using tamoxifen for 5 years to treat breast cancer. The tumor was initially diagnosed by hysteroscopy biopsy on the basis of morphologic and immunohistochemical features. Hysterectomy revealed a polypoid mass measuring 20 mm. After an 18-month follow-up, the patient remains disease free. Here, we review the clinical, pathologic, and immunohistochemical features of uterine tumors resembling ovarian sex cord tumors and endometrial stromal tumors with a sex cord component associated with tamoxifen treatment. PMID:24487470

  9. Uterine tumor resembling ovarian sex cord tumors treated by resectoscopic surgery.

    Science.gov (United States)

    Garuti, Giancarlo; Gonfiantini, Cristina; Mirra, Maurizio; Galli, Carlo; Luerti, Massimo

    2009-01-01

    Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare neoplasms of uncertain malignancy, affecting either pre or menopausal women. Only 48 cases of UTROSCTs have been reported and in most patients the diagnosis was made incidentally, after a hysterectomy as a result of the assumption of a leiomyoma. Although no death from progressive disease was reported, locoregional spread or abdominal relapse was detected in some patients. Up until now, a treatment sparing the uterus was reported in only 2 patients with UTROSCTs. Both patients conceived after surgery and were free from recurrent disease after a mean follow-up of 16.5 months. We report a third case of a young patient affected by pure UTROSCTs and treated conservatively. A 29-year-old woman underwent resectoscopic hysteroscopy because of the assumption of a grade-1 submucous myoma measuring about 5 cm. To accomplish the removal of the endometrial mass, a 2-step hysteroscopic resection was required. Histology showed epithelioid cells arranged in nests, cords, tubules, and trabeculae infiltrating the myometrium; no sarcoma cell differentiation was detected. Immunohistochemistry resulted in positivity to CD99, inhibin, calretinin, cytokeratin, and estrogen receptor, whereas a negative staining to epithelial membrane antigen, actin, desmin, and human melanoma black 45 was obtained. Based on histologic pattern and immunohistochemical phenotype, a diagnosis of pure UTROSCTs was made; the staging of disease revealed neither locoregional spread nor distant metastases. Two months after surgery, reassessment by hysteroscopy and endometrial biopsy revealed no residual endometrial disease. The patient was free from disease 13 months after surgery. Because of the uncertain malignant potential of UTROSCTs and based on the poor data available from current literature, a fertility-sparing surgery in young patients appears safe. However, a close long-term follow-up is required and a quick completion of a patient's childbearing desire seems advisable. PMID:19249718

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

    Directory of Open Access Journals (Sweden)

    Simone Alves Dantas

    2010-01-01

    Full Text Available 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.

  11. Parent–offspring resemblance in colony-specific adult survival of cliff swallows

    Science.gov (United States)

    Brown, Charles R.; Roche, Erin A.; Brown, Mary Bomberger

    2015-01-01

    Survival is a key component of fitness. Species that occupy discrete breeding colonies with different characteristics are often exposed to varying costs and benefits associated with group size or environmental conditions, and survival is an integrative net measure of these effects. We investigated the extent to which survival probability of adult (?1-year old) cliff swallows (Petrochelidon pyrrhonota) occupying different colonies resembled that of their parental cohort and thus whether the natal colony had long-term effects on individuals. Individuals were cross-fostered between colonies soon after hatching and their presence as breeders monitored at colonies in the western Nebraska study area for the subsequent decade. Colony-specific adult survival probabilities of offspring born and reared in the same colony, and those cross-fostered away from their natal colony soon after birth, were positively and significantly related to subsequent adult survival of the parental cohort from the natal colony. This result held when controlling for the effect of natal colony size and the age composition of the parental cohort. In contrast, colony-specific adult survival of offspring cross-fostered to a site was unrelated to that of their foster parent cohort or to the cohort of non-fostered offspring with whom they were reared. Adult survival at a colony varied inversely with fecundity, as measured by mean brood size, providing evidence for a survival–fecundity trade-off in this species. The results suggest some heritable variation in adult survival, likely maintained by negative correlations between fitness components. The study provides additional evidence that colonies represent non-random collections of individuals.

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Muirhead William

    2010-08-01

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

  14. Simultaneous compression and encryption of closely resembling images: application to video sequences and polarimetric images.

    Science.gov (United States)

    Aldossari, M; Alfalou, A; Brosseau, C

    2014-09-22

    This study presents and validates an optimized method of simultaneous compression and encryption designed to process images with close spectra. This approach is well adapted to the compression and encryption of images of a time-varying scene but also to static polarimetric images. We use the recently developed spectral fusion method [Opt. Lett.35, 1914-1916 (2010)] to deal with the close resemblance of the images. The spectral plane (containing the information to send and/or to store) is decomposed in several independent areas which are assigned according a specific way. In addition, each spectrum is shifted in order to minimize their overlap. The dual purpose of these operations is to optimize the spectral plane allowing us to keep the low- and high-frequency information (compression) and to introduce an additional noise for reconstructing the images (encryption). Our results show that not only can the control of the spectral plane enhance the number of spectra to be merged, but also that a compromise between the compression rate and the quality of the reconstructed images can be tuned. We use a root-mean-square (RMS) optimization criterion to treat compression. Image encryption is realized at different security levels. Firstly, we add a specific encryption level which is related to the different areas of the spectral plane, and then, we make use of several random phase keys. An in-depth analysis at the spectral fusion methodology is done in order to find a good trade-off between the compression rate and the quality of the reconstructed images. Our new proposal spectral shift allows us to minimize the image overlap. We further analyze the influence of the spectral shift on the reconstructed image quality and compression rate. The performance of the multiple-image optical compression and encryption method is verified by analyzing several video sequences and polarimetric images. PMID:25321707

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

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2015-01-01

    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, ?TrkA 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.

  16. Anaplastic lymphoma kinase protein expression, genetic abnormalities, and phosphorylation in soft tissue tumors: Phosphorylation is associated with recurrent metastasis.

    Science.gov (United States)

    Ishibashi, Yukinao; Miyoshi, Hiroaki; Hiraoka, Koji; Arakawa, Fumiko; Haraguchi, Toshiaki; Nakashima, Shinji; Hashiguchi, Toshihiro; Shoda, Takanori; Hamada, Tetsuya; Okawa, Takahiro; Higuchi, Fujio; Shiba, Naoto; Nagata, Kensei; Ohshima, Koichi

    2015-04-01

    Gene and protein abnormalities of anaplastic lymphoma kinase (ALK) play an important role in the pathogenesis of various cancers and serve as important therapeutic targets. We investigated ALK protein expression, phosphorylation, and genetic aberrations using fluorescence in situ hybridization (FISH) in 81 soft tissue tumor samples: inflammatory myofibroblastic tumor, n=1; alveolar soft part sarcoma, n=2; leiomyosarcoma, n=10; well-differentiated liposarcoma, n=7; pleomorphic liposarcoma, n=2; extraskeletal osteosarcoma, n=1; epithelioid sarcoma, n=1; synovial sarcoma, n=4; malignant peripheral nerve sheath tumor, n=4; undifferentiated pleomorphic sarcoma, n=19; rhabdomyosarcoma, n=6; myxofibrosarcoma, n=8; myxoid liposarcoma, n=11; fibrosarcoma, n=4; and desmoid-type fibromatosis, n=1. ALK protein expression, gene signal gain (without translocation), and phosphorylation were observed in 33/81 (40.7%), 55/81 (67.9%), and 30/81 (37.0%) tumor samples, respectively. ALK protein expression was statistically associated with phosphorylation, but not with gene signal gain. ALK phosphorylation-positive cases showed a statistically worse metastasis-free survival compared with phosphorylation-negative cases (P=0.0215). Particularly, metastasis of myxoid liposarcoma was associated with ALK phosphorylation (P=0.0019), but not with ALK protein expression or gene signal gain. However, the prognosis had no association with ALK protein expression, gene signal gain, or phosphorylation. ALK protein expression and phosphorylation play an important role in tumor biology and provide potential therapeutic targets for soft tissue tumors. Future research should focus on the oncogenic role and the efficacy of potential inhibitors of ALK. PMID:25683346

  17. MART-10, the vitamin D analog, is a potent drug to inhibit anaplastic thyroid cancer cell metastatic potential.

    Science.gov (United States)

    Chiang, Kun-Chun; Kuo, Sheng-Fong; Chen, Chih-Hung; Ng, Sohching; Lin, Shu-Fu; Yeh, Chun-Nan; Chen, Li-Wei; Takano, Masashi; Chen, Tai C; Juang, Horng-Heng; Kittaka, Atsushi; Lin, Jen-Der; Pang, Jong-Hwei S

    2015-12-01

    The survival rate of anaplastic thyroid cancer (ATC) is still very poor due to its fast growth and high metastatic potential. Currently, no effective treatment is available. The active form of vitamin D3, 1?,25(OH)2D3, has been shown to have a anti-metastatic effect in pre-clinical studies, however induction of hypercalcemia hampered its clinical application. The new class of less-calcemic vitamin D analog, 19-nor-2?-(3-hydroxypropyl)-1?,25-dihydroxyvitamin D3 (MART-10), is much more potent than 1?,25(OH)2D3 to repress cancer growth and metastasis in a variety of cancers. In this study, we demonstrated that both 1?,25(OH)2D3 and MART-10 could effectively inhibit the migration and invasion of ATC cells, 8305C and 8505C, with MART-10 much more potent than 1?,25(OH)2D3. The anti-metastatic effect of 1?,25(OH)2D3 and MART-10 on ATC cells is mediated by reversal of cadherin switch (upregulation of E-cadherin and downregulation of N-cadherin), which led to the attenuation of EMT process, and decrease of F-actin formation. We further showed that the expressions of Slug, the EMT-related transcriptional factor, and MMP-9 were inhibited by 1?,25(OH)2D3 and MART-10 in 8505C cells, but not in 8303C cells. Since metastasis is the important cause of ATC-related death, our results strongly encourage the further in vivo study of MART-10 application against ATC. PMID:26282787

  18. 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

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu [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)

    2014-03-15

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

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

    Directory of Open Access Journals (Sweden)

    Jerzy Sowinski

    2009-01-01

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

  20. 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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2011-01-01

    Full Text Available The primary cutaneous T-cell lymphomas (CTCL represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30+ T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the "tumor lymphocytes". The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30 + /ALK? anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin, Vincristin (Oncovin®, Predniso(lon. Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF-?, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30 + cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis.

  2. A novel chemo-radiotherapy with low-dose daily cisplatin, 5-fluorouracil and doxorubicin for anaplastic thyroid carcinoma. A preliminary report

    International Nuclear Information System (INIS)

    Although anaplastic thyroid carcinoma has a dismal prognosis, some patients show favorable survival following multimodal treatment with surgery, external irradiation and chemotherapy. However, no regimen has yet been established. We reviewed outcomes for patients who underwent a unique chemoradiotherapy regimen between 1998 and 2007. The regimen consists of external irradiation (40 Gy at 2 Gy/day) combined with concurrent low-dose cisplatin at 5 mg/m2 on Days 1-5, 8-12, 15-19 and 22-26, 5-fluorouracil at 200 mg/m2 on Days 1-26 and doxorubicin at 20 mg/m2 on Days 1 and 15. This regimen was performed on 21 patients (13 men, 8 women) with anaplastic thyroid carcinoma. Median age at the time of treatment was 66 years (range, 54-81 years). The treatment regimen was completed in 19 patients (90%) and was interrupted in 2 (10%) due to progressive distant metastases. After excluding 10 patients who underwent complete resection before chemoradiotherapy, 1 patient (11%) showed partial response, 7 (78%) showed stable disease and 1 (11%) had progressive disease on the basis of Response Evaluation Criteria in Solid Tumors. Overall, 6-month survival rate for patients treated with chemoradiotherapy was 57%. With this novel chemoradiotherapy, death from loco-regional disease was seen in only two patients (11%). Grade 3-4 toxicities were observed in 12 patients (63%), but no treatment-related deaths were encountered. Our new chemoradiotherapy is effective for loco-regional control of anaplastic thyroid carcinoma, particularly when combined with radical surgery. This regimen could not prevent distant metastases, but offers acceptable toxicity while maintaining patient quality of life. (author)

  3. Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis.

    OpenAIRE

    Bischof, D; Pulford, K.; Mason, D. Y.; Morris, S.W.

    1997-01-01

    The NPM-ALK fusion gene, formed by the t(2;5)(p23;q35) translocation in non-Hodgkin's lymphoma, encodes a 75-kDa hybrid protein that contains the amino-terminal 117 amino acid residues of the nucleolar phosphoprotein nucleophosmin (NPM) joined to the entire cytoplasmic portion of the receptor tyrosine kinase ALK (anaplastic lymphoma kinase). Here, we demonstrate the transforming ability of NPM-ALK and show that oncogenesis by the chimeric protein requires the activation of its kinase function...

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

    OpenAIRE

    Sur Monalisa; Ross Cathy; Bishara Mona RY

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Sun, S; Karemore, Gopal Raghunath

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

  6. Imaging manifestations of acquired elastopathy resembling pseudoxanthoma elasticum in patients with beta thalassaemia major and sickle cell disease.

    Science.gov (United States)

    Narayanan, Harish; Cheng, Ken; Lau, Ken; Harish, Radhika; Bowden, Donald K

    2016-02-01

    Development of an acquired systemic elastopathy resembling pseudoxanthoma elasticum in patients with chronic haemoglobinopathies such as beta thalassaemia major and sickle cell disease is well documented. There is paucity of any comprehensive literature on the radiological manifestations of this entity. This pictorial review aims to describe and illustrate the multi system and multi modality imaging findings of this condition. PMID:26548799

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

    DEFF Research Database (Denmark)

    Nielsen, Mads; Karemore, Gopal Raghunath; Loog, Marco; Raundahl, Jakob; Karssemeijer, N; Otten, J. D. M.; Karsdal, M.A.; Vachon, C. M.; Christiansen, C

    2011-01-01

    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 to dia...

  8. Evaluation of the proliferation markers Ki-67/MIB-1, mitosin, survivin, pHH3, and DNA topoisomerase II? in human anaplastic astrocytomas - an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Gulati Sasha

    2011-05-01

    Full Text Available Abstract Background Histological malignancy grading of astrocytomas can be challenging despite criteria given by the World Health Organisation (WHO. Grading is fundamental for optimal prognostication and treatment, and additional biomarkers are needed to support the histopathological diagnosis. Estimation of proliferative activity has gained much enthusiasm, and the present study was designed to evaluate and compare novel immunohistochemical proliferative markers in human anaplastic astrocytomas. Methods Proliferative activity was determined in twenty-seven cases with antibodies reactive against the Ki-67 antigen, mitosin, survivin, pHH3, and DNA topoisomerase II?, and they were mutually compared as well as related to mitotic activity. Results The markers correlated well with each other, but poorly with mitoses, probably because of small and squeezed tumour samples, in which identification of mitoses can be difficult. Positive association to overall survival was observed as well. Conclusions Our data show that these markers may assist significantly in the evaluation of proliferative activity in anaplastic astrocytomas and even have prognostic value.

  9. Constitutive control of AKT1 gene expression by JUNB/CJUN in ALK+ anaplastic large-cell lymphoma: a novel crosstalk mechanism.

    Science.gov (United States)

    Atsaves, V; Zhang, R; Ruder, D; Pan, Y; Leventaki, V; Rassidakis, G Z; Claret, F X

    2015-11-01

    Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is an aggressive T-cell non-Hodgkin lymphoma characterized by the t(2;5), resulting in the overexpression of nucleophosmin (NPM)-ALK, which is known to activate the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, resulting in cell cycle and apoptosis deregulation. ALK+ ALCL is also characterized by strong activator protein-1 (AP-1) activity and overexpression of two AP-1 transcription factors, CJUN and JUNB. Here, we hypothesized that a biologic link between AP-1 and AKT kinase may exist, thus contributing to ALCL oncogenesis. We show that JUNB and CJUN bind directly to the AKT1 promoter, inducing AKT1 transcription in ALK+ ALCL. Knockdown of JUNB and CJUN in ALK+ ALCL cell lines downregulated AKT1 mRNA and promoter activity and was associated with lower AKT1 protein expression and activation. We provide evidence that this is a transcriptional control mechanism shared by other cell types even though it may operate in a way that is cell context-specific. In addition, STAT3 (signal transducer and activator of transcription 3)-induced control of AKT1 transcription was functional in ALK+ ALCL and blocking of STAT3 and AP-1 signaling synergistically affected cell proliferation and colony formation. Our findings uncover a novel transcriptional crosstalk mechanism that links AP-1 and AKT kinase, which coordinate uncontrolled cell proliferation and survival in ALK+ ALCL. PMID:25987255

  10. Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma

    International Nuclear Information System (INIS)

    Sox2 (sex-determining region Y-Box) is one of the master transcriptional factors that are important in maintaining the pluripotency of embryonic stem cells (ESCs). In line with this function, Sox2 expression is largely restricted to ESCs and somatic stem cells. We report that Sox2 is expressed in cell lines and tumor samples derived from ALK-positive anaplastic large cell lymphoma (ALK+ALCL), for which the normal cellular counterpart is believed to be mature T-cells. The expression of Sox2 in ALK+ALCL can be attributed to nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), the oncogenic fusion protein carrying a central pathogenetic role in these tumors. By confocal microscopy, Sox2 protein was detectable in virtually all cells in ALK+ALCL cell lines. However, the transcriptional activity of Sox2, as assessed using a Sox2-responsive reporter construct, was detectable only in a small proportion of cells. Importantly, downregulation of Sox2 using short interfering RNA in isolated Sox2active cells, but not Sox2inactive cells, resulted in a significant decrease in cell growth, invasiveness and tumorigenicity. To conclude, ALK+ALCL represents the first example of a hematologic malignancy that aberrantly expresses Sox2, which represents a novel mechanism by which NPM-ALK mediates tumorigenesis. We also found that the transcriptional activity and oncogenic effects of Sox2 can be heterogeneous in cancer cells

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

    OpenAIRE

    Preisinger Rudolf; Sharifi Ahmad R; Weigend Steffen; Philipp Hans-Christian; Schwarz Susanne CN; Trapp Sascha; Kothlow Sonja; Bader Sophie R; Schmahl Wolfgang; Kaspers Bernd; Matiasek Kaspar

    2010-01-01

    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 o...

  12. Isolation of gram-positive rods that resemble but are clearly distinct from Actinomyces pyogenes from mixed wound infections.

    OpenAIRE

    Wüst, J; Lucchini, G M; Lüthy-Hottenstein, J; Brun, F.; Altwegg, M.

    1993-01-01

    Beginning in 1990, gram-positive rods resembling Actinomyces pyogenes were found with increasing frequency in mixed cultures from various infectious processes, most of them from patients with otitis, empyema, pilonidal cysts, perianal abscesses, and decubitus ulcers. Ribotyping and hybridization showed that these gram-positive rods could be divided into five groups not related to known Actinomyces species. Biochemical markers for reliable differentiation into these groups, however, could not ...

  13. Cognitive restraint, uncontrolled eating and emotional eating: correlations between parent and adolescent. : Familial resemblance in eating behavior

    OpenAIRE

    de Lauzon-Guillain, Blandine; Romon, Monique; Musher-Eizenman, Dara; Heude, Barbara; Basdevant, Arnaud; Charles, Marie-Aline

    2009-01-01

    The purpose of this study was to examine, in a general population, the resemblance in eating behaviour between adolescents and their parents. This study was based on the first examination of a community-based epidemiological study in Northern France. Subjects were offspring aged 14-22 years (135 boys and 125 girls) and their parents (174 fathers and 205 mothers). The Three-Factor Eating Questionnaire Revised 18-item version (TFEQ-R18) identified three aspects of eating behaviour: cognitive re...

  14. MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme

    OpenAIRE

    Lin, J.; Teo, S; Lam, D H; Jeyaseelan, K; Wang, S.

    2012-01-01

    Glioblastoma multiforme (GBM) is a heterogeneous disease despite its seemingly uniform pathology. Deconvolution of The Cancer Genome Atlas's GBM gene expression data has unveiled the existence of distinct gene expression signature underlying discrete GBM subtypes. Recent conflicting findings proposed that microRNA (miRNA)-10b exclusively regulates glioma growth or invasion but not both. We showed that silencing of miRNA-10b by baculoviral decoy vectors in a glioma cell line resembling the mes...

  15. Experimental and numerical investigation of the flow-induced resonance of slender deep cavities that resemble automotive door gaps:

    OpenAIRE

    De Jong, A.T.; Bijl, H.

    2010-01-01

    Cavity aeroacoustic noise is relevant for aerospace and automotive industries and widely investigated since the 1950’s. Most investigations so far consider cavities where opening length and width are of similar scale. The present investigation focuses on a less investigated setup, namely cavities that resemble the door gaps of automobiles. These cavities are both slender (width much greater than length or depth) and partially covered. Furthermore they are under influence of a low Mach number ...

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

    OpenAIRE

    Hsin-Jen Chen; Yinghui Liu; Youfa Wang

    2014-01-01

    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-...

  17. Socioeconomic and demographic factors for spousal resemblance in obesity status and habitual physical activity in the United States.

    Science.gov (United States)

    Chen, Hsin-Jen; Liu, Yinghui; Wang, Youfa

    2014-01-01

    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. PMID:25332834

  18. Generational status, neighborhood context, and mother-child resemblance in dietary quality in Mexican-origin families.

    Science.gov (United States)

    Dondero, Molly; Van Hook, Jennifer

    2016-02-01

    Children of immigrants in the United States often grow up in very different nutrition environments than their parents. As a result, parent-child concordance in diet may be particularly weak in immigrant families. Yet, little is known about parent-child dietary resemblance in immigrant families and how local contexts shape it. This study uses data from the 1999/2000-2009/2010 Continuous National Health and Nutrition Examination Survey to examine mother-child resemblance in dietary quality in Mexican-origin families in the United States. We investigate how immigrant generational status and neighborhood context shape the association between mothers' and children's dietary quality. We find that mother-child resemblance in dietary quality is weaker for first-generation children relative to third-generation children. However, residence in an immigrant enclave strengthens the mother-child association in dietary quality for first-generation children. Findings offer a unique within-family perspective of immigrant health. Results suggest that the healthy eating advantage of Mexican immigrant mothers may not be sustained across family generations and that Mexican immigrant mothers may face unique challenges in promoting healthy eating among their children. PMID:26773704

  19. Anaplastic meningioma: case report

    OpenAIRE

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

    2001-01-01

    Intracranial meningiomas continue to challenge our best clinical efforts to eliminate them once discovered and deemed appropriate for treatment. Malignant meningiomas constitute 10% to 15% of all meningiomas and limited information exists regarding adjuvant treatment. The external whole brain irradiation is recommended. Traditional chemotherapy has proven ineffective; thus, new chemotherapeutic agents and new methods of delivery should be developed. Immunotherapy may be considered for patient...

  20. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma: dissociation between phenotype and genotype.

    Science.gov (United States)

    Herbst, H; Tippelmann, G; Anagnostopoulos, I; Gerdes, J; Schwarting, R; Boehm, T; Pileri, S; Jones, D B; Stein, H

    1989-01-01

    We have determined the tumor cell immunophenotype and the rearrangement configuration of immunoglobulin and T-cell receptor genes in 39 cases of Hodgkin's disease (HD), six HD-derived cell lines and 22 cases of Ki-1-positive anaplastic large cell lymphomas (Ki-1-ALC). Rearrangements were observed in 11/39 HD cases, 15/22 Ki-1-ALC, and all cell lines. Epstein-Barr virus DNA was found in five HD cases, one cell line, and one Ki-1-ALC. Both HD and Ki-1-ALC frequently displayed a dissociated genotypic and phenotypic maturation status, i.e. an immature genotype in association with late activation markers. We postulate that the tumor cells in many cases of HD and some cases of Ki-1-ALC may be derived from immature lymphoid cells by a transformation process that superimposes characteristics of mature activated lymphocytes on these cells. PMID:2538681

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

    Directory of Open Access Journals (Sweden)

    Koji Kato

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

  2. Chronic Phase Intracranial Hemorrhage Caused by Ruptured Pseudoaneurysm Induced by Carmustine Wafer Implantation for Insulo-opercular Anaplastic Astrocytoma: A Case Report.

