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Sample records for anaplastic large cell

  1. Primary cutaneous anaplastic large-cell lymphoma.

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    Perry, Edward; Karajgikar, Jay; Tabbara, Imad A

    2013-10-01

    Since the recognition of the anaplastic large-cell lymphomas in the 1980s, much has been learned about the diagnosis, clinical presentation, and treatment of these malignant conditions. The systemic and primary cutaneous types of anaplastic large cell lymphomas have been differentiated on clinical and immunophenotypical findings, but further research is required to elucidate their exact etiologies and pathogeneses. Primary cutaneous anaplastic large-cell lymphoma has a 95% disease-specific 5-year survival, owing partly to the relatively benign course of the disease and partly to the variety of effective treatments that are available. As with many other oncological diseases, new drugs are continually being tested and developed, with immunotherapy and biological response modifiers showing promise.

  2. Synchronous meningioma and anaplastic large cell lymphoma.

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

    2010-06-01

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

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

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    Anupama Bains

    2016-01-01

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

  4. [A case of primary central nervous system anaplastic lymphoma kinase positive anaplastic large cell lymphoma manifested as a unilateral pachymeningits].

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    Fujisawa, Etsuco; Shibayama, Hidehiro; Mitobe, Fumi; Katada, Fumiaki; Sato, Susumu; Fukutake, Toshio

    2017-11-25

    There have been 23 reports of primary central nervous system anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we report the 24th case of a 40-year-old man who presented with occipital headache for one month. His contrast-enhanced brain MRI showed enhancement around the right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis. He improved with steroid therapy. After discharge, however, he was readmitted with generalized convulsive seizures. Finally, he was diagnosed as primary central nervous system ALK-positive anaplastic large cell lymphoma by brain biopsy. Primary central nervous system lymphoma invading dura matter can rarely manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis, we should pay attention to the possibility of infiltration of lymophoma with meticulous clinical follow-up.

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

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

    2012-01-01

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

  6. Pathobiology of Anaplastic Large Cell Lymphoma

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    Pier Paolo Piccaluga

    2010-01-01

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

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

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    Gao KH

    2016-07-01

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

  8. The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL

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    Ivonne A. Montes-Mojarro

    2018-04-01

    Full Text Available Anaplastic large cell lymphoma (ALCL represents a group of malignant T-cell lymphoproliferations that share morphological and immunophenotypical features, namely strong CD30 expression and variable loss of T-cell markers, but differ in clinical presentation and prognosis. The recognition of anaplastic lymphoma kinase (ALK fusion proteins as a result of chromosomal translocations or inversions was the starting point for the distinction of different subgroups of ALCL. According to their distinct clinical settings and molecular findings, the 2016 revised World Health Organization (WHO classification recognizes four different entities: systemic ALK-positive ALCL (ALK+ ALCL, systemic ALK-negative ALCL (ALK− ALCL, primary cutaneous ALCL (pC-ALCL, and breast implant-associated ALCL (BI-ALCL, the latter included as a provisional entity. ALK is rearranged in approximately 80% of systemic ALCL cases with one of its partner genes, most commonly NPM1, and is associated with favorable prognosis, whereas systemic ALK− ALCL shows heterogeneous clinical, phenotypical, and genetic features, underlining the different oncogenesis between these two entities. Recognition of the pathological spectrum of ALCL is crucial to understand its pathogenesis and its boundaries with other entities. In this review, we will focus on the morphological, immunophenotypical, and molecular features of systemic ALK+ and ALK− ALCL. In addition, BI-ALCL will be discussed.

  9. ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma

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    Rachel Hudacko

    2011-01-01

    Full Text Available Anaplastic lymphoma kinase protein (ALK-negative anaplastic large cell lymphoma (ALCL has a vast morphologic spectrum and may mimic many other types of malignancies both cytologically and histologically. There are only a few published case reports/series describing the cytomorphologic features of ALCL on fine-needle aspiration (FNA biopsy specimens. We describe a case of ALK-negative ALCL mimicking a high-grade soft tissue sarcoma of the thigh in a 62-year-old man. The characteristic morphologic findings on FNA and core biopsy along with the immunophenotypic profile are described and reviewed. The diagnosis of ALCL on FNA biopsy may be difficult, but can be done successfully with the use of ancillary tests. Therefore, it must be considered in the differential diagnosis of lesions with pleomorphism, anaplasia, and wreath-like or horseshoe-shaped nuclei to ensure that adequate material is obtained for ancillary studies.

  10. Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

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    Li, Meng-Fang; Hsiao, Cheng-Hsiang; Chen, Yi-Lin; Huang, Wen-Ya; Lee, Yi-Hsuan; Huang, Hsien-Neng; Lien, Huang-Chun

    2012-02-01

    Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Copyright © 2011 John Wiley & Sons A/S.

  11. Primary cutaneous CD30+ anaplastic large-cell lymphoma in a young patient with psoriasis

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    Ming-Chun Chen

    2013-03-01

    Full Text Available Psoriasis is a common chronic inflammatory cutaneous disease, while primary cutaneous CD30+ anaplastic large-cell lymphoma (PC-ALCL is a rare T-cell lymphoma which always has an excellent prognosis, although multifocal PC-ALCL tends to relapse after systemic chemotherapy. Psoriasis associated with PC-ALCL is exceptionally rare. We report a 29-year-old Chinese female with a 5-year history of psoriasis treated with Chinese herbs alone, who was referred to our institution with a tumor on the left clavicular region for 1 year and another one on the left palm for 2 months. Skin biopsies of both lesions showed diffuse infiltration of tumor cells, composed of large atypical cells with marked nuclear pleomorphism, prominent nucleoli, and eosinophilic cytoplasm. Large numbers of neutrophilic infiltrations were also noted in the lesion. Immunostaining revealed the lesion to be positive for CD30, vimentin, CD45, and CD68, and weakly positive for epithelial membrane antigen, but negative for anaplastic lymphoma receptor tyrosine kinase. The patient was diagnosed to have psoriasis associated with PC-ALCL; she died 18 months after the final diagnosis with unknown cause. We consider that immune dysregulation and/or Chinese herbs may play roles in the development of the present PC-ALCL.

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

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    Fabrizio eTabbo

    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.

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

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    Vibhu Mendiratta

    2016-01-01

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

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

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    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.

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

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    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

  16. Anaplastic Large-Cell Lymphoma in a Child with Type I Diabetes and Unrecognised Coeliac Disease

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    Jemima Sharp

    2012-01-01

    Full Text Available Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

  17. Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

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    Million, Lynn, E-mail: lmillion@stanford.edu [Stanford Cancer Institute, Stanford, California (United States); Yi, Esther J.; Wu, Frank; Von Eyben, Rie [Stanford Cancer Institute, Stanford, California (United States); Campbell, Belinda A. [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Dabaja, Bouthaina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsang, Richard W. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ng, Andrea [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Wilson, Lynn D. [Department of Therapeutic Radiology/Radiation Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut (United States); Ricardi, Umberto [Department of Oncology, University of Turin, Turin (Italy); Kirova, Youlia [Institut Curie, Paris (France); Hoppe, Richard T. [Stanford Cancer Institute, Stanford, California (United States)

    2016-08-01

    Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

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

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

    2006-10-19

    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. 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. 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.

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

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    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.

  20. [A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

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    Gorgidze, L A; Vorob'ev, I A

    2009-01-01

    To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

  1. Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL: Current Standard and beyond

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    Nina Prokoph

    2018-03-01

    Full Text Available Anaplastic Lymphoma Kinase (ALK-positive Anaplastic Large Cell Lymphoma (ALCL, remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65–90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and ‘renewed’ agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and ‘renewed’ agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials.

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

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

    2014-01-01

    Systemic anaplastic large cell lymphoma (ALCL) is a distinct disease classification provisionally sub-divided into ALCL, Anaplastic Lymphoma Kinase (ALK)(+) and ALCL, ALK(-) entities. More recently, another category of ALCL has been increasingly reported in the literature and is associated with the presence of breast implants. A comprehensive review of the 71 reported cases of breast implant associated ALCL (iALCL) is presented indicating the apparent risk factors and main characteristics of this rare cancer. The average patient is 50 years of age and most cases present in the capsule surrounding the implant as part of the periprosthetic fluid or the capsule itself on average at 10 years post-surgery suggesting that iALCL is a late complication. The absolute risk is low ranging from 1:500,000 to 1:3,000,000 patients with breast implants per year. The majority of cases are ALK-negative, yet are associated with silicone-coated implants suggestive of the mechanism of tumorigenesis which is discussed in relation to chronic inflammation, immunogenicity of the implants and sub-clinical infection. In particular, capsulotomy alone seems to be sufficient for the treatment of many cases suggesting the implants provide the biological stimulus whereas others require further treatment including chemo- and radiotherapy although reported cases remain too low to recommend a therapeutic approach. However, CD30-based therapeutics might be a future option. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. 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

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    Peh, SC; Kim, LH; Poppema, S

    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

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

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    Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud

    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 macrophages correlates with an adverse outcome in ALK-negative ALCL....

  5. Anaplastic large cell lymphoma associated with breast implants

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    Vid Bajuk

    2017-02-01

    Full Text Available An increasing number of women worldwide decide for esthetic correction of breasts with silicone implants and post-cancer breast reconstruction with tissue expanders and silicone breast implants. It is estimated that more than 10 million women around the globe have them. Tere are approximately 200 known cases of patients with anaplastic large cell lymphoma (ALCL linked with silicone breast implants reported in medical literature. ALCL is a rare disease with an annual incidence of 0.1–0.3/100 000 women with breast silicone implants. In the presence of clinical signs, physician should also consider this rare form of ALCL in differential diagnosis. Patients are on average 50 years old. Long afer implantation surgery, the patient may experience breast swelling, pain and/or asymmetry. In diagnostics, ultrasound and cytological examination are required. During ultrasound examination fluid formation (seroma or solid tumor mass can be detected. Treatment is individualized. Due to tumor nature, implant resection and total capsulectomy are usually indicated; also, chemo- and radiotherapy might rarely be required. Five-year survival rate depends on tumor form and correlates well with clinical fndings of seroma or solid mass. In the more frequent form, seroma, fve-year survival rate is 100 %, while in the case of solid tumor mass fve-year survival rate is 75 %. The rarity of this disease makes it difficult to diagnose, but nevertheless, early detection and treatment are important for better recovery.

  6. Fine needle aspiration cytology of ALK1(-), CD30+ anaplastic large cell lymphoma post renal transplantation: a case report and literature review.

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    Balachandran, Indra; Walker, Joe W; Broman, Jerry

    2010-03-01

    Post transplant lymphoproliferative disorders (PTLD) complicates the course of 0.3 to 3% of renal transplant patients receiving immunosuppression. Epstein-Barr virus (EBV) related non-Hodgkin's lymphomas of B-cell type is more common than those of T-cell origin. CD30 positive Anaplastic Large Cell Lymphoma (ALCL) is a Non-Hodgkin's lymphoma (B or T cell type) that accounts for a small percentage of PTLD's. ALCL of T-cell type are a spectrum of disease ranging from primary cutaneous to systemic nodal ALCL. The systemic nodal ALCL is further subdivided into anaplastic lymphoma kinase-1 (ALK-1) positive or negative. ALK-1 protein is a gene fusion product of translocation (2;5) and carries prognostic implications. We present an unusual manifestation of ALK-1 negative CD30 positive ALCL in a post renal transplant patient in FNA cytology with all supportive adjuvant studies and differential diagnoses and review the cytology literature on this topic.

  7. The non-specific symptoms of breast implant-associated anaplastic large cell lymphoma resulting in delayed diagnosis: A case-based review

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    Reem Dina Jarjis

    2015-12-01

    Full Text Available Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL is a rare entity that has become known as a distinct clinical condition recently. In general, BIA-ALCL patients with a history of breast implants present with non-specific implant-related complications, resulting in delayed diagnosis and appropriate treatment because of the lack of awareness of BIA-ALCL. The cause and pathogenesis have still not been identified, and there are no evidence-based guidelines on how this condition should be detected, treated or followed up because of the rarity of available data. We present the first published Danish case of anaplastic lymphoma kinase negative BIA-ALCL, and review the current literature to raise awareness of and discuss management options for this rare clinical entity.

  8. Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling

    Directory of Open Access Journals (Sweden)

    Melanie R. Hassler

    2016-10-01

    Full Text Available Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+ and NPM-ALK-negative (ALK− anaplastic large-cell lymphoma (ALCL. We find that ALK+ and ALK− ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy.

  9. Change in the diagnosis from classical Hodgkin's lymphoma to anaplastic large cell lymphoma by 18F flourodeoxyglucose positron emission tomography/computed tomography: Importance of recognising disease pattern on imaging and immunohistochemistry

    International Nuclear Information System (INIS)

    Senthil, Raja; Mohapatra, Ranjan Kumar; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is a rare type of nonHodgkin's lymphoma (NHL), but one of the most common subtypes of T-cell lymphoma. It is an aggressive T-cell lymphoma, and some ALCL may mimic less aggressive classical HL histopathlogically. It may be misdiagnosed unless careful immunohistochemical examination is performed. As the prognosis and management of these two lymphomas vary significantly, it is important to make a correct diagnosis. We describe a case who was diagnosed as classical HL by histopathological examination of cervical lymph node, in whom 18 F-flouro deoxyglucose positron emission tomography/computed tomography appearances were unusual for HL and warranted review of histopathology that revealed anaplastic lymphoma kinase-1 negative anaplastic large T-cell lymphoma, Hodgkin-like variant, thereby changing the management

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

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    Miguel Ángel Serra Valdés

    2014-03-01

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

  11. Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature.

    Science.gov (United States)

    Berlin, Eva; Singh, Kunwar; Mills, Christopher; Shapira, Ilan; Bakst, Richard L; Chadha, Manjeet

    2018-01-01

    We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging). The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

  12. Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

    Science.gov (United States)

    Hu, Honghua; Johani, Khalid; Almatroudi, Ahmad; Vickery, Karen; Van Natta, Bruce; Kadin, Marshall E; Brody, Garry; Clemens, Mark; Cheah, Chan Yoon; Lade, Stephen; Joshi, Preeti Avinash; Prince, H Miles; Deva, Anand K

    2016-06-01

    A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant-associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. Twenty-six breast implant-associated ALCL samples were analyzed for the presence of biofilm by real-time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. Both the breast implant-associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant-associated ALCL, 4.7 × 10 cells/mg of tissue; capsule, 4.9 × 10 cells/mg of tissue). Analysis of the microbiome in breast implant-associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p capsule specimens compared with breast implant-associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. This novel finding of bacterial biofilm and a distinct microbiome in breast implant-associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. Risk, V.

  13. Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Eva Berlin

    2018-01-01

    Full Text Available We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging. The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

  14. Breast implants and anaplastic large-cell lymphoma: a danish population-based cohort study.

    Science.gov (United States)

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

    2013-11-01

    A potential link between breast implants and anaplastic large-cell lymphoma (ALCL) has been suggested. We examined lymphoma occurrence in a nationwide cohort of 19,885 Danish women who underwent breast implant surgery during 1973-2010. Standardized incidence ratios (SIR), with 95% confidence intervals (CI), for ALCL and lymphoma overall associated with breast implantation were calculated. During 179,246 person-years of follow-up, we observed 31 cases of lymphoma among cohort members. No cases of ALCL were identified. SIRs for ALCL and lymphoma overall were zero (95% CI, 0-10.3) and 1.20 (95% CI, 0.82-1.70), respectively. In our nationwide cohort study, we did not find an increased risk of lymphoma in general, or ALCL in particular, among Danish women who underwent breast implantation. However, our evaluation of ALCL risk was limited by the rarity of the disease. Our results do not support an association between breast implants and ALCL and are consistent with other studies on cancer risk and breast implants. ©2013 AACR.