    Science.gov (United States)

    Sato, Kimitoshi; Dan, Mitsuru; Yamamoto, Daisuke; Miyajima, Yoshiteru; Hara, Atsuko; Kumabe, Toshihiro

    2015-11-16

    Carmustine wafers improve the survival of patients with high-grade gliomas, but several adverse events have been reported. A 42-year-old man with left insulo-opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6 months previously. Intraoperative finding demonstrated a dissection of the insular portion of the MCA, and pathological examination identified the resected pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes in local vessels. Therefore, implantation of carmustine wafers near to important vessels passing close to the resection cavity should be considered with great caution. PMID:26423018

  3. Chronic Phase Intracranial Hemorrhage Caused by Ruptured Pseudoaneurysm Induced by Carmustine Wafer Implantation for Insulo-opercular Anaplastic Astrocytoma: A Case Report

    Science.gov (United States)

    SATO, Kimitoshi; DAN, Mitsuru; YAMAMOTO, Daisuke; MIYAJIMA, Yoshiteru; HARA, Atsuko; KUMABE, Toshihiro

    2015-01-01

    Carmustine wafers improve the survival of patients with high-grade gliomas, but several adverse events have been reported. A 42-year-old man with left insulo-opercular anaplastic astrocytoma developed a massive intra-cavital hematoma with subarachnoid hemorrhage caused by ruptured pseudoaneurysm of the left middle cerebral artery (MCA) adjacent to the site of carmustine wafers implanted 6 months previously. Intraoperative finding demonstrated a dissection of the insular portion of the MCA, and pathological examination identified the resected pseudoaneurysm. This case demonstrates that carmustine wafers can cause changes in local vessels. Therefore, implantation of carmustine wafers near to important vessels passing close to the resection cavity should be considered with great caution. PMID:26423018

  4. Absence of anaplastic lymphoma kinase-1 expression in inflammatory myofibroblastic tumors of the central nervous system: Does it signify a different nosologic entity from its systemic counterpart?

    Directory of Open Access Journals (Sweden)

    Aparna Govindan

    2014-01-01

    Full Text Available Background and Aim: Inflammatory myofibroblastic tumors (IMFTs are uncommon neoplasms of the central nervous system (CNS of intermediate grade biologic potential. Anaplastic lymphoma kinase (ALK-1, a diagnostic marker of anaplastic large cell lymphoma, is also expressed in a subset of IMFTs and appears to have prognostic significance. Though, few studies have evaluated expression of ALK-1 in IMFTs of the CNS. This retrospective study was undertaken to evaluate the expression of ALK-1 expression in IMFT of CNS by immunohistochemistry and correlate with the clinical, radiological and pathologic features. Materials and Methods: Five cases diagnosed as IMFT/inflammatory pseudotumour/plasma cell granuloma, diagnosed in CNS over 10 year period (1998-2007 were retrieved from the archives of Department of Neuropathology of a tertiary referralcenter. The clinical profile and imaging features were collected from the case records. Hematoxylin and eosin stained sections were reviewed with immunohistochemistry for smooth muscle actin (SMA, vimentin, desmin, ALK-1, p53, MIB-1, CD68, leukocyte common antigen, CD3, and CD20. Results: All five cases of IMFTs presented as dural-based space occupying or en-plaque lesions. Histologically, four cases had combined plasma cell granuloma-fibrous histiocytoma morphology, and one had fibrous histiocytoma-like morphology. Immunohistochemically, SMA was strongly positive in spindle cell component of the tumors confirming diagnosis. ALK-1 expression could not be detected by immunohistochemistry in any of the cases. Conclusion: Further studies analyzing ALK-1 gene mutation and rearrangements are required to determine pathogenetic role, if any, in CNS IMFTs.

  5. Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity.

    Science.gov (United States)

    Hernández, Luis; Beà, Sílvia; Bellosillo, Beatriz; Pinyol, Magda; Falini, Brunangelo; Carbone, Antonino; Ott, German; Rosenwald, Andreas; Fernández, Alberto; Pulford, Karen; Mason, David; Morris, Stephan W; Santos, Eugenio; Campo, Elias

    2002-04-01

    Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5' TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALK(S)) and 97 kd (TFG-ALK(L)), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALK(XL)), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK. PMID:11943732

  6. Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials hit 88/89 and hit 91

    International Nuclear Information System (INIS)

    Purpose: To evaluate the outcome in children with anaplastic ependymomas after surgery, irradiation, and chemotherapy; and to identify prognostic factors for survival. Methods and Materials: Fifty-five children (n = 27 girls, 28 boys; median age at diagnosis, 6.2 years) with newly diagnosed anaplastic ependymomas were treated in the multicenter, prospective trials HIT 88/89 and HIT 91. Macroscopic complete resection was achieved in 28 patients; 27 patients underwent incomplete resection. All patients received chemotherapy before (n = 40) or after irradiation (n = 15). The irradiation volume encompassed either the neuraxis followed by a boost to the primary tumor site (n = 40) or the tumor region only (n = 13). No radiotherapy was administered in two patients. Results: Median follow-up was 38 months. The overall survival rate at 3 years after surgery was 75.6%. Disease progression occurred in 25 children with local progression occurring in 20. The median time to disease progression was 45 months. The only significant prognostic factor was the extent of resection (estimated progression-free survival [EPFS] after 3 years was 83.3% after complete resection and 38.5% after incomplete resection) and the presence of metastases at the time of diagnosis (0% vs. 65.8% 3-year EPFS in localized tumors). Age, sex, tumor site, mode of chemotherapy, and irradiation volume did not influence survival. Conclusions: Treatment centers should be meticulous about surgery and diagnostic workup. Because the primary tumor region is the predominant site of failure it is important to intensify local treatment. Dose escalation by hyperfractionation or stereotactic radiotherapy might be a promising approach in macroscopically residual disease. The role of adjuvant chemotherapy requires further study

  7. Generation of self-mode-locked resembling pulses in a fast gain-switched thulium-doped fiber laser.

    Science.gov (United States)

    Swiderski, Jacek; Michalska, Maria

    2013-05-15

    We report on a generation of self-starting mode-locked resembling (MLR) pulses in an all-fiber, gain-switched Tm(3+)-doped fiber laser operating at 2 ?m wavelength, which we believe to be the first demonstration of such an approach. The laser delivers 100% modulated MLR pulses within an envelope of ~30 ns gain-switched pulse at a repetition rate of 30 kHz. The maximum average output power is 0.4 W and the maximum peak-power of MLR pulses can be as high as 1.1 kW. The performance of the laser is described. PMID:23938890

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

    Directory of Open Access Journals (Sweden)

    Preisinger Rudolf

    2010-01-01

    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.

  9. Vaginal Microbiota of Adolescent Girls Prior to the Onset of Menarche Resemble Those of Reproductive-Age Women

    Science.gov (United States)

    Hickey, Roxana J.; Zhou, Xia; Settles, Matthew L.; Erb, Julie; Malone, Kristin; Hansmann, Melanie A.; Shew, Marcia L.; Van Der Pol, Barbara

    2015-01-01

    ABSTRACT Puberty is an important developmental stage wherein hormonal shifts mediate the physical and physiological changes that lead to menarche, but until now, the bacterial composition of vaginal microbiota during this period has been poorly characterized. We performed a prospective longitudinal study of perimenarcheal girls to gain insight into the timing and sequence of changes that occur in the vaginal and vulvar microbiota during puberty. The study enrolled 31 healthy, premenarcheal girls between the ages of 10 and 12 years and collected vaginal and vulvar swabs quarterly for up to 3 years. Bacterial composition was characterized by Roche 454 pyrosequencing and classification of regions V1 to V3 of 16S rRNA genes. Contrary to expectations, lactic acid bacteria, primarily Lactobacillus spp., were dominant in the microbiota of most girls well before the onset of menarche in the early to middle stages of puberty. Gardnerella vaginalis was detected at appreciable levels in approximately one-third of subjects, a notable finding considering that this organism is commonly associated with bacterial vaginosis in adults. Vulvar microbiota closely resembled vaginal microbiota but often exhibited additional taxa typically associated with skin microbiota. Our findings suggest that the vaginal microbiota of girls begin to resemble those of adults well before the onset of menarche. PMID:25805726

  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

    2003-11-01

    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. Additionally, we observed typical histological images of dissolution of the connective tissue matrix around eosinophils. Conclusion The present study shows that a timely regulated influx of infiltrating leukocytes is associated with an extensive collagen remodeling process that allows the pubic separation for a normal delivery in guinea-pig. Thus, the findings in this study support the hypothesis that the guinea-pig pubic symphyseal relaxation at parturition resembles an inflammatory process.

  11. Ex-post evaluation by bibliometric method. Institutional comparison between JAERI and 8 resembled foreign research institutes

    International Nuclear Information System (INIS)

    By using research papers produced both by the Japan Atomic Energy Research Institute (JAERI) and by 8 resembled foreign research institutes (5 in the U.S.A., 2 in Germany and 1 in France), an institutional comparison was tried. A bibliometric method was used together with INIS (owned by IAEA) as a database and SOCIOECO as an evaluation tool. (1) A total number of papers produced in the duration of 25 years (1978-2002) was of the order of the Oak Ridge National Laboratory (ORNL) > JAERI > Brookhaven National Laboratory (BNL) > Sandia National Laboratory (SNL) > Karlsruhe > Argonne National Laboratory (ANL) > Juelich > Idaho National Laboratory (INL) > Cadarache. JAERI was in the 2nd position. Through interviews with corresponding managers in each institutes in the U.S.A., it was understood that the change of nuclear policies (e.g., retardation from the reprocessing policy in the U.S.A.), the nuclear accidents (e.g., TMI (1979) and Chernobyl (1986)), the economical dynamics (e.g., the 2nd oil shock in Japan) etc., were attributed much to the research achievements, hence papers. Number of papers in Japan increased with every 5 years while those in the resembled foreign research institutes decreased with the same time spans. This may lead a diametrical opposite conclusion at a certain time; therefore a deep attention must be paid in this kind of comparison. (2) At three specified research areas the institutional comparison was further made with time span by 25 years. They are 'actinides' related markedly to fuel reprocessing, 'electromagnetic radiation' related deeply to an application of radiation and 'neutron' related significantly to the whole nuclear. Institutional comparison with actinides led the order of ORNL > JAERI > Karlsruhe. For the latter two cases, it was JAERI > ORNL > BNL. Interviews made with corresponding personnel in the U.S.A. pointed out that ORNL and BNL data was by-passed to the magnitude of 20-30% at their registration desks, this means that comparison was made as much as minimum level. Additionally, those specific areas were not originated from the U.S.A. sides. From the viewpoint of equality, data acquisition at those resembled foreign research institutes is requested to be done more efficiently. (3) Socio-economic networking was measured and evaluated by a total number of co-authorized papers. It developed to the magnitude of 15% per 25 years in average. JAERI however could not exceed those of INL and BNL. (4) The most prominent conclusion in this study is that the institutional comparison with a specified keyword can tell you whether or not your institute is advanced in the specified research field among resembled foreign research institutes. It leads that one has a possibility to reach the champion data through wider comparison. This method is also helpful for finding out the research present status and for predicting the direction of current research trend from the view point of ex ante evaluation. (5) It is verified that INSPEC has as the same capability as observed in the INIS. (author)

  12. 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

    2011-01-01

    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.

  13. 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

    2009-06-01

    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.

  14. Clinical Benefit From Pemetrexed Before and After Crizotinib Exposure and From Crizotinib Before and After Pemetrexed Exposure in Patients With Anaplastic Lymphoma Kinase-Positive Non–Small-Cell Lung Cancer

    OpenAIRE

    Berge, Eamon M; Lu, Xian; Maxson, DeLee; Barón, Anna E.; Gadgeel, Shirish M.; Solomon, Benjamin J; Doebele, Robert C.; Varella-Garcia, Maria; Camidge, D. Ross

    2013-01-01

    Retrospective analyses suggest enhanced sensitivity to pemetrexed in crizotinib-naive anaplastic lymphoma kinase-positive (ALK+) non–small-cell lung cancer (NSCLC). We report the results of a retrospective analysis of ALK+ patients exposed to crizotinib and pemetrexed to determine if any clinical cross-resistance exists. Progression-free survival (PFS) results for ALK+ patients administered pemetrexed followed by crizotinib (PEM-CRIZ) and ALK+ patients first treated with crizotinib and then p...

  15. A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for “smart” small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells

    OpenAIRE

    Li, Guanhua; Hu, Zuojun; Yin, Henghui; Zhang, Yunjian; Huang, Xueling; Wang, ShenMing; Li, Wen

    2013-01-01

    The application of RNA interference techniques is promising in gene therapeutic approaches, especially for cancers. To improve safety and efficiency of small interfering RNA (siRNA) delivery, a triblock dendritic nanocarrier, polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD), was developed and studied as an siRNA vector targeting the human ether-à-go-go-related gene (hERG) in human anaplastic thyroid carcinoma cells. Structure characterization, particle size, zeta potential, and ...

  16. Linfoma anaplásico de células grandes ALK-1 positivo, primario de pulmón: Informe de un caso pediátrico / ALK-1 positive anaplastic large cell lymphoma of the lung: Report of a pediatric case

    Scientific Electronic Library Online (English)

    A. Georgina, Siordia-Reyes; Floribel, Ferman-Cano; Alicia, Rodríguez-Velasco.

    2005-12-01

    Full Text Available El linfoma no Hodgkin anaplásico de células grandes, positivo al antígeno Ki-1, es una entidad bien reconocida. La característica clínica usual es la linfadenopatía con extensión mediastinal y en la enfermedad extranodal, que ocurre en la mitad de los casos, es la piel el sitio más común, con afecci [...] ón poco frecuente a médula ósea, pulmón y sistema nervioso. La mayor frecuencia de presentación del linfoma anaplásico de células grandes es en la población joven, con pronóstico más favora ble que en la población adulta. El linfoma anaplásico de células grandes primario de pulmón es una entidad clínica rara. Su comportamiento clínico corresponde a un linfoma de alto grado y en la mayoría de los casos se presentan al diagnóstico como una enfermedad en estadio avanzado. Se informa un caso pediátrico de linfoma anaplásico de células grandes primario de pulmón, ALK 1 positivo, que es un marcador pronóstico y específico de esta entidad. Abstract in english Ki 1 anaplastic large cell non Hodgkin lymphoma is a well recognized clinical entity. The main clinical feature includes lymphadenopathy with mediastinal sparing. In the extranodal disease, which occurs in approximately half of the cases, the skin is the most common site; bone marrow, lung and centr [...] al nervous system are generally not involved. Anaplastic large cell lymphoma is more common among young people, in whom the prognosis is more favorable. Primary anaplastic large cell lymphoma of the lung is a rare clinical entity. Its clinical expression is similar to a high grade malignant lymphoma, and in most cases the diagnosis is made in advanced stages. We present a pediatric case with ALK1 positive anaplastic large cell lymphoma of the lung.

  17. Adult family members and their resemblance of coronary heart disease risk factors: The Cardiovascular Disease Study in Finnmark

    International Nuclear Information System (INIS)

    Coronary heart disease tends to run in families, and the familial resemblance of major risk factors for the disease was examined among various types of adult family members. Family units were assembled from a total of 4,738 men and women who took part in a cross sectional health survey in four Norwegian municipalities where all inhabitants between 20 and 52 years of age were invited. After adjusting for age and other confounders, correlation coefficients were derived as a measure of the degree of resemblance. Viewed across all types of investigated familial relationships, similarity was found to be stronger for total cholesterol than for high-density lipoprotein cholesterol and triglycerides, and also stronger for systolic than for diastolic blood pressure. Between husbands and wives (3,060 subjects), correlations were small (between 0.02 and 0.06), except for 0.11 for total cholesterol. Lipid and blood pressure correlations ranged from 0.13 to 0.27 for parents and their offspring (471 subjects, p < 0.05) and from 0.11 to 0.22 among siblings (2,166 subjects, p < 0.01). Sibling correlations were consistent across age groups. Furthermore, reports from each individual on daily smoking (yes or no) revealed that husbands and wives had similar habits in 63.5% of all marriages as compared with the expected 49.4% had no smoking similarity at all been present. Smoking concordance was also demonstrated among siblings (p < 0.01). The persistent pattern of lipid and blood pressure aggregation among genetically related individuals from 20 to 52 years of age and the much weaker such similarity between husbands and wives, point towards genes or commonly shared environment at early ages as a major reason why coronary heart disease runs in families

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

    2006-10-15

    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.)

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

    Science.gov (United States)

    Suzuki, Osamu; Abe, Masafumi

    2014-05-01

    Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic acid enhanced Arachis hypogaea (PNA), Helix pomatia (HPA) and Phaseolus vulgaris-L (L-PHA) lectin binding reactivity to cell surface of lymphoma cells suggesting that neuraminidase removes cell surface sialic acid. In cell adhesion and invasion assays treatment with neuraminidase markedly enhanced cell adhesion to galectin-1 and decreased cell invasive capacity through galectin-1. α2,6-linked sialic acid may be involved in masking the effect of the interaction between galectin-1 and cell surface glycans. H-ALCL cells expressed the β-galactoside-α2,6-sialyltransferase ST6Gal1. On resialylation assay by recombinant ST6Gal1 with CMP-Neu5Ac, α2,6-resialylation of L-PHA reactive oligosaccharide by ST6Gal1 resulted in inhibition of H-ALCL cell adhesion to galectin-1 compared to the desialylated H-ALCL cells. On knockdown experiments, knockdown of ST6Gal1 dramatically enhanced cell adhesion to galectin-1. N-glycosylation inhibitor swainsonine treatment resulted in enhancement of cell adhesion to galectin-1. In glycomic analysis using the lectin blocking assay treatment with PNA, Artocarpus integrifolia (Jacalin), Glycine max (SBA), Helix pomatia (HPA), Vicia villosa (VVA), Ulex europaeus (UEA-1), Triticum vulgaris (WGA), Canavalia ensiformis (ConA), Phaseolus vulgaris-L (L-PHA), Phaseolus vulgaris-E4 (E-PHA), Datura stramonium (DSA) lectins resulted in modulation of lymphoma cell to galectin-1 suggesting that several types of glycans may regulate cell adhesion to galectin-1 by steric hindrance. The adhesive capacity of H-ALCL cells is regulated by phosphatidylinositol 3 phosphate kinase (PI3K) and actin cytoskeleton, and the invasive capacity of H-ALCL cells is regulated by PI3K, mitogen-activated protein kinase (MAPK), Rho and actin cytoskeleton. Furthermore, galectin-1-induced cell death in H-ALCL cells was accompanied by inhibition of CD45 protein tyrosine phosphatase (PTP) activity. In conclusion, cell adhesion and invasion to galectin-1 appeared to be regulated by cell surface sialylation and N-glycosylation, and galectin-1 regulates cell death through inhibition of CD45 PTP activity of H-ALCL. PMID:24589677

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

    International Nuclear Information System (INIS)

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

  2. An Investigation into the Mechanics of Windblown Dust Entrainment from Nickel Slag Surfaces Resembling Armoured Desert Pavements

    Science.gov (United States)

    Sanderson, Robert Steven

    The purpose of this thesis is to investigate the dynamics of PM 10 emission from a nickel slag stockpile that closely resembles a desert pavement in physical characteristics. In the field, it was observed that slag surfaces develop by natural processes into a well-armoured surface over some period of time. The surface then consists of two distinct layers; a surficial armour layer containing only non-erodible gravel and cobble-sized clasts, and an underlying dust-laden layer, which contains a wide size range of slag particles, from clay-sized to cobble-sized. This surficial armour layer protects the underlying fines from wind entrainment, at least under typical wind conditions; however, particle emissions still do occur under high wind speeds. The dynamics of particle entrainment from within these surfaces are investigated herein. It is shown that the dynamics of the boundary layer flow over these lag surfaces are influenced by the inherent roughness and permeability of the surficial armour layer, such that the flow resembles those observed over and within vegetation canopies, and those associated with permeable gravel-bed river channels. Restriction of air flow within the permeable surface produces a high-pressure zone within the pore spaces, resulting in a Kelvin-Helmholtz shear instability, which triggers coherent motions in the form of repeating burst-sweep cycles. Using Laser Doppler Anemometry (LDA), it is demonstrated that the lower boundary layer is characterized by both Q4 sweeping motions and Q2 bursting motions, while the upper boundary layer is dominated by Q2 bursts. Pore air motions within the slag material were measured using buried pressure ports. It is shown that the mean pressure gradient which forms within the slag material results in net upward displacement of air, or wind pumping. However, this net upward motion is a result of rapid oscillatory motions which are directly driven by coherent boundary layer motions. It is also demonstrated that these coherent motions are able to penetrate at least 4 cm through the surficial armour layer, thereby transporting turbulent kinetic energy (TKE) downward to the dust-laden sub-surface layer. This represents a mechanism of momentum transfer that is able to reach the erodible material, while the wind pumping effect represents a mechanism for particle exhaustion.

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

    Directory of Open Access Journals (Sweden)

    Rocco Piazza

    2013-05-01

    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.

  4. Promising response of anaplastic lymphoma kinase-positive large B-cell lymphoma to crizotinib salvage treatment: case report and review of literature.

    Science.gov (United States)

    Li, Jian; Ouyang, Jian; Zhou, Rongfu; Chen, Bing; Xu, Yong

    2015-01-01

    Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (ALK + DLBCL) is a rare and poorly characterized subtype of lymphoma. Reports suggest that this type of tumor responds poorly to standard regimens for non-Hodgkin's lymphoma, with rituximab playing no therapeutic role due to the absence of CD20 expression. In view of the expression of ALK in this disease, it is plausible that the ALK inhibitor crizotinib may be an effective treatment. We report a case of a 21-year-old male ALK + DLBCL patient. He initially received five cycles of CHOP-21 (vincristine, pirarubicin, cyclophosphamide and prednisone) and achieved a partial remission (PR) but soon deteriorated. He was subsequently treated with five courses of the salvage chemotherapy regimen ICE (ifosfamide, carboplatin and etoposide) and achieved PR again. He refused to accept an autologous stem-cell transplantation, after which the disease progressed rapidly. We administered two courses of an alternative salvage chemotherapy regimen containing GEMOX and dexamethasone with the addition of the ALK inhibitor crizotinib. His symptoms alleviated for a short time but soon worsened and the patient died of massive progressive disease. PMID:26221234

  5. TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.

    Science.gov (United States)

    Hernández, L; Pinyol, M; Hernández, S; Beà, S; Pulford, K; Rosenwald, A; Lamant, L; Falini, B; Ott, G; Mason, D Y; Delsol, G; Campo, E

    1999-11-01

    Anaplastic large cell lymphoma (ALCL) is associated with the t(2;5)(p23;q35), which generates the NPM-ALK fusion gene encoding an 80-kD protein. Several studies have suggested that genes other than NPM may be fused to the ALK gene. Here we have identified TRK-fused gene (TFG) as a new ALK partner in 2 ALCL, 1 of which exhibited a t(2;3)(p23;q21). In these cases, TFG was involved in 2 different fusion genes, TFG-ALK(S) and TFG-ALK(L), coding respectively 85-kD and 97-kD chimeric proteins. The ALK breakpoint in these translocations was the same as in the classic t(2;5) translocation. These 2 proteins were both active in an in vitro tyrosine kinase assay showing that the new cloned cDNA sequences are translated into chimeric proteins with functional activity. These findings indicate that TFG can provide an alternative to NPM as a fusion partner responsible for activation of the ALK and the pathogenesis of ALCL. PMID:10556217

  6. 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

    2012-04-01

    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.

  7. 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

    2011-03-01

    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

  8. The heat shock protein 90 inhibitor SNX5422 has a synergistic activity with histone deacetylase inhibitors in induction of death of anaplastic thyroid carcinoma cells.