  15. Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature.

    Science.gov (United States)

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

    2015-11-01

    Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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.

  17. The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression.

    Science.gov (United States)

    Georgakis, Georgios V; Li, Yang; Rassidakis, Georgios Z; Medeiros, L Jeffrey; Younes, Anas

    2006-12-01

    Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.

  18. 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 β-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

  19. EMMPRIN (CD147) is induced by C/EBPβ and is differentially expressed in ALK+ and ALK- anaplastic large-cell lymphoma.

    Science.gov (United States)

    Schmidt, Janine; Bonzheim, Irina; Steinhilber, Julia; Montes-Mojarro, Ivonne A; Ortiz-Hidalgo, Carlos; Klapper, Wolfram; Fend, Falko; Quintanilla-Martínez, Leticia

    2017-09-01

    Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPβ, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro. To analyze the role of C/EBPβ for the unusual phenotype of ALK+ ALCL cells, C/EBPβ was knocked down by RNA interference in two ALK+ ALCL cell lines, and surface antigen expression profiles of these cell lines were generated using a Human Cell Surface Marker Screening Panel (BD Biosciences). Interesting candidate antigens were further analyzed by immunohistochemistry in primary ALCL ALK+ and ALK- cases. Antigen expression profiling revealed marked changes in the expression of the activation markers CD25, CD30, CD98, CD147, and CD227 after C/EBPβ knockdown. Immunohistochemical analysis confirmed a strong, membranous CD147 (EMMPRIN) expression in ALK+ ALCL cases. In contrast, ALK- ALCL cases showed a weaker CD147 expression. CD274 or PD-L1, an immune inhibitory receptor ligand, was downregulated after C/EBPβ knockdown. PD-L1 also showed stronger expression in ALK+ ALCL compared with ALK- ALCL, suggesting an additional role of C/EBPβ in ALK+ ALCL in generating an immunosuppressive environment. Finally, no expression changes of T-cell or monocytic markers were detected. In conclusion, surface antigen expression profiling demonstrates that C/EBPβ plays a critical role in the activation state of ALK+ ALCL cells and reveals CD147 and PD-L1 as important downstream targets. The multiple roles of CD147 in migration, adhesion, and invasion, as well as

  20. ALK-1-negative anaplastic large cell lymphoma associated with breast implants: a new clinical entity.

    Science.gov (United States)

    Lazzeri, Davide; Agostini, Tommaso; Bocci, Guido; Giannotti, Giordano; Fanelli, Giovanni; Naccarato, Antonio Giuseppe; Danesi, Romano; Tuccori, Marco; Pantaloni, Marcello; D'Aniello, Carlo

    2011-10-01

    Concerns have been raised recently regarding the increasing number of reports of non-Hodgkin lymphoma (NHL) that developed in close proximity to silicone or saline breast implants. In particular, an increased risk of anaplastic large cell lymphoma (ALCL) in patients with breast prostheses has been proposed. We reviewed clinical and pathologic findings in 40 women who received a diagnosis of breast NHL arising in association with breast implants and of 27 patients who had a diagnosis of ALCL with breast involvement reported in the published literature. Among the 40 reported cases of prosthesis-associated breast lymphomas, 28 were anaplastic lymphoma kinase-1-negative (ALK-1(-)) ALCLs, whereas of 27 ALCLs in patients without implants found in the literature, only 10 were ALK-1(-). The finding of 28 cases of breast ALK-1(-) ALCL occurring in patients with implants compared with 10 cases in women without implants is in favor of an association between silicone breast prostheses and ALK-1(-) ALCL. Although the incidence of this type of lymphoma remains remarkably low given that breast prostheses have been widely used for decades, clinical and pathologic evidence for a causative role is becoming dramatically strong. The histologic, phenomenologic, and clinical similarities of the majority of implant-related ALK-1(-) ALCLs suggest a common mechanism, especially when compared with the counterpart of patients without implants in which very few and highly dishomogeneous cases of the same malignancy were detected. There is convincing evidence that primary implant-related ALK-1(-) ALCL represents a distinct clinicopathologic entity that has been inappropriately fitted into the category of systemic ALK-1(-) ALCL. Thus it should be recognized as a separate category and classified on its own. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration

    DEFF Research Database (Denmark)

    Voena, Claudia; Conte, Chiara; Ambrogio, Chiara

    2007-01-01

    Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades......, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine...... phosphatase Shp2 as a candidate substrate. We found that NPM-ALK was able to bind Shp2 in coprecipitation experiments and to induce its phosphorylation in the tyrosine residues Y542 and Y580 both in HEK293 cells and ALCL cell lines. In primary lymphomas, antibodies against the phosphorylated tyrosine Y542...

  2. Treatment of primary cutaneous anaplastic large cell lymphoma with superficial x-rays

    DEFF Research Database (Denmark)

    Jepsen, Malene E; Gniadecki, Robert

    2015-01-01

    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...

  3. 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)

    Gao, Ju; Yin, Minzhi; Zhu, Yiping; Gu, Ling; Zhang, Yanle; Li, Qiang; Jia, Cangsong; Ma, Zhigui

    2013-01-01

    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

  4. Anaplastic pleomorphic xanthoastrocytoma

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    Li-wei SHAO

    2017-09-01

    Full Text Available Objective To investigate the clinicopathological features, immune phenotype and gene mutation characteristics, and diagnosis or differential diagnosis of anaplastic pleomorphic xanthoastrocytoma (PXA. Methods and Results A 11 - year- old male patient presented with more than half month of headache, and left upper limb weakness. Cranial CT and MRI revealed a large space-occupying lesion in the right parietal lobe and basal ganglia which was suggested as glioma. During operation the tumor was examined. It was a cystic-solid lesion. The solid part was soft and greyish yellow with rich blood supply and without membrane, and the boundary was clear. Intraoperative freezing pathologic examination showed the tumor was a low grade glioma. The right parietal glioma was completely removed piece by piece under the microscopy. Histologically, the tumor cells were polymorphism, including spindle or round astrocytes, monocytes and multinuclear tumor giant cells. Mitoses were rarely seen. Differentiation of mature neuronal cells or ganglion cells with lymphocyte infiltration were seen in focal region. In some regions, tumor cells were anaplastic, and cellularity were increased. Atypical round or spindle cells were seen, and atypical mitoses > 5/10 high power field (HPF were found. icrovascular proliferation, perivascular pseudorosettes and localized necrosis were also evident. Immunohistochemically, tumor cells were positive for glial fibrillary acidic protein (GFAP, BRAF V600E, S-100 protein (S-100, CD34, synaptophysin (Syn, non- phosphorylation neurofilament heauy chain SMI- 32 and P53, but negative for isocitrate dehydrogenase 1(IDH1, neurofilament protein (NF and epithelial membrane antigen (EMA. Ki - 67 labeling index was about 3% in low grade tumor cells, while Ki-67 labeling index was about 30% in high grade tumor cells. In reticular fibre tissue staining, a lot of reticular fibre tissue were seen. BRAF V600E heterozygous mutation c.1799A > T was

  5. 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.

  6. Anaplastic Large Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

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

    Directory of Open Access Journals (Sweden)

    Margarita Baka

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-01-28

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

  9. Renal Cell Carcinoma Metastatic to Thyroid Gland, Presenting Like Anaplastic Carcinoma of Thyroid

    Directory of Open Access Journals (Sweden)

    Khalid Riaz

    2013-01-01

    Full Text Available Background. Renal cell carcinoma (RCC has unpredictable and diverse behavior. The classic triad of hematuria, loin pain, and abdominal mass is uncommon. At time of diagnosis, 25%–30% of patients are found to have metastases. Bones, lungs, liver, and brain are the frequent sites of metastases. RCC with metastasis to the head and neck region and thyroid gland is the rarest manifestation and anaplastic carcinoma behaving metastatic thyroid mass is an extremely rare presentation of RCC. Case Presentation. A 56-year-old Saudi man with past history of right radical nephrectomy 5 years back presented with 3 months history of rapid increasing neck mass with dysphagia, presenting like anaplastic thyroid carcinoma. Tru-cut biopsy turned out to be metastatic renal cell carcinoma. Patient was treated with radiation therapy 30 Gy in 10 fractions to mass. Patient died 4 months after the discovery of anaplastic thyroid looking metastasis. Conclusion. Rapidly progressing thyroid metastases secondary to RCC are rare and found often unresectable which are not amenable to surgery. Palliative radiotherapy can be considered for such patients.

  10. Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.

    Science.gov (United States)

    Pasqualini, Claudia; Minard-Colin, Veronique; Saada, Veronique; Lamant, Laurence; Delsol, Georges; Patte, Catherine; Le Deley, Marie-Cécile; Valteau-Couanet, Dominique; Brugières, Laurence

    2014-04-01

    Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL. © 2014 John Wiley & Sons Ltd.

  11. The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis.

    Science.gov (United States)

    Unger, Christine; Popescu, Ruxandra; Giessrigl, Benedikt; Laimer, Daniela; Heider, Susanne; Seelinger, Mareike; Diaz, Rene; Wallnöfer, Bruno; Egger, Gerda; Hassler, Melanie; Knöfler, Martin; Saleh, Leila; Sahin, Emine; Grusch, Michael; Fritzer-Szekeres, Monika; Dolznig, Helmut; Frisch, Richard; Kenner, Lukas; Kopp, Brigitte; Krupitza, Georg

    2013-01-01

    The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor β was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)' is warranted.

  12. An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

    Science.gov (United States)

    Lollies, A; Hartmann, S; Schneider, M; Bracht, T; Weiß, A L; Arnolds, J; Klein-Hitpass, L; Sitek, B; Hansmann, M-L; Küppers, R; Weniger, M A

    2018-01-01

    Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30 + lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30 + diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

  13. Primary peritoneal anaplastic giant cell carcinoma: case report of an unusual and highly malignant müllerian neoplasm.

    Science.gov (United States)

    Lu, Xian; Zhang, Cunxian; Liu, Fang; Sung, C James; Steinhoff, Margaret M; Lawrence, W Dwayne

    2008-01-01

    Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical müllerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peritoneum as a primary tumor.

  14. Gingival Anaplastic Large-Cell Lymphoma Mimicking Hyperplastic Benignancy as the First Clinical Manifestation of AIDS: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Rafaela Elvira Rozza-de-Menezes

    2013-01-01

    Full Text Available This paper presents an unusual case of gingival ALCL, which mimicked a benign hyperplastic lesion that occurred in a 57-year-old white man representing the first clinical manifestation of acquired immunodeficiency syndrome (AIDS. The patient was referred to the Dental Clinic of PUCPR complaining of a lobulated nodule on the gingiva of his upper central incisors. The presence of advanced chronic periodontitis and dental plaque raised suspicion for a benignancy. An excisional biopsy was performed, and large pleomorphic cells with an abundant cytoplasm, sometimes containing prominent nucleoli and “Hallmark” cells, were observed through hematoxylin and eosin staining. The tumor cells showed strong CD30 expression, EMA, Ki-67, and LCA, and negative stain for p80NPM/ALK, CKAE1/AE3, CD20, CD3, CD56, and CD15. The final diagnosis was ALCL (ALK-negative. Further laboratory tests revealed positivity for human immunodeficiency virus (HIV. The patient was submitted to chemotherapy, but four months after diagnosis, the patient died due to pneumonia and respiratory failure. Oral anaplastic large-cell lymphoma (ALCL is a rare disorder. Only 5 cases involving the gingiva have been reported, and to our knowledge, this is the first case reported of the ALCL, which mimicked a hyperplastic benignancy as the first clinical manifestation of AIDS.

  15. Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients

    Science.gov (United States)

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

    2014-01-01

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

  16. Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients.

    Science.gov (United States)

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

    2014-01-10

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

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

    Science.gov (United States)

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

    2012-10-01

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

  18. 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.

  19. 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

    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 ...

  20. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

    Science.gov (United States)

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

    2016-01-10

    Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. © 2015 by American Society of Clinical Oncology.

  1. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma

    Science.gov (United States)

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

    2016-01-01

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

  2. Anaplastic thyroid cancer

    Science.gov (United States)

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

  3. Anaplastic large cell lymphoma of the breast arising around mammary implant capsule: an Italian report.

    Science.gov (United States)

    Farace, Francesco; Bulla, Antonio; Marongiu, Francesco; Campus, Gian Vittorio; Tanda, Francesco; Lissia, Amelia; Cossu, Antonio; Fozza, Claudio; Rubino, Corrado

    2013-06-01

    Anaplastic large cell lymphoma (ALCL) of the breast is a very rare nonepithelial neoplasm. In the literature, this tumor has sometimes been described in proximity of breast implants (60 implant-related ALCL reported). In 2010, a patient who had undergone a right mastectomy and tissue expander/implant reconstruction for a "ductal" carcinoma 10 years before was referred to our unit for evaluation. On examination, an enlarged reconstructed right breast was found. The reconstructed breast did not show tenderness or signs of infection, ulceration, or breakdown. Mammograms and ultrasound scan did not suggest the presence of recurrent cancer, infection, deflation of the implant, or severe capsule contracture. The patient underwent mammary implant replacement. About 3 weeks after surgery, the patient came back to our unit for a new mild enlargement of the operated breast and the implant was removed. Three months later, the patient returned with a skin lesion in the right parasternal region. A radical excisional biopsy was performed under local anesthesia and the diagnosis of ALK-1-negative ALCL was finally made. The clinical and histological diagnosis of this disease is difficult as it can often be mistaken for a simple seroma (breast enlargement), an infection, or an unspecific reaction to silicone (redness and/or tension of the skin, itching, and fever). We strongly suggest considering ALCL in any patient with a spontaneous breast seroma lasting more than 6 months after mammary prosthesis implantation. The suspicion of ALCL must be suggested to the pathologist immediately. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  4. Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review.

    Science.gov (United States)

    Salama, S

    2005-06-01

    Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

  5. Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.

    Science.gov (United States)

    Galdiero, Francesca; Bello, Anna Maria; Spina, Anna; Capiluongo, Anna; Liuu, Sophie; De Marco, Margot; Rosati, Alessandra; Capunzo, Mario; Napolitano, Maria; Vuttariello, Emilia; Monaco, Mario; Califano, Daniela; Turco, Maria Caterina; Chiappetta, Gennaro; Vinh, Joëlle; Chiappetta, Giovanni

    2018-01-30

    BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation, defines a distinct type of T/null-cell lymphoma (TCL). The resulting nucleophosmin (NPM) /ALK chimeric kinase is constitutively active and oncogenic. Downstream effector mol...

  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

  8. An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma.

    Science.gov (United States)

    Verma, Sonal; Kumar, Madhu; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

    2017-07-01

    Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients.

  9. Intravesicular taxane-induced dermatotoxicity in a 78-year-old man with urothelial carcinoma and primary cutaneous anaplastic large cell lymphoma.