    Science.gov (United States)

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

    2016-02-01

    The influence of the heat shock protein 90 (hsp90) inhibitor SNX5422 alone or in combination with the histone deacetylase (HDAC) inhibitors PXD101, suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA) on survival of anaplastic thyroid carcinoma (ATC) cells was investigated. In 8505C and CAL62 cells, SNX5422 caused cell death with concomitant changes in the expression of hsp90 client proteins. After treatment of both SNX5422 and PXD101, SAHA and TSA, compared with treatment of SNX5422 alone, cell viability was diminished, whereas inhibition rate and cytotoxic activity were enhanced. All of the combination index values were lower than 1.0, suggesting the synergism between SNX5422 and PXD101, SAHA and TSA in induction of cell death. In cells treated with both SNX5422 and PXD101, SAHA and TSA, compared with cells treated with SNX5422 alone, the protein levels of Akt, phospho-4EBP1, phospho-S6 K, and survivin were diminished, while those of ?H2AX, acetyl. histone H3, acetyl. histone H4, cleaved PARP, and cleaved caspase-3 were enhanced. In conclusion, these results demonstrate that SNX5422 has a cytotoxic activity in conjunction with alterations in the expression of hsp90 client proteins in ATC cells. Moreover, SNX5422 synergizes with HDAC inhibitors in induction of cytotoxicity accompanied by the suppression of PI3K/Akt/mTOR signaling and survivin, and the overexpression of DNA damage-related proteins in ATC cells. PMID:26219406

  9. 2MASS J035523.37+113343.7: A YOUNG, DUSTY, NEARBY, ISOLATED BROWN DWARF RESEMBLING A GIANT EXOPLANET

    International Nuclear Information System (INIS)

    We present parallax and proper motion measurements, near-infrared spectra, and Wide-field Infrared Survey Explorer photometry for the low surface gravity L5? 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 ?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 ?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.

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

    Science.gov (United States)

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

    2015-01-01

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

  11. 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

    2016-01-01

    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...

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

    Science.gov (United States)

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

    2014-03-28

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

  13. RNA polymerase III-specific general transcription factor IIIC contains a heterodimer resembling TFIIF Rap30/Rap74

    Science.gov (United States)

    Taylor, Nicholas M. I.; Baudin, Florence; von Scheven, Gudrun; Müller, Christoph W.

    2013-01-01

    Transcription of tRNA-encoding genes by RNA polymerase (Pol) III requires the six-subunit general transcription factor IIIC that uses subcomplexes ?A and ?B to recognize two gene-internal promoter elements named A- and B-box. The Schizosaccharomyces pombe ?A subcomplex comprises subunits Sfc1, Sfc4 and Sfc7. The crystal structure of the Sfc1/Sfc7 heterodimer reveals similar domains and overall domain architecture to the Pol II-specific general transcription factor TFIIF Rap30/Rap74. The N-terminal Sfc1/Sfc7 dimerization module consists of a triple ?-barrel similar to the N-terminal TFIIF Rap30/Rap74 dimerization module, whereas the C-terminal Sfc1 DNA-binding domain contains a winged-helix domain most similar to the TFIIF Rap30 C-terminal winged-helix domain. Sfc1 DNA-binding domain recognizes single and double-stranded DNA by an unknown mechanism. Several features observed for A-box recognition by ?A resemble the recognition of promoters by bacterial RNA polymerase, where ? factor unfolds double-stranded DNA and stabilizes the non-coding DNA strand in an open conformation. Such a function has also been proposed for TFIIF, suggesting that the observed structural similarity between Sfc1/Sfc7 and TFIIF Rap30/Rap74 might also reflect similar functions. PMID:23921640

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

    International Nuclear Information System (INIS)

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

  15. 2MASS J035523.37+113343.7: A YOUNG, DUSTY, NEARBY, ISOLATED BROWN DWARF RESEMBLING A GIANT EXOPLANET

    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: jfaherty17@gmail.com, E-mail: jfaherty@amnh.org [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile)

    2013-01-01

    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.

  16. Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis.

    Science.gov (United States)

    Greer, K A; Wong, A K; Liu, H; Famula, T R; Pedersen, N C; Ruhe, A; Wallace, M; Neff, M W

    2010-08-01

    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. PMID:20403140

  17. ATM deficiency promotes development of murine B-cell lymphomas that resemble diffuse large B-cell lymphoma in humans.

    Science.gov (United States)

    Hathcock, Karen S; Padilla-Nash, Hesed M; Camps, Jordi; Shin, Dong-Mi; Triner, Daniel; Shaffer, Arthur L; Maul, Robert W; Steinberg, Seth M; Gearhart, Patricia J; Staudt, Louis M; Morse, Herbert C; Ried, Thomas; Hodes, Richard J

    2015-11-12

    The serine-threonine kinase ataxia-telangiectasia mutated (ATM) plays a central role in maintaining genomic integrity. In mice, ATM deficiency is exclusively associated with T-cell lymphoma development, whereas B-cell tumors predominate in human ataxia-telangiectasia patients. We demonstrate in this study that when T cells are removed as targets for lymphomagenesis and as mediators of immune surveillance, ATM-deficient mice exclusively develop early-onset immunoglobulin M(+) B-cell lymphomas that do not transplant to immunocompetent mice and that histologically and genetically resemble the activated B cell-like (ABC) subset of human diffuse large B-cell lymphoma (DLBCL). These B-cell lymphomas show considerable chromosomal instability and a recurrent genomic amplification of a 4.48-Mb region on chromosome 18 that contains Malt1 and is orthologous to a region similarly amplified in human ABC DLBCL. Of importance, amplification of Malt1 in these lymphomas correlates with their dependence on nuclear factor (NF)-?B, MALT1, and B-cell receptor (BCR) signaling for survival, paralleling human ABC DLBCL. Further, like some human ABC DLBCLs, these mouse B-cell lymphomas also exhibit constitutive BCR-dependent NF-?B activation. This study reveals that ATM protects against development of B-cell lymphomas that model human ABC DLBCL and identifies a potential role for T cells in preventing the emergence of these tumors. PMID:26400962

  18. 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

    2014-01-01

    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...

  19. Changing the term "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" to "tall cell variant of papillary breast carcinoma".

    Science.gov (United States)

    Masood, Shahla; Davis, Cindy; Kubik, Melanie J

    2012-03-01

    Papillary lesions of the breast continue to be a diagnostic challenge because of the wide morphologic spectrum that may be encountered in these lesions. A rare entity termed "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" is considered to be a subtype of papillary carcinoma of the breast. It is characterized by distinct morphologic features, setting it apart from typical papillary carcinoma of the breast. Its resemblance to papillary thyroid carcinoma in conjunction with the established terminology may cause confusion, resulting in unnecessary ancillary studies to exclude the association of this lesion with papillary thyroid carcinoma. As immunohistochemical and molecular studies have shown no evidence to support any association between this entity and papillary thyroid carcinoma, we propose to change the current terminology of "breast tumor resembling the tall cell variant of papillary thyroid carcinoma" to the term "tall cell variant of papillary breast carcinoma." PMID:22313838

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

    DEFF Research Database (Denmark)

    Nielsen, Mads; Karemore, Gopal Raghunath

    2011-01-01

    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 to diagnosis, the following mammographic parameters were analysed for relation to breast cancer risk: (C) categorical parenchymal pattern scores; (R) radiologist's percentage density, (P) computer-based percentage density; (H) computer-based breast cancer risk MTR marker; (E) computer-based hormone replacement treatment MTR marker; and (A) an aggregate of P and H. Results: Density scores, C, R, and P correlated (tau=0.3-0.6); no other pair of scores showed large (tau>0.2) correlation. For the parameters, the odds ratios of future incidence of breast cancer comparing highest to lowest categories (146 and 106 subject respectively) were C: 2.4(1.4-4.2), R: 2.4(1.4-4.1), P: 2.5(1.5-4.2), E: non-significant, H: 4.2(2.4-7.2), and A: 5.6(3.2-9.8). The AUC analysis showed a similarly increasing pattern (C: 0.58±0.02, R: 0.57±0.03, P: 0.60±0.03, H: 0.63±0.02, A: 0.66±0.02). The AUC of the aggregate marker (A) surpasses others significantly except H. HRT-MTR (E) did not significantly identify future cancers or correlate with any other marker. Conclusions: Breast cancer risk MTR marker was independent of density scores and more predictive of risk. The hormone replacement treatment MTR marker did not identify patients at risk.

  1. Hybrid copolymer-phospholipid vesicles: phase separation resembling mixed phospholipid lamellae, but with mechanical stability and control.

    Science.gov (United States)

    Chen, Dong; Santore, Maria M

    2015-04-01

    Vesicles whose bilayer membranes contain phospholipids mixed with co-polymers or surfactants comprise new hybrid materials having potential applications in drug delivery, sensors, and biomaterials. Here we describe a model polymer-phospholipid hybrid membrane system exhibiting strong similarities to binary phospholipid mixtures, but with more robust membrane mechanics. A lamella-forming graft copolymer, PDMS-co-PEO (polydimethylsiloxane-co-polyethylene oxide) was blended with a high melting temperature phospholipid, DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), over a broad compositional range. The resulting giant hybrid unilamellar vesicles were compared qualitatively and quantitatively to analogous mixed phospholipid membranes in which a low melting temperature phospholipid, DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), was blended with DPPC. The mechanical properties of the hybrid vesicles, even when phase separated, were robust with high lysis stresses and strains approaching those of the pure copolymer vesicles. The temperature-composition phase diagram of the hybrid vesicles closely resembled that of the mixed phospholipids; with only slightly greater nonidealities in the hybrid compared with DOPC/DPPC mixed membranes. In both systems, it was demonstrated that tension could be used to manipulate DPPC solidification into domains of patchy or striped morphologies that exhibited different tracer incorporation. The patch and stripe-shaped domains are thought to be different solid DPPC polymorphys: ripple and tilt (or gel). This work demonstrates that in mixed-phospholipid bilayers where a high-melting phospholipid solidifies on cooling, the lower-melting phospholipid may be substituted by an appropriate copolymer to improve mechanical properties while retaining the underlying membrane physics. PMID:25687473

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-15

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

  3. Exploratory evaluation of two-dimensional and three-dimensional methods of FDG PET quantification in pediatric anaplastic astrocytoma: a report from the Pediatric Brain Tumor Consortium (PBTC)

    International Nuclear Information System (INIS)

    The rationale of this study was to investigate the feasibility of three-dimensional (3D) methods to analyze 18F-fluoro-deoxy-glucose (FDG) uptake in children with anaplastic astrocytoma (AA) in a multi-institutional trial, to compare 3D and two-dimensional (2D) methods and explore data associations with progression-free survival (PFS). 3D tumor volumes from pretreatment MR images (fluid attenuation inversion recovery and postgadolinium) of children with recurrent AA on a phase I trial of imatinib mesylate were coregistered to FDG positron emission tomography (PET) images. PET data were normalized. Four metrics were defined: the maximum ratio (maximum pixel value within the 3D tumor volume, normalized), the total ratio (cumulative pixel values within the tumor volume, normalized) and tumor mean ratio (total pixel value divided by volume, normalized). 2D analysis methods were compared. Cox proportional hazards models were used to estimate the association between these methods and PFS. Strongest correlations between 2D and 3D methods were with analyses using postcontrast T1 images for volume of interest (VOI). The analyses suggest 3D maximum tumor and mean tumor ratios, whether normalized by gray matter or white matter, were associated with PFS. This study of a series of pretreatment AA patients suggests that 3D PET methods using VOIs based on postcontrast T1 correlate with 2D methods and are related to PFS. These methods yield an estimate of metabolically active tumor burden and may add prognostic information after tumor grade is determined. Future rigorous multi-institutional protocols with larger numbers of patients will be required for validation. (orig.)

  4. Exploratory evaluation of two-dimensional and three-dimensional methods of FDG PET quantification in pediatric anaplastic astrocytoma: a report from the Pediatric Brain Tumor Consortium (PBTC)

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Gethin; Treves, S. Ted [Harvard Medical School, Joint Program in Nuclear Medicine, Children' s Hospital Boston, Boston, MA (United States); Fahey, Frederic H. [Harvard Medical School, Joint Program in Nuclear Medicine, Children' s Hospital Boston, Boston, MA (United States); Harvard Medical School, Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States); Kocak, Mehmet; Boyett, James M.; Kun, Larry E. [St Jude Children' s Research Hospital, Memphis, TN (United States); Pollack, Ian F. [Children' s Hospital Pittsburgh, Pittsburgh, PA (United States); Young Poussaint, Tina [Harvard Medical School, Division of Neuroradiology, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States)

    2008-09-15

    The rationale of this study was to investigate the feasibility of three-dimensional (3D) methods to analyze {sup 18}F-fluoro-deoxy-glucose (FDG) uptake in children with anaplastic astrocytoma (AA) in a multi-institutional trial, to compare 3D and two-dimensional (2D) methods and explore data associations with progression-free survival (PFS). 3D tumor volumes from pretreatment MR images (fluid attenuation inversion recovery and postgadolinium) of children with recurrent AA on a phase I trial of imatinib mesylate were coregistered to FDG positron emission tomography (PET) images. PET data were normalized. Four metrics were defined: the maximum ratio (maximum pixel value within the 3D tumor volume, normalized), the total ratio (cumulative pixel values within the tumor volume, normalized) and tumor mean ratio (total pixel value divided by volume, normalized). 2D analysis methods were compared. Cox proportional hazards models were used to estimate the association between these methods and PFS. Strongest correlations between 2D and 3D methods were with analyses using postcontrast T1 images for volume of interest (VOI). The analyses suggest 3D maximum tumor and mean tumor ratios, whether normalized by gray matter or white matter, were associated with PFS. This study of a series of pretreatment AA patients suggests that 3D PET methods using VOIs based on postcontrast T1 correlate with 2D methods and are related to PFS. These methods yield an estimate of metabolically active tumor burden and may add prognostic information after tumor grade is determined. Future rigorous multi-institutional protocols with larger numbers of patients will be required for validation. (orig.)

  5. 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)

    2012-07-01

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

  6. 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: Stephanie.Combs@med.uni-heidelberg.de [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)

    2011-12-01

    Purpose: To evaluate the correlation between the 1993 and 2000/2007 World Health Organization (WHO) classification with the outcome in patients with high-grade meningiomas. Patients and Methods: Between 1985 and 2004, 73 patients diagnosed with atypical or anaplastic meningiomas were treated with radiotherapy. Sections from the paraffin-embedded tumor material from 66 patients (90%) from 13 different pathology departments were re-evaluated according to the first revised WHO classification from 1993 and the revised classifications from 2000/2007. In 4 cases, the initial diagnosis meningioma was not reproducible (5%). Therefore, 62 patients with meningiomas were analyzed. Results: All 62 tumors were reclassified according to the 1993 and 2000/2007 WHO classification systems. Using the 1993 system, 7 patients were diagnosed with WHO grade I meningioma (11%), 23 with WHO grade II (37%), and 32 with WHO grade III meningioma (52%). After scoring using the 2000/2007 system, we found 17 WHO grade I meningiomas (27%), 32 WHO grade II meningiomas (52%), and 13 WHO grade III meningiomas (21%). According to the 1993 classification, the difference in overall survival was not statistically significant among the histologic subgroups (p = .96). Using the 2000/2007 WHO classifications, the difference in overall survival became significant (p = .02). Of the 62 reclassified patients 29 developed tumor progression (47%). No difference in progression-free survival was observed among the histologic subgroups (p = .44). After grading according to the 2000/2007 WHO classifications, significant differences in progression-free survival were observed among the three histologic groups (p = .005). Conclusion: The new 2000/2007 WHO classification for meningiomas showed an improved correlation between the histologic grade and outcome. This classification therefore provides a useful basis to determine the postoperative indication for radiotherapy. According to our results, a comparison of the published data for future treatment decision-making remains difficult when the histologic diagnosis has not been based on the new improved classification system.

  7. Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy

    International Nuclear Information System (INIS)

    Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy

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

    International Nuclear Information System (INIS)

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

  9. Anaplastic lymphoma kinase gene rearrangements in patients with advanced-stage non-small-cell lung cancer: CT characteristics and response to chemotherapy.

    Science.gov (United States)

    Park, Jangchul; Yamaura, Hidekazu; Yatabe, Yasushi; Hosoda, Waki; Kondo, Chiaki; Shimizu, Junichi; Horio, Yoshitsugu; Yoshida, Kimihide; Tanaka, Kosuke; Oguri, Tomoyo; Kobayashi, Yoshihisa; Hida, Toyoaki

    2014-02-01

    Few articles have been published on the imaging findings of anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC). To investigate the radiological findings of ALK-positive NSCLC in the advanced stage, CT scans were examined. In addition, the response to chemotherapy was evaluated. Of the 36 patients with ALK-rearranged NSCLC, a mass and a nodule were identified in 17 (47.2%) and 16 (44.4%), respectively, indicating that more than 40% had a small-sized tumor. Overall, 31 (86.1%) patients had lymphadenopathy, seven (19.4%) had extranodal lymph node invasion, and three (8.3%) had lymphangitis. A pleural effusion was seen in 15 patients (41.7%). All but one patient had no ground-glass opacity (GGO) lesions, indicating that most ALK-positive tumors showed a solid growth pattern without GGO on CT. Twenty were evaluable for response to chemotherapy; 10 (50.0%) had a partial response (PR), nine (45.0%) had stable disease (SD), and one (5.0%) had progressive disease (PD) with first-line chemotherapy. With second-line chemotherapy, five (26.3%) had PR, 11 (57.9%) had SD, and three (15.8%) had PD. The five patients with PR were all treated by using crizotinib. Time to progression was 8.2 months with first-line chemotherapy, and 6.0 months with second-line chemotherapy. Advanced-stage ALK-positive tumors have a relatively aggressive phenotype, which cannot be inferred from the size of the tumor alone. ALK-positive patients have a good response to first-line cytotoxic drugs and to crizotinib as second-line therapy, but a relatively poor response to cytotoxic drugs as second-line therapy. PMID:24403104

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Shiu-Feng Huang

    2012-08-01

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

  12. ALK Kinase Domain Mutations in Primary Anaplastic Large Cell Lymphoma: Consequences on NPM-ALK Activity and Sensitivity to Tyrosine Kinase Inhibitors

    Science.gov (United States)

    Lovisa, Federica; Cozza, Giorgio; Cristiani, Andrea; Cuzzolin, Alberto; Albiero, Alessandro; Mussolin, Lara; Pillon, Marta; Moro, Stefano; Basso, Giuseppe; Bonvini, Paolo

    2015-01-01

    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. PMID:25874976

  13. Evaluation of RANO response criteria compared to clinician evaluation in WHO grade III anaplastic astrocytoma: implications for clinical trial reporting and patterns of failure.

    Science.gov (United States)

    Kazda, Tomas; Hardie, John G; Pafundi, Deanna H; Kaufmann, Timothy J; Brinkmann, Debra H; Laack, Nadia N

    2015-03-01

    The utility of current response criteria has not been established in anaplastic astrocytoma (AA). We retrospectively reviewed MR images for 20 patients with AA and compared RANO-based approaches to clinician impression described as follow: (1) standard RANO-based criteria met by growth of or development of new enhancing lesion (RANO-C), (2) RANO criteria for progression based on significant FLAIR increase (RANO-F) and (3) clinical progression usually resulting in change of treatment (Clinical). Patterns of failure (POF) were analyzed utilizing all proposed progression MRIs fused with the patients' radiotherapy treatment plan. With an overall median survival of 24.3 months, development of new enhancing lesion was the most common determinant of progression (70 % of patients). Median time to RANO-C, RANO-F and Clinical progression was 9.2, 9.2 and 11.76 months respectively. RANO-C and RANO-F preceded Clinical in 70 and 55 % of patients, respectively. In six patients (30 %) Clinical was concurrent with RANO-F; four of six also met RANO-C. POF for FLAIR component differed based on time point used to determine progression. FLAIR POF was more often marginal or distant when progression was defined clinically compared to either RANO-C or RANO-F criteria. Central POF based on FLAIR at Clinical determination of progression was associated with significantly poorer OS (9.8 vs. 34.4 months). Clinical progression occurs later than progression determined by RANO-based criteria. Evaluation of POF based on FLAIR signal abnormality at the time of clinical progression suggests central recurrences are associated with worse survival. PMID:25577400

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

    Science.gov (United States)

    Froelich, Amy G.; Nettleton, Dan

    2013-01-01

    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…

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

    Science.gov (United States)

    2015-04-21

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

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

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

    1999-11-01

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

  17. 131I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma. Phase I and II study

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

    Purpose: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were ? 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) ? 60%. Methods and Materials: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m2) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m2) given at 6-week intervals or 6-mercaptopurine (6-MP, 750 mg/m2 IV daily for 3 days every 6 weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average age 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS ? 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age ? 45 years (b) KPS < 90%; (c) GBM/Gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). Conclusions: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU

  19. Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines: final report of RTOG 86-12, phase I-II study

    International Nuclear Information System (INIS)

    Purpose: This study evaluated the toxicity and tumor efficacy of the halopyrimidine IUdR as a chemical modifier of radiation response in patients with malignant glioma. The preliminary results published in 1993 demonstrated no real advantage in the group of patients with glioblastoma. However, a benefit appeared to be evolving in the group of patients with Anaplastic Astrocytoma (AA). We are now presenting the results on the long-term follow-up of patients with AA. Methods and Materials: Between August 1987 and October 1991, 79 patients were entered in a prospective study with newly diagnosed malignant glioma. Twenty-one of 79 were AA. The study was designed to have a fixed dose of radiation consisting of 60.16 Gy in 32 fractions in 6.5 weeks but varying the dose schedule of IUdR, delivered in a continuous intravenous infusion of long (96 h) or short (48 and 24 h) duration, every week for the 6.5 weeks of radiation treatment. Results: The last AA patient was entered in March 1991. Ninety-five percent of the AA patients were under 59 years of age and 86% had a Karnofsky score 80. Thirty-eight percent had a tumor diameter of less than 5 cm and 52% had a tumor diameter between 5-10 cm. Seventy-six percent had partial or total tumor resection. The toxicity of this treatment was acceptable and has already been published elsewhere. At the time of this report, 14 out of 21 patients with AA are dead. The median survival, calculated from the Kaplan-Meier, is 3.2 years. Thirty-three percent of the patients have survived 5 years. These results compare favorably with the best results reported in the literature with postoperative external radiation plus chemotherapy, median survival time (MST) of 3 years, and previous Radiation Therapy Oncology Group (RTOG) experience with radiation alone, MST of 2 years. Conclusions: Our findings in patients with AA corroborate the improved therapeutic results published recently when combining external radiation with 'long' infusion of i.v. BUdR and indicate the need to proceed with randomized Phase III studies utilizing halogenated pyrimidines and radiation. One such study has already been activated, RTOG no. 94-04

  20. Survival improvement in anaplastic astrocytoma, combining external radiation with halogenated pyrimidines. Final report of RTOG 86-12, phase I-II study

    International Nuclear Information System (INIS)

    Purpose: This study evaluated the toxicity and tumor efficacy of the halopyrimidine IUdR as a chemical modifier of radiation response in patients with malignant glioma. The preliminary results published in 1993 demonstrated no real advantage in the group of patients with glioblastoma. However, a benefit appeared to be evolving in the group of patients with Anaplastic Astrocytoma (AAF). We are now presenting the results on the long-term follow-up of patients with AAF. Methods and Materials: Between August 1987 and October 1991, 79 patients were entered in a prospective study with newly diagnosed AAF and glioblastoma. (21(79)) were AAF. The study was designed to have a fixed dose of radiation (60.16 Gy in 32 fractions in 6.5 weeks) but varying the dose schedule of IUdR, delivered in a continuous intravenous infusion of long (96 hours) or short (48 and 24 hours) duration, every week for the 6.5 weeks of radiation treatment. Results: The last patient with AAF was entered in March 1991. 95% of the AAF patients were ? 59 years of age, 86% had a Karnofsky score ? 80, 38% had a tumor diameter of less than 5 cm and 52% between 5-10 cm. 76% had partial or total tumor resection. The toxicity of this treatment is acceptable and has already been published elsewhere. At the time of this report, 14 out of 21 patients with AAF are dead. The median survival calculated from the Kaplan-Meier plot is 3 years. Thirty-three percent of the patients have survived 5 years. These results compare favorably with the best results reported in the literature with post-op external radiation plus chemotherapy, median survival of 3 years and previous RTOG experience with radiation alone, median survival of 2 years. As was the case with glioblastoma patients, there is a trend for a better survival experience in the patients who received the long 96-hour course schedule of IUdR (Median survival not yet reached after 6 years). Conclusion: Our findings in patients with AAF corroborate the improved therapeutic results published recently when combining external radiation with IV BUdR and indicate the need to proceed with randomized phase III studies utilizing halogenated pyrimidines and radiation. One such study has already been activated, RTOG no. 94-04

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

    Science.gov (United States)

    Bishara, Mona RY; Ross, Cathy; Sur, Monalisa

    2009-01-01

    Background Primary non-Hodgkin lymphoma (NHL) of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML), the association between lymphoma and administration of chemotherapy has never been clearly demonstrated. Case Presentation In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago. Conclusion Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude sarcomatoid carcinoma, malignant melanoma and pleomorphic sarcoma by an appropriate panel of immunostains to arrive at the correct diagnosis of ALCL. PMID:19341480

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

    Directory of Open Access Journals (Sweden)

    Sur Monalisa

    2009-04-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  4. 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

    2015-02-01

    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 inhibits ALK catalytic activity and potentiates the activity of the ALK-targeted drug crizotinib. Keywords: adenocarcinoma, ALK, BNP7787, chemo-enhancing, crizotinib, non-small-cell lung cancer, Tavocept

  5. Characterization of an organism that produces type E botulinal toxin but which resembles Clostridium butyricum from the feces of an infant with type E botulism.

    OpenAIRE

    McCroskey, L M; Hatheway, C L; Fenicia, L; Pasolini, B; Aureli, P

    1986-01-01

    The apparent causative organism from the only reported case of type E infant botulism was isolated and characterized. Except for its ability to produce type E botulinal toxin, this organism (strain 5262) would be unquestionably identified as Clostridium butyricum. This is the second time an organism resembling a defined Clostridium species other than a member of the C. botulinum group has been implicated in infant botulism.

  6. Fetuin-A/Albumin-Mineral Complexes Resembling Serum Calcium Granules and Putative Nanobacteria: Demonstration of a Dual Inhibition-Seeding Concept

    OpenAIRE

    Wu, Cheng-Yeu; Martel, Jan; Young, David; John D. Young

    2009-01-01

    Serum-derived granulations and purported nanobacteria (NB) are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin) and heat inactivation studies. When inoculated into cell culture medium, the purified proteins fetuin-A and albumin fail to induce mineralization, but they will readily combine wit...

  7. Amastigota forms resembling Leishmania sp. on corneal ulceration in a dog: case report Formas amastigotas compatíveis com Leishmania sp. em ulceração corneal de cão: relato de caso

    OpenAIRE

    F.L.C. Brito; L.C. Alves; F.C.L. Maia; A.R. Albuquerque; J.P.D. Ortiz; J.L Laus

    2007-01-01

    One dog with visceral leishmaniasis is reported presenting cutaneous lesions, cachexia, and corneal ulceration. Parasitological and serological diagnoses were performed by exam of contents of the aspirative punction of the bone marrow and by immunofluorecence, respectively. Amastigota forms resembling Leishmania sp. were visualized by citology.Relata-se o caso de um cão com leishmaniose visceral apresentando lesões cutâneas, caquexia e úlcera de córnea. Realizou-se o diagnóstico parasitológic...

  8. A novel dendritic nanocarrier of polyamidoamine-polyethylene glycol-cyclic RGD for “smart” small interfering RNA delivery and in vitro antitumor effects by human ether-à-go-go-related gene silencing in anaplastic thyroid carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li G

    2013-03-01

    Full Text Available Guanhua Li,1,2 Zuojun Hu,1 Henghui Yin,1 Yunjian Zhang,1 Xueling Huang,1 Shenming Wang,1 Wen Li2 1Department of Vascular and Thyroid Surgery, 2Key Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China Abstract: The application of RNA interference techniques is promising in gene therapeutic approaches, especially for cancers. To improve safety and efficiency of small interfering RNA (siRNA delivery, a triblock dendritic nanocarrier, polyamidoamine-polyethylene glycol-cyclic RGD (PAMAM-PEG-cRGD, was developed and studied as an siRNA vector targeting the human ether-à-go-go-related gene (hERG in human anaplastic thyroid carcinoma cells. Structure characterization, particle size, zeta potential, and gel retardation assay confirmed that complete triblock components were successfully synthesized with effective binding capacity of siRNA in this triblock nanocarrier. Cytotoxicity data indicated that conjugation of PEG significantly alleviated cytotoxicity when compared with unmodified PAMAM. PAMAM-PEG-cRGD exerted potent siRNA cellular internalization in which transfection efficiency measured by flow cytometry was up to 68% when the charge ratio (N/P ratio was 3.5. Ligand-receptor affinity together with electrostatic interaction should be involved in the nano-siRNA endocytosis mechanism and we then proved that attachment of cRGD enhanced cellular uptake via RGD-integrin recognition. Gene silencing was evaluated by reverse transcription polymerase chain reaction and PAMAM-PEG-cRGD-siRNA complex downregulated the expression of hERG to 26.3% of the control value. Furthermore, gene knockdown of hERG elicited growth suppression as well as activated apoptosis by means of abolishing vascular endothelial growth factor secretion and triggering caspase-3 cascade in anaplastic thyroid carcinoma cells. Our study demonstrates that this novel triblock polymer, PAMAM-PEG-cRGD, exhibits negligible cytotoxicity, effective transfection, “smart” cancer targeting, and therefore is a promising siRNA nanocarrier. Keywords: small interfering RNA, dendrimer, gene silencing, human ether-à-go-go-related gene, anaplastic thyroid cancer

  9. Research progress of IDH1 and IDH2 mutations in gliomas

    Directory of Open Access Journals (Sweden)

    Shan-shan ZHANG

    2015-11-01

    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

  10. 18F-FDG PET/CT-Negative Recurrent High-Grade Anaplastic Astrocytoma Detected by 18F-FDOPA PET-CT

    International Nuclear Information System (INIS)

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. 18F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine (18F-FDOPA) PET-CT was done, 5 days after 18F-FDG PET-CT. The study revealed an 18F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. 18F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. 18F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas. Therefore, in spite of its limitations, 18F-FDG PET-CT is used for imaging of high-grade glioma. Amino acid PET radiotracers including 18F-FDOPA display superior contrast to 18F-FDG because of low uptake of amino acids in normal brain tissue. They have particularly special value in the detection of low-grade gliomas. However, 18F-FDOPA tumour uptake cannot provide reasonable predictions about tumour grade and proliferation in recurrent tumours that have undergone treatments. Also, their difficult synthesis or need for an on-site cyclotron limits their widespread use. The present case shows the utility of 18F-FDOPA PET-CT in detection of a recurrent high-grade AA that was missed by 18F-FDG PET-CT. It highlights that 18F-FDG PET-CT can be falsely negative, even in high-grade recurrent gliomas and, therefore, in cases with strong clinical suspicion 18F-FDOPA PET-CT can be an alternative imaging modality to rule out recurrence even when 18F-FDG PET-CT is negative

  11. {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)

    2013-12-15

    A 37-year-old woman with grade 3 anaplastic astrocytoma (AA) of the left frontal lobe, underwent surgical excision, chemotherapy and external beam radiation therapy in 2004. After being in remission for 5 years, recurrence was suspected clinically when she presented with seizures. The result of contrast-enhanced magnetic resonance imaging (MRI) was equivocal for recurrence and radiation necrosis (not available ). The patient was then referred for {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography-computed tomography (PET-CT), as the initial primary tumour was high grade in nature. {sup 18}F-FDG PET-CT was negative for recurrence and demonstrated only post-operative changes in the left frontal region (Fig. 1a, b, arrow). Due to strong clinical suspicion, 3,4-dihydroxy-6-{sup 18}F-fluoro-L-phenylalanine ({sup 18}F-FDOPA) PET-CT was done, 5 days after {sup 18}F-FDG PET-CT. The study revealed an {sup 18}F-FDOPA-avid mass lesion in the left frontal region (Fig. 1c, d, arrow), thereby confirming the presence of recurrent disease. The patient underwent surgical resection of the mass, and it was confirmed by histopathology as grade 3 AA. However, after a short asymptomatic period of 4 months the patient became symptomatic again. Follow-up MRI after 6 months of surgery revealed presence of ipsilateral and contralateral multifocal contrast enhancing recurrent mass lesions (Fig. 1e, f, arrow), suggesting the progression of disease. The patient was started on temozolamide but she died after 8 months' follow-up. Though MRI is routinely used in assessment of brain tumours, its ability to differentiate between treatment-induced changes and residual or recurrent tumour is limited. {sup 18}F-FDG PET was the first tracer used for assessment of brain tumours; however, it has a low tumour-to-background ratio in brain, limiting its utility. {sup 18}F-FDG uptake correlates with tumour grade, with high-grade gliomas (grades III and IV) showing higher uptake than low-grade gliomas. Therefore, in spite of its limitations, {sup 18}F-FDG PET-CT is used for imaging of high-grade glioma. Amino acid PET radiotracers including {sup 18}F-FDOPA display superior contrast to {sup 18}F-FDG because of low uptake of amino acids in normal brain tissue. They have particularly special value in the detection of low-grade gliomas. However, {sup 18}F-FDOPA tumour uptake cannot provide reasonable predictions about tumour grade and proliferation in recurrent tumours that have undergone treatments. Also, their difficult synthesis or need for an on-site cyclotron limits their widespread use. The present case shows the utility of {sup 18}F-FDOPA PET-CT in detection of a recurrent high-grade AA that was missed by {sup 18}F-FDG PET-CT. It highlights that {sup 18}F-FDG PET-CT can be falsely negative, even in high-grade recurrent gliomas and, therefore, in cases with strong clinical suspicion {sup 18}F-FDOPA PET-CT can be an alternative imaging modality to rule out recurrence even when {sup 18}F-FDG PET-CT is negative.

  12. Anaplastic transformation of an atypical intraventricular meningioma with metastases to the liver: case report / Transformación anaplásica de un meningioma atípico intraventricular con metástasis hepáticas: caso clínico

    Scientific Electronic Library Online (English)

    M., García-Conde; H., Roldan-Delgado; D., Martel-Barth-Hansen; C., Manzano-Sanz.

    2009-12-01

    Full Text Available Objetivos. Los meningiomas malignos intraventriculares son muy infrecuentes. En la bibliografía existente sólo se han descrito once casos hasta ahora. Siete de ellos desarrollaron metástasis a través del líquido cefalorraquídeo (LCR). Presentamos el primer caso de un meningioma maligno intraventricu [...] lar con metástasis extraneurales. Caso clínico. Paciente varón de 44 años de edad con una clínica de cefalea progresiva y desorientación. La resonancia magnética mostraba un proceso expansivo intracraneal en el trígono derecho con captación de contraste de forma homogénea. Intervención. Se practicó una resección total de la lesión a través de un acceso transcortical. El análisis histológico mostró un meningioma atípico. A pesar de la resección total, el tumor recidivó otras dos veces. Después de la primera recidiva, el tumor fue extirpado nuevamente y el paciente recibió radioterapia externa. En la segunda recidiva, el tumor se comportó de forma más agresiva, invadiendo el parénquima cerebral. El análisis histológico mostraba un meningioma anaplásico. El paciente fue ingresado nuevamente por fiebre y dolor en el hipocondrio derecho. Una ecografía abdominal mostró múltiples lesiones hipoecogénicas hepáticas. La biopsia de dichas lesiones fue compatible con metástasis del meningioma maligno. El paciente falleció debido a una insuficiencia hepática aguda siete meses después del diagnóstico inicial. Conclusiones. Los meningiomas malignos intraventriculares tienden a recurrir y producir metástasis, principalmente a través del LCR. Sin embargo, nuestro caso muestra que los meningioma malignos intraventriculares también pueden metastatizar fuera del sistema nervioso central, siendo el primer caso descrito. Por lo tanto, cuando un deterioro sistémico ocurra en un paciente con un meningioma maligno intraventricular debería descartarse la posibilidad de metástasis extraneurales como sucedió en este caso. Abstract in english Objective. Malignant intraventricular meningiomas are very rare. To the best of our knowledge, only eleven cases have been reported thus far. Seven of them developed cerebrospinal fluid (CSF) metastases. We present herein the first case of a malignant intraventricular meningioma with extraneural met [...] astases. Clinical presentation. We report a 44 year-old-man with a history of progressive headache and disorientation. Magnetic resonance imaging (MRI) revealed a 5-cm homogeneously-enhancing mass in the right trigone. Intervention. The lesion was totally resected via a parietooccipital transcortical approach. Histological examination demonstrated an atypical meningioma. Thereafter, the tumor recurred twice. At first recurrence, the tumor was completely removed again and external radiotherapy was administered. At surgery at second recurrence, the tumor was more aggressive, invading the brain parenchyma. Histological examination showed anaplastic meningioma. The patient was readmitted to hospital with fever and pain in right hypochondrium. Abdominal ultrasound examination disclosed multiple hypoechoic liver lesions. Biopsy was consistent with liver metastases of a malignant meningioma. The patient died of acute liver failure seven months after initial diagnosis. Conclusion. Malignant intraventricular meningiomas are prone to recur and develop metastases, mainly through the CSF. Nevertheless, our case shows that extraneural metastases are also possible. Therefore, when systemic deterioration occurs in a patient with a malignant intraventricular meningioma, metastases to extraneural organs such as the liver must be ruled out.

  13. Amastigota forms resembling Leishmania sp. on corneal ulceration in a dog: case report Formas amastigotas compatíveis com Leishmania sp. em ulceração corneal de cão: relato de caso

    Directory of Open Access Journals (Sweden)

    F.L.C. Brito

    2007-02-01

    Full Text Available One dog with visceral leishmaniasis is reported presenting cutaneous lesions, cachexia, and corneal ulceration. Parasitological and serological diagnoses were performed by exam of contents of the aspirative punction of the bone marrow and by immunofluorecence, respectively. Amastigota forms resembling Leishmania sp. were visualized by citology.Relata-se o caso de um cão com leishmaniose visceral apresentando lesões cutâneas, caquexia e úlcera de córnea. Realizou-se o diagnóstico parasitológico e sorológico por meio de exame do material da medula óssea e por imunofluorescência indireta, respectivamente. À citologia da úlcera corneana, visibilizaram-se formas amastigotas compatíveis com Leishmania sp.

  14. Amastigota forms resembling Leishmania sp. on corneal ulceration in a dog: case report / Formas amastigotas compatíveis com Leishmania sp. em ulceração corneal de cão: relato de caso

    Scientific Electronic Library Online (English)

    F.L.C., Brito; L.C., Alves; F.C.L., Maia; A.R., Albuquerque; J.P.D., Ortiz; J.L., Laus.

    2007-02-01

    Full Text Available Relata-se o caso de um cão com leishmaniose visceral apresentando lesões cutâneas, caquexia e úlcera de córnea. Realizou-se o diagnóstico parasitológico e sorológico por meio de exame do material da medula óssea e por imunofluorescência indireta, respectivamente. À citologia da úlcera corneana, visi [...] bilizaram-se formas amastigotas compatíveis com Leishmania sp. Abstract in english One dog with visceral leishmaniasis is reported presenting cutaneous lesions, cachexia, and corneal ulceration. Parasitological and serological diagnoses were performed by exam of contents of the aspirative punction of the bone marrow and by immunofluorecence, respectively. Amastigota forms resembli [...] ng Leishmania sp. were visualized by citology.

  15. TARC, a CC chemokine, is frequently expressed in classic Hodgkin's lymphoma but not in NLP Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and most cases of anaplastic large cell lymphoma.

    Science.gov (United States)

    Peh, S C; Kim, L H; Poppema, S

    2001-07-01

    Thymus and activation-regulated chemokine (TARC) has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans. Recent studies showed that the T cells surrounding Reed-Sternberg cells in Hodgkin's lymphomas (HL) are Th2 type. Anaplastic large cell lymphomas (ALCL), T-cell-rich B-cell lymphoma (TCRBCL) can mimic HL in some instances. This study aimed to establish the pattern of TARC expression in these diseases. Immunohistochemical stain using a polyclonal goat anti-human antibody to TARC was performed on 119 cases of confirmed HL; 99 were classical type (43 mixed cellularity, 43 nodular sclerosis, 5 lymphocyte depleted, 4 lymphocyte rich, 4 unclassifiable) and 20 lymphocyte predominant HL. Additional 27 ALCL (9 T-, 18 null-cell phenotype), 16 T-cell and 8 B-cell non-Hodgkin's lymphoma (NHL) were studied. A total of 85.8% of the classical HL, one case of ALCL, and one case of large cell B-cell lymphoma with anaplastic morphology showed positive TARC expression in the tumor cells. The expression was paranuclear and/or diffuse in the cell cytoplasm. The tumor cells in all cases of lymphocyte predominant HL, TCRBCL, null ALCL, and T-NHL did not express TARC. The high frequency of TARC expression in the Reed-Sternberg cells of classical HL may explain the characteristic T-cell infiltrate in this disease. The absence in other types that may be morphologically similar indicates that staining for TARC may aid in differential diagnosis. PMID:11420464

  16. Mother-offspring and nest-mate resemblance but no heritability in early-life telomere length in white-throated dippers.

    Science.gov (United States)

    Becker, Philipp J J; Reichert, Sophie; Zahn, Sandrine; Hegelbach, Johann; Massemin, Sylvie; Keller, Lukas F; Postma, Erik; Criscuolo, François

    2015-05-22

    Telomeres are protective DNA-protein complexes located at the ends of eukaryotic chromosomes, whose length has been shown to predict life-history parameters in various species. Although this suggests that telomere length is subject to natural selection, its evolutionary dynamics crucially depends on its heritability. Using pedigree data for a population of white-throated dippers (Cinclus cinclus), we test whether and how variation in early-life relative telomere length (RTL, measured as the number of telomeric repeats relative to a control gene using qPCR) is transmitted across generations. We disentangle the relative effects of genes and environment and test for sex-specific patterns of inheritance. There was strong and significant resemblance among offspring sharing the same nest and offspring of the same cohort. Furthermore, although offspring resemble their mother, and there is some indication for an effect of inbreeding, additive genetic variance and heritability are close to zero. We find no evidence for a role of either maternal imprinting or Z-linked inheritance in generating these patterns, suggesting they are due to non-genetic maternal and common environment effects instead. We conclude that in this wild bird population, environmental factors are the main drivers of variation in early-life RTL, which will severely bias estimates of heritability when not modelled explicitly. PMID:25904662

  17. Analysis of high–dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer

    International Nuclear Information System (INIS)

    The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high–dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25 Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30 Gy in 3 fractions of HDR brachytherapy regimen. The D5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41 Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86 Gy. The mean HDR fractionation equivalent dose, D98%, was 27.93 ± 0.84 Gy. The V100% of the prostate target was 95.57% ± 3.47%. The V100% of the bladder and the rectum were 717.16 and 79.6 mm3, respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D98% to D80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D10% and D5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife

  18. Synthetic nanoemulsion resembling a protein-free model of 7-ketocholesterol containing low density lipoprotein: In vitro and in vivo studies

    Scientific Electronic Library Online (English)

    Giovani M, Favero; Raul C, Maranhão; Durvanei A, Maria; Débora, Levy; Sérgio P, Bydlowski.

    Full Text Available 7-ketocholesterol (7-KC) differs from cholesterol by a functional ketone group at C7. It is an oxygenated cholesterol derivative (oxysterol), commonly present in oxidized low-density lipoprotein (LDL). Oxysterols are generated and participate in several physiologic and pathophysiologic processes. Fo [...] r instance, the cytotoxic effects of oxidized LDL have been widely attributed to bioactive compounds like oxysterols. The toxicity is in part due to 7-KC. Here we aimed to demonstrate the possibility of incorporating 7-KC into the synthetic nanoemulsion LDE, which resembles LDL in composition and behavior. This would provide a suitable artificial particle resembling LDL to study 7-KC metabolism. We were able to incorpórate 7-KC in several amounts into LDE. The incorporation was evaluated and confirmed by several methods, including gel filtration chromatography, using radiolabeled lipids. The incorporation did not change the main lipid composition characteristics of the new nanoparticle. Particle sizes were also evaluated and did not differ from LDE. In vivo studies were performed by injecting the nanoemulsion into mice. The plasma kinetics and the targeted organs were the same as described for LDE. Therefore, 7-KC-LDE maintains composition, size and some functional characteristics of LDE and could be used in experiments dealing with 7-ketocholesterol metabolism in lipoproteins.

  19. [Rolandic spikes as an electroencephalography manifestation of oligodendroglioma].

    Science.gov (United States)

    Kaschnitz, W; Scheer, P; Körner, E; Kratky-Dunitz, M; Lechner, H

    1988-01-01

    A 10 5/12 year old boy was presented with seizures of uncertain origin on to the psychosomatic ward of our University Children's Hospital. The question and problem was the distinction of psychogenic versus epileptogenic origin (repeatedly performed EEG's had shown normal findings, the seizures did not response to anticonvulsive therapy). The exploration of a psychodynamic causes of the presenting problem was excluded by family therapeutic and psychoanalytical case history and psychodynamic interview. The first pathological finding was seen with registration of a long term EEG with typical findings of temporal central spikes and waves as seen in the benign rolandic-epilepsia. The following diagnostic considerations were discussed and differentiated. a) benign rolandi epilepsia b) malign rolandi epilepsia c) psychomotoric seizures d) rolandic spikes as symptomatic finding of a brain tumor. The definite diagnosis was finally confirmed by a cerebral computer-tomography which showed a large expensive process in the interferior right regio temporalis, which was identified histologically after operation as a oligodendrogliom grad-I. The tumor was removed successfully as a whole without any neurological defects. PMID:3241731

  20. 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.

    2013-06-01

    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.

  1. A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404

    International Nuclear Information System (INIS)

    Purpose: This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. Methods and Materials: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. Results: As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. Conclusions: Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years

  2. 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

    International Nuclear Information System (INIS)

    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. 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. 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 be due to a decrease in NPM-ALK levels or the ability of this oncoprotein to signal. This is the first study demonstrating that the expression of immunophilin family co-chaperones is promoted by an oncogenic tyrosine kinase. Moreover, this is the first report establishing an important role for Cyp40 in lymphoma

  3. 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

    2012-06-01

    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 be due to a decrease in NPM-ALK levels or the ability of this oncoprotein to signal. Conclusions This is the first study demonstrating that the expression of immunophilin family co-chaperones is promoted by an oncogenic tyrosine kinase. Moreover, this is the first report establishing an important role for Cyp40 in lymphoma.

  4. 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

    2010-11-01

    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 sporophylls represent the ancestral state of fructifications. Conclusions Some evidence is provided for the existence of ancestral laminar ginkgophyte sporophylls. Homology of the newly found fossil ginkgophyte fructifications with the aberrant O-ha-tsuki fructifications of Ginkgo biloba is proposed. This would support the interpretation of the apical part of the common Ginkgo biloba fructification (stalklet/collar/ovule as a sporophyll with reduced leaf lamina.

  5. Fetuin-A/albumin-mineral complexes resembling serum calcium granules and putative nanobacteria: demonstration of a dual inhibition-seeding concept.