    Science.gov (United States)

    J Pelletier, Daniel; O'Donnell, Michael; Stone, Mary Seabury; Liu, Vincent

    2018-06-01

    Patients treated with intravesical bacillus Calmette-Guérin therapy for urothelial carcinoma often become refractory and experience recurrent disease, thus necessitating alternative intravesical treatment modalities if the patient is to be spared the morbidities associated with radical cystectomy. Intravesical treatment with taxane-based chemotherapy, such as docetaxel, has gained traction in urologic oncology, proving to be an effective salvage therapy in such patients. Systemic taxane-based chemotherapeutic regimens have long been used in several advanced malignancies, and their systemic side-effects and associated histologic correlates have been extensively documented. In contrast to adverse effects associated with systemic administration, intravesical taxane administration has thus far proven to be well-tolerated, with little to no systemic absorption. To our knowledge, features of taxane-induced systemic effects have not been reported in this setting. Herein, we report a case of a patient with recurrent urothelial carcinoma treated with intravesical docetaxel, along with primary cutaneous anaplastic large cell lymphoma, who developed characteristic dermatotoxic histologic findings associated with intravenous taxane administration. As such histopathologic findings often represent close mimickers of neoplastic and infectious etiologies, knowledge of the potential for systemic manifestations of taxane therapy in patients treated topically may prevent potentially costly diagnostic pitfalls. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Fleury EF

    2017-03-01

    Full Text Available Eduardo de Faria Castro Fleury,1 Milena Morais Rêgo,1 Luciana Costa Ramalho,1 Veronica Jorge Ayres,1 Rodrigo Oliveira Seleti,2 Carlos Alberto Pecci Ferreira,2 Decio Roveda Jr 2 1Radiology Department, IBCC – Instituto Brasileiro de Controle do Câncer, 2Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil Abstract: Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease. Keywords: lymphoma, granuloma, breast cancer, implant

  11. Postoperative radiotherapy of supratentorial anaplastic gliomas

    International Nuclear Information System (INIS)

    Wendt, T.G.; Bacherler, B.; Baumer, K.; Rohloff, R.; Willich, N.

    1986-01-01

    Between 1970 and 1983, 149 patients with high grade anaplastic supratentorial gliomas received a postoperative irradiation during primary treatment. 118 out of these patients had an anaplastic astrocytoma, 18 an anaplastic oligodendroglioma, and 13 an anaplastic ependymoma. Most of these patients were treated by irradiation of a great volume with 50 Gy within five weeks, the others by irradiation of the total brain with 50 Gy within five weeks and saturation with 10 Gy within one week. The one-year survival of the total group was 35.5% and the two-year survival 10.6%. Patients at an age of less than 40 years show a significantly longer survival than older patients (one-year survival rates 40% and 30.7%, respectively). Patients suffering from anaplastic tumors with astrocytic and oligodendrocytic differentiation have a comparable prognosis. Patients suffering from anaplastic tumors with ependymal differentiation, however, have prolonged survival times. The therapy results of different treatment methods are discussed using the communications of literature. (orig.) [de

  12. 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)

    Pearson, Joel D; Mohammed, Zubair; Bacani, Julinor T C; Lai, Raymond; Ingham, Robert J

    2012-01-01

    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

  13. Classical and anaplastic seminoma: Difference in survival

    International Nuclear Information System (INIS)

    Bobba, V.S.; Mittal, B.B.; Hoover, S.V.; Kepka, A.

    1987-01-01

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

  14. ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma.

    NARCIS (Netherlands)

    Paepe, P. de; Baens, M; Krieken, J.H.J.M. van; Verhasselt, B.; Stul, M.; Simons, A.; Poppe, B.; Laureys, G.; Brons, P.P.T.; Vandenberghe, P.; Speleman, F.; Praet, M.; Wolf-Peeters, C. de; Marynen, P.; Wlodarska, I.

    2003-01-01

    We present 3 cases of large B-cell lymphoma (LBCL) with a granular cytoplasmic staining for anaplastic lymphoma kinase (ALK). All of the cases showed striking similarities in morphology and immunohistochemical profile characterized by a massive monomorphic proliferation of CD20-/CD138+

  15. Primary nodal peripheral T-cell lymphomas: diagnosis and therapeutic considerations

    Directory of Open Access Journals (Sweden)

    Luis Alberto de Pádua Covas Lage

    2015-08-01

    Full Text Available Nodal peripheral T-cell lymphomas are a rare group of neoplasms derived from post-thymic and activated T lymphocytes. A review of scientific articles listed in PubMed, Lilacs, and the Cochrane Library databases was performed using the term "peripheral T-cell lymphomas". According to the World Health Organization classification of hematopoietic tissue tumors, this group of neoplasms consists of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, angioimmunoblastic T-cell lymphoma (AITL, anaplastic large cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+, and a provisional entity called anaplastic large cell lymphoma-anaplastic lymphoma kinase negative (ALCL-ALK-. Because the treatment and prognoses of these neoplasms involve different principles, it is essential to distinguish each one by its clinical, immunophenotypic, genetic, and molecular features. Except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, which has no adverse international prognostic index, the prognosis of nodal peripheral T-cell lymphomas is worse than that of aggressive B-cell lymphomas. Chemotherapy based on anthracyclines provides poor outcomes because these neoplasms frequently have multidrug-resistant phenotypes. Based on this, the current tendency is to use intensified cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP regimens with the addition of new drugs, and autologous hematopoietic stem cell transplantation. This paper describes the clinical features and diagnostic methods, and proposes a therapeutic algorithm for nodal peripheral T-cell lymphoma patients.

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

    Science.gov (United States)

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

    2016-05-26

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

  17. Cerebral oligodendroglioma: MR features indicating anaplastic changes

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    Choi, Choong Gon; Chang, Kee Hyun; Han, Moon Hee; Chi, Je Geun [Seoul National Univ., Seoul (Korea, Republic of); Yoon, Hyun Ki [Ulsan Univ., Seoul (Korea, Republic of)

    1995-10-15

    The purpose of this study is to find helpful MR findings for predicting anaplastic oligodendrogliomas. Retrospective analysis of 46 MR images and 37 CT scans was performed for 46 patients with pathologically-proven cerebral oligodendrogliomas. A neuropathologist graded the tumors as one of low-grade (n = 16), intermediate-grade (n = 12), or anaplastic oligodendroglioma (n 18). MR imaging features were retrospectively analysed with respect to histologic grading of the tumors. Contrast enhancement was observed always in anaplastic group (17/17), in a portion of intermediate-grade group (4/10) but not in low-grade group (0/4). Peritumoral edema was observed infrequently in anaplastic group (4/18) or intermediate-grade group (1/12). Cystic changes (25/46) or calcifications on CT Scans (14/37) were not related with histologic grading. Grossly identifiable hemorrhage was rare in this series (2/46). Among the various imaging features, only tumor enhancement and peritumoral edema were statistically significant for trend test ({rho} < 0.05). When considering the diagnosis of oligodendrogliomas, the presence of contrast enhancement or peritumoral edema is a helpful features suggesting anaplastic oligodendrogliomas.

  18. Anaplastic ganglioglioma arising from a Lhermitte-Duclos-like lesion. Case report.

    Science.gov (United States)

    Takei, Hidehiro; Dauser, Robert; Su, Jack; Chintagumpala, Murali; Bhattacharjee, Meenakshi B; Jones, Jeremy; Adesina, Adekunle M

    2007-08-01

    The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.

  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

  20. 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-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

  1. Leptomeningeal metastases from anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Solomon, B.; Rischin, D.; Lyons, B.; Peters, L.J.

    2000-01-01

    Anaplastic thyroid carcinoma is an extremely aggressive neoplasm that accounts for 1-3% of all thyroid cancers. ' Most patients have metastatic disease at presentation and die in a short period of time, often with uncontrolled local disease. We report a case of anaplastic thyroid cancer characterised by good response to initial treatment both locally and in distant metastases, and the subsequent development of refractory metastatic disease in an unusual site, the leptomeninges

  2. Small Cell Anaplastic Carcinoma of Primary Lung Tumor in a Miniature Schnauzer Dog

    Directory of Open Access Journals (Sweden)

    J. M. Kim, H. J. Han, B. Ku, G. Kim, K. M. Shim1, S. S. Kang2 and S. H. Choi*

    2011-04-01

    Full Text Available 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 resected although adhered part of CVC could not be completely resected. On histopathological findings, the mass was diagnosed as small-cell anaplastic carcinoma.

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

    International Nuclear Information System (INIS)

    Kim, J.M.; Han, H.J.; Ku, B.; Kim, G.; Shim, K.M.; Kang, S.S.; Choi, S.H.

    2011-01-01

    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

  4. Anaplastic carcinoma

    International Nuclear Information System (INIS)

    Parikh, D.M.; Agarwal, S.; Rao, R.S.

    1999-01-01

    Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

  5. Anaplastic Carcinoma and Toxic Multinodular Goiter: An Unusual Presentation

    Science.gov (United States)

    Marcelino, Mafalda; Marques, Pedro; Lopes, Luis; Leite, Valeriano; de Castro, João Jácome

    2014-01-01

    A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far. PMID:25759806

  6. Suprasellar Anaplastic Meningioma Masquerading As Craniopharyngioma: A Case Report

    Directory of Open Access Journals (Sweden)

    Eman Abdelzaher

    2014-06-01

    Full Text Available Anaplastic meningiomas are uncommon. We report the clinical, radiological and pathological features of an anaplastic meningioma in a young male Egyptian patient presenting as a suprasellar solid/cystic enhancing mass resembling a craniopharyngioma. [J Interdiscipl Histopathol 2014; 2(3.000: 154-157

  7. Anaplastic myxopapillary ependymoma in an infant: Case report and literature review.

    Science.gov (United States)

    Trivedi, Darshan; Xiong, Zhenggang

    2017-05-01

    A 7-month-old boy presented with gastrointestinal disturbance, mild neurologic deficit of the left lower extremity and levo-scoliosis of the thoracic spine. Magnetic resonance imaging demonstrated a large intramedullary lesion involving the thoracic spine, from level T1 to T11. Histologic analysis showed a glial tumor with fibrillary processes arranged in radial pattern around mucoid fibrovascular cores with a high proliferative index (focally up to 80%) and prominent vascular endothelial hyperplasia. These findings were consistent with an anaplastic myxopapillary ependymoma. Subtotal resection was performed via a T3-T10 laminoplasty. A ventricular shunt was placed, and the patient subsequently received chemoradiation therapy. To date, this is the second case of a myxopapillary ependymoma with high-grade anaplastic features and the first case in an infant reported in the literature.

  8. Anaplastic meningioma: The dark side of meningiomas

    Directory of Open Access Journals (Sweden)

    Andreea Cioca

    2017-06-01

    Full Text Available Anaplastic meningioma is a rare malignant tumor of the meninges, with a very aggressive behavior and a grim prognosis. Here we report a case of a 64-year old man which presented to the neurosurgery department with motor deficit in the right hemi–body, loss of speech and disorientation. Magnetic resonance imaging detected a mass located in the left frontal lobe that measured 7/8/7 cm, leading to the conclusion that surgery is necessary. Microscopic examination of the tumor showed great number of hypercellular areas with a high mitotic index, and focal necrosis with psammoma bodies. Using a panel of antibodies such as EMA, vimentin, CD34 GFAP, pancytokeratin and Ki67, we concluded that he final diagnosis was anaplastic meningioma, WHO grade III. Due to its morphological similarity with other tumors, the diagnosis of anaplastic meningioma may be challenging.

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

    International Nuclear Information System (INIS)

    Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

    2005-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Shah Keerti V

    2005-02-01

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

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

    Science.gov (United States)

    Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

    2005-01-01

    Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein. PMID:15717928

  12. Remarkable Presentation: Anaplastic Thyroid Carcinoma Arising from Chronic Hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Habib G. Zalzal

    2018-01-01

    Full Text Available Background. Undifferentiated anaplastic carcinoma rarely develops from chronic hyperthyroidism. Although acute hyperthyroidism can develop prior to anaplastic transformation, chronic hyperthyroidism was thought to be a protective measure against thyroid malignancy. Methods. A 79-year-old female presented acutely to the hospital with dyspnea. She had been taking methimazole for chronic hyperthyroidism due to toxic thyroid nodules, previously biopsied as benign. Upon admission, imaging showed tracheal compression, requiring a total thyroidectomy with tracheostomy for airway management. Results. Pathology demonstrated undifferentiated anaplastic thyroid carcinoma. The patient passed away shortly after hospital discharge. Despite treatment with methimazole for many years, abrupt enlargement of her toxic multinodular goiter was consistent with malignant transformation. Chronic hyperthyroidism and toxic nodules are rarely associated with thyroid malignancy, with only one previous report documenting association with anaplastic thyroid carcinoma. Conclusion. Progressive thyroid enlargement and acute worsening of previously controlled hyperthyroidism should promote concern for disease regardless of baseline thyroid function.

  13. The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.

    Science.gov (United States)

    Gravanis, Iordanis; Tzogani, Kyriaki; van Hennik, Paula; de Graeff, Pieter; Schmitt, Petra; Mueller-Berghaus, Jan; Salmonson, Tomas; Gisselbrecht, Christian; Laane, Edward; Bergmann, Lothar; Pignatti, Francesco

    2016-01-01

    On October 25, 2012, a conditional marketing authorization valid throughout the European Union (EU) was issued for brentuximab vedotin for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL) and for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). For HL, the indication is restricted to treatment after autologous stem cell transplantation (ASCT) or after at least two previous therapies when ASCT or multiagent chemotherapy is not a treatment option. Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody (recombinant chimeric IgG1) that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE). Binding of the ADC to CD30 on the cell surface initiates internalization of the MMAE-CD30 complex, followed by proteolytic cleavage that releases MMAE. The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Brentuximab vedotin as a single agent was evaluated in two single-arm studies. Study SG035-003 included 102 patients with relapsed or refractory HL. An objective response was observed in 76 patients (75%), with complete remission in 34 (33%). Study SG035-004 included 58 patients with relapsed or refractory sALCL. An objective response was observed in 50 patients (86%), with complete remission in 34 (59%). The most frequently observed toxicities were peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, vomiting, pyrexia, and upper respiratory tract infection. The present report summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of the product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu). Brentuximab vedotin was approved in the European Union for the treatment of adult

  14. 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

  15. Garlic-derived compound S-allylmercaptocysteine (SAMC) is active against anaplastic thyroid cancer cell line 8305C (HPACC).

    Science.gov (United States)

    Liu, Yuexin; Yan, Jinyin; Han, Xiaochen; Hu, Wanning

    2015-01-01

    Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic have anticancer activity. In this study, the apoptotic effects of Garlic-derived compound S-allylmercaptocysteine (SAMC) were investigated in 8305C human anaplastic thyroid carcinoma cells. The cell line 8305C (HPACC) were treated with SAMC and the MTT assay, flow cytometry (FCM), electron microscope method were used to test cell cycle, inhibitory rate and morphologic changes respectively. HPACC-8305C cells were suppressed after exposure to SAMC of 0.02 mg/ml, 0.06 mg/ml, and 0.1 mg/ml for 48 h. Compared with the control, the difference was significant (P< 0.05). SAMC could induce apoptosis of the cells in a dose-dependent and non-linear manner and increase the proportion of cells in the G2/M phase. Compared with the control, the difference was significant in terms of the percentage of cells in the G2/M phase (P< 0.05). After exposure to SAMC at 0.02 mg/ml for 24 hours, HPACC-8305C cells showed typical morphologic change. SAMC inhibits the growth of HPACC-8305C cells by induction of apoptotic cell death and inhibit telomerase activity, which appears to account for its anti-cancer activity.

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

    Science.gov (United States)

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

    2014-10-01

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

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

    International Nuclear Information System (INIS)

    Shao, Mingchen; Geng, Yiwei; Lu, Peng; Xi, Ying; Wei, Sidong; Wang, Liuxing; Fan, Qingxia; Ma, Wang

    2015-01-01

    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

  19. CT imaging features of anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    Shi Zhenshan; You Ruixiong; Cao Dairong; Li Yueming; Zhuang Qian

    2013-01-01

    Objective: To investigate the CT characteristics of anaplastic thyroid carcinoma and evaluate the diagnostic value of CT in this disease. Methods: The CT findings of 10 patients with pathologically proved anaplastic thyroid carcinoma were retrospectively reviewed. The patients included 7 females and 3 males. Their age ranged from 25.0 to 78 years with median of 61 years. Multi-slices plain and post contrast CT scans were performed in all patients. Results: Unilateral thyroid was involved in 6 patients. Unilateral thyroid and thyroid isthmus were both involved in 2 patients due to big size. Bilateral thyroid were involved in 2 patients. The maximum diameter of anaplastic thyroid carcinoma ranged from 2.9-12.8 cm with mean of (4.5 ± 1.4) cm. All lesions demonstrated unclear margins and envelope invasion. The densities of all lesions were heterogeneous and obvious necrosis areas were noted on precontrast images. Seven lesions showed varied calcifications, and coarse granular calcifications were found in 5 lesions among them. All lesions showed remarkable heterogenous enhancement on post-contrast CT. The CT value of solid portion of the tumor increased 40 HU after contrast media administration. The ratios of CT value which comparing of the tumor with contralateral sternocleidomastoid muscle were 0.69-0.82 (0.76 ± 0.18) and 1.25-1.41 (1.33 ± 0.28) on pre and post CT, respectively. Enlarged cervical lymph nodes were found in 6 cases (60.0%). It showed obvious homogeneous enhancement or irregular ring-like enhancement on post-contrast images and dot calcifications were seen in 1 case. Conclusions: Relative larger single thyroid masses with coarse granular calcifications, necrosis,envelope invasion, remarkable heterogeneous enhancing and enlarged lymph nodes on CT are suggestive of anaplastic thyroid carcinoma. (authors)

  20. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer

    DEFF Research Database (Denmark)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju

    2017-01-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib......-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review...... (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated...

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

    Science.gov (United States)

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

    2016-08-01

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

  2. Successful Management of Crizotinib-Induced Neutropenia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Jun Osugi

    2016-01-01

    Full Text Available Crizotinib, the first clinically available inhibitor of anaplastic lymphoma kinase (ALK gene rearrangement, is generally well tolerated. In contrast, neutropenia induced by crizotinib is a commonly reported grade 3 or 4 adverse event. In such cases, interruption and dose reduction of crizotinib might be necessary for some patients with severe neutropenia. However, information concerning clinical experience and management of severe neutropenia is currently limited. In this report, the successful management of crizotinib-induced neutropenia by dose reduction of crizotinib in a patient with ALK-positive non-small cell lung cancer is described.

  3. Thirty-nine cases of intracranial hemangiopericytoma and anaplastic hemangiopericytoma: A retrospective review of MRI features and pathological findings

    International Nuclear Information System (INIS)

    Zhou, Jun-lin; Liu, Jian-li; Zhang, Jing; Zhang, Ming

    2012-01-01

    Objective: To retrospectively review the imaging features of surgically and pathologically confirmed intracranial hemangiopericytoma and anaplastic hemangiopericytoma. Methods: Thirty-nine cases of surgically and pathologically confirmed hemangiopericytoma and anaplastic hemangiopericytoma were analyzed retrospectively. The MRI features were compared with pathological findings in all cases. Results: Of the 39 cases, 21 were anaplastic hemangiopericytoma (WHO grade III) and the remaining cases were hemangiopericytoma (WHO grade II); all lesions were solitary. MRI of anaplastic hemangiopericytoma showed that 20 cases were lobulated, and nine grew cross-leaf. The lesions showed mixed iso-high-low signal (n = 20) or iso-signal (n = 1) on plain T1WI, and mixed high-low signal (n = 20) or iso-signal (n = 1) on plain T2WI. After contrast injection, marked heterogeneous enhancement was seen in 19 cases. Significant necrosis and cystic changes were seen in 16 cases, and the “dural tail sign” was found in two cases. Ten cases had bony destruction, and 16 showed significant peritumoral edema. In 18 cases of hemangiopericytoma, nine were oval-shaped and three grew cross-leaf. The lesions showed mixed iso-low signal (n = 10) or iso-signal (n = 8) on plain T1WI, and mixed iso-high signal (n = 10) or iso-signal (n = 8) on plain T2WI. After contrast injection, significant uniform enhancement was seen in 10 cases. Significant necrosis and cystic changes were seen in seven cases, and “dural tail sign” was seen in six cases. Two cases had bony destruction. No case showed significant peritumoral edema. Pathological immunohistochemical Ki67 staining showed a concentration of ∼18.4% positive cells in anaplastic hemangiopericytoma, whereas in hemangiopericytoma it was 7.12%. Conclusion: Imaging findings of intracranial anaplastic hemangiopericytoma had more pronounced lobulation, cross-leaf growth tendency, more and easier bleeding, more necrosis, more cystic changes giving

  4. A comparative study of cell cycle mediator protein expression patterns in anaplastic and papillary thyroid carcinoma.

    Science.gov (United States)

    Evans, Juanita J; Crist, Henry S; Durvesh, Saima; Bruggeman, Richard D; Goldenberg, David

    2012-07-01

    Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

  5. CTOP/ITE/MTX Compared With CHOP as the First-line Therapy for Newly Diagnosed Young Patients With T Cell Lymphoma

    Science.gov (United States)

    2017-11-10

    ALK-negative Anaplastic Large Cell Lymphoma; Peripherial T Cell Lymphoma,Not Otherwise Specified; Angioimmunoblastic T Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Hepatosplenic T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma

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

    Directory of Open Access Journals (Sweden)

    Giovanni Zito

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

  7. Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    Smith, Sonali M.; Burns, Linda J.; van Besien, Koen; LeRademacher, Jennifer; He, Wensheng; Fenske, Timothy S.; Suzuki, Ritsuro; Hsu, Jack W.; Schouten, Harry C.; Hale, Gregory A.; Holmberg, Leona A.; Sureda, Anna; Freytes, Cesar O.; Maziarz, Richard Thomas; Inwards, David J.; Gale, Robert Peter; Gross, Thomas G.; Cairo, Mitchell S.; Costa, Luciano J.; Lazarus, Hillard M.; Wiernik, Peter H.; Maharaj, Dipnarine; Laport, Ginna G.; Montoto, Silvia; Hari, Parameswaran N.

    2013-01-01

    Purpose To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma. Patients and Methods Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes. Results AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival. Conclusion These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology. PMID:23897963

  8. Is Latin America Ready to Identify Anaplastic Large Cell Lymphoma in Breast Implants Patients? Regional Encounter During the National Plastic Surgery Meeting in Cancun, Mexico.

    Science.gov (United States)

    Ramos-Gallardo, Guillermo; Cuenca-Pardo, Jesus; Cardenas-Camarena, Lazaro; Duran-Vega, Hector; Rodríguez-Olivares, Eugenio; Bayter-Marin, Jorge Enrique; Levelier De Doig Alvear, Gerardo; Vazquez, Guillermo; Fontbona-Torres, Montserrat; Galán-Suárez, Ricardo; Guzman-Stein, Gabriela; Guzmán-Padilla, Sergio; Echeverría-Roldán, Guillermo; Silva-Gavarrete, Jose Fernando; Vallarta-Rodríguez, Alfonso; Contreras-Bulnes, Livia; Oaxaca-Escobar, Carlos Guillemro; Caravantes-Cortes, Isabel; Flores, María Eugenia; Cowes-McGowen, Jorge; Maciel-Sosa, María Liz; Delgado-Binasco, Ricardo; Rincón-Rubio, Linda

    2018-05-16

    Anaplastic large cell lymphoma associated with breast implants is receiving increased attention. Most cases have been reported in Europe, North America (USA and Canada), Australia and New Zealand. Fewer cases have been reported in Latin America (including Mexico), Africa and Asia. This report was delivered during our national plastic surgery meeting in Cancun in May 2017. Before the meeting, two participants reviewed the literature. The review was performed using the following information sources: PubMed, Embase, Cochrane, Fisterra, Google Scholar and LILACS, with entries from 1980 to August 2015 in several languages (English, Spanish, French and Portuguese). The results were revealed during the meeting to the other participants. The consensus was divided into two parts. The first part included an open-ended question regarding the incidence and prevalence of the problem. The second part included clinical scenarios with different items that were rated by the participants. After this activity, accordance among the responses was evaluated. Seven cases were reported during the meeting (3 from Mexico, 3 from Chile and 1 from Argentina). Fifty percent of the participants reported consulting with guidelines and clinical centers to help with potential cases. Most agreed that further studies must be done in cases of chronic seroma where the capsule plays an important role. A current debate exists about the incidence of this problem in Latin America because we did not report the same number of cases as Europe, Australia or North America. More studies are required to determine the differences among reports in Latin America. Most representatives agreed that further studies must be done. Concern is increasing, and the problem is known. Other factors involved may be considered, and the problem must not be ignored. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the

  9. Anaplastic thyroid carcinoma in Denmark 1996-2012

    DEFF Research Database (Denmark)

    Hvilsom, Gitte Bjørn; Londero, Stefano Christian; Hahn, Christoffer Holst

    2018-01-01

    BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC...

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

    Directory of Open Access Journals (Sweden)

    Maher Kurdi

    2014-01-01

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

  11. 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.

  12. 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.

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Antonietta R. Farina

    2013-01-01

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

  15. Radiotherapy in anaplastic thyroid carcinoma: An Australian experience

    International Nuclear Information System (INIS)

    So, Kevin; Smith, Robin E.; Davis, Sidney R.

    2017-01-01

    Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period. A retrospective review of prospectively collected data from a single Australian Institution (Alfred Health Radiation Oncology) was carried out on patients referred with anaplastic thyroid carcinoma between 1992 and 2013. Thirty patients (17 females and 13 males) were identified with a median age at presentation of 72 years. At presentation, six (20%), 14 (47%) and 10 (33%) patients had stage IVA, IVB and IVC disease respectively. Thirteen patients underwent radical surgical resection with five having microscopic residual (R1) and eight having macroscopic residual (R2) disease. Twenty-eight patients were offered radiotherapy with 27 proceeding with treatment. Of those who received radiotherapy, three, six and 18 were treated with adjuvant, definitive and palliative intent respectively. Six patients had concomitant chemotherapy of which three received trimodality therapy. Only one patient experienced a grade 3 toxicity (oesophagitis). Median survival was 5.3 months and at last follow-up or time of death, 19 of 27 (70.4%) maintained loco-regional control. All patients who had R1 surgical resections and radiotherapy had loco-regional control. Seven of nine (77.8%) and 12 of 18 (66.7%) achieved loco-regional control after receiving definitive or palliative radiotherapy, respectively. Our study suggests that radiotherapy with or without surgery or chemotherapy is well-tolerated and results in durable loco-regional control in a high proportion of patients with anaplastic thyroid carcinoma.

  16. Juvenile Granulosa Cell Tumour: Anaplastic Variant with Omental Deposits

    Science.gov (United States)

    Rao, Anuradha C.K.; Monappa, Vidya

    2016-01-01

    Juvenile Granulosa Cell Tumour (JGCT) of ovary represents a small fraction of all primary ovarian malignancies. It is a subtype of granulosa cell tumour that is almost always found during the first three decades of life. Histologically, it differs from the typical adult type of granulosa cell tumour. It accounts for 5-15% of all granulosa cell tumours, majority being unilateral. Herein, we describe an unusual histopathological variant of JGCT with numerous large cystic spaces, anaplasia and focal syncytiotrophoblast like giant cells. PMID:27042471

  17. Establishment and characterization of new cell lines of anaplastic pancreatic cancer, which is a rare malignancy: OCUP-A1 and OCUP-A2

    International Nuclear Information System (INIS)

    Miura, Kotaro; Kimura, Kenjiro; Amano, Ryosuke; Yamazoe, Sadaaki; Ohira, Go; Murata, Akihiro; Nishio, Kohei; Hasegawa, Tsuyoshi; Yashiro, Masakazu; Nakata, Bunzo; Ohira, Masaichi; Hirakawa, Kosei

    2016-01-01

    Anaplastic pancreatic cancer (APC) cell lines have been scarcely established. The morphology, gene expressions, karyotyping and epithelial-mesenchymal transition markers of newly established APC cell lines OCUP-A1 and OCUP-A2 were analyzed. Their abilities of proliferation under normoxia and hypoxia, migration and invasion were compared to 4 commercially available pancreatic ductal adenocarcinoma (PDA) cell lines. Their induction of angiogenesis, stem-like cell population and subcutaneous tumor growth in nude mice were estimated, comparing 2 PDA cell lines examined here. OCUP-A1 and OCUP-A2 cells continuously grew with spindle and polygonal shapes, respectively. Gene analysis revealed 9 gene mutations including KRAS and TP53. Karyotyping clarified numerical structural abnormalities in both cells. Loss of E-cadherin and expression of vimentin in both cell lines were observed. The doubling time of both cell lines was approximately 20 h. Proliferation, migration and invasion abilities were not notable compared to other PDA cell lines. However stem-like cell population of both cell lines was superior to a part of PDA cell lines. Moreover OCUP-A1 showed stronger hypoxia tolerance and induction of angiogenesis than other PDA cell lines. The tumorigenicity in vivo of OCUP-A2 was stronger than conventional PDA cell lines. The OCUP-A1 and OCUP-A2 cell lines of rare malignancies might be useful for investigating the biology of pancreatic cancer

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zeliha Esin Celik

    2016-01-01

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

  20. Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-06-03

    Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  2. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    International Nuclear Information System (INIS)

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

    2011-01-01

    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

  3. 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.

  4. The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression.

    Science.gov (United States)

    Heiden, Katherine B; Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Wang, Yimin; Liu, Dingxie; Xing, Mingzhao; Prinz, Richard A; Xu, Xiulong

    2014-11-01

    Cancer stem cells (CSCs) have been recently identified in thyroid neoplasm. Anaplastic thyroid cancer (ATC) contains a higher percentage of CSCs than well-differentiated thyroid cancer. The signaling pathways and the transcription factors that regulate thyroid CSC self-renewal remain poorly understood. The objective of this study is to use two ATC cell lines (KAT-18 and SW1736) as a model to study the role of the sonic hedgehog (Shh) pathway in maintaining thyroid CSC self-renewal and to understand its underlying molecular mechanisms. The expression and activity of aldehyde dehydrogenase (ALDH), a marker for thyroid CSCs, was analyzed by Western blot and ALDEFLUOR assay, respectively. The effect of three Shh pathway inhibitors (cyclopamine, HhAntag, GANT61), Shh, Gli1, Snail knockdown, and Gli1 overexpression on thyroid CSC self-renewal was analyzed by ALDEFLUOR assay and thyrosphere formation. The sensitivity of transfected KAT-18 cells to radiation was evaluated by a colony survival assay. Western blot analysis revealed that ALDH protein levels in five thyroid cancer cell lines (WRO82, a follicular thyroid cancer cell line; BCPAP and TPC1, two papillary thyroid cancer cell lines; KAT-18 and SW1736, two ATC cell lines) correlated with the percentage of the ALDH(High) cells as well as Gli1 and Snail expression. The Shh pathway inhibitors, Shh and Gli1 knockdown, in KAT-18 cells decreased thyroid CSC self-renewal and increased radiation sensitivity. In contrast, Gli1 overexpression led to increased thyrosphere formation, an increased percentage of ALDH(High) cells, and increased radiation resistance in KAT-18 cells. Inhibition of the Shh pathway by three specific inhibitors led to decreased Snail expression and a decreased number of ALDH(High) cells in KAT-18 and SW1736. Snail gene knockdown decreased the number of ALDH(High) cells in KAT-18 and SW1736 cells. The Shh pathway promotes the CSC self-renewal in ATC cell lines by Gli1-induced Snail expression.

  5. Therapeutic options in peripheral T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Yaping Zhang

    2016-04-01

    Full Text Available Abstract Peripheral T cell lymphoma (PTCL is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK-positive anaplastic large cell lymphoma (ALCL, the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10–30 %. Novel targeted therapies and combination chemotherapies are required for the treatment of patients with PTCL. In recent years, some retrospective and prospective studies have been performed concerning PTCL. Consequently, a number of novel agents and their relevant combination therapies have been identified, including histone deacetylase inhibitors, immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, bendamustine, l-asparaginase, and other targeted agents. It is hoped that these innovative approaches will finally improve outcomes in patients with PTCL. This review summarizes the currently available approaches for the treatment of PTCL with an emphasis on potential new agents, including the role of stem cell transplantation.