    Science.gov (United States)

    Wu, Cheng-Yeu; Martel, Jan; Young, David; Young, John D

    2009-01-01

    Serum-derived granulations and purported nanobacteria (NB) are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin) and heat inactivation studies. When inoculated into cell culture medium, the purified proteins fetuin-A and albumin fail to induce mineralization, but they will readily combine with exogenously added calcium and phosphate, even in submillimolar amounts, to form complexes that will undergo morphological transitions from nanoparticles to spindles, films, and aggregates. As a mineralization inhibitor, fetuin-A is much more potent than albumin, and it will only seed particles at higher mineral-to-protein concentrations. Both proteins display a bell-shaped, dose-dependent relationship, indicative of the same dual inhibitory-seeding mechanism seen with whole serum. As ascertained by both seeding experiments and gel electrophoresis, fetuin-A is not only more dominant but it appears to compete avidly for nanoparticle binding at the expense of albumin. The nanoparticles formed in the presence of fetuin-A are smaller than their albumin counterparts, and they have a greater tendency to display a multi-layered ring morphology. In comparison, the particles seeded by albumin appear mostly incomplete, with single walls. Chemically, spectroscopically, and morphologically, the protein-mineral particles resemble closely serum granules and NB. These particles are thus seen to undergo an amorphous to crystalline transformation, the kinetics and completeness of which depend on the protein-to-mineral ratios, with low ratios favoring faster conversion to crystals. Our results point to a dual inhibitory-seeding, de-repression model for the assembly of particles in supersaturated solutions like serum. The presence of proteins and other inhibitory factors tend to block apatite nuclei formation or to stabilize the nascent nuclei as amorphous or semi-crystalline spherical nanoparticles, until the same inhibitory influences are overwhelmed or de-repressed, whereby the apatite nuclei grow in size to coalesce into crystalline spindles and films-a mechanism that may explain not only the formation of calcium granules in nature but also normal or ectopic calcification in the body. PMID:19956594

  6. Afasia de conducción como consecuencia de un astrocitoma anaplásico parieto-temporo-occipital izquierdo: estudio de caso / Conduction Aphasia as a Result of Left Parietal-Temporal-Occipital Anaplastic Astrocytoma: A Case Study

    Scientific Electronic Library Online (English)

    OSCAR MAURICIO, AGUILAR MEJÍA; BEATRIZ, RAMÍREZ BERBERJO; JUAN CARLOS, ACEVEDO GONZÁLEZ; MIGUEL ENRIQUE, BERBEO CALDERÓN.

    2011-01-01

    Full Text Available La afasia de conducción es un trastorno caracterizado por un lenguaje espontáneo relativamente fluido, buena comprensión, pero dificultades en la repetición asociadas con parafasias fonológicas. Se ha atribuido a lesiones del fascículo arqueado por desconexión entre el lóbulo temporal posterior y el [...] frontal; sin embargo, se ha debatido esta postura, planteando que la integridad y funcionamiento del fascículo arqueado no es indispensable en la repetición verbal. Se presenta un caso de un sujeto varón de 23 años que, como consecuencia de un astrocitoma anaplásico recidivante que abarca áreas parietales y temporo-occipitales, presenta una afasia de conducción. Se plantea una reconceptualización de esta afasia, analizándola en términos clínicos, neuropsicológicos y en las redes neuronales existentes entre áreas cerebrales posteriores ipsilaterales y contralaterales. Abstract in english 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 betwe [...] en 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.

  7. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition.

    Science.gov (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

    2015-01-01

    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 ?-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. PMID:26426013

  8. Insecticidal activity of an alpha-amylase inhibitor-like protein resembling a putative precursor of alpha-amylase inhibitor in the common bean, Phaseolus vulgaris L.

    Science.gov (United States)

    Ishimoto, M; Yamada, T; Kaga, A

    1999-06-15

    alpha-Amylase inhibitor (alphaAI) in the common bean, Phaseolus vulgaris L., protects seeds from insect pests such as the cowpea weevil (Callosobruchus maculatus) and the azuki bean weevil (C. chinensis). Cultivars which lack alphaAI still show resistance to both bruchids. These cultivars have a glycoprotein that reacts with anti-alphaAI-1 antibodies. The glycoprotein with a molecular mass of 29 kDa (Gp29) was purified and the encoding gene was isolated. The primary structure of Gp29 is the same as alpha-amylase inhibitor-like protein (AIL) from which the encoding gene has already been isolated. AIL resembles a putative precursor of alphaAI, even though it does not form the active inhibitor. However, AIL has some inhibitory effect on the growth of C. maculatus but not C. chinensis. The presence of AIL alone is insufficient to explain the bruchid resistance of common bean cultivars lacking alpha-AI. Common bean seeds appear to contain several factors responsible for the bruchid resistance. PMID:10366733

  9. A naturally derived gastric cancer cell line shows latency I Epstein-Barr virus infection closely resembling EBV-associated gastric cancer

    International Nuclear Information System (INIS)

    In a process seeking out a good model cell line for Epstein-Barr virus (EBV)-associated gastric cancer, we found that one previously established gastric adenocarcinoma cell line is infected with type 1 EBV. This SNU-719 cell line from a Korean patient expressed cytokeratin without CD19 or CD21 expression. In SNU-719, EBNA1 and LMP2A were expressed, while LMP1 and EBNA2 were not. None of the tested lytic EBV proteins were detected in this cell line unless stimulated with phorbol ester. EBV infection was also shown in the original carcinoma tissue of SNU-719 cell line. Our results support the possibility of a CD21-independent EBV infection of gastric epithelial cells in vivo. As the latent EBV gene expression pattern of SNU-719 closely resembles that of the EBV-associated gastric cancer, this naturally derived cell line may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis

  10. 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

    2015-09-01

    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 ?-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.

  11. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    Science.gov (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.

    2015-01-01

    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 ?-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. PMID:26426013

  12. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

    Science.gov (United States)

    Wong-Baeza, Carlos; Tescucano, Alonso; Astudillo, Horacio; Reséndiz, Albany; Landa, Carla; España, Luis; Serafín-López, Jeanet; Estrada-García, Iris; Estrada-Parra, Sergio; Flores-Romo, Leopoldo; Wong, Carlos; Baeza, Isabel

    2015-01-01

    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. PMID:26568960

  13. Anti-Hu antibody-positive paraneoplastic limbic encephalitis with acute motor sensory neuropathy resembling Guillain-Barré syndrome: a case study.

    Science.gov (United States)

    Sakurai, Takeo; Wakida, Kenji; Kimura, Akio; Inuzuka, Takashi; Nishida, Hiroshi

    2015-12-23

    A 69-year-old man experienced general malaise, weight loss, amnesia, gait disturbance, and restlessness a month prior to admission. Brain MRI showed high intensity areas in the bilateral medial temporal lobes and insular cortices on FLAIR images, and therefore, he was diagnosed with limbic encephalitis. After admission, quadriplegia and respiratory failure progressed rapidly, and he needed ventilatory management. A nerve conduction study revealed low compound muscle action potential amplitude with loss of sensory nerve action potential, which indicated axonal sensorimotor neuropathy. We administered intravenous immunoglobulin and methylprednisolone pulse therapy, but he did not recover. Although no tumor was found on CT, his serum was positive for anti-Hu antibody; therefore, we diagnosed him with paraneoplastic neurological syndrome. An FDG-PET study showed accumulation at lesions on two hilar lymph nodes. Small cell lung carcinoma was detected by endobronchial ultrasound-guided transbronchial needle aspiration. Although paraneoplastic acute sensorimotor neuropathy with respiratory failure resembling Guillain-Barré syndrome is rare, identification of antibodies and servey of tumors aids accurate diagnosis. PMID:26511029

  14. Phenotype in a patient with p.D50N mutation in GJB2 gene resemble both KID and Clouston syndromes.

    Science.gov (United States)

    Markova, T G; Brazhkina, N B; Bliznech, E A; Bakhshinyan, V V; Polyakov, A V; Tavartkiladze, G A

    2016-02-01

    Keratitis-ichthyosis-deafness (KID) syndrome (OMIM 148210) is a rare ectodermal dysplasia syndrome characterized by vascularizing keratitis, congenital profound sensorineural hearing loss, and progressive erythrokeratoderma. We have found a 148G-A transition in the GJB2 gene, resulting in an asp50-to-asn (D50N) substitution in a girl with congenital deafness. This finding allowed us to diagnose ? KID syndrome. But clinical features were uncommon because of a mild skin manifestation, lack of keratitis and unusual appearance resembling Clouston syndrome. Molecular genetic tests showed that it was de novo mutation because parents have normal genotype. Several autosomal dominant mutations in the GJB2 gene (?onnexin 26) now established to underlie many of the affected cases, with the majority of patients harboring the p.D50N mutation. Skin disease-associated mutation of connexin proteins can cause functional disturbances in gap junction intercellular conductance. It is likely that multiple disease mechanisms are involved across the wide spectrum of hereditary diseases relating to connexin proteins. The clinical data may provide additional insights into the dysregulation mechanisms of mutations result in the disease. PMID:26810281

  15. Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

    Energy Technology Data Exchange (ETDEWEB)

    Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting, E-mail: BTZhu@kumc.edu

    2012-07-15

    Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K{sub 3}) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ? 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ? Menadione causes mitochondrial superoxide accumulation and injury. ? Menadione-induced cell death is caspase-independent, due to rapid depletion of ATP. ? The release of AIF and Endo G contributes importantly to cell death. ? Alterations of SOD1 or SOD2 levels alter menadione-induced neuronal cytotoxicity.

  16. Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

    International Nuclear Information System (INIS)

    Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K3) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ∼ 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of ATP. ► The release of AIF and Endo G contributes importantly to cell death. ► Alterations of SOD1 or SOD2 levels alter menadione-induced neuronal cytotoxicity.

  17. Some phorbol esters might partially resemble bryostatin 1 in their actions on LNCaP prostate cancer cells and U937 leukemia cells.

    Science.gov (United States)

    Kedei, Noemi; Lubart, Emanuel; Lewin, Nancy E; Telek, Andrea; Lim, Langston; Mannan, Poonam; Garfield, Susan H; Kraft, Matthew B; Keck, Gary E; Kolusheva, Sofiya; Jelinek, Raz; Blumberg, Peter M

    2011-05-16

    Phorbol 12-myristate 13-acetate (PMA) and bryostatin 1 are both potent protein kinase C (PKC) activators. In LNCaP human prostate cancer cells, PMA induces tumor necrosis factor alpha (TNF?) secretion and inhibits proliferation; bryostatin 1 does not, and indeed blocks the response to PMA. This difference has been attributed to bryostatin 1 not localizing PKC? to the plasma membrane. Since phorbol ester lipophilicity influences PKC? localization, we have examined in LNCaP cells a series of phorbol esters and related derivatives spanning some eight logs in lipophilicity (logP) to see if any behave like bryostatin 1. The compounds showed marked differences in their effects on proliferation and TNF? secretion. For example, maximal responses for TNF? secretion relative to PMA ranged from 97?% for octyl-indolactam V to 24?% for phorbol 12,13-dibenzoate. Dose-response curves ranged from monophasic for indolactam V to markedly biphasic for sapintoxin D. The divergent patterns of response, however, correlated neither to lipophilicity, to plasma membrane translocation of PKC?, nor to the ability to interact with model membranes. In U937 human leukemia cells, a second system in which PMA and bryostatin 1 have divergent effects, viz. PMA but not bryostatin 1 inhibits proliferation and induces attachment, all the compounds acted like PMA for proliferation, but several induced a reduced level or a biphasic dose-response curve for attachment. We conclude that active phorbol esters are not all equivalent. Depending on the system, some might partially resemble bryostatin 1 in their behavior; this encourages the concept that bryostatin-like behavior may be obtained from other structural templates. PMID:21542090

  18. A rare case of primary clear cell sarcoma of the pubic bone resembling small round cell tumor: an unusual morphological variant

    Directory of Open Access Journals (Sweden)

    Nakayama Shoko

    2012-11-01

    Full Text Available Abstract Background Clear cell sarcoma (CCS and malignant melanoma share overlapping immunohistochemistry with regard to the melanocytic markers HMB45, S100, and Melan-A. However, the translocation t(12; 22(q13; q12 is specific to CCS. Therefore, although these neoplasms are closely related, they are now considered to be distinct entities. However, the translocation is apparently detectable only in 50%–70% of CCS cases. Therefore, the absence of a detectable EWS/AFT1 rearrangement may occasionally lead to erroneous exclusion of a translocation-negative CCS. Therefore, histological assessment is essential for the correct diagnosis of CCS. Primary CCS of the bone is exceedingly rare. Only a few cases of primary CCS arising in the ulna, metatarsals, ribs, radius, sacrum, and humerus have been reported, and primary CCS arising in the pubic bone has not been reported till date. Case presentation We present the case of an 81-year-old man with primary CCS of the pubic bone. Histological examination of the pubic bone revealed monomorphic small-sized cells arranged predominantly as a diffuse sheet with round, hyperchromatic nuclei and inconspicuous nucleoli. The cells had scant cytoplasm, and the biopsy findings indicated small round cell tumor (SRCT. Immunohistochemical staining revealed the tumor cells to be positive for HMB45, S100, and Melan-A but negative for cytokeratin (AE1/AE3 and epithelial membrane antigen. To the best of our knowledge, this is the first case report of primary CCS of the pubic bone resembling SRCT. This ambiguous appearance underscores the difficulties encountered during the histological diagnosis of this rare variant of CCS. Conclusion Awareness of primary CCS of the bone is clinically important for accurate diagnosis and management when the tumor is located in unusual locations such as the pubic bone and when the translocation t(12; 22(q13; q12 is absent.

  19. It’s beginning to look a lot like my hand: Fake hand perceived to resemble own hand for people with body dysmorphic disorder but not controls.

    Directory of Open Access Journals (Sweden)

    Ryan A Kaplan

    2012-10-01

    Full Text Available BACKGROUND AND AIMS Body dysmorphic disorder (BDD is characterised by misperception of one’s own bodily features. This study aimed to investigate whether visual perceptual processes and own-body-related multisensory integration processes differ in people with BDD compared to controls, and the roles those processes play in BDD aetiology and symptomatology. METHODS We attempted to induce the rubber hand illusion (RHI on 16 people with BDD and 15 controls, using the standard procedure (see Botvinick & Cohen, 1998, wherein a visible fake hand and the participant’s hidden real hand are stroked either synchronously (experimental condition or asynchronously (control condition. This was repeated on both hands. RESULTS Participants in the BDD group endorsed response items indicating that during the experiment, the fake hand began to visually resemble their own hand, for the right hand only, and irrespective of the synchronicity of the stroking (F(1,15=6.74, p=.02. No such effect was observed for the control group. CONCLUSIONS For people with BDD, simply gazing at a body-related stimulus can affect the way it is perceived. These results support the idea that people with BDD may have a more malleable perceptual body image than others, which may predispose them to the disorder. Moreover, most BDD sufferers spend an inordinate amount of time mirror-gazing. These results support the notion that mirror-gazing may play a critical role in the development of BDD, and may emphasise the importance of encouraging restriction of such behaviour as part of a treatment protocol.

  20. Identification and characterization of a viroid resembling apple dimple fruit viroid in fig (Ficus carica L.) by next generation sequencing of small RNAs.

    Science.gov (United States)

    Chiumenti, M; Torchetti, E M; Di Serio, F; Minafra, A

    2014-08-01

    Viroids are small (246-401 nt) circular and non coding RNAs infecting higher plants. They are targeted by host Dicer-like enzymes (DCLs) that generate small RNAs of 21-24 nt (sRNAs), which are involved in the host RNA silencing pathways. The accumulation in plant tissues of such viroid-derived small RNAs (vd-sRNAs) is a clear sign of an ongoing viroid infection. In this study, next generation sequencing of a sRNAs library and assembling of the sequenced vd-sRNAs were instrumental for the identification of a viroid resembling apple dimple fruit viroid (ADFVd) in a fig accession. After confirming by molecular methods the presence of this viroid in the fig tree, its population was characterized, showing that the ADFVd master sequence from fig diverges from that of the ADFVd reference variant from apple. Moreover, since this viroid accumulates at a low level in fig, a semi-nested RT-PCR assay was developed for detecting it in other fig accessions. ADFVd seems to have a wider host range than thought before and this poses questions about its epidemiology. A further characterization of ADFVd-sRNAs showed similar accumulation of (+) or (-) vd-sRNAs that mapped on the viroid genome generating hotspot profiles. Moreover, similarly to other nuclear-replicating viroids, vd-sRNAs of 21, 22 and 24 nt in size prevailed in the distribution profiles. Altogether, these data support the involvement of double-stranded RNAs and different DCLs, targeting the same restricted viroid regions, in the genesis of ADFVd-sRNAs. PMID:24704673

  1. Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans.

    Science.gov (United States)

    Warraich, Sumeeta; Bone, Derek B J; Quinonez, Diana; Ii, Hisataka; Choi, Doo-Sup; Holdsworth, David W; Drangova, Maria; Dixon, S Jeffrey; Séguin, Cheryle A; Hammond, James R

    2013-05-01

    Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy, characterized by ectopic calcification of spinal tissues. Symptoms include spine pain and stiffness, and in severe cases dysphagia and spinal cord compression. The etiology of DISH is unknown and there are no specific treatments. Recent studies have suggested a role for purine metabolism in the regulation of biomineralization. Equilibrative nucleoside transporter 1 (ENT1) transfers hydrophilic nucleosides, such as adenosine, across the plasma membrane. In mice lacking ENT1, we observed the development of calcified lesions resembling DISH. By 12 months of age, ENT1(-/-) mice exhibited signs of spine stiffness, hind limb dysfunction, and paralysis. Micro-computed tomography (µCT) revealed ectopic mineralization of paraspinal tissues in the cervical-thoracic region at 2 months of age, which extended to the lumbar and caudal regions with advancing age. Energy-dispersive X-ray microanalysis of lesions revealed a high content of calcium and phosphorus with a ratio similar to that of cortical bone. At 12 months of age, histological examination of ENT1(-/-) mice revealed large, irregular accumulations of eosinophilic material in paraspinal ligaments and entheses, intervertebral discs, and sternocostal articulations. There was no evidence of mineralization in appendicular joints or blood vessels, indicating specificity for the axial skeleton. Plasma adenosine levels were significantly greater in ENT1(-/-) mice than in wild-type, consistent with loss of ENT1--a primary adenosine uptake pathway. There was a significant reduction in the expression of Enpp1, Ank, and Alpl in intervertebral discs from ENT1(-/-) mice compared to wild-type mice. Elevated plasma levels of inorganic pyrophosphate in ENT1(-/-) mice indicated generalized disruption of pyrophosphate homeostasis. This is the first report of a role for ENT1 in regulating the calcification of soft tissues. Moreover, ENT1(-/-) mice may be a useful model for investigating pathogenesis and evaluating therapeutics for the prevention of mineralization in DISH and related disorders. PMID:23184610

  2. Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17 / Doença priônica com características clínicas semelhantes à demência frontotemporal e parkinsonismo associada ao cromossoma 17

    Scientific Electronic Library Online (English)

    Ricardo, Nitrini; Luís Sidônio Teixeira da, Silva; Sérgio, Rosemberg; Paulo, Caramelli; Paulo Eduardo Mestrinelli, Carrilho; Paula, Iughetti; Maria Rita, Passos-Bueno; Mayana, Zatz; Stephen, Albrecht; Andrea, LeBlanc.

    2001-06-01

    Full Text Available OBJETIVO: comparar as características clínicas de doença priônica com as da demência frontotemporal e parkinsonismo associada ao cromossoma 17 (FTDP-17). FUNDAMENTOS: doenças priônicas não são usualmente incluídas no diagnóstico diferencial da FTDP-17 porque a doença de Creutzfeldt-Jakob (DCJ), a ma [...] is comum entre as doenças priônicas hereditárias, frequentemente manifesta-se como demência rapidamente progressiva. Por outro lado, a FTDP-17 apresenta-se insidiosamente na quinta década, com alterações do comportamento e sinais parkinsonianos. MÉTODO: apresentamos as características clínicas de 12 membros de uma família com DCJ associada à mutação de ponto no codon 183 do gene da proteína priônica. RESULTADOS: os sintomas iniciaram-se aos 44.0 ± 3.7 anos e a duração até o óbito foi de dois a cinco anos. Alterações do comportamento foram os sintomas iniciais mais frequentes. Nove pacientes foram atendidos inicialmente por psiquiatras. Oito pacientes manifestaram sinais parkinsonianos. CONCLUSÃO: as características clínicas apresentam considerável semelhança com as descritas na FTDP-17. Abstract in english 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.

  3. Cytokeratin immunoreactivity in gliomas.

    Science.gov (United States)

    Ng, H K; Lo, S T

    1989-04-01

    Monoclonal antibodies (AE1/3, CAM 5.2 and PKK-1) and polyclonal antisera against the cytokeratin proteins were reacted with a range of astrocytic tumours, oligodendrogliomas and ependymomas. Seven of 12 cases (58%) of glioblastoma multiforme, five of eight (63%) anaplastic astrocytomas and two of five (40%) well-differentiated astrocytomas were immunoreactive with AE1/3 but not with the other anti-cytokeratin antibodies. In oligodendrogliomas, AE1/3 stained isolated astrocyte-like cells as well as scattered neoplastic oligodendrocytes in four of eight cases (50%) cases. Four ependymomas were negative for all cytokeratin markers examined. The immunostaining of astrocytomas and oligodendrogliomas with AE1/3 might represent co-expression of cytokeratin with glial fibrillary acidic protein by gliomas and calls for caution in the use of these antibodies in the differential diagnosis between gliomas and carcinomas. PMID:2472343

  4. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling.

    Science.gov (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

    2007-11-01

    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. PMID:17690253

  5. Mammographic Texture Resemblance generalizes as an independent risk factor of breast cancer : 5th International Workshop on Breast Densitometry and Breast Cancer Risk Assessment, San Francisco, United States

    DEFF Research Database (Denmark)

    Chernoff, Konstantin; Christopher, S G

    PURPOSE Breast density has been established as a risk factor of breast cancer in numerous studies. Mammographic Texture Resemblance (MTR) has shown to be a density independent risk factor, but only on a single study. We examine if the statistics of the texture recorded in one study generalize as an independent risk factor in an unrelated cohort. METHOD AND MATERIALS The statistics of texture were recorded in digitalized film-mammograms of one 4-year prospective study (S1, Dutch screening program) of 245 breast cancers and 250 matched controls. From an independent cohort study (S2, Mayo Mammography Health Study cohort) 226 incident breast cancer cases diagnosed through 2008 and 442 matched controls (on age) were used for scoring screening digitized mammograms that were ascertained years prior to diagnosis 1993-2006. Mammographic percent density (PD), using Cumulus, and other major risk factors were ascertained in S2. Finally S2 was MTR scored based on textures from S1 and S2 in a leave-two-out fashion. Scores on S2 were related to future breast cancer incidence by AUC and analyses of quartiles adjusted for BMI, menopause status, and postmenopausal hormone (PMH) use. A combined density and MTR model was also evaluated. RESULTS The MTR scores on S1 showed in a cross validation fashion significant capability to separate cancers from controls (AUC=0.63±0.02, p<0.001). This persisted after adjustment for mammographic density. Age of S1 was 58.0±5.7 years while age in S2 was younger with higher variation: 55.2±10.5 years. No significant difference in BMI, menopause status, or PMH was found between cases and matched controls in S2. S2 showed an AUC of 0.633, 0.613, and 0.600 based on respectively percentage density, MTR scores trained on S2, and MTR scores trained on S1 respectively. Adjusted for PD, MTR scores of S2 trained on S1 showed OR in quartiles of ref; 1.10 (0.64-1.89); 0.93 (0.52-1.68); 1.96 (1.19-3.23) respectively and a combined AUC of 0.654. CONCLUSION The heterogeneities that are recorded to characterize breast cancer risk in S1 were also a density independent risk factor in S2. Hence the textural patterns that indicated elevated risk persisted under differences in x-ray technology, population demographics, follow up time, and geography.

  6. 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

    2005-04-01

    Full Text Available O osteossarcoma é um tumor mesenquimal maligno, no qual as células cancerosas produzem matriz óssea. É o tumor maligno primário mais comum do osso, responsável por aproximadamente 20% dos sarcomas, sendo que 5% destes ocorrem nos maxilares. Possuem variados aspectos não só clínicos e histopatológicos como também no curso e prognóstico. Este artigo apresenta um relato de caso de paciente do sexo feminino, com 20 anos de idade, que nos foi encaminhada apresentando aumento de volume na região de pré-molar inferior esquerdo. Após diagnóstico clínico de lesão do periápice dental, a paciente foi submetida previamente a tratamento endodôntico do dente envolvido, a partir do qual, em um período de 11 dias, pode-se observar um considerável aumento da lesão provocando visível assimetria facial. A radiografia oclusal mostrava imagem compatível com área de destruição óssea e formação de osso anormal na região, com cortical externa exibindo evidente radiopacidade semelhante a raios de sol, sugerindo o diagnóstico de osteossarcoma. A lesão foi biopsiada e obteve-se o diagnóstico histopatológico de osteossarcoma. A paciente foi então submetida à mandibulectomia parcial e uma reconstrução da área, usando osso de costela e enxerto de pele da nádega, para o revestimento da mucosa oral envolvida. Aos 8 meses após a cirurgia houve recorrência local da lesão e a paciente foi a óbito aproximadamente 1 ano depois da recidiva.Osteosarcoma is a malignant mesenchymal tumor whose cancerous cells produce osteoid matrix. It is the most common primary malignant bone tumor, accounting for approximately 20% of the sarcomas, but only 5% of the osteosarcomas occur in the jaws. They present various clinical and histological aspects, as well as variable disease progression and outcome. This article shows a case report of a 20-year-old woman who presented swelling near the mandibular left premolar. After clinical diagnosis of lesion of 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.