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

    International Nuclear Information System (INIS)

    Zhang, L.; Wang, H.; Liang, S.; Ma, C.

    2015-01-01

    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.

  7. 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

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

  9. The importance of Notch signaling in peripheral T-cell lymphomas

    DEFF Research Database (Denmark)

    Kamstrup, Maria Rørbæk; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek

    2014-01-01

    Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL...... cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment...... with Notch inhibitors has cytotoxic effects....

  10. Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH.

    Science.gov (United States)

    Rianthavorn, Pornpimol; Cain, Joan P; Turman, Martin A

    2008-08-01

    The available treatment options for hyponatremia secondary to SIADH are limited and not completely effective. Conivaptan is a vasopressin 1a and 2 receptor antagonist recently approved by the US Food and Drug Administration (FDA) for treating euvolemic and hypervolemic hyponatremia in adult patients. However, data on efficacy and safety of conivaptan in pediatrics are limited. We report a case of a 13-year-old boy with extensively metastasized anaplastic large-cell lymphoma. He also developed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) prior to chemotherapy initiation. SIADH management in this case was complicated when fluid restriction was not safely attainable. Conivaptan played a significant role in this situation by allowing provision of a large amount of intravenous fluid prior to and during induction chemotherapy. It proved to be an important component in preventing uric acid nephropathy/tumor lysis syndrome. Conivaptan induced free-water clearance as indicated by increased urine output and decreased urine osmolality. The patient responded to conivaptan without any adverse effects.

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

    Science.gov (United States)

    2013-01-15

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

  12. Initiative For Thyroid Cancer Diagnosis: Decision Support System For Anaplast Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Jamil Ahmed Chandio

    2017-12-01

    Full Text Available Due to the high level exposure of biomedical image analysis, Medical image mining has become one of the well-established research area(s of machine learning. AI (Artificial Intelligence techniques have been vastly used to solve the complex classification problems of thyroid cancer. Since the persistence of copycat chromatin properties and unavailability of nuclei measurement techniques, it is really problem for doctors to determine the initial phases of nuclei enlargement and to assess the early changes of chromatin distribution. For example involvement of multiple transparent overlapping of nuclei may become the cause of confusion to infer the growth pattern of nuclei variations. Un-decidable nuclei eccentric properties may become one of the leading causes for misdiagnosis in Anaplast cancers. In-order to mitigate all above stated problems this paper proposes a novel methodology so called “Decision Support System for Anaplast Thyroid Cancer” and it proposes a medical data preparation algorithm AD (Analpast_Cancers which helps to select the appropriate features of Anaplast cancers such as (1 enlargement of nuclei, (2 persistence of irregularity in nuclei and existence of hyper chromatin. Proposed methodology comprises over four major layers, first layer deals with the noise reduction, detection of nuclei edges and object clusters. Second layer selects the features of object of interest such as nuclei enlargement, irregularity and hyper chromatin. Third layer constructs the decision model to extract the hidden patterns of disease associated variables and final layer evaluates the performance evaluation by using confusion matrix, precision and recall measures. The overall classification accuracy is measured about 97.2% with 10-k fold cross validation.

  13. Massage Therapy Given by Caregiver in Treating Quality of Life of Young Patients Undergoing Treatment for Cancer

    Science.gov (United States)

    2018-05-24

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Noncontiguous Stage II Mantle Cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Childhood Anaplastic Large Cell

  14. 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)

    2017-11-07

    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

  15. Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

    Science.gov (United States)

    2017-10-10

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

  16. Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in vivo.

    Science.gov (United States)

    Stenner, Frank; Liewen, Heike; Zweifel, Martin; Weber, Achim; Tchinda, Joelle; Bode, Beata; Samaras, Panagiotis; Bauer, Stefan; Knuth, Alexander; Renner, Christoph

    2008-09-01

    Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies, being responsible for the majority of thyroid cancer-related deaths. Despite multimodal therapy including surgery, chemotherapy, and radiotherapy, the outcome of ATC is poor. The human ATC cell line MB1, derived from tumor tissue of a 57-year-old man with thyroid cancer and pronounced neutrophilia, was established from surgically excised tumor tissue. The karyotype of the cell line shows many chromosomal abnormalities. Preclinical investigations have shown antitumor activity and effectiveness of the BRAF kinase inhibitor Sorafenib and the proteasome inhibitor Bortezomib. After establishment of the MB1 cell line these agents were applied in vitro and, showing activity in a cell culture model, were also used for in vivo treatment. Sorafenib had some clinical effect, namely normalization of leucocytosis, but had no sustained impact on subsequent tumor growth and development of distant metastasis. Molecular diagnostics of the tumor demonstrated no BRAF mutations in exons 11 and 15 concordant with a rather modest effect of Sorafenib on MB1 cell growth. Clinical benefit was seen with subsequent bortezomib therapy inducing a temporary halt to lymph node growth and a progression-free interval of 7 weeks. Our observations together with previous data from preclinical models could serve as a rationale for selecting those patients suffering from ATC most likely to benefit from targeted therapy. A prospective controlled randomized trial integrating kinase and proteasome inhibitors into a therapeutic regime for ATC is warranted.

  17. An extraneural primary anaplastic ependymoma at the subcutaneous inguinal region: Report of a rare case

    Directory of Open Access Journals (Sweden)

    Hamide Sayar

    2015-01-01

    Full Text Available Ependymomas commonly arise in the central nervous system. Extraneural presentation is quite rare. Herein, we describe a primary extraneural ependymoma in a young female. The mass was located in the right inguinal area. The cut surface of the 7.5 mm × 6.5 mm × 4.5 mm sized tumor was brownish-yellow in color. Histologically, it was hypercellular exhibiting pseudorosette or rosette formations and some papillary structures. Mitosis was counted as high as 10 per 10 high power fields. Neither necrosis nor vascular endothelial proliferation within the tumor was observed. Tumor cells showed strong glial fibrillary acidic protein immunoreactivity. On epithelial membrane antigen, intracytoplasmic dot-like immunostaining was observed. This is the first report presenting a primary extraneural anaplastic ependymoma arising in the inguinal subcutaneous region.

  18. An extraneural primary anaplastic ependymoma at the subcutaneous inguinal region: Report of a rare case.

    Science.gov (United States)

    Sayar, Hamide; Ersen, Ayca; Kurtul, Neslihan; Yazar, Mehmet Fatih; Balakan, Ozan

    2015-01-01

    Ependymomas commonly arise in the central nervous system. Extraneural presentation is quite rare. Herein, we describe a primary extraneural ependymoma in a young female. The mass was located in the right inguinal area. The cut surface of the 7.5 mm × 6.5 mm × 4.5 mm sized tumor was brownish-yellow in color. Histologically, it was hypercellular exhibiting pseudorosette or rosette formations and some papillary structures. Mitosis was counted as high as 10 per 10 high power fields. Neither necrosis nor vascular endothelial proliferation within the tumor was observed. Tumor cells showed strong glial fibrillary acidic protein immunoreactivity. On epithelial membrane antigen, intracytoplasmic dot-like immunostaining was observed. This is the first report presenting a primary extraneural anaplastic ependymoma arising in the inguinal subcutaneous region.

  19. Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases.

    Science.gov (United States)

    Bonhomme, Benjamin; Godbert, Yann; Perot, Gaelle; Al Ghuzlan, Abir; Bardet, Stéphane; Belleannée, Geneviève; Crinière, Lise; Do Cao, Christine; Fouilloux, Geneviève; Guyetant, Serge; Kelly, Antony; Leboulleux, Sophie; Buffet, Camille; Leteurtre, Emmanuelle; Michels, Jean-Jacques; Tissier, Frédérique; Toubert, Marie-Elisabeth; Wassef, Michel; Pinard, Clémence; Hostein, Isabelle; Soubeyran, Isabelle

    2017-05-01

    Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened. Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic

  20. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2018-04-10

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  1. De novo anaplastic Kaposi sarcoma in a HIV-negative man: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Slim Charfi

    2017-07-01

    Full Text Available Anaplastic Kaposi sarcoma is a rare variant of Kaposi’s and is typically associated with an agressive clinical course. We report a case of a 67-year-old HIV negative man, presented with multiple, pink nodules on the left ankle and a keratotic lesion of the right heel. Initial histopathological exam concluded to an undifferentiated sarcoma. A second biopsy was performed and concluded to an anaplastic Kaposi sarcoma. Immunohistochemical study was positive for HHV8. Treatment consisted on a tumor excision of all lesions. Our case and the review of the literature highlight the benefit of the non conservative surgical treatment for this aggressive form of Kaposi sarcoma.

  2. Expression of activating natural killer-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas.

    Science.gov (United States)

    Uemura, Yu; Isobe, Yasushi; Uchida, Akiko; Asano, Junko; Nishio, Yuji; Sakai, Hirotaka; Hoshikawa, Masahiro; Takagi, Masayuki; Nakamura, Naoya; Miura, Ikuo

    2018-04-01

    Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) was detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D were expressed in 7 (32%), 9 (41%), and 5 (23%) cases, respectively. Although LILRB1 was detected regardless of the disease entity, the activating NK-cell receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%; NKp46, 69%; and NKG2D, 38%). In addition, NKp46 and NKG2D were detected only in NK-cell neoplasms and cytotoxic T-lymphocyte-derived lymphomas including monomorphic epitheliotropic intestinal T-cell lymphoma. One Epstein-Barr virus-harboring cytotoxic T-lymphocyte-derived lymphoma mimicking extranodal NK/T-cell lymphoma, nasal type lacked these NK-cell receptors, indicating different cell origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a negative impact on survival among the 22 examined cases, which mainly received the standard chemotherapy regimen (log-rank test, P = .024). We propose that the presence of activating NK-cell receptors may provide new insights into understanding peripheral T-cell lymphomas and characterizing them as innate-like T-cell neoplasm. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on

  3. Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

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    DiBonaventura MD

    2017-12-01

    Full Text Available Marco D DiBonaventura,1 William Wong,2 Bijal Shah-Manek,3,4 Mathias Schulz2 1Ipsos Healthcare, Global Evidence, Value & Access, New York, NY, 2Genentech, US Medical Affairs, San Francisco, CA, 3Ipsos Healthcare, Global Evidence, Value & Access, San Francisco, CA, 4College of Pharmacy, Touro University California, CA, USA Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods: Participating oncologists (N=95 in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor, collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results: A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male. The patients in our sample were older (median age of 60 vs 53 years, were more likely to be current smokers (12% vs 1%, had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0, and were less likely to have an adenocarcinoma histology (83% vs 96% relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively as was the disease control rate (89.9% vs 78.8%, respectively, though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0% and dose reductions (3.4% due to adverse events were uncommon in alectinib.Conclusion: Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically

  4. 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.

  5. Metronomic chemotherapy in anaplastic thyroid carcinoma: a potentially feasible alternative to therapeutic nihilism.

    Science.gov (United States)

    Revannasiddaiah, Swaroop; Madabhavi, Irappa; Bodh, Anita; Thakur, Priyanka; Sharma, Mukesh

    2015-01-01

    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.

  6. CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL

    Science.gov (United States)

    2016-04-18

    Peripheral T-Cell Lymphoma; Angioimmunoblastic T Cell Lymphoma; ALK-negative Anaplastic Large Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma; Acute Adult T-Cell Leukemia/Lymphoma

  7. Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

    Science.gov (United States)

    Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

    2013-07-01

    Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

  8. A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

    Science.gov (United States)

    2018-01-29

    Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

  9. CRISPR/Cas9 Genome Editing of Epidermal Growth Factor Receptor Sufficiently Abolished Oncogenicity in Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Li-Chi Huang

    2018-01-01

    Full Text Available Anaplastic carcinoma of the thyroid (ATC, also called undifferentiated thyroid cancer, is the least common but most aggressive and deadly thyroid gland malignancy of all thyroid cancers. The aim of this study is to explore essential biomarker and use CRISPR/Cas9 with lentivirus delivery to establish a gene-target therapeutic platform in ATC cells. At the beginning, the gene expression datasets from 1036 cancers from CCLE and 8215 tumors from TCGA were collected and analyzed, showing EGFR is predominantly overexpressed in thyroid cancers than other type of cancers (P=0.017 in CCLE and P=0.001 in TCGA. Using CRISPR/Cas9 genomic edit system, ATC cells with EGFR sgRNA lentivirus transfection obtained great disruptions on gene and protein expression, resulting in cell cycle arrest, cell growth inhibition, and most importantly metastasis turn-off ability. In addition, the FDA-approved TKI of afatinib for EGFR targeting also illustrates great anticancer activity on cancer cell death occurrence, cell growth inhibition, and cell cycle arrest in SW579 cells, an EGFR expressing human ATC cell line. Furthermore, off-target effect of using EGFR sgRNAs was measured and found no genomic editing can be detected in off-target candidate gene. To conclude, this study provides potential ATC therapeutic strategies for current and future clinical needs, which may be possible in increasing the survival rate of ATC patients by translational medicine.

  10. Investigation of the results of therapy of anaplastic thyroid gland carcinomas

    International Nuclear Information System (INIS)

    Ooijen, M. van.

    1979-01-01

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Walter Arancio

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-03-01

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

  14. c-myc overexpression causes anaplasia in medulloblastoma.

    Science.gov (United States)

    Stearns, Duncan; Chaudhry, Aneeka; Abel, Ty W; Burger, Peter C; Dang, Chi V; Eberhart, Charles G

    2006-01-15

    Both anaplasia and increased c-myc gene expression have been shown to be negative prognostic indicators for survival in medulloblastoma patients. myc gene amplification has been identified in many large cell/anaplastic medulloblastoma, but no causative link between c-myc and anaplastic changes has been established. To address this, we stably overexpressed c-myc in two medulloblastoma cell lines, DAOY and UW228, and examined the changes in growth characteristics. When analyzed in vitro, cell lines with increased levels of c-myc had higher rates of growth and apoptosis as well as significantly improved ability to form colonies in soft agar compared with control. When injected s.c. into nu/nu mice, flank xenograft tumors with high levels of c-myc in DAOY cell line background were 75% larger than those derived from control. Overexpression of c-myc was required for tumor formation by UW228 cells. Most remarkably, the histopathology of the Myc tumors was severely anaplastic, with large areas of necrosis/apoptosis, increased nuclear size, and macronucleoli. Indices of proliferation and apoptosis were also significantly higher in Myc xenografts. Thus, c-myc seems to play a causal role in inducing anaplasia in medulloblastoma. Because anaplastic changes are often observed in recurrent medulloblastoma, we propose that c-myc dysregulation is involved in the progression of these malignant embryonal neoplasms.

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

    Science.gov (United States)

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

    2015-03-01

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

  16. Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2017-04-17

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

  17. An infant with hyperalertness, hyperkinesis, and failure to thrive: a rare diencephalic syndrome due to hypothalamic anaplastic astrocytoma.

    Science.gov (United States)

    Stival, Alessia; Lucchesi, Maurizio; Farina, Silvia; Buccoliero, Anna Maria; Castiglione, Francesca; Genitori, Lorenzo; de Martino, Maurizio; Sardi, Iacopo

    2015-09-04

    Diencephalic Syndrome is a rare clinical condition of failure to thrive despite a normal caloric intake, hyperalertness, hyperkinesis, and euphoria usually associated with low-grade hypothalamic astrocytomas. We reported an unusual case of diencephalic cachexia due to hypothalamic anaplastic astrocytoma (WHO-grade III). Baseline endocrine function evaluation was performed in this patient before surgery. After histological diagnosis, he enrolled to a chemotherapy program with sequential high-dose chemotherapy followed by hematopoietic stem cell rescue. The last MRI evaluation showed a good response. The patient is still alive with good visual function 21 months after starting chemotherapy. Diencephalic cachexia can rarely be due to high-grade hypothalamic astrocytoma. We suggest that a nutritional support with chemotherapy given to high doses without radiotherapy could be an effective strategy for treatment of a poor-prognosis disease.