  7. Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV closely resembles lung cancer in sheep infected with JSRV

    Directory of Open Access Journals (Sweden)

    York Denis

    2006-12-01

    Full Text Available Abstract Background Jaagsiekte sheep retrovirus (JSRV causes a lethal lung cancer in sheep and goats. Expression of the JSRV envelope (Env protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (AAV6 vector, induces tumors resembling those seen in sheep. However, the mouse and sheep tumors have not been carefully compared to determine if Env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep are important, such as oncogene activation following retrovirus integration into the host cell genome. Results We have generated mouse monoclonal antibodies (Mab against JSRV Env and have used these to study mouse and sheep lung tumor histology. These Mab detect Env expression in tumors in sheep infected with JSRV from around the world with high sensitivity and specificity. Mouse and sheep tumors consisted mainly of well-differentiated adenomatous foci with little histological evidence of anaplasia, but at long times after vector exposure some mouse tumors did have a more malignant appearance typical of adenocarcinoma. In addition to epithelial cell tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses that expressed Env and appeared to be separate neoplasms. The Mab also stained nasal adenocarcinoma tissue from one United States sheep, which we show was due to expression of Env from ovine enzootic nasal tumor virus (ENTV, a virus closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV Env to mice produced numerous hepatocellular tumors, and some hemangiomas and hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell types. Conclusion Lung cancers induced by JSRV infection in sheep and by JSRV Env expression in mice have similar histologic features and are primarily characterized by adenomatous proliferation of peripheral lung epithelial cells. Thus it is unnecessary to invoke a role for insertional mutagenesis, gene activation, viral replication, or expression of other viral gene products in sheep lung tumorigenesis, although these processes may play a role in other clinically less important sequelae of JSRV infection such as metastasis observed with variable frequency in sheep.

  8. Stable expression of constitutively-activated STAT3 in benign prostatic epithelial cells changes their phenotype to that resembling malignant cells

    Directory of Open Access Journals (Sweden)

    Barton Arnold B

    2005-01-01

    Full Text Available Abstract Background Signal transducers and activators of transcription (STATs are involved in growth regulation of cells. They are usually activated by phosphorylation at specific tyrosine residues. In neoplastic cells, constitutive activation of STATs accompanies growth dysregulation and resistance to apoptosis through changes in gene expression, such as enhanced anti-apoptotic gene expression or reduced pro-apoptotic gene expression. Activated STAT3 is thought to play an important role in prostate cancer (PCA progression. Because we are interested in how persistently-activated STAT3 changes the cellular phenotype to a malignant one in prostate cancer, we used expression vectors containing a gene for constitutively-activated STAT3, called S3c, into NRP-152 rat and BPH-1 human benign prostatic epithelial cells. Results We observed that prostatic cell lines stably expressing S3c required STAT3 expression for survival, because they became sensitive to antisense oligonucleotide for STAT3. However, S3c-transfected cells were not sensitive to the effects of JAK inhibitors, meaning that STAT3 was constitutively-activated in these transfected cell lines. NRP-152 prostatic epithelial cells lost the requirement for exogenous growth factors. Furthermore, we observed that NRP-152 expressing S3c had enhanced mRNA levels of retinoic acid receptor (RAR-α, reduced mRNA levels of RAR-β and -γ, while BPH-1 cells transfected with S3c became insensitive to the effects of androgen, and also to the effects of a testosterone antagonist. Both S3c-transfected cell lines grew in soft agar after stable transfection with S3c, however neither S3c-transfected cell line was tumorigenic in severe-combined immunodeficient mice. Conclusions We conclude, based on our findings, that persistently-activated STAT3 is an important molecular marker of prostate cancer, which develops in formerly benign prostate cells and changes their phenotype to one more closely resembling transformed prostate cells. That the S3c-transfected cell lines require the continued expression of S3c demonstrates that a significant phenotypic change occurred in the cells. These conclusions are based on our data with respect to loss of growth factor requirement, loss of androgen response, gain of growth in soft agar, and changes in RAR subunit expression, all of which are consistent with a malignant phenotype in prostate cancer. However, an additional genetic change may be required for S3c-transfected prostate cells to become tumorigenic.

  9. Osteossarcoma de mandíbula inicialmente mimetizando lesão do periápice dental: relato de caso / Osteosarcoma of mandible initially resembling lesion of dental periapex: a case report

    Scientific Electronic Library Online (English)

    Rosilene C., Soares; Andréa F., Soares; Lélia B., Souza; Aldo L. V. dos, Santos; Leão P., Pinto.

    2005-04-01

    Full Text Available O osteossarcoma é um tumor mesenquimal maligno, no qual as células cancerosas produzem matriz óssea. É o tumor maligno primário mais comum do osso, responsável por aproximadamente 20% dos sarcomas, sendo que 5% destes ocorrem nos maxilares. Possuem variados aspectos não só clínicos e histopatológico [...] s como também no curso e prognóstico. Este artigo apresenta um relato de caso de paciente do sexo feminino, com 20 anos de idade, que nos foi encaminhada apresentando aumento de volume na região de pré-molar inferior esquerdo. Após diagnóstico clínico de lesão do periápice dental, a paciente foi submetida previamente a tratamento endodôntico do dente envolvido, a partir do qual, em um período de 11 dias, pode-se observar um considerável aumento da lesão provocando visível assimetria facial. A radiografia oclusal mostrava imagem compatível com área de destruição óssea e formação de osso anormal na região, com cortical externa exibindo evidente radiopacidade semelhante a raios de sol, sugerindo o diagnóstico de osteossarcoma. A lesão foi biopsiada e obteve-se o diagnóstico histopatológico de osteossarcoma. A paciente foi então submetida à mandibulectomia parcial e uma reconstrução da área, usando osso de costela e enxerto de pele da nádega, para o revestimento da mucosa oral envolvida. Aos 8 meses após a cirurgia houve recorrência local da lesão e a paciente foi a óbito aproximadamente 1 ano depois da recidiva. Abstract in english Osteosarcoma is a malignant mesenchymal tumor whose cancerous cells produce osteoid matrix. It is the most common primary malignant bone tumor, accounting for approximately 20% of the sarcomas, but only 5% of the osteosarcomas occur in the jaws. They present various clinical and histological aspects [...] , as well as variable disease progression and outcome. This article shows a case report of a 20-year-old woman who presented swelling near the mandibular left premolar. After clinical diagnosis of lesion of 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.

  10. Duodenal gastrointestinal stromal tumor resembling a pancreatic neuroendocrine tumor in a patient with neurofibromatosis type I (von Recklinghausen's disease: a case report

    Directory of Open Access Journals (Sweden)

    Ohtake Shinji

    2010-09-01

    Full Text Available Abstract Introduction Gastrointestinal stromal tumor is the most frequent nonepithelial tumor found in the gastrointestinal tract. One important clinical problem is that gastrointestinal stromal tumors, especially the extramural growth type, can be difficult to distinguish from other organ tumors. The case of a patient with an extramural gastrointestinal stromal tumor of the duodenum that mimicked a pancreatic head tumor has previously been reported. Here, we report a rare case of a patient with a duodenal gastrointestinal stromal tumor with extramural growth that mimicked a pancreatic neuroendocrine tumor. In this case, the gastrointestinal stromal tumor was also associated with neurofibromatosis type 1 (also known as von Recklinghausen's disease. To the best of our knowledge, this is the first report to describe the case of a patient with a duodenal gastrointestinal stromal tumor with neurofibromatosis type 1 in which the radiological findings resembled those of a pancreatic neuroendocrine tumor. Case presentation A 60-year-old Japanese woman with a history of neurofibromatosis type 1 was admitted to our hospital for the treatment of a tumor of her pancreas. She had no symptoms, but an abdominal ultrasonography screening examination had revealed a hypoechoic mass in the head of her pancreas. Laboratory data, including tumor markers, were within the normal ranges, and her insulin and glucagon levels were also within the normal ranges. However, her plasma gastrin level was elevated at 580 pg/mL (30 to 150 pg/mL. A computed tomography examination revealed a hypervascular tumor measuring 14 mm in diameter in the head of her pancreas. We diagnosed the patient as having a pancreatic neuroendocrine tumor and performed a tumor resection with a duodenal wedge resection. Microscopic analysis revealed spindle cell tumors in a trabecular pattern. The patient was finally diagnosed as having a duodenal gastrointestinal stromal tumor of the uncommitted type. Conclusion Extramural growth-type gastrointestinal stromal tumors can be difficult to distinguish from other organ tumors. In our case, a duodenal gastrointestinal stromal tumor was difficult to distinguish from a pancreatic neuroendocrine tumor based on radiological findings. When patients are identified as having hypervascular lesions that have adhered to the gastrointestinal tract, the possibility of an extramural growth-type gastrointestinal stromal tumor as a differential diagnosis should be considered in patients with neurofibromatosis type 1.

  11. P64QUANTITATIVE MGMT METHYLATION ANALYSIS BY PYROSEQUENCING REVEALS A STRONG CORRELATION BETWEEN 1P/19Q CO-DELETION AND HIGH LEVEL METHYLATION IN HIGH GRADE GLIOMAS

    OpenAIRE

    Laxton, R.; Doey, L.; Aizpurua, M.; Bodi, I; King, A.; Chandler, C.; Bhangoo, R; Beaney, R; Brazil, L.; Ashkan, K; Al-Sarraj, S.

    2014-01-01

    INTRODUCTION: Pyrosequencing is a method that allows MGMT methylation to be measured in a quantitative manner. MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit from the addition of chemotherapy to radiotherapy. Aim: To compare the average MGMT promoter methylation level of high gra...

  12. Multicentric pleomorphic xanthoastrocytoma in a patient with neurofibromatosis type 1. Case report and review of the literature.

    Science.gov (United States)

    Saikali, Stephan; Le Strat, Anne; Heckly, Anne; Stock, Nathalie; Scarabin, Jean-Marie; Hamlat, Abderrahmane

    2005-02-01

    The authors report an unusual case of multicentric pleomorphic xanthoastrocytoma (PXA) in a 36-year-old woman with neurofibromatosis Type 1 (NF1). Both lesions were diagnosed as PXA but demonstrated different neuroimaging features and very different outcomes. Although the occipital lesion was cured surgically, the cerebellar tumor recurred three times and underwent malignant transformation into an anaplastic oligodendroglioma. The authors discuss the causes of PXA and suggest that it could originate from common bipotential precursor cells with two phenotypes. PMID:15739569

  13. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials.

    Science.gov (United States)

    Marsilje, Thomas H; Pei, Wei; Chen, Bei; Lu, Wenshuo; Uno, Tetsuo; Jin, Yunho; Jiang, Tao; Kim, Sungjoon; Li, Nanxin; Warmuth, Markus; Sarkisova, Yelena; Sun, Frank; Steffy, Auzon; Pferdekamper, AnneMarie C; Li, Allen G; Joseph, Sean B; Kim, Young; Liu, Bo; Tuntland, Tove; Cui, Xiaoming; Gray, Nathanael S; Steensma, Ruo; Wan, Yongqin; Jiang, Jiqing; Chopiuk, Greg; Li, Jie; Gordon, W Perry; Richmond, Wendy; Johnson, Kevin; Chang, Jonathan; Groessl, Todd; He, You-Qun; Phimister, Andrew; Aycinena, Alex; Lee, Christian C; Bursulaya, Badry; Karanewsky, Donald S; Seidel, H Martin; Harris, Jennifer L; Michellys, Pierre-Yves

    2013-07-25

    The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients. PMID:23742252

  14. Ex-post evaluation by bibliometric method. Institutional comparison among 9 resembled foreign research institutes by using the energy citation database (ECD)

    International Nuclear Information System (INIS)

    From a viewpoint of ex-post evaluation, research papers published from nine resembled nuclear research institutes located in Japan, the U.S.A., Germany and France were compared by a bibliometric method. A research database used was the Energy Citation Database (ECD) owned by USDOE. ECD is a database run by USDOE and has a high frequency of research paper acquisition assembled in the U.S. Response speed of ECD on the Website is quick and all logged data can be handled easily. INIS database is run by the International Atomic Energy Agency (IAEA) and contains a lot of nuclear research papers collected from the member countries such as the U.S.A., Japan, Germany and France. INIS underestimates about 20% of the U.S.A. data than that of ECD. I. Institutional Comparison. (1) ECD shows that a total number of research papers published during 25 years (1978-2002) was of the order of the ORNL (34, 149 papers)>SNL>ANL>BNL>Idaho (>Karlsruhe>JAERI>Jeulich>Cadarache). Where, INIS shows it as ORNL>JAERI. (2) ECD can show a long-term data comparison with a time span more than 50 years (1953-2002). Disclosed research papers were of the order of the ORNL (55,857)>ANL (37,129)>SNL (24,628)>BNL (24,829)> Idaho (2,398). There were many records loaded without publication dates-over 50,000. Because of this, any searches which use dates are not finding these documents. Typically, the author found over 5,000 SNL items in the NSA range of records. SNL also kept a lot of defense reports, those are not disclosed yet. One had better know a historical background of each cite as to the case for long-range dates comparison. (3) ECD founds that research papers at a five-year period varied those numbers. At past (10), thus 1988-1922, paper reduction occurred sharply at most US-institutes. This might be attributed to lay-offs, funding shifts or complete elimination of programs, a policy change in reporting requirements for contract reporting deliverables. Definitions of what constituted STI (science and technology information) were beginning to vary also. II. Comparison at the research field of material science. With time span of 25 years, a comparison was made in the U.S. (1) Actinides; a number of papers disclosed was of the order of ORNL (944 papers) > ANL (927) > SNL (255). The difference is negligible between ORNL and ANL. ORNL was also the champion for the case of INIS. (2) Electromagnetic radiation; this case was of the order of ORNL (1.043 papers) > BNL (673) > SNL (605). ORNL was a champion, too. The activity of radiation application represented by this keyword might be degraded in the U.S. around a year of 1993. For INIS comparison, it was of the order of JAERI > ORNL > BNL. The champion was JAERI. (3) Neutron; it was of the order of ORNL (3,934 papers) > ANL (2718) > BNL (1568). The champion was ORNL > For the case of INIS, it was JAERI > ORNL > BNL. The neutron study in JAERI was most advanced. III. Comparison by CPI. CPI shows that ORNL research activities were beginning to vary from time to time. Covering period from past (20) to past (10), ORNL activity indicated by CPI was high but was low at the present (1998-2002). The tendency coincided with that observed in INIS. (author)

  15. Abordaje multidisciplinar de un carcinoma sebáceo anaplásico palpebral en una paciente de 40 años / Multidisciplinary management of an anaplastic sebaceous carcinoma of the eyelid in a 40-year-old woman

    Scientific Electronic Library Online (English)

    R., Gallego-Pinazo; E., España Gregori; J., Aviñó Martínez; L., Salom Alonso; A., Tormo Micó; R., Villanueva Martí; M., Díaz-Llopis.

    2010-02-01

    Full Text Available Caso clínico: Mujer de 40 años remitida a nuestro servicio por persistencia durante meses de un cuadro de blefaritis anterior de aspecto indolente con aparición de un nódulo indurado en el párpado superior derecho filiado como chalazion refractario al tratamiento convencional, asociado a adenopatía [...] preauricular ipsilateral. La biopsia extemporánea se informó como carcinoma sebáceo. Procedimos a la exéresis completa de dicho párpado y a su reconstrucción con injerto de mucosa palatina y colgajo glabelar. Posteriormente se practicó un vaciamiento cervical radical por la presencia de adenopatías de aspecto necrótico en diversos territorios linfáticos. Se biopsió el párpado inferior que resultó positivo para infiltración carcinomatosa que se trató mediante braquiterapia. Discusión: La precocidad en el diagnóstico de los carcinomas sebáceos palpebrales es el principal factor pronóstico. La reconstrucción en casos de necesidad de exéresis completa del párpado es factible mediante un injerto de mucosa de paladar. En nuestro caso, el carácter anaplásico y la alta agresividad de la neoplasia han supuesto un reto terapéutico. Abstract in english Case report: A 40-year-old woman was referred to our department due to an apparent indolent anterior blepharitis with an indurated node in her right upper eyelid, which had persisted for months. It was believed to be a chalazion associated with an ipsilateral swollen pre-aurical lymph node, which ha [...] d not responded to conventional treatment. The extemporaneous biopsy was reported as sebaceous carcinoma. Complete exeresis was performed on that eyelid and it was reconstructed with a palate mucosa graft and a glabelar flap. A radical neck dissection was performed later, in order to remove the lymph nodes that appeared necrotic in several lymphatic areas. A biopsy was also performed on the lower eyelid, which was reported as positive for carcinomatous infiltration, and therefore it was treated with Curie-therapy. Discussion: The precocity in diagnosing sebaceous carcinomas of the eyelids is the main prognostic factor. The reconstruction in cases with need of complete eyelid exeresis is feasible by means of a palate mucosa graft. In our case, both the anaplastic character and the high aggressiveness of the neoplasm were a therapeutic challenge.

  16. CD56 might be a useful diagnostic marker of müllerian-derived tumors: report of an uterine tumor resembling ovarian sex cord tumor (UTROSCT) suggesting polyphenotypic origin and review of the literature

    OpenAIRE

    Özer, Hatice; Aker, Handan; Mutlu, Ahmet Emin; Yanık, Ali; Koç, Tülay; Keser, Hande

    2014-01-01

    AbstractWe present the clinicopathologic and immunophenotypic features of a case of uterine tumor resembling ovarian sex cord tumor. The patient age was 38 years and presented with discomfort in the lower abdomen, vaginal bleeding, and dysmenorrhea. Pelvic ultrasound and computed tomography of the lower abdomen revealed a semisolid mass extending to umbilicus. Bilateral adnexal tenderness was found. The patient underwent operation with an ovarian tumor as a preoperative diagnosis. In the intr...

  17. Coronary fistula resembling patent ductus arteriosus

    Directory of Open Access Journals (Sweden)

    Sgarbieri Ricardo Nilsson

    2003-01-01

    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.

  18. Does Anorexia Nervosa Resemble an Addiction?

    OpenAIRE

    Barbarich-Marsteller, Nicole C.; Foltin, Richard W; Walsh, B. Timothy

    2011-01-01

    Anorexia nervosa is a severe psychiatric disorder characterized by unrelenting self-starvation and life-threatening weight loss. The relentlessness with which individuals with anorexia nervosa pursue starvation and in some cases exercise despite the negative physical, emotional, and social consequences parallels features of addictive disorders. From a clinical perspective, individuals with anorexia nervosa behave similarly to individuals with substance abuse by narrowing their behavioral repe...

  19. Molecular genetic study of human malignant gliomas

    International Nuclear Information System (INIS)

    Loss of heterozygosity for loci on chromosome 10 were found in four of 9 (44%) informative cases of malignant gliomas. Deletions on RB1 locus were seen in six of 11 (54%) informative glioblastomas. LOH on chromosome 17p was found in eight of 16 (50%) malignant gliomas, including 2 cases of anaplastic oligodendroglioma. On the basis of the data presented here, it is possible to associate certain molecular abnormalities with malignant gliomas, LOH on chromosome 10, RB1 gene, and 17p. (Author)

  20. 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.; BRAENDSTRUP, O.

    1995-01-01

    mean survival time of 23.5 months and 26.2 months, respectively. No significant correlation between LI (or survival) and tumor size, cerebral localization, radiation, resection/biopsy, sex, age, or cytologic atypia was found. Conclusions. The use of Ki-67 and PCNA LI higher than 3% and 4%, respectively...

  1. MicroRNA 25, microRNA 145, and microRNA 210 as biomarkers for predicting the efficacy of maintenance treatment with pemetrexed in lung adenocarcinoma patients who are negative for epidermal growth factor receptor mutations or anaplastic lymphoma kinase translocations.

    Science.gov (United States)

    Shi, Sheng-Bin; Wang, Meng; Tian, Jing; Li, Rui; Chang, Chun-Xiao; Qi, Jie-Lin

    2016-04-01

    This study was conducted to evaluate microRNAs (miRNAs) as biomarkers for use in predicting the efficacy of maintenance therapy with pemetrexed in patients with stage IIIb or IV lung adenocarcinoma and who had already received first-line treatment with pemetrexed plus platinum. Patients who were negative for epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocations were assigned to a pemetrexed group and an observation group. Patients in the pemetrexed group (n = 76) received maintenance treatment with pemetrexed (500 mg/m(2), once every 21 days) plus best supportive care. Patients in the observation group (n = 72) agreed to receive only best supportive care until disease progression. Blood samples were collected from all patients in both groups before treatment and were used to detect expression levels of various miRNAs in serum by the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) method. The expression levels of miR-25, miR-145, and miR-210 were significantly different in the 2 groups of patients. Furthermore, the median progression-free survival (PFS) times for patients in the pemetrexed and observation groups were 4.5 and 2.9 months, respectively. The PFS times among patients in the pemetrexed group varied significantly and were related to patient expression levels of miR-25, miR-145, and miR-210, whereas patients in the observation group showed no differences in PFS time. Our data suggest miR-25, miR-145, and miR-210 as predictors for the efficacy of maintenance treatment with pemetrexed in lung adenocarcinoma patients who were negative for EGFR mutations or ALK translocations. PMID:26687391

  2. First step toward the "fingerprinting" of brain tumors based on synchrotron radiation X-ray fluorescence and multiple discriminant analysis.

    Science.gov (United States)

    Szczerbowska-Boruchowska, Magdalena; Lankosz, Marek; Adamek, Dariusz

    2011-12-01

    Synchrotron-radiation-based X-ray fluorescence was applied to the elemental microimaging of neoplastic tissues in cases of various types of brain tumors. The following cases were studied: glioblastoma multiforme, gemistocytic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, ganglioglioma, fibrillary astrocytoma, and atypical transitional meningioma. Apart from neoplastic tissue, the analysis included areas of tissue apparently without malignant infiltration. The masses per unit area of P, S, Cl, K, Ca, Fe, Cu, Zn, Br, and Rb were used to construct a diagnostic classifier for brain tumors using multiple discriminant analysis. It was found that S, Cl, Cu, Fe, K, Br, and Zn are the most significant elements in the general discrimination of tumor type. The highest similarity in elemental composition was between atypical transitional meningioma and fibrillary astrocytoma. The smallest differentiation was between glioblastoma multiforme and oligodendroglioma. The mean percentage of correct classifications, estimated according to the a posteriori probabilities procedure, was 99.9%, whereas the mean prediction ability of 87.6% was achieved for ten new cases excluded previously from the model construction. The results showed that multiple discriminant analysis based on elemental composition of tissue may be a potentially valuable method assisting differentiation and/or classification of brain tumors. PMID:21725853

  3. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    International Nuclear Information System (INIS)

    Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas

  4. Gliomas cerebrales de bajo grado en el adulto

    Scientific Electronic Library Online (English)

    Julio César, Suárez; S, Zunino; Juan Carlos, Viano; Enrique, Herrera; R, Theaux; A, Surur; G, Jarchum; M, Lavarda; B, Sonzini Astudillo; M, Arneodo.