  18. Why large cells dominate estuarine phytoplankton

    Science.gov (United States)

    Cloern, James E.

    2018-01-01

    Surveys across the world oceans have shown that phytoplankton biomass and production are dominated by small cells (picoplankton) where nutrient concentrations are low, but large cells (microplankton) dominate when nutrient-rich deep water is mixed to the surface. I analyzed phytoplankton size structure in samples collected over 25 yr in San Francisco Bay, a nutrient-rich estuary. Biomass was dominated by large cells because their biomass selectively grew during blooms. Large-cell dominance appears to be a characteristic of ecosystems at the land–sea interface, and these places may therefore function as analogs to oceanic upwelling systems. Simulations with a size-structured NPZ model showed that runs of positive net growth rate persisted long enough for biomass of large, but not small, cells to accumulate. Model experiments showed that small cells would dominate in the absence of grazing, at lower nutrient concentrations, and at elevated (+5°C) temperatures. Underlying these results are two fundamental scaling laws: (1) large cells are grazed more slowly than small cells, and (2) grazing rate increases with temperature faster than growth rate. The model experiments suggest testable hypotheses about phytoplankton size structure at the land–sea interface: (1) anthropogenic nutrient enrichment increases cell size; (2) this response varies with temperature and only occurs at mid-high latitudes; (3) large-cell blooms can only develop when temperature is below a critical value, around 15°C; (4) cell size diminishes along temperature gradients from high to low latitudes; and (5) large-cell blooms will diminish or disappear where planetary warming increases temperature beyond their critical threshold.

  19. 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.

  20. Unusual presentation of anaplastic thyroid carcinoma with diffuse neck and thoracic nodules and hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Yun-Hsuan Lin

    2017-06-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is a highly aggressive endocrine tumor that can be expected to have a poor clinical outcome. Cutaneous metastases from ATC are rare and in the context of disseminated metastases. Owing to the rarity of the disease, no standard treatment has been documented, and few treatment modalities are effective. This case reports neck and thoracic cutaneous metastasis from ATC, with concurrent hyperthyroidism.

  1. Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

    Science.gov (United States)

    Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

    2003-01-01

    The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

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

    Science.gov (United States)

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

    2014-11-26

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

  3. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    International Nuclear Information System (INIS)

    Junor, E.J.; Paul, J.; Reed, N.S.

    1992-01-01

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

  4. Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Junor, E.J.; Paul, J.; Reed, N.S. (Beatson Oncology Centre, Glasgow (United Kingdom))

    1992-04-01

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

  5. 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).

  6. Anaplastic astrocytoma 14 years after radiotherapy for pituitary adenoma

    International Nuclear Information System (INIS)

    Tamura, Masaru; Misumi, Syuuzou; Kurosaki, Syuuhei; Shibasaki, Takashi; Ohye, Chihiro

    1992-01-01

    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. 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)

  7. BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.

    Science.gov (United States)

    Chiappetta, Gennaro; Basile, Anna; Arra, Claudio; Califano, Daniela; Pasquinelli, Rosa; Barbieri, Antonio; De Simone, Veronica; Rea, Domenica; Giudice, Aldo; Pezzullo, Luciano; De Laurenzi, Vincenzo; Botti, Gerardo; Losito, Simona; Conforti, Daniela; Turco, Maria Caterina

    2012-01-01

    Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism. BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

  8. Stages of Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  9. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer

    NARCIS (Netherlands)

    Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit.

  10. Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Chien-Chih Ke

    2011-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy.

  11. 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.

  12. Treatment Option Overview (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  13. General Information about Non-Small Cell Lung Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  14. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  15. Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood non-Hodgkin lymphoma has different types including Burkitt, diffuse large B-cell, primary mediastinal B-cell, lymphoblastic, and anaplastic large cell lymphoma. Get information about the risk factors, symptoms, tests to diagnose, staging, and treatment of all types of newly diagnosed and recurrent NHL and lymphoproliferative disease in this expert-reviewed summary.

  16. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E-mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease.

  17. Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

    Science.gov (United States)

    Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

    2014-04-01

    CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

  18. Treatment Options for Childhood Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Patients with anaplastic large cell lymphoma have a receptor , called CD30, on the surface of their T ...

  19. Treatment Option Overview (Childhood Non-Hodgkin Lymphoma)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Patients with anaplastic large cell lymphoma have a receptor , called CD30, on the surface of their T ...

  20. Stages of Childhood Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Patients with anaplastic large cell lymphoma have a receptor , called CD30, on the surface of their T ...

  1. Treatment Options by Stage (Non-Small Cell Lung Cancer)

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

  2. Clonal expansion to anaplasia in Wilms` tumors is associated with p53 mutations

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, J.; Beckwith, B.; Bardeesy, N. [Loma Linda Univ., CA (United States)]|[McGill Univ., Montreal (Canada)

    1994-09-01

    The genetics of Wilms` tumor (WT), a pediatric malignancy of the kidney, is complex. Three loci are implicated in WT initiation and include the WT1 tumor suppressor gene (residing at 11p13), an 11p15 locus, and a non-11p locus. As well, allelic loss at 16q24 in {approximately}20% of sporadic WTs suggests the location of (an) additional gene(s) involved in tumor progression. Initiation and progression in WTs is associated with multiple histological variants. Anaplasia is a rare WT subtype associated with poor prognosis and defined by enlarged and multipolar mitotic figures, a threefold nuclear enlargement (compared with adjacent nuclei of the same cell type), and hyperchromasia of the enlarged nuclei. We have previously demonstrated that p53 gene mutations are exclusively associated with anaplastic WTs, being absent from a large number of non-anaplastic WTs analyzed. To determine if such mutations are involved in clonal progression to anaplasia, we performed a retrospective analysis of histologically defined sections from tumor specimens. Six of ten WTs demonstrated p53 mutations by PCR-single stranded conformational polymorphism analysis. Two of these samples were paired, consisting of geographically demarcated anaplastic cells embedded within a non-anaplastic tumor bed. In these cases, p53 mutations were only present in the anaplastic region of the tumor. An overall decrease in the number of apoptotic cells was found associated with the anaplastic tumor region, compared to adjacent non-anaplastic tumor bed. These results indicate that p53 mutations arise during progression to anaplasia late in Wilms` tumor etiology and are associated with a more aggressive form of this cancer.

  3. An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.

    Science.gov (United States)

    Daou, Badih; Zanello, Marc; Varlet, Pascale; Brugieres, Laurence; Jabbour, Pascal; Caron, Olivier; Lavoine, Noémie; Dhermain, Frederic; Willekens, Christophe; Beuvon, Frederic; Malka, David; Lechapt-Zalcmann, Emmanuèle; Abi Lahoud, Georges

    2015-07-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed. We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors. Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.

  4. Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing

    DEFF Research Database (Denmark)

    Nagasawa, T; Zhang, Q; Raghunath, P N

    2006-01-01

    To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-express...

  5. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600–Mutant Anaplastic Thyroid Cancer

    Science.gov (United States)

    Subbiah, Vivek; Kreitman, Robert J.; Wainberg, Zev A.; Cho, Jae Yong; Schellens, Jan H.M.; Soria, Jean Charles; Wen, Patrick Y.; Zielinski, Christoph; Cabanillas, Maria E.; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima

    2018-01-01

    Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E–mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit. Methods In this phase II, open-label trial, patients with predefined BRAF V600E–mutated malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once daily until unacceptable toxicity, disease progression, or death. The primary end point was investigator-assessed overall response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results Sixteen patients with BRAF V600E–mutated anaplastic thyroid cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All patients had received prior radiation treatment and/or surgery, and six had received prior systemic therapy. The confirmed overall response rate was 69% (11 of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of response, progression-free survival, and overall survival were not reached as a result of a lack of events, with 12-month estimates of 90%, 79%, and 80%, respectively. The safety population was composed of 100 patients who were enrolled with seven rare tumor histologies. Common adverse events were fatigue (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected. Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have robust clinical activity in BRAF V600E–mutated anaplastic thyroid cancer and was well tolerated. These findings represent a meaningful therapeutic advance for this orphan disease. PMID:29072975

  6. Estimation of radiotherapy and MCNU versus radiotherapy and MCNU plus interferon-[beta] for the treatment of anaplastic astrocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Kiya, Katsuzo; Uozumi, Tohru; Kurisu, Kaoru; Ogasawara, Hidenori; Sugiyama, Kazuhiko; Maeda, Hitoshi; Harada, Kunyu (Hiroshima Univ. (Japan). School of Medicine)

    1993-02-01

    The efficacy of radiotherapy and MCNU (MR) was estimated in comparison with radiotherapy and MCNU plus interferon-[beta] (IMR) in 25 patients with anaplastic astrocytoma. The MR group received irradiation with 50[approx]60 Gy and intravenous administration of 2 mg/kg of MCNU on the initial day of irradiation and following every 6[approx]8 weeks interval. The IMR group also received the same regimen in addition to intravenous infusion of 2 x 10[sup 6] IU/m[sup 2] of interferon-[beta] for 5 serial days every eight weeks and following once every two weeks. There were no significant differences between the two groups in terms of background. The response rates of MR and IMR group were 38.5% and 66.7%, respectively. The times to tumor progression (TTP) in the two groups were 11.9[+-]5.8 months and 13.6[+-]7.7 months, respectively. Thus, IMR therapy seems to be more efficacious for patients with anaplastic astrocytoma than MR therapy, but further trials are necessary. (author).

  7. Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3β/ANG Signaling Pathway in Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Zhijian Jin

    2017-12-01

    Full Text Available Background/Aims: Anaplastic thyroid carcinoma (ATC is one of the most lethal human malignancies, and there is no efficient method to slow its process. Apatinib, a novel tyrosine kinase inhibitor (TKI, has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma patients. However, the effects of Apatinib in ATC are still unknown. Methods: In this study, we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array was utilized to detect the expression of angiogenesis-related genes after Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt inhibitor and GSK3β inhibitor to further study the mechanism for how Apatinib suppressed angiogenesis. Results: Apatinib treatment could suppress the growth of ATC cells in a dose- and time-dependent manner via inducing apoptosis and blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment decreased the expression of angiogenin (ANG and inhibited angiogenesis of ATC cells in vitro and in vitro. We further confirmed that recombinant human ANG (rhANG significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC cells. Additionally, Apatinib treatment decreased the level of p-Akt and p-GSK3β. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic ability were partly reversed when an Akt activator, SC79, was administered. Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the presence of Akt inhibitor, and the inhibition of GSK3β attenuated the anti-angiogenic ability of Apatinib. Conclusion: Our results demonstrated that Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of Akt/GSK3β/ANG signaling pathway may play an important role in the inhibition of angiogenesis in ATC, supporting a potential therapeutic approach for using Apatinib in the treatment of ATC.

  8. Recent advances and emerging therapies in anaplastic thyroid carcinoma [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Maria E. Cabanillas

    2018-01-01

    Full Text Available Anaplastic thyroid cancer is a rare and aggressive thyroid cancer with an overall survival measured in months. Because of this poor prognosis and often advanced age at presentation, these patients have traditionally been treated palliatively and referred for hospice. However, recent progress using novel therapies has energized the field, and several promising clinical trials are now available for these patients. This review will highlight this progress and the potential treatments that could pave the way to improved outcomes and quality of life for patients with this disease.

  9. The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

    Science.gov (United States)

    Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

    2014-01-01

    Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This

  10. Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood non-Hodgkin lymphoma (NHL) has three main types (aggressive mature B-cell [Burkitt, diffuse large B-cell, primary mediastinal B-cell], lymphoblastic and anaplastic large cell lymphoma) and other less common types of NHL. Get detailed information about the presentation, diagnosis, staging, prognosis, and treatment of all types of newly diagnosed and recurrent childhood NHL and lymphoproliferative disease in this summary for clinicians.

  11. 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.

  12. Breast Augmentation

    Science.gov (United States)

    ... Administration (FDA) has identified a possible association between breast implants and the development of anaplastic large cell lymphoma (ALCL), a rare cancer of the immune system. The FDA believes that ...

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

    International Nuclear Information System (INIS)

    Wang Renfei; Tan Jian; Li Wei; Meng Zhaowei; Zheng Wei

    2012-01-01

    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. 125 I 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 μmol/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, 125 I out-flowed rapidly when removed from the medium, and the retention rate of 125 I in the NIS-FRO cells was only 10.5% of the initial amount after 30 rin. After treatment with 1 μmol/L 17-AAG for 24 h, the 125 I uptake ability of NIS-FRO cells further increased. During the 20-60 min incubation with 125 I, 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 125 I 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 125 I efflux was reduced. After 30 min, 125 I 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

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

    Directory of Open Access Journals (Sweden)

    Barbara Klink

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

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

    Directory of Open Access Journals (Sweden)

    Moira Ragazzi

    2014-01-01

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

  16. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice

    DEFF Research Database (Denmark)

    Choudhari, Ramesh; Minero, Valerio Giacomo; Menotti, Matteo

    2016-01-01

    Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity. In ...

  17. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke; Ito, Hideki; Shimonohara, Nozomi; Tsuji, Takahiro; Nakajima, Noriko; Suzuki, Yoshio; Matsuo, Koma; Nakagawa, Hidemi; Sata, Tetsutaro; Katano, Harutaka

    2010-01-01

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal in any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.

  18. MGMT-STP27 Methylation Status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A Report from EORTC Study 26951

    NARCIS (Netherlands)

    van den Bent, Martin J.; Erdem-Eraslan, Lale; Idbaih, Ahmed; de Rooi, Johan; Eilers, Paul H. C.; Spliet, Wim G. M.; den Dunnen, Wilfred F. A.; Tijssen, Cees; Wesseling, Pieter; Smitt, Peter A. E. Sillevis; Kros, Johan M.; Gorlia, Thierry; French, Pim J.

    2013-01-01

    Purpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV

  19. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic oligodendrogliomas and oligoastrocytomas. A report from EORTC study 26951

    NARCIS (Netherlands)

    M.J. van den Bent (Martin); L. Erdem-Eraslan (Lale); A. Idbaih (Ahmed); J.J. de Rooi (Johan); P.H.C. Eilers (Paul); W.G.M. Spliet (Wim); W.F.A. den Dunnen (Wilfred); C.C. Tijssen (Cees); P. Wesseling (Pieter); P.A.E. Sillevis Smitt (Peter); J.M. Kros (Johan); T.S. Gorlia (Thierry); P.J. French (Pim)

    2013-01-01

    textabstractPurpose: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/ oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more

  20. MGMT-STP27 methylation status as predictive marker for response to PCV in anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study 26951

    NARCIS (Netherlands)

    Bent, M.J. van den; Erdem-Eraslan, L.; Idbaih, A.; Rooi, J. de; Eilers, P.H.; Spliet, W.G.; Dunnen, W.F. den; Tijssen, C.; Wesseling, P.; Smitt, P.A.; Kros, J.M.; Gorlia, T.; French, P.J.

    2013-01-01

    PURPOSE: The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV

  1. A case of paraventricular anaplastic astrocytoma following radiation therapy for craniopharyngioma

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Hiroaki; Fujiwara, Kazunori; Kobayashi, Shin-ichi; Kitahara, Masakazu (Ishinomaki Red Cross Hospital, Miyagi (Japan))

    1994-04-01

    A 20-year-old man received 60 Gy of radiation therapy after partial removal of craniopharyngioma. The patient had been well and follow-up CT scans did not show any aggravation for 16 years. Since his activity gradually diminished, he underwent an MRI at the age of 36 which revealed and abnormal mass on the corpus callosum. The mass lesion progressively enlarged thereafter, and was diagnosed as anaplastic astrocytoma by a stereotactic biopsy. He was treated with interferon, however, died at the age of 37. Review of the literature disclosed 19 other cases of glioma following radiation therapy for sellar/parasellar tumors. Characteristic features of these cases included (1) lowness of age compared to common glioma cases, (2) tendency to be malignant, (3) tendency to occur in areas where significant doses of radiation had been received previously. (author).

  2. Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    Science.gov (United States)

    2017-12-11

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2) or t(3;3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With Inv(3) (q21.3;q26.2); GATA2, MECOM; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9) (p23;q34.1); DEK-NUP214; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma

  3. Precision Medicine Approach to Anaplastic Thyroid Cancer: Advances in Targeted Drug Therapy Based on Specific Signaling Pathways.

    Science.gov (United States)

    Samimi, Hilda; Fallah, Parviz; Naderi Sohi, Alireza; Tavakoli, Rezvan; Naderi, Mahmood; Soleimani, Masoud; Larijani, Bagher; Haghpanah, Vahid

    2017-03-01

    Personalized medicine is a set of diagnostic, prognostic and therapeutic approaches in which medical interventions are carried out based on individual patient characteristics. As life expectancy increases in developed and developing countries, the incidence of diseases such as cancer goes up among people in the community. Cancer is a disease that the response to treatment varies from one person to another and also it is costly for individuals, families, and society. Among thyroid cancers, anaplastic thyroid carcinoma (ATC) is the most aggressive, lethal and unresponsive form of the disease. Unfortunately, current drugs are not targetable, and therefore they have restricted role in ATC treatment. Consequently, mortality of this cancer, despite advances in the field of diagnosis and treatment, is one of the most important challenges in medicine. Cellular, molecular and genetic evidences play an important role in finding more effective diagnostic and therapeutic approaches. Review of these evidences confirms the application of personalized medicine in cancer treatment including ATC. A growing body of evidence has elucidated that cellular and molecular mechanisms of cancer would pave the way for defining new biomarkers for targeted therapy, taking into account individual differences. It should be noted that this approach requires further progress in the fields of basic sciences, pharmacogenetics and drug design. An overview of the most important aspects in individualized anaplastic thyroid cancer treatment will be discussed in this review.

  4. Upper-half body irradiation for oat cell carcinoma of the bronchus

    International Nuclear Information System (INIS)

    Stockdale, A.D.; Rostom, A.Y.

    1989-01-01

    Small-cell anaplastic carcinoma of the bronchus (SCCB) is considered to be a chemosensitive tumour. For many physicians, chemotherapy is the treatment of first choice. However, despite prolonged and aggressive therapy, overall 2-year survival of less than 10% may be expected. Radiotherapy has an established role in the palliation of advances disease. We have previously investigated the use of single, large fractions of radiotherapy in patients with drug-resistant multiple myeloma and shown excellent responses and prolonged survival. As the majority of patients present with disseminated disease, we have investigated the use of a single fraction of radiotherapy to the upper half of the body (including the liver) in 24 patients with SCCB. (author)

  5. Upper-half body irradiation for oat cell carcinoma of the bronchus

    Energy Technology Data Exchange (ETDEWEB)

    Stockdale, A.D.; Rostom, A.Y. (Saint Luke' s Hospital, Guildford (UK))

    1989-06-01

    Small-cell anaplastic carcinoma of the bronchus (SCCB) is considered to be a chemosensitive tumour. For many physicians, chemotherapy is the treatment of first choice. However, despite prolonged and aggressive therapy, overall 2-year survival of less than 10% may be expected. Radiotherapy has an established role in the palliation of advances disease. We have previously investigated the use of single, large fractions of radiotherapy in patients with drug-resistant multiple myeloma and shown excellent responses and prolonged survival. As the majority of patients present with disseminated disease, we have investigated the use of a single fraction of radiotherapy to the upper half of the body (including the liver) in 24 patients with SCCB. (author).

  6. Endometrioid Adenocarcinoma Metastatic to the Thyroid, Presenting Like Anaplastic Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Natasha Pollak

    2011-01-01

    Full Text Available Metastasis of uterine cancer to the head and neck is extremely rare. We report what we believe to be the first documented case of endometrioid adenocarcinoma metastasizing to the thyroid gland. An 80-year-old woman was referred to the otolaryngology service with a rapidly growing neck mass. The mass appeared to originate from the thyroid gland. Her clinical presentation was consistent with anaplastic thyroid carcinoma. A tracheostomy was performed. An open biopsy established the diagnosis of moderately differentiated adenocarcinoma, consistent with a gynecologic primary. The patient had undergone a hysterectomy 5 years prior for endometrioid adenocarcinoma. The thyroid tumor histology and immunophenotype corresponded well with her prior endometrial carcinoma, indicating that the thyroid mass was a metastasis from the endometrial primary. Radiotherapy appears to offer good local disease control in this rare case of endometrioid adenocarcinoma metastatic to the thyroid.

  7. Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

    Science.gov (United States)

    2017-11-29

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Fanconi Anemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma

  8. 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.

  9. Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma

    International Nuclear Information System (INIS)

    He, Xiayun; Li, Duanshu; Hu, Chaosu; Wang, Zhuoying; Ying, Hongmei; Wu, Yi

    2014-01-01

    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

  10. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report.

    Science.gov (United States)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-06-13

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child's kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15-20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance.

  11. Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report

    International Nuclear Information System (INIS)

    Santoro, Claudia; Apicella, Andrea; Casale, Fiorina; La Manna, Angela; Di Martino, Martina; Di Pinto, Daniela; Indolfi, Cristiana; Perrotta, Silverio

    2016-01-01

    Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child’s kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15–20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance

  12. Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

    Directory of Open Access Journals (Sweden)

    Gulati Michel

    2010-03-01

    Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

  13. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  14. [Anaplastic carcinoma of the thyroid at the Instituto Nacional de la Nutrición Salvador Zubirán].

    Science.gov (United States)

    Sierra, M; Gamboa-Domínguez, A; Herrera, M F; Barredo-Prieto, B; Alvarado de la Barrera, C; Llorente, L; Pérez-Enriquez, B; Rivera, R; González, O; Rull, J A

    1997-01-01

    Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor with a median survival rate of 6 months. To analyze presentation, treatment, morphology, immunohistochemistry, and nuclear DNA analysis of a cohort of patients with ATC. Twelve patients with ATC (11 female) with a mean age of 65 years were seen at our hospital from 1970-1995. The data were obtained from the clinical records and the morphology, immunohistochemic studies and DNA pattern were performed in slides obtained from archival specimens. Previous or coexisting thyroide disease was documented in 10 patients (9 multinodular goiters and one Grave's). The most frequent presentation was a rapidly growing tumor associated with dysphagia, cervical pain, hoarseness and dyspnea. A cold thyroid nodule was detected by thyroid scan in 10 patients. The most frequent subtype was the spindle cell variety. Papillary thyroid carcinoma coexisted in eight cases, two of them corresponded to the tall cell variant. Reactivity for S-100 protein and vimentin was studied in six patients: all were positive for S-100 protein and vimentin, 5/6 for epithelial membrane antigen, half for carcinoembriogenic antigen, 2/6 for thyroglobulin and calcitonin, and one for neuronal specific enolase. These six tumors showed a diploid DNA pattern. Tumor resection was achieved in 2/11 and none survived six years after diagnosis. ATC is a highly aggressive tumor coexisting with thyroid pathologies. Spindle cell variant is the most frequent with positive reactivity for S-100 protein, vimentin and epithelial membrane antigen. Most tumors have a diploid DNA content.

  15. Primary focal T-cell lymphoma of the liver: a case report and review of the literature.

    Science.gov (United States)

    Cerban, Razvan; Gheorghe, Liana; Becheanu, Gabriel; Serban, Valentin; Gheorghe, Cristian

    2012-06-01

    We present the case of a previously healthy 62 year old man who developed primary non-Hodgkin lymphoma of the liver. Biopsy confirmed that it was a diffuse large anaplastic T-cell lymphoma of an extremely rare type. The diagnosis of this type of lesions is suggested by the presence of a hepatic mass without lymphadenopathy, splenomegaly or bone marrow involvement associated with normal tumor markers (carcinoembryonic antigen, alpha-fetoprotein and CA 19-9 levels). Histological examination of tissue is essential to confirm the diagnosis. Treatment options are surgical resection and/or chemotherapy but the rate of response to treatment varies widely. Some patients can achieve prolonged remission.

  16. Multimodal 18F-Fluciclovine PET/MRI and Ultrasound-Guided Neurosurgery of an Anaplastic Oligodendroglioma.

    Science.gov (United States)

    Karlberg, Anna; Berntsen, Erik Magnus; Johansen, Håkon; Myrthue, Mariane; Skjulsvik, Anne Jarstein; Reinertsen, Ingerid; Esmaeili, Morteza; Dai, Hong Yan; Xiao, Yiming; Rivaz, Hassan; Borghammer, Per; Solheim, Ole; Eikenes, Live

    2017-12-01

    Structural magnetic resonance imaging (MRI) and histopathologic tissue sampling are routinely performed as part of the diagnostic workup for patients with glioma. Because of the heterogeneous nature of gliomas, there is a risk of undergrading caused by histopathologic sampling errors. MRI has limitations in identifying tumor grade and type, detecting diffuse invasive growth, and separating recurrences from treatment induced changes. Positron emission tomography (PET) can provide quantitative information of cellular activity and metabolism, and may therefore complement MRI. In this report, we present the first patient with brain glioma examined with simultaneous PET/MRI using the amino acid tracer 18 F-fluciclovine ( 18 F-FACBC) for intraoperative image-guided surgery. A previously healthy 60-year old woman was admitted to the emergency care with speech difficulties and a mild left-sided hemiparesis. MRI revealed a tumor that was suggestive of glioma. Before surgery, the patient underwent a simultaneous PET/MRI examination. Fused PET/MRI, T1, FLAIR, and intraoperative three-dimensional ultrasound images were used to guide histopathologic tissue sampling and surgical resection. Navigated, image-guided histopathologic samples were compared with PET/MRI image data to assess the additional value of the PET acquisition. Histopathologic analysis showed anaplastic oligodendroglioma in the most malignant parts of the tumor, while several regions were World Health Organization (WHO) grade II. 18 F-Fluciclovine uptake was found in parts of the tumor where regional WHO grade, cell proliferation, and cell densities were highest. This finding suggests that PET/MRI with this tracer could be used to improve accuracy in histopathologic tissue sampling and grading, and possibly for guiding treatments targeting the most malignant part of extensive and eloquent gliomas. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Risks of Breast Implants

    Science.gov (United States)

    ... have a risk of developing a type of cancer called breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in the breast tissue surrounding the implant. BIA-ALCL is not breast cancer. Women diagnosed with BIA-ALCL may need to ...

  18. Primary Hepatosplenic Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    M.R. Morales-Polanco

    2008-03-01

    Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

  19. Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics

    Directory of Open Access Journals (Sweden)

    Martina Tavarelli

    2017-10-01

    Full Text Available BackgroundAnaplastic thyroid cancer (ATC is a rare but extremely aggressive cancer of the thyroid, contributing up to 30–40% of thyroid cancer-specific mortality. We analyzed ATC characteristics and survival rates in Sicily to evaluate the possible influence of environmental factors. With this aim, data regarding ATC incidences in urban/rural and industrial, iodine-deficient, and volcanic vs control areas were compared in Sicily as well as ATC data from Sicily and USA.MethodsUsing the Sicilian Register of Thyroid Cancer (SRTC database incidence, age, gender, tumor size and histotype, extrathyroidal extension, stage, and coexistence with pre-existing differentiated thyroid cancer (DTC were evaluated in different areas of Sicily and also compared with Surveillance Epidemiology and End Results data in USA.ResultsForty-three ATCs were identified in Sicily in the period 2002–2009. In our series only age <70 years at diagnosis (p = 0.01, coexistence with DTC (p = 0.027 and tumor size ≤6 cm (p = 0.012 were significant factors for increased survival at univariate analysis (only age at multivariate analysis. No difference in ATC incidence was found in urban vs rural areas and in iodine-deficient and industrial vs control areas. By contrast, in the volcanic area of Sicily, where DTC incidence is doubled relative to the rest of the island, also ATC incidence was increased. ATC data in Sicily were similar to those reported in the same period in the USA where overall survival rate at 6 and 12 months, however, was smaller.ConclusionThe similar ATC data observed in Sicily and USA (having different genetic background and lifestyle and the increased ATC incidence in the volcanic area of Sicily paralleling the increased incidence of papillary thyroid cancer are compatible with the possibility that casual additional mutations, more frequent in a background of increased cell replication like DCT, are the major causes of ATC rather than

  20. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C.; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-01-01

    Background Optimal treatment and precise classification for anaplastic glioma are needed. Methods The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Results Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6–10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4–5.1] y vs 4.4 [3.3–5.3) y), PFS (2.5 [1.3–3.5] y vs 2.7 [1.9–3.2] y), and OS (8 [5.5–10.3] y vs 6.5 [5.4–8.3] y). Oligodendroglial versus astrocytic histology—but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status—revealed a strong prognostic value of CIMPpos with (CIMPcodel) versus without 1p/19 co-deletion (CIMPnon-codel) versus CIMPneg. but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMPcodel tumors (HR B1 vs B2 0.39 [0.17–0.92], P = .031). In CIMPneg. tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. Conclusions There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. Trial Registration: clinicaltrials.gov Identifier: NCT00717210. PMID:27370396

  1. Rhabdoid and Undifferentiated Phenotype in Renal Cell Carcinoma: Analysis of 32 Cases Indicating a Distinctive Common Pathway of Dedifferentiation Frequently Associated With SWI/SNF Complex Deficiency.

    Science.gov (United States)

    Agaimy, Abbas; Cheng, Liang; Egevad, Lars; Feyerabend, Bernd; Hes, Ondřej; Keck, Bastian; Pizzolitto, Stefano; Sioletic, Stefano; Wullich, Bernd; Hartmann, Arndt

    2017-02-01

    Undifferentiated (anaplastic) and rhabdoid cell features are increasingly recognized as adverse prognostic findings in renal cell carcinoma (RCC), but their molecular pathogenesis has not been studied sufficiently. Recent studies identified alterations in the Switch Sucrose nonfermentable (SWI/SNF) chromatin remodeling complex as molecular mechanisms underlying dedifferentiation and rhabdoid features in carcinomas of different organs. We herein have analyzed 32 undifferentiated RCCs having in common an undifferentiated (anaplastic) phenotype, prominent rhabdoid features, or both, irrespective of the presence or absence of conventional RCC component. Cases were stained with 6 SWI/SNF pathway members (SMARCB1, SMARCA2, SMARCA4, ARID1A, SMARCC1, and SMARCC2) in addition to conventional RCC markers. Patients were 20 males and 12 females aged 32 to 85 years (mean, 59). A total of 22/27 patients with known stage presented with ≥pT3. A differentiated component varying from microscopic to major component was detected in 20/32 cases (16 clear cell and 2 cases each chromophobe and papillary RCC). The undifferentiated component varied from rhabdoid dyscohesive cells to large epithelioid to small monotonous anaplastic cells. Variable loss of at least 1 SWI/SNF complex subunit was noted in the undifferentiated/rhabdoid component of 21/32 cases (65%) compared with intact or reduced expression in the differentiated component. A total of 15/17 patients (88%) with follow-up died of metastatic disease (mostly within 1 y). Only 2 patients were disease free at last follow-up (1 and 6 y). No difference in survival, age distribution, or sex was observed between the SWI/SNF-deficient and the SWI/SNF-intact group. This is the first study exploring the role of SWI/SNF deficiency as a potential mechanism underlying undifferentiated and rhabdoid phenotype in RCC. Our results highlight the association between the aggressive rhabdoid phenotype and the SWI/SNF complex deficiency, consistent

  2. Case Report

    DEFF Research Database (Denmark)

    Sylvester-Hvid, Amalie; Avnstorp, Magnus B; Wagenblast, Lene

    2017-01-01

    Introduction Breast seroma may be caused by a variety of factors including lymphatic disruption, continuous inflammation and foreign bodies such as breast implants. In cases of breast implants associated seroma the diagnosis of Anaplastic Large Cell Lymphoma (ALCL) should be investigated. Present...