    2008-03-01

    Full Text Available Objetivo. Bajo esta denominación se incluyen a los astrocitomas fibrilares y protoplasmáticos, a los oligodendrogliomas, y a los oligoastrocitomas o tumores mixtos, que corresponden a los grados II de la nueva clasificación de la OMS . Los astrocitomas de bajo grado representan el 15% de los gliomas [...] hemisféricos cerebrales en el adulto. Los oligodendrogliomas tienen una incidencia del 4% (2,4). Presentamos la experiencia de nuestro grupo de trabajo con este tipo de tumores entre enero de 1972 y diciembre de 2006. Material y método. Se analizaron las historias clínicas de 25 pacientes adultos que presentaron esta variedad de tumor, de los cuales 15 eran mujeres y 10 varones, que representan el 15,6% de los gliomas cerebrales en este grupo etario. Resultados. Quince eran astrocitomas fibrilares, ocho oligodendrogliomas y dos oligoastrocitomas. El principal estudio de imagen fue la resonancia nuclear magnética con espectroscopia. El tratamiento dependió de la ubicación y del volumen tumoral, siendo la cirugía y la radioterapia las modalidades terapéuticas mas empleadas. El tumor recidivó en 16 enfermos, con una media de 37 ± 21 meses después del diagnóstico, cuyas histopatologías mostraron ser: astrocitomas anaplásicos en 7 y glioblastomas multiformes en 9. Han fallecido 16 enfermos, 14 por el tumor cerebral, uno por cáncer de lengua y otro por embolia pulmonar producida a los 10 días de la cirugía, con una mediana de sobrevida de 44 meses (10 días a 120 meses). De los 9 pacientes que viven, 7 tienen oligodendrogliomas, 2 astrocitomas, y uno tiene un oligoastrocitoma; 7 requieren medicación antiepilética, ninguno tiene secuelas neurológicas, con una mediana de sobrevida de 36 meses (6 a 120 meses); dos han tenido recidiva, correspondientes a un oligodendroglioma y a un oligoastrocitoma, a los 22 y 60 meses respectivamente del diagnóstico, en los dos casos el tumor pasó de ser un grado II a grado III. Conclusión. La frecuencia relativa del 15,6% de todos los gliomas del adulto en nuestra serie coincide con cifras internacionales. Edad menor de 40 años, convulsiones como síntoma de presentación y extensión de la resección quirúrgica son factores pronósticos favorables de importancia, junto con un bajo índice del Ki 67 en los astrocitomas y la presencia de alteraciones en los cromosomas 1p y 19q en los oligodendrogliomas. La IRM en sus variedades estándar, con gadolinio, espectroscopia y funcional es el estudio más útil durante las diferentes alternativas del proceso diagnóstico y los estudios inmunohistoquímicos juntos con los de biología molecular son los mas importantes para el pronóstico de estos tumores. Abstract in english Objective. Gliomas reviewed in this article are grade II tumors according to the World Health Organization (WHO), that include: fibrillary and protoplasmic astrocytomas, oligodendrogliomas and oligoastrocytomas or mix tumors (1,2,3).Low grade astrocytomas constitute 15% of brain tumors in adults, wh [...] ile low grade oligodendrogliomas represent 4% (2,4). We present our experience with this type of tumor operated on between January 1972 and December 2006. Material and Method. The clinical reports of 25 patients with this type of tumor were analyzed, 15 women and 10 men, which represent 15,6% of hemispheric brain gliomas in adults in our series. Results. Fifteen were fibrillary astrocytomas, 8 oligodendrogliomas and 2 oligoastrocytomas. Treatment depended on tumor localization and size. Surgery and radiotherapy were the therapeutic modalities most frequently used. Tumor recurrence was observed in 16 patients, with a media of 37+/- 21 months after diagnosis: 7 anaplastic astrocytomas and 9 glioblastomas multiforme. In this series, 16 patients died with a median of 44 months (10 days to 120 months) after diagnosis. Cause of death were: tumor itself, in 14 cases, tongue cancer in 1, and pulmonary embolism after surgery in another. From the 9 surviving patients, 6 have oligodendrogliomas, 2 astrocytomas and 1 an oligoastrocytoma. Seven pa

  5. Intraoperative direct electrical stimulations of central nervous system during surgery of gliomas near eloquent areas

    Directory of Open Access Journals (Sweden)

    WANG Wei-min

    2012-12-01

    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?

  6. Anaplastic Large Cell Lymphoma Associated With Breast Implants

    OpenAIRE

    Ravi-Kumar, Shalini; Sanaei, Omid; Vasef, Mohammad; Rabinowitz, Ian; Fekrazad, Mohammad Houman

    2012-01-01

    A forty two years old woman with a history of bilateral breast augmentation for cosmetic reasons was presented for poor healing of the surgical site. Tissue and periprosthetic fluid were removed from the wound site revealing an atypical lymphoid infiltrate. Subsequently the patient developed axillary lymph adenopathy. Excisional biopsy was performed. Flow cytometry was non-diagnostic. She continued to heal poorly and eventually had removal of implant during a simple mastectomy. A nodular area...

  7. Post transplant anaplastic large T-cell lymphoma

    International Nuclear Information System (INIS)

    Post transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoid proliferation that ranges from polyclonal hyperplasia to monoclonal malignant lymphoma. We report a 13-year-old boy who was diagnosed with PTLD in February 2007 after 3 1/2 years of deceased renal transplantation. We treated him with an adapted ACVBP (doxorubicin, cyclo-phosphamide, vincristine, bleomycin and prednisone) regimen. He responded well to the chemotherapy without deterioration of graft function. (author)

  8. Selective activity of BS-RNase against Anaplastic Thyroid Cancer.

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Josef

    2001-01-01

    Ro?. 21, ?. 2 (2001), s. 1035-1042. ISSN 0250-7005 R&D Projects: GA ?R GA523/01/0114; GA AV ?R KSK5052113 Keywords : thyroid cancer * BS-RNase * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.416, year: 2001

  9. Anaplastic meningioma: case report Meningioma anaplásico: relato de caso

    OpenAIRE

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

    2001-01-01

    Intracranial meningiomas continue to challenge our best clinical efforts to eliminate them once discovered and deemed appropriate for treatment. Malignant meningiomas constitute 10% to 15% of all meningiomas and limited information exists regarding adjuvant treatment. The external whole brain irradiation is recommended. Traditional chemotherapy has proven ineffective; thus, new chemotherapeutic agents and new methods of delivery should be developed. Immunotherapy may be considered for patient...

  10. Irradiation of Pediatric High-Grade Spinal Cord Tumors

    International Nuclear Information System (INIS)

    Purpose: To report the outcome using radiation therapy (RT) for pediatric patients with high-grade spinal cord tumors. Methods and Materials: A retrospective chart review was conducted that included 17 children with high-grade spinal cord tumors treated with RT at St. Jude Children's Research Hospital between 1981 and 2007. Three patients had gross total resection, 11 had subtotal resection, and 3 underwent biopsy. The tumor diagnosis was glioblastoma multiforme (n = 7), anaplastic astrocytoma (n = 8), or anaplastic oligodendroglioma (n = 2). Seven patients received craniospinal irradiation (34.2-48.6 Gy). The median dose to the primary site was 52.2 Gy (range, 38-66 Gy). Results: The median progression-free and overall survivals were 10.8 and 13.8 months, respectively. Local tumor progression at 12 months (79% vs. 30%, p = 0.02) and median survival (13.1 vs. 27.2 months, p = 0.09) were worse for patients with glioblastoma multiforme compared with anaplastic astrocytoma or oligodendroglioma. The median overall survival was shorter for patients when failure included neuraxis dissemination (n = 8) compared with local failure alone (n = 5), 9.6 vs. 13.8 months, p = 0.08. Three long-term survivors with World Health Organization Grade III tumors were alive with follow-up, ranging from 88-239 months. Conclusions: High-grade spinal cord primary tumors in children have a poor prognosis. The propensity for neuraxis metastases as a component of progression after RT suggests the need for more aggressive therapy.

  11. Laing distal myopathy pathologically resembling inclusion body myositis

    OpenAIRE

    Roda, Ricardo H; Schindler, Alice B.; Blackstone, Craig; Mammen, Andrew L.; Corse, Andrea M.; Lloyd, Thomas E

    2014-01-01

    Mutations in MYH7 cause autosomal dominant Laing distal myopathy. We present a family with a previously reported deletion (c.5186_5188delAGA, p.K1729del). Muscle pathology in one family member was characterized by an inflammatory myopathy with rimmed vacuoles, increased MHC Class I expression, and perivascular and endomysial muscle inflammation comprising CD3+, CD4+, CD8+, and CD68+ inflammatory cells. Interestingly, this biopsy specimen contained TDP-43, p62, and SMI-31-positive protein aggr...

  12. Mouse Transcobalamin Has Features Resembling both Human Transcobalamin and Haptocorrin

    DEFF Research Database (Denmark)

    Hygum, Katrine; Lildballe, Dorte L

    2011-01-01

    In humans, the cobalamin (Cbl) -binding protein transcobalamin (TC) transports Cbl from the intestine and into all the cells of the body, whereas the glycoprotein haptocorrin (HC), which is present in both blood and exocrine secretions, is able to bind also corrinoids other than Cbl. The aim of this study is to explore the expression of the Cbl-binding protein HC as well as TC in mice. BLAST analysis showed no homologous gene coding for HC in mice. Submaxillary glands and serum displayed one protein capable of binding Cbl. This Cbl-binding protein was purified from 300 submaxillary glands by affinity chromatography. Subsequent sequencing identified the protein as TC. Further characterization in terms of glycosylation status and binding specificity to the Cbl-analogue cobinamide revealed that mouse TC does not bind Concanavalin A sepharose (like human TC), but is capable of binding cobinamide (like human HC). Antibodies raised against mouse TC identified the protein in secretory cells of the submaxillary glandand in the ducts of the mammary gland, i.e. at locations where HC is also found in humans. Analysis of the TC-mRNA level showed a high TC transcript level in these glands and also in the kidney. By precipitation to insolubilised antibodies against mouse TC, we also showed that >97% of the Cbl-binding capacity and >98% of the Cbl were precipitated in serum. This indicates that TC is the only Cbl-binding protein in the mouse circulation. Our data show that TC but not HC is present in the mouse. Mouse TC is observed in tissues where humans express TC and/or HC. Mouse TC has features in common with both human TC and HC. Our results suggest that the Cbl-binding proteins present in the circulation and exocrine glands may vary amongst species.

  13. HD 98618: A Star Closely Resembling our Sun

    CERN Document Server

    Melendez, J; Robles, J A; Dodds-Eden, Katie; Melendez, Jorge; Observatory, RSAA/Mt Stromlo

    2006-01-01

    Despite the observational effort carried out in the last few decades, no perfect solar twin has been found to date. An important milestone was achieved a decade ago by Porto de Mello & da Silva, who showed that 18 Sco is almost a solar twin. In the present work, we use extremely high resolution (R = 10^5) high S/N Keck HIRES spectra to carry out a differential analysis of sixteen solar twin candidates. We show that HD 98618 is the second closest solar twin, and that the fundamental parameters of both HD 98618 and 18 Sco are very similar (within a few percent) to the host star of our solar system, including the likelihood of hosting a terrestrial planet within their habitable zone. We suggest that these stars should be given top priority in exoplanet and SETI surveys.

  14. A sacral lesion resembling osteochondrosis in the German Shepherd dog

    International Nuclear Information System (INIS)

    More than 30% (21 of 65) of German Shepherd dogs with clinical signs of cauda equina compression had radiographic and pathologic abnormalities compatible with osteochondrosis of the sacral endplate. Most of these dogs had a defect in the dorsal part of the sacral endplate and a detached bone fragment in the vertebral canal. Similar lesions were also found in growing and young adult dogs without clinical signs. The dogs with clinical signs of cauda equina compression also had severe degenerative disc disease with protrusion of the lumbosacral disc and compression of the cauda equina, suggesting that the signs of cauda equina compression more likely were related to the secondary degenerative changes (disc protrusions) rather than the primary disease. Clinically normal German Shepherds with sacral osteochondrosis usually were younger than 18 months, the dogs with cauda equina compression and sacral osteochondrosis older than 18 months (mean age 4.8 years). On the average, these dogs were two years younger as compared to dogs with cauda equina compression without sacral osteochondrosis. Male dogs are more often affected than females (5:1). There is a breed predisposition: in dogs other than German Shepherds, osteochondrosis of the sacral endplate seems to be extremely rare

  15. Reason, Education, and Liberalism: Family Resemblance within an Overlapping Consensus.

    Science.gov (United States)

    Halliday, John

    2001-01-01

    Discusses recent debates concerning the nature of liberalism and its central feature of reason. Examines ideas from Jonathan, Hirst, Rawls, Gadamer, Wittgenstein, Taylor, and Ackerman. Suggests that the search for transcendental conceptions of justice and reason must be abandoned in favor of a more fluid curriculum structure. (Contains 18…

  16. A Case of Classic Polyarteritis Nodosa Resembling Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Ali BAKAN

    2014-05-01

    Full Text Available Classic polyarteritis nodosa (cPAN is a systemic necrotizing vasculitis of medium-sized muscular arteries. Glomerular involvement is not expected in the course of cPAN. Herein, we describe a case of cPAN with glomerular and multiple arterial involvement. The patient presented with severe abdominal pain and high fever. Urine analysis showed hematuria and 1g/day proteinuria. Kidney biopsy showed fibrinoid necrosis of arterioles and IgG, IgA and C1q positivity raising a suspicion of lupus nephritis. However digital subtraction angiography revealed typical multiple micro-aneurysms in the coronary, mesenteric, splenic and renal arteries establishing the diagnosis of cPAN. Kidney biopsy in cPAN may reveal non-specific immune-deposits and fibrinoid necrosis of arterioles mimicking lupus nephritis and microscopic polyangiitis. c-PAN should be carefully differentiated from these entities.

  17. Neurotized Congenital Melanocytic Nevus Resembling a Pigmented Neurofibroma

    OpenAIRE

    Singh, Nidhi; Chandrashekar, Laxmisha; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

    2015-01-01

    Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma.

  18. Neurotized congenital melanocytic nevus resembling a pigmented neurofibroma.

    Science.gov (United States)

    Singh, Nidhi; Chandrashekar, Laxmisha; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

    2015-01-01

    Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma. PMID:25657396

  19. Neurotized congenital melanocytic nevus resembling a pigmented neurofibroma

    Directory of Open Access Journals (Sweden)

    Nidhi Singh

    2015-01-01

    Full Text Available Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma.

  20. CT appearance of congenital defect resembling the Hangman's fracture

    International Nuclear Information System (INIS)

    Purpose. Congenital defects of C2 are rare and can be confused with Hangman's fractures. CT has been advocated as aiding in differentiation between an acute fracture and congenital defects. Methods. We present a case of a 2-year-old recent accident victim, who was erroneously diagnosed by plain film and CT as having a Hangman's fracture. Results. The CT demonstrated an atypical appearance of a congenital defect. Conclusion. This case shows that the radiographic differentiation between a Hangman's fracture and a congenital defect is more difficult than previously described. (orig.)

  1. Laing distal myopathy pathologically resembling inclusion body myositis.

    Science.gov (United States)

    Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig; Mammen, Andrew L; Corse, Andrea M; Lloyd, Thomas E

    2014-12-01

    Mutations in MYH7 cause autosomal dominant Laing distal myopathy. We present a family with a previously reported deletion (c.5186_5188delAGA, p.K1729del). Muscle pathology in one family member was characterized by an inflammatory myopathy with rimmed vacuoles, increased MHC Class I expression, and perivascular and endomysial muscle inflammation comprising CD3(+), CD4(+), CD8(+), and CD68(+) inflammatory cells. Interestingly, this biopsy specimen contained TDP-43, p62, and SMI-31-positive protein aggregates typical of inclusion body myositis. These findings should alert physicians to the possibility that patients with MYH7 mutations may have muscle biopsies showing pathologic findings similar to inclusion body myositis. PMID:25574480

  2. Uterine tumour resembling an ovarian sex cord tumour

    OpenAIRE

    Sutak, J; Lazic, D.; Cullimore, J E

    2005-01-01

    Endometrial stromal sarcomas account for 0.25% of all uterine malignancies. These tumours were originally divided into low grade and high grade stromal sarcomas, but the recent World Health Organisation classification (2003) recognises low grade stromal sarcoma and undifferentiated endometrial sarcoma. Low grade sarcomas may exhibit other forms of differentiation, including smooth muscle and sex cord differentiation. In the latter form, the tumour contains epithelial-like or sex cord-like ele...

  3. Central retinal artery occlusion resembling Purtscher-like retinopathy

    Directory of Open Access Journals (Sweden)

    Etomi T

    2011-08-01

    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

  4. Hummingbirds at artificial flowers made to resemble ornithophiles versus melittophiles

    Directory of Open Access Journals (Sweden)

    Wyndee A. Guzman

    2012-06-01

    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.

  5. Antitumor activity of 9-deazapurines resembling to myoseverin.

    Czech Academy of Sciences Publication Activity Database

    Otmar, Miroslav; Kre?merová, Marcela

    2012-01-01

    Ro?. 156, Suppl. 1 (2012), S69-S69. ISSN 1213-8118. [International Congress Natural Anticancer Drugs. 30.06.2012-04.07.2012, Olomouc] R&D Projects: GA MPO FR-TI4/625 Institutional support: RVO:61388963 Keywords : antitumor * 9-deazapurines * myoseverin analog Subject RIV: CC - Organic Chemistry

  6. MRI reveals reversible lesions resembling posterior reversible encephalopathy in porphyria

    Energy Technology Data Exchange (ETDEWEB)

    Celik, M. [Huesrev Gerede c, 128/4 Tesvikiye, 80690 Istanbul (Turkey); Department of Neurology, Sisli Etfal Education and Research Hospital, Sisli Etfal S., Sisli, Istanbul (Turkey); Forta, H.; Babacan, G. [Department of Neurology, Sisli Etfal Education and Research Hospital, Sisli Etfal S., Sisli, Istanbul (Turkey); Dalkilic, Tuerker [Department of Neurosurgery, Sisli Etfal Education and Research Hospital, Sisli Etfal S., Sisli, Istanbul (Turkey)

    2002-10-01

    We report a 20-year-old woman who had an attack of acute intermittent porphyria with seizures, hallucinations, autonomic and somatic neuropathy. T2-weighted MRI revealed multiple lesions which were no longer visible 3 months later. We suggest a similar mechanism to posterior reversible encephalopathy underlying cerebral symptoms in porphyria. (orig.)

  7. Congenital bladder diverticulum with benign bladder wall lesion resembling rhabdomyosarcoma

    OpenAIRE

    David K-C Mak; Ruth Wragg; Eva Macharia; Karan Parashar

    2010-01-01

    Congenital bladder diverticula in children are uncommon and rarely present with bladder outlet obstruction. We present a case highlighting an interesting association between a congenital bladder diverticulum and a benign inflammatory bladder wall lesion mimicking a rhabdomyosarcoma. Open surgery was required as different imaging modalities and cystoscopy were insufficient to exclude a malignant process.

  8. Mucormycotic hepatic lesions resembling bacillary hemoglobinuria infarcts in irradiated calves

    International Nuclear Information System (INIS)

    To produce hematopoietic chimeras, 3 young, healthy calves were exposed to whole-body irradiation and, 6 days after irradiation, were injected with a bone-marrow suspension prepared from an unrelated, normal donor calf. Antibiotics were administered daily to control bacterial infection. One calf died 8 days postirradiation (PI), another died 10 days PI, and the third calf was killed in extremis 11 days PI. In addition to lesions of acute radiation injury, one to several spherical, firm, dry, reddish-black nodules were found in the liver of each calf. Hepatic changes and blood-stained urine were suggestive of bacillary hemoglobinuria. Fungi, identified by their morphologic features as members of the class Phycomycetes, were widely distributed in the tissues and lesions

  9. MYCOPLASMA GENITALIUM PROTEIN RESEMBLING THE MYCOPLASMA PNEUMONIAE ATTACHMENT PROTEIN

    Science.gov (United States)

    In previous studies with hyperimmune rabbit sera and monoclonal antibodies against P1 protein of M. pneumoniae, we obtained evidence of a shared antigenic determinant with a single protein of M. genitalium. ecause of biological and morphological similarities between these two hum...

  10. Radiopharmaceutical regulation world wide - the resemblances and the differences

    OpenAIRE

    Reza Dowlatabadi Bazaz; "Davood Beiki; Ali Khalaj

    2005-01-01

    A Radiopharmaceutical is a radioactive compound used for the diagnosis and treatment of human diseases. Radiopharmaceuticals are among the most highly regulated materials administered to patients because they are controlled both as drugs and as radioactive substances. The use of radiopharmaceuticals for any purpose is governed by regulatory agencies in different countries all over the world. Application of radiopharmaceuticals in humans was almost unregulated until the late 1950s. Since then ...

  11. Leukemia cutis resembling a flare-up of psoriasis

    OpenAIRE

    Ferreira, M.; Caetano, M.; Amorim, I; M. Selores

    2006-01-01

    Abstract Leukemia cutis represents a skin infiltration by leukemic cells. Clinically it can mimic a wide variety of dermatoses. We describe the case of a 64-year-old man with psoriasis who presented with a 4-day history of erythematous, slightly scaly, asymptomatic plaques distributed on the trunk and upper-extremities, and associated asthenia, myalgias, and anorexia. A skin biopsy revealed a leukemic infiltrate. Studies of peripheral blood and bone marrow provided a diagnosis of acute mon...

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

    International Nuclear Information System (INIS)

    We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas. A total of 133 patients with anaplastic astrocytoma (AA, n = 56), anaplastic oligodendroglioma (AO, n = 67), or anaplastic oligoastrocytoma (AOA, n = 10) were included in the study. These patients were treated with either radiotherapy alone or radiotherapy followed by PCV chemotherapy after surgery. Five prognostic factors, including histological subsets, age, performance status, extent of resection, and treatment modality were incorporated into the RPA. The final nodes of RPA were grouped according to their survival times, and the Kaplan-Meier graphs are presented as the final set of prognostic groups. Four risk groups were defined based on the clinical prognostic factors excluding age, and split variables were all incorporated into the RPA. Survival analysis showed significant differences in mean survival between the different groups: 163.4 months (95% CI: 144.9-182.0), 109.5 months (86.7-132.4), 66.6 months (50.8-82.4), and 27.7 months (16.3-39.0), respectively, from the lowest to the highest risk group (p = 0.00). The present study shows that RPA grouping with clinical prognostic factors can successfully predict the survival of patients with WHO grade III glioma

  13. Isla de Pascua e Isla Grande de Tierra del Fuego: semejanzas y diferencias en los vínculos de las compañías explotadoras y los "indígenas" / Easter Island and Isla Grande de Tierra del Fuego: resemblances and differences in the links of the exploitative societies and the "indigenous people"

    Scientific Electronic Library Online (English)

    ROLF, FOERSTER.

    Full Text Available Este artículo sostiene que las diferencias y semejanzas acaecidas a Rapanui y Selk’nam en sus relaciones con las "compañías o sociedades explotadoras" y el Estado de Chile, en el contexto de los fujos de personas y de capitales en los procesos de colonización en el contexto del imperialismo, permite [...] n una mejor comprensión de los factores detonantes de sus destinos como pueblos. La hipótesis central es que la doble convergencia -de colonos y de capital- en Tierra del Fuego hace superfuo a los Selk’nam (de allí la discrepancia y la controversia sobre su destino), mientras que en Pascua sólo el capital fuyó con lo cual la población autóctona debió ser transformada en funcional, en "colonos" y en "mano de obra". Se explora entonces las respuestas de las sociedades originarias a esta realidad. Abstract in english This article supports the idea that the differences and resemblances between Rapanui and Selk’nam in its relations with the "companies or exploitative societies" and the State of Chile, in the context of the flow of persons and of capitals in the colonization process in the context of imperialism, a [...] llow a better comprehension of the detonator factors of its destinations as peoples. The central hypothesis is that the double convergence -of colonists and capital- in Tierra del Fuego does superfuously to the Selk’nam (there is the discrepancy and the controversy on its destination), while in Easter Island only the capital few with which the indigenous population must be transformed in functional, in "colonists" and in "manpower". We explore then the answers of the native societies to this reality.

  14. Isla de Pascua e Isla Grande de Tierra del Fuego: semejanzas y diferencias en los vínculos de las compañías explotadoras y los "indígenas" Easter Island and Isla Grande de Tierra del Fuego: resemblances and differences in the links of the exploitative societies and the "indigenous people"

    Directory of Open Access Journals (Sweden)

    ROLF FOERSTER

    2012-01-01

    Full Text Available Este artículo sostiene que las diferencias y semejanzas acaecidas a Rapanui y Selk’nam en sus relaciones con las "compañías o sociedades explotadoras" y el Estado de Chile, en el contexto de los fujos de personas y de capitales en los procesos de colonización en el contexto del imperialismo, permiten una mejor comprensión de los factores detonantes de sus destinos como pueblos. La hipótesis central es que la doble convergencia -de colonos y de capital- en Tierra del Fuego hace superfuo a los Selk’nam (de allí la discrepancia y la controversia sobre su destino, mientras que en Pascua sólo el capital fuyó con lo cual la población autóctona debió ser transformada en funcional, en "colonos" y en "mano de obra". Se explora entonces las respuestas de las sociedades originarias a esta realidad.This article supports the idea that the differences and resemblances between Rapanui and Selk’nam in its relations with the "companies or exploitative societies" and the State of Chile, in the context of the flow of persons and of capitals in the colonization process in the context of imperialism, allow a better comprehension of the detonator factors of its destinations as peoples. The central hypothesis is that the double convergence -of colonists and capital- in Tierra del Fuego does superfuously to the Selk’nam (there is the discrepancy and the controversy on its destination, while in Easter Island only the capital few with which the indigenous population must be transformed in functional, in "colonists" and in "manpower". We explore then the answers of the native societies to this reality.

  15. EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines

    DEFF Research Database (Denmark)

    Bax, Dorine A; Gaspar, Nathalie; Little, Suzanne E; Marshall, Lynley; Perryman, Lara; Regairaz, Marie; Viana-Pereira, Marta; Vuononvirta, Raisa; Sharp, Swee Y; Reis-Filho, Jorge S; Stávale, João N; Al-Sarraj, Safa; Reis, Rui M; Vassal, Gilles; Pearson, Andrew D J; Hargrave, Darren; Ellison, David W; Workman, Paul; Jones, Chris

    2009-01-01

    data are lacking. We have sought to clarify the role of EGFR in pediatric high-grade glioma (HGG). EXPERIMENTAL DESIGN: We retrospectively studied a total of 90 archival pediatric HGG specimens for EGFR protein overexpression, gene amplification, and mutation and assessed the in vitro sensitivity of......, including two anaplastic oligodendrogliomas and a gliosarcoma overexpressing EGFRvIII in the absence of gene amplification and coexpressing platelet-derived growth factor receptor alpha. Pediatric glioblastoma cells transduced with wild-type or deletion mutant EGFRvIII were not rendered more sensitive to...... efficacy in this model. CONCLUSIONS: These data identify an elevated frequency of EGFR gene amplification and EGFRvIII mutation in pediatric HGG than previously recognized and show the likely necessity of targeting multiple genetic alterations in the tumors of these children....

  16. Radiation-induced brain injury: retrospective analysis of twelve pathologically proven cases

    International Nuclear Information System (INIS)

    This study was designed to determine the influencing factors and clinical course of pathologically proven cases of radiation-induced brain injury (RIBI). The pathologic records of twelve patients were reviewed; these patients underwent surgery following radiotherapy due to disease progression found by follow-up imaging. However, they were finally diagnosed with RIBI. All patients had been treated with 3-dimensional conventional fractionated radiotherapy and/or radiosurgery for primary or metastatic brain tumors with or without chemotherapy. The histological distribution was as follows: two falx meningioma, six glioblastoma multiform (GBM), two anaplastic oligodendroglioma, one low grade oligodendroglioma, and one small cell lung cancer with brain metastasis. Radiation necrosis was noted in eight patients and the remaining four were diagnosed with radiation change. Gender (p 0.061) and biologically equivalent dose (BED)3 (p = 0.084) were the only marginally influencing factors of radiation necrosis. Median time to RIBI was 7.3 months (range, 0.5 to 61 months). Three prolonged survivors with GBM were observed. In the subgroup analysis of high grade gliomas, RIBI that developed <6 months after radiotherapy was associated with inferior overall survival rates compared to cases of RIBI that occurred ?6 months (p = 0.085). Our study demonstrated that RIBI could occur in early periods after conventional fractionated brain radiotherapy within normal tolerable dose ranges. Studies with a larger number of patients are required to identify the strong influencing factors for RIBI development

  17. Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

    Science.gov (United States)

    Siegal, Tali

    2016-01-01

    Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated. PMID:26508407

  18. Prognostic value of volume-based measurements on {sup 11}C-methionine PET in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kentaro; Manabe, Osamu; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Hirata, Kenji [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Yamaguchi, Shigeru; Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University, Department of Neurosurgery, Graduate School of Medicine, Sapporo (Japan); Hattori, Naoya [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan); Tanaka, Shinya [Hokkaido University, Department of Cancer Pathology, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2015-04-08

    {sup 11}C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor. (orig.)

  19. Induction of CD8+ T-Cell Responses Against Novel Glioma–Associated Antigen Peptides and Clinical Activity by Vaccinations With ?-Type 1 Polarized Dendritic Cells and Polyinosinic-Polycytidylic Acid Stabilized by Lysine and Carboxymethylcellulose in Patients With Recurrent Malignant Glioma

    Science.gov (United States)

    Okada, Hideho; Kalinski, Pawel; Ueda, Ryo; Hoji, Aki; Kohanbash, Gary; Donegan, Teresa E.; Mintz, Arlan H.; Engh, Johnathan A.; Bartlett, David L.; Brown, Charles K.; Zeh, Herbert; Holtzman, Matthew P.; Reinhart, Todd A.; Whiteside, Theresa L.; Butterfield, Lisa H.; Hamilton, Ronald L.; Potter, Douglas M.; Pollack, Ian F.; Salazar, Andres M.; Lieberman, Frank S.

    2011-01-01

    Purpose A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with ?-type 1 polarized dendritic cells (?DC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2+ patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-?2, YKL-40, and gp100. Patients and Methods Twenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two ?DC1 dose levels (1 × or 3 × 107/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 ?g/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays. Results The regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-? and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by ?DC1 positively correlated with time to progression. Conclusion These data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted ?DC1-based vaccines. PMID:21149657

  20. Intensity-modulated radiotherapy in high-grade gliomas: Clinical and dosimetric results

    International Nuclear Information System (INIS)

    Purpose: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. Methods and Materials: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. Results: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. Conclusions: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy

  1. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma.

    Science.gov (United States)

    Crescenzo, Ramona; Abate, Francesco; Lasorsa, Elena; Tabbo', Fabrizio; Gaudiano, Marcello; Chiesa, Nicoletta; Di Giacomo, Filomena; Spaccarotella, Elisa; Barbarossa, Luigi; Ercole, Elisabetta; Todaro, Maria; Boi, Michela; Acquaviva, Andrea; Ficarra, Elisa; Novero, Domenico; Rinaldi, Andrea; Tousseyn, Thomas; Rosenwald, Andreas; Kenner, Lukas; Cerroni, Lorenzo; Tzankov, Alexander; Ponzoni, Maurilio; Paulli, Marco; Weisenburger, Dennis; Chan, Wing C; Iqbal, Javeed; Piris, Miguel A; Zamo', Alberto; Ciardullo, Carmela; Rossi, Davide; Gaidano, Gianluca; Pileri, Stefano; Tiacci, Enrico; Falini, Brunangelo; Shultz, Leonard D; Mevellec, Laurence; Vialard, Jorge E; Piva, Roberto; Bertoni, Francesco; Rabadan, Raul; Inghirami, Giorgio

    2015-04-13

    A systematic characterization of the genetic alterations driving ALCLs has not been performed. By integrating massive sequencing strategies, we provide a comprehensive characterization of driver genetic alterations (somatic point mutations, copy number alterations, and gene fusions) in ALK(-) ALCLs. We identified activating mutations of JAK1 and/or STAT3 genes in ?20% of 88 [corrected] ALK(-) ALCLs and demonstrated that 38% of systemic ALK(-) ALCLs displayed double lesions. Recurrent chimeras combining a transcription factor (NFkB2 or NCOR2) with a tyrosine kinase (ROS1 or TYK2) were also discovered in WT JAK1/STAT3 ALK(-) ALCL. All these aberrations lead to the constitutive activation of the JAK/STAT3 pathway, which was proved oncogenic. Consistently, JAK/STAT3 pathway inhibition impaired cell growth in vitro and in vivo. PMID:25873174

  2. The effect of combined action of Taxol and ionizing radiation on thyroid anaplastic cancer cells

    International Nuclear Information System (INIS)

    We studied the effects of Taxol, gamma-irradiation, and their combination on apoptotic processes in KTC-2 and ARO cell lines. The combined effect of radiation and Taxol on apoptotic processes was significantly higher that effects of single agents. The combination of Taxol in apoptotic concentrations and low doses of gamma-radiation is a promising pharmacological strategy for further preclinical trials

  3. The enhancement of cytotoxic action of Taxol on thyroid anaplastic cancer by ?-irradiation

    International Nuclear Information System (INIS)

    The effect of Taxol, ?-irradiation, and their combination on the survival of undifferentiated thyroid cancer cells and the growth of xenograft tumors derived from these cells are studied. The effect of ?-irradiation on the cancer cells survival is not very significant, and most efficient turned out low (1-2 Gy) doses of ionizing radiation. In the in vivo experiments, irradiation also did not stop the growth of tumors - we observed the retardation of their growth only. Taxol occurred much more effective, and the combined action of radiation and the drug caused the decrease of tumor volume to 0-0.3% of control.

  4. Extreme neutrophil granulocytosis in a patient with anaplastic large cell lymphoma of T-cell lineage

    DEFF Research Database (Denmark)

    Engsig, Frederik Neess; Møller, Michael Boe; Hasselbalch, Hans K; Mahdi, Bassam; Obel, Niels

    2007-01-01

    We describe a 47-year-old male admitted with fever and extreme neutrophil granulocytosis (up to 80 x 10(9)/L). All microbiology tests and test for autoimmune disease were negative. CT scan showed pulmonary infiltrates bilaterally, mediastinal lymphadenopathy and splenomegaly. Conventional pathological examination of bone marrow and lymph node biopsies did not demonstrate malignant cells and inflammatory disease was suspected. The patient died of multiorgan failure 23 days after admission. Autops...

  5. Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas

    DEFF Research Database (Denmark)

    Berntsson, Shala Ghaderi; Wibom, Carl; Sjöström, Sara; Henriksson, Roger; Brännström, Thomas; Broholm, Helle; Johansson, Christoffer; Fleming, Sarah J; McKinney, Patricia A; Bethke, Lara; Houlston, Richard; Smits, Anja; Andersson, Ulrika; Melin, Beatrice S

    2011-01-01

    The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P <0.05) were taken forward for confirmation in a second dataset ...

  6. Protective effect of Paclitaxel against gamma-radiation in anaplastic thyroid carcinoma cells

    International Nuclear Information System (INIS)

    The aim of the paper was to study the biochemical effects of Paclitaxel (Ptx), ?-irradiation (IR) and their combination in undifferential thyroid cancer cells (ATC). There was a clear antagonism between Ptx and IP relative to cell cycle regulators. The net effect of these events during the first 48 H of cells incubation can be considered as antiapoptotic -Ptx attenuated cytotoxic effect of IR

  7. Transformación anaplásica tardía de bocio multinodular Late anaplastic transformation Of multinodular goitre

    Directory of Open Access Journals (Sweden)

    Lidia Martínez Ramos

    2012-01-01

    Full Text Available Introducción: el Cáncer tiroideo se caracteriza por su baja incidencia, comportamiento maligno infrecuente y baja mortalidad. La mayoría de ellos procede de bocios multinodulares de larga duración por lo que es muy importante tener en cuenta factores que constituyen riesgos potenciales como: tiempo de establecimiento de la enfermedad, tamaño, así como las características particulares personales y la evolución de la entidad en cada caso. Si tenemos en cuenta el gran avance tecnológico que constituye la Biopsia Aspirativa con Aguja Fina (BAAF, que nos permite no solamente evitar su transformación neoplásica maligna, sino que también podemos prolongar la vida con la calidad que humanamente se requiere que es en definitiva la meta principal de la Salud Pública Cubana. Objetivo: destacar la importancia del adecuado seguimiento evolutivo del Bocio multinodular como elemento significativo en la prevención de su transformación maligna. Presentación del caso: Paciente femenina de 80 años de edad con aumento de volumen de la región anterior del cuello y antecedentes patológicos personales de Bocio Multinodular (BMN con tratamiento inconstante e irregular de años de evolución, quien no solamente pudo haber mejorado la calidad de su vida sino que no la hubiera truncado, considerando las condiciones atenuantes en la forma de presentación que tuvo su caso. Al examen físico: Aumento de la región anterior del cuello, palpándose masa de superficie irregular, consistencia firme, dolorosa, de aproximadamente 6x5 cm que había aumentado considerablemente en los últimos meses sin fecha precisada. La paciente fue ingresada por el gran agobio respiratorio y la toma del estado general, pudiéndose realizar únicamente la Biopsia Aspirativa con Aguja Fina (BAAF. Desde su ingreso presenta evolución tórpida con incremento del compromiso respiratorio requiriendo la práctica de la traqueotomía que sólo ayuda como medida de soporte al estadio terminal de esta enfermedad neoplásica maligna. (Carcinoma Anaplásico del Tiroides. A pesar de ello la paciente fallece y los familiares autorizan la necropsia. Conclusiones: los BMN deben tener seguimiento evolutivo que permita precisar una tiroidectomía a tiempo como prevención en enfermedades benignas del Tiroides, por los cambios malignos que pueden producirse cuando la glándula es irradiada. La tiroidectomía a tiempo permite evitar no solamente la transformación maligna que puede producirse, sino también previene las metástasis que ocurren en los Carcinoma Anaplásicos.Introduction: the thyroid carcinoma is characterized by low incidence, low malignant behaviour as well as low mortality. The most of they are developed from multinodular goitres of long duration so is important to be into account the risk factors such as: time of the establishment of the disease, size and the particular and personal characterists and the evolution of the each case. If we take into account the great technological advance of the BAAF from its performance in the past century to be united to the National Health System of our country ,we have to say that the multinodular goitres in any group of age are easily manageable and accessible which may us to avoid the malignant transformation besides we can do that the life continues with the quality humanely requested . Finally, this is the first goal of the Cuban Public Health. Objective: to highlight the importance of an appropriate follow-up of multinodular goitre as a significant element in the prevention of its multinodular malignant transformation. Case presentation: an 80 year- old, female patient presents an increase of the volumen of the anterior section of the neck, with pathologic antecedents of a multinodular goitre which the evolution has been characterized by an irregular and non systematic treatment along of years .She could have better quality of life as well as to avoid to death taking into account the wild conditions of that disease was presented herself. Physical examination: It has been observed an increase o

  8. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2?-deoxycytidine in anaplastic large cell lymphoma

    OpenAIRE

    Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

    2012-01-01

    DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2?-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematologi...

  9. Extreme neutrophil granulocytosis in a patient with anaplastic large cell lymphoma of T-cell lineage

    DEFF Research Database (Denmark)

    Engsig, Frederik Neess; Møller, Michael Boe; Hasselbalch, Hans K; Mahdi, Bassam; Obel, Niels

    2007-01-01

    We describe a 47-year-old male admitted with fever and extreme neutrophil granulocytosis (up to 80 x 10(9)/L). All microbiology tests and test for autoimmune disease were negative. CT scan showed pulmonary infiltrates bilaterally, mediastinal lymphadenopathy and splenomegaly. Conventional...

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

    Directory of Open Access Journals (Sweden)

    Benjamin Kim, MD, MPhil

    2015-01-01

    Conclusions: Our assessment yielded consistent results on a number of key, incompletely addressed issues regarding BIA-ALCL, but additional research is needed to support these statement ratings and enhance our understanding of the biology, treatment, and outcomes associated with this disease.

  11. Protective effects of Paclitaxel on gamma-irradiation action on anaplastic thyroid cancer cells

    International Nuclear Information System (INIS)

    The aim of the paper was to describe the effects of Paclitaxel (Ptx), y-irradiation (IR) and their combination in undifferentiated thyroid cancer cells (ATC). The Ptx at low concentrations caused noticeable radioprotective effect. The combined effect of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, and survivine expression. The effect of these events can be considered as antiapoptotic - Ptx attenuated cytotoxic effect of IR

  12. Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming

    DEFF Research Database (Denmark)

    Marzec, Michal; Halasa, Krzysztof; Liu, Xiaobin; Wang, Hong Y; Cheng, Mangeng; Baldwin, Donald; Tobias, John W; Schuster, Stephen J; Andersen, Anders Woetmann; Zhang, Qian; Turner, Suzanne D; Ødum, Niels; Wasik, Mariusz A

    2013-01-01

    Anaplastic lymphoma kinase (ALK), physiologically expressed only by nervous system cells, displays a remarkable capacity to transform CD4(+) T lymphocytes and other types of nonneural cells. In this study, we report that activity of nucleophosmin (NPM)/ALK chimeric protein, the dominant form of ALK expressed in T cell lymphomas (TCLs), closely resembles cell activation induced by IL-2, the key cytokine supporting growth and survival of normal CD4(+) T lymphocytes. Direct comparison of gene expre...

  13. A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue

    Directory of Open Access Journals (Sweden)

    Meng Zhenhang

    2004-07-01

    Full Text Available Abstract Background To identify the spectrum of malignant attributes maintained outside the host environment, we have compared global gene expression in primary breast tumors and matched short-term epithelial cultures. Results In contrast to immortal cell lines, a characteristic 'limited proliferation' phenotype was observed, which included over expressed genes associated with the TGF? signal transduction pathway, such as SPARC, LOXL1, RUNX1, and DAPK1. Underlying this profile was the conspicuous absence of hTERT expression and telomerase activity, a significant increase in T?RII, its cognate ligand, and the CDK inhibitor, p21CIP1/WAF1. Concurrently, tumor tissue and primary cultures displayed low transcript levels of proliferation-related genes, such as, TOP2A, ANKT, RAD51, UBE2C, CENPA, RRM2, and PLK. Conclusions Our data demonstrate that commonly used immortal cell lines do not reflect some aspects of tumor biology as closely as primary tumor cell cultures. The gene expression profile of malignant tissue, which is uniquely retained by cells cultured on solid substrates, could facilitate the development and testing of novel molecular targets for breast cancer.

  14. Unmistakable Morphology? Infantile Malignant Osteopetrosis Resembling Juvenile Myelomonocytic Leukemia in Infants.

    Science.gov (United States)

    Strauss, Anne; Furlan, Ingrid; Steinmann, Sandra; Buchholz, Bernd; Kremens, Bernhard; Rossig, Claudia; Corbacioglu, Selim; Rajagopal, Revathi; Lahr, Georgia; Yoshimi, Ayami; Strahm, Brigitte; Niemeyer, Charlotte M; Schulz, Ansgar

    2015-08-01

    The initial clinical and hematologic presentation of infantile malignant osteopetrosis may be indistinguishable from that of juvenile myelomonocytic leukemia in infants. Timely radiographic imaging, however, allows straightforward delineation of these 2 severe diseases and facilitates immediate initiation of appropriate therapy. PMID:25982139

  15. Unusual anogenital apocrine tumor resembling mammary-like gland adenoma in male perineum: a case report

    Directory of Open Access Journals (Sweden)

    Yoshioka Takako

    2010-06-01

    Full Text Available Abstract A rare case of an apocrine tumor in the male perineal region is reported. A dermal cystic lesion developed in the region between the anus and scrotum of a 74-year-old Japanese male. The cystic lesion, measuring 3.5 × 5.0 cm in size, was lined by columnar or flattened epithelium with occasional apocrine features and supported by a basal myoepithelium lining. A mural nodule, measuring 1 × 1.5 cm in size, protruded into the cystic space and consisted of a solid proliferation of tubular glands with prominent apocrine secretion and basal myoepithelial cells. Immunohistochemical examination showed that the luminal cells were partially positive for gross cystic disease fluid protein 15 and human milk fat globulin 1, and the basal myoepithelial cells were positive for alpha-smooth muscle actin and S-100 protein. Estrogen and progesterone hormone receptors were focally and weakly positive for luminal epithelium. Although no mammary-like glands were present in the dermis around the tumor, this unusual apocrine tumor has been suggested to be derived from male anogenital mammary-like glands and mimic a mammary-like gland adenoma in the male perineum.

  16. Irritable bowel syndrome (IBS) subtypes: Nothing resembles less an IBS than another IBS.

    Science.gov (United States)

    Mearin Manrique, Fermín

    2016-02-01

    Two new members of "IBS Patient Association" met at a meeting. Feeling somewhat lost, not knowing anybody present, they introduced themselves to each other. After exchanging names, one asks the other - "What's your problem?" The other one answers - "I got constipation that laxatives fail to relieve, and my belly, which is always bloated, sometimes hurts so much that I can´t even leave home". Deeply surprised, the first individual inquires - "What are you doing here then?" "Why, I came to this meeting looking for some help for my irritable colon", she answered. "Irritable colon? That's no irritable colon. Irritable bowel syndrome is what I suffer from, and it's diarrhea that won't let me be; can't stop running to the toilet, and cramps just pop up any time". Now both looked surprised. Both thought they had come to the wrong meeting, and both were on the verge of leaving. Luckily, the Association's secretary showed up and explained that both had IBS. PMID:26838485

  17. Halobacterium halobium strains lysogenic for phage phi H contain a protein resembling coliphage repressors.

    OpenAIRE

    Ken, R; Hackett, N. R.

    1991-01-01

    DNA-binding proteins such as bacteriophage repressors belong to the helix-turn-helix family. Ionic interactions drive DNA binding, which means that repressors bind DNA most tightly at low salt concentrations. This raises the question of who gene expression might be regulated in obligate halophiles, which maintain internal salt concentrations of about 5 M. As a model system we have investigated the phage phi H, which infects the archaebacterium Halobacterium halobium. Previous genetic data and...

  18. [A case of cytomegalovirus colitis with endoscopic finding resembling Crohn's disease].

    Science.gov (United States)

    Huh, Cheal Wung; Youn, Young Hoon; Jung, Da Hyun; Kim, Do Whan; Kho, Bo Gun; Kim, Jie Hyun; Park, Hyojin; Lee, Sang In

    2012-04-01

    Cytomegalovirus (CMV) colitis is common among immunocompromised patients, and often diagnosed by pathologic confirmation because it is associated with a diverse spectrum of clinical and endoscopic features. However, Crohn's disease has no definitive diagnostic criteria, but longitudinal ulcers and cobble stone appearance are accepted as typical endoscopic features of Crohn's disease. An 83 year-old male with a history of radiotherapy for hypopharyngeal cancer visited our hospital with a complaint of melena for 1 week. His colonoscopic exam showed multiple longitudinal ulcers along the entire colon. Most of the ulcers were longer than 4 cm, these endoscopic findings were suspected as typical endoscopic features of Crohn's disease. Pathologic reports revealed multiple inclusion bodies with CMV on immunohistochemistry. He was finally diagnosed as having CMV colitis, and received a 3 week-course of intravenous ganciclovir. A colonoscopic follow-up showed complete healing of the multiple longitudinal ulcers, and he is doing well now without further treatment. PMID:22544028

  19. The Texas Adoption Project: Adopted Children and Their Intellectual Resemblance to Biological and Adoptive Parents.

    Science.gov (United States)

    Horn, Joseph M.

    1983-01-01

    Intelligence test scores were obtained from parents and children in 300 adoptive families and compared with similar data available from the children's biological mothers. Results support the hypothesis that genetic variability is an important influence in the development of individual differences in intelligence. (Author/RH)

  20. Artifacts resembling budding bacteria produced in placer-gold amalgams by nitric acid leaching

    Science.gov (United States)

    Watterson, J.R.

    1994-01-01

    Microscopic filiform morphologies in gold which are indistinguishable from forms originally interpreted as bacterial in origin were produced in the laboratory by treating amalgams made from natural and artificial gold with hot nitric acid. Textures ranging from cobblestone to deeply crenulated to nodular filiform were produced in the laboratory from all tested natural and artificial gold amalgams; analogous textures widespread in Alaskan placer gold may have a similar inorganic origin. These results indicate that morphology alone cannot be considered adequate evidence of microbial involvement in gold formation.