  3. Disease: H01601 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ype ICD-10: C84.6 C84.7 MeSH: D017728 PMID:25869285 (gene, drug) ... AUTHORS ... Hapgood G, Savage KJ ... TITLE ... The biology and managem...ent of systemic anaplastic large cell lymphoma. ... JOURNAL ... Blood 126:17-25 (2015)

  4. Phase II trial of carmustine, cisplatin, and oral etoposide chemotherapy before radiotherapy for grade 3 astrocytoma (anaplastic astrocytoma): Results of North Central Cancer Treatment Group trial 98-72-51

    International Nuclear Information System (INIS)

    Rao, Ravi D.; Krishnan, Sunil; Fitch, Tom R.; Schomberg, Paula J.; Dinapoli, Robert P.; Nordstrom, Kathleen; Scheithauer, Bernd; O'Fallon, Judith R.; Maurer, Matthew J. M.S.; Buckner, Jan C.

    2005-01-01

    Purpose: To evaluate the efficacy of preradiotherapy (RT) chemotherapy with carmustine, cisplatin, and oral etoposide combined with RT in the treatment of newly diagnosed anaplastic astrocytoma. Methods and materials: Therapy consisted of carmustine (40 mg/m 2 /d) on Days 1-3, oral etoposide (50 mg/d) on Days 1-21 and 29-49, and cisplatin (20 mg/m 2 /d i.v.) on Days 1-3 and 29-31. The regimen was repeated every 8 weeks for three cycles, with conventionally fractionated RT (5000 cGy with a 1000-cGy boost) delivered concurrently with the third cycle. Results: A total of 29 patients were enrolled between December 1999 and March 2001. For varying reasons (e.g., progression, refusal, death, or toxicity), only 48% completed the chemotherapy regimen and 76% completed RT. Grade 3-4 toxicities were observed in 14 patients (48%). The primary study endpoint was the 23-month (700-day) survival, the median survival of patients with anaplastic astrocytoma in a previous North Central Cancer Treatment Group trial. To be considered an active treatment, a maximum of 9 patient deaths (of the first 25) were allowed before 700 days. However, 14 patients had died by 700 days after therapy. Conclusion: Our results have demonstrated that pre-RT chemotherapy with this regimen is insufficiently active in patients with anaplastic astrocytoma

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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, mi...

  6. The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.

    Science.gov (United States)

    Pierie, Jean-Pierre E N; Muzikansky, Alona; Gaz, Randall D; Faquin, William C; Ott, Mark J

    2002-01-01

    Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We analyzed our experience for prognosis and the effect of surgery and radiotherapy on patients with ATC. We conducted a retrospective review of all patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999. Survivor median follow-up was 51 months. Tumor and patient characteristics and therapy were assessed for effect on survival by multivariate analysis. Patients presented with a neck mass (99%), change of voice (51%), dysphagia (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12 complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%, and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%, and 0% after no resection, respectively (P 45 Gy improved survival as compared with a lower dose (P = .02). Multivariate analysis showed that age 45 Gy improves outcome.

  7. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2017-07-27

    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

  8. Intravascular Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Maria S. Khan MD, FACP

    2014-03-01

    Full Text Available Case Presentation . A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH 1231 IU/L. Except for a positive DNA test for Epstein–Barr virus (EBV infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion . Intravascular large cell B-cell lymphoma (IVLBCL is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH

  9. Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.

    Science.gov (United States)

    Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju; Reckamp, Karen L; Hansen, Karin Holmskov; Kim, Sang-We; Huber, Rudolf M; West, Howard L; Groen, Harry J M; Hochmair, Maximilian J; Leighl, Natasha B; Gettinger, Scott N; Langer, Corey J; Paz-Ares Rodríguez, Luis G; Smit, Egbert F; Kim, Edward S; Reichmann, William; Haluska, Frank G; Kerstein, David; Camidge, D Ross

    2017-08-01

    Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed

  10. Mediastinal large cell lymphoma with sclerosis

    International Nuclear Information System (INIS)

    Franco, Sergio; Pulcheri, Wolmar; Spector, Nelson; Nucci, Marcio; Oliveira, Halley P. de; Morais, Jose Carlos; Romano, Sergio

    1995-01-01

    Five cases of primary mediastinal large-cell lymphoma with sclerosis diagnosed at the University Hospital Clementino Fraga Filho (Federal University of Rio de Janeiro) between 1986 and 1994 were identified. They were studied on clinical, morphological and immuno-histochemical grounds. Clinically, the disease was characterized by the young age of the patients, mediastinal involvement by bulky disease and compressive symptoms. None of the patients had evidence of extra-thoracic disease as presentation. On morphological grounds they had evidence of extra-thoracic disease at presentation. On morphological grounds they showed a mixture of immuno blasts and large follicular enter cell with sclerosis. Three of five cases proved to be of B-cell origin. Four of five patients were treated with chemotherapy. Cases 1 and with MACOP-B, and cases 3 and 4 with Pro-MACE-cytaBOM and consolidation radiation therapy. All the patients achieved a complete remission, and are alive, free of disease, with a follow-up of 1 to 8 years. (author). 28 refs., 8 figs., 2 tabs

  11. Large remote manipulator operating and maintenance experience at IEM cell

    International Nuclear Information System (INIS)

    Hicks, D.F.; McGuinness, P.W.

    1985-01-01

    The Interim Examination and Maintenance (IEM) Cell at the Fast Flux Test Facility (FFTF) has two large Electro-Mechanical Manipulators (EMM's). These manipulators are used for cell operations (processing of reactor core components) as well as general cell maintenance. From our eleven years of operation and maintenance experience with these large EMM's, we have learned many lessons concerning manipulator design. This paper describes the IEM Cell EMM design features and discusses operating and maintenance experience at the IEM Cell

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

    Science.gov (United States)

    2017-04-27

    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

  13. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide.

    Science.gov (United States)

    Wick, Wolfgang; Roth, Patrick; Hartmann, Christian; Hau, Peter; Nakamura, Makoto; Stockhammer, Florian; Sabel, Michael C; Wick, Antje; Koeppen, Susanne; Ketter, Ralf; Vajkoczy, Peter; Eyupoglu, Ilker; Kalff, Rolf; Pietsch, Torsten; Happold, Caroline; Galldiks, Norbert; Schmidt-Graf, Friederike; Bamberg, Michael; Reifenberger, Guido; Platten, Michael; von Deimling, Andreas; Meisner, Christoph; Wiestler, Benedikt; Weller, Michael

    2016-11-01

    Optimal treatment and precise classification for anaplastic glioma are needed. The objective for long-term follow-up of NOA-04 is to optimize the treatment sequence for patients with anaplastic gliomas. Patients were randomized 2:1:1 to receive the standard radiotherapy (RT) (arm A), procarbazine, lomustine and vincristine (PCV) (arm B1), or temozolomide (TMZ) (arm B2). Primary endpoint was time-to-treatment-failure (TTF), defined as progression after 2 lines of therapy or any time before if no further therapy was administered. Exploratory analyses examined associations of molecular marker status with TTF, progression-free survival (PFS), and overall survival (OS). At 9.5 (95% CI: 8.6-10.2) years, no difference between arms (A vs B1/B2) was observed: median TTF (4.6 [3.4-5.1] y vs 4.4 [3.3-5.3) y), PFS (2.5 [1.3-3.5] y vs 2.7 [1.9-3.2] y), and OS (8 [5.5-10.3] y vs 6.5 [5.4-8.3] y). Oligodendroglial versus astrocytic histology-but more so the subgroups according to CpG island methylator phenotype (CIMP) and 1p/19q co-deletion status-revealed a strong prognostic value of CIMP pos with (CIMP codel ) versus without 1p/19 co-deletion (CIMP non-codel ) versus CIMP neg . but no differential efficacy of RT versus chemotherapy for any of the endpoints. PFS was better for PCV- than for TMZ-treated patients with CIMP codel tumors (HR B1 vs B2 0.39 [0.17-0.92], P = .031). In CIMP neg . tumors, hypermethylation of the O6-methyl-guanyl-DNA methyltransferase promoter (MGMT) provided a risk reduction for PFS with chemotherapy. There is no differential activity of primary chemotherapy versus RT in any subgroup of anaplastic glioma. Molecular diagnosis is superior to histology. clinicaltrials.gov Identifier: NCT00717210. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada.

    Science.gov (United States)

    Hurry, Manjusha; Zhou, Zheng-Yi; Zhang, Jie; Zhang, Chenxue; Fan, Liangyi; Rebeira, Mayvis; Xie, Jipan

    2016-10-01

    To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective. A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed. Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings. Based on the willingness-to-pay threshold for

  15. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  16. Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules

    Directory of Open Access Journals (Sweden)

    S. Suresh Kumar

    2014-12-01

    Full Text Available Human pluripotent stem cells, including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs, hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4, epidermal growth factor (EGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, hepatocyte growth factor (HGF, noggin, transforming growth factor (TGF-α, and WNT3A are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.

  17. Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules

    Science.gov (United States)

    Kumar, S. Suresh; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Singh, A. J. A. Ranjith; Peng, I-Chia; Priya, Sivan Padma; Hamat, Rukman Awang; Higuchi, Akon

    2014-01-01

    Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation. PMID:25526563

  18. Imaging findings of anaplastic astrocytoma in a child with maple syrup urine disease: a case report.

    Science.gov (United States)

    Aw-Zoretic, Jessie; Wadhwani, Nitin R; Lulla, Rishi R; Rishi, Lulla R; Ryan, Maura E

    2015-09-01

    Maple syrup urine disease (MSUD) is an inborn error of branched-chain amino acid metabolism, which usually presents in childhood with encephalopathy due to cerebral edema and dysmyelination. Even with treatment, metabolic stressors may precipitate later episodes of acute decompensation. Changes related to cerebral and white matter edema have been described by magnetic resonance imaging (MRI), and imaging can aid in both initial diagnosis and evaluation of decompensation. To date, there are no published known reports of cancer in patients with MSUD. Here, we present the first case report of an anaplastic astrocytoma in a teenager with MSUD, with a discussion of imaging findings and the use of magnetic resonance spectroscopy (MRS) to help distinguish between tumor and metabolic changes.

  19. EBV-positive diffuse large B-cell lymphoma of the elderly

    NARCIS (Netherlands)

    C.Y. Ok (Chi Young); T.G. Papathomas (Thomas); L.J. Medeiros (L. Jeffrey); K.H. Young (Ken)

    2013-01-01

    textabstractEpstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the elderly, initially described in 2003, is a provisional entity in the 2008World Health Organization classification system and is defined as an EBV-positive monoclonal large B-cell proliferation that occurs in

  20. Plasma Cell-Free DNA in Paediatric Lymphomas

    Science.gov (United States)

    Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

    2013-01-01

    Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

  1. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Katherine Devitt

    2014-01-01

    Full Text Available Hemophagocytic lymphohistiocytosis (HLH is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  2. Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma.

    Science.gov (United States)

    Devitt, Katherine; Cerny, Jan; Switzer, Bradley; Ramanathan, Muthalagu; Nath, Rajneesh; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

    2014-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare. We describe a case of a 30-year-old man who presented with fever, splenomegaly, and hyperferritinemia. Bone marrow biopsy revealed T-cell/histiocyte-rich large B-cell lymphoma, a rare, aggressive B-cell malignancy. This case highlights the interplay between a pro-inflammatory cytokine microenvironment and tumor-mediated immune suppression, and addresses the importance of accurately diagnosing these entities for appropriate clinical management.

  3. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  4. Endogenous Sheet-Averaged Tension Within a Large Epithelial Cell Colony.

    Science.gov (United States)

    Dumbali, Sandeep P; Mei, Lanju; Qian, Shizhi; Maruthamuthu, Venkat

    2017-10-01

    Epithelial cells form quasi-two-dimensional sheets that function as contractile media to effect tissue shape changes during development and homeostasis. Endogenously generated intrasheet tension is a driver of such changes, but has predominantly been measured in the presence of directional migration. The nature of epithelial cell-generated forces transmitted over supracellular distances, in the absence of directional migration, is thus largely unclear. In this report, we consider large epithelial cell colonies which are archetypical multicell collectives with extensive cell-cell contacts but with a symmetric (circular) boundary. Using the traction force imbalance method (TFIM) (traction force microscopy combined with physical force balance), we first show that one can determine the colony-level endogenous sheet forces exerted at the midline by one half of the colony on the other half with no prior assumptions on the uniformity of the mechanical properties of the cell sheet. Importantly, we find that this colony-level sheet force exhibits large variations with orientation-the difference between the maximum and minimum sheet force is comparable to the average sheet force itself. Furthermore, the sheet force at the colony midline is largely tensile but the shear component exhibits significantly more variation with orientation. We thus show that even an unperturbed epithelial colony with a symmetric boundary shows significant directional variation in the endogenous sheet tension and shear forces that subsist at the colony level.

  5. Advanced manipulator system for large hot cells

    International Nuclear Information System (INIS)

    Vertut, J.; Moreau, C.; Brossard, J.P.

    1981-01-01

    Large hot cells can be approached as extrapolated from smaller ones as wide, higher or longer in size with the same concept of using mechanical master slave manipulators and high density windows. This concept leads to a large number of working places and corresponding equipments, with a number of penetrations through the biological protection. When the large cell does not need a permanent operation of number of work places, as in particular to serve PIE machines and maintain the facility, use of servo manipulators with a large supporting unit and extensive use of television appears optimal. The advance on MA 23 and supports will be described including the extra facilities related to manipulators introduction and maintenance. The possibility to combine a powered manipulator and MA 23 (single or pair) on the same boom crane system will be described. An advance control system to bring the minimal dead time to control support movement, associated to the master slave arm operation is under development. The general television system includes over view cameras, associated with the limited number of windows, and manipulators camera. A special new system will be described which brings an automatic control of manipulator cameras and saves operator load and dead time. Full scale tests with MA 23 and support will be discussed. (author)

  6. COPBLAM: infusion chemotherapy for large cell lymphoma

    International Nuclear Information System (INIS)

    Coleman, M.; Bernhardt, B.; Boyd, D.B.; Gerstein, G.

    1986-01-01

    This chapter describes a new combination chemotherapy program that was initiated at the New York Hospital-Cornell Medical Center for large cell lymphoma (LCL). The program, known as COPBLAM (Cyclophosphamide, Oncovin, Prednisone, Bleomycin, Adriamycin, Matulane) was an intensive multidrug regimen designed to maximize tumor cell kill. Some of the novel concepts and features are described. The treatment was fully successful in 60% of the 48 patients studied that were undergoing radiation therapy

  7. Glutathione peroxidase 4 overexpression inhibits ROS-induced cell death in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Kinowaki, Yuko; Kurata, Morito; Ishibashi, Sachiko; Ikeda, Masumi; Tatsuzawa, Anna; Yamamoto, Masahide; Miura, Osamu; Kitagawa, Masanobu; Yamamoto, Kouhei

    2018-02-20

    Regulation of oxidative stress and redox systems has important roles in carcinogenesis and cancer progression, and for this reason has attracted much attention as a new area of cancer therapeutic targets. Glutathione peroxidase 4 (GPX4), an antioxidant enzyme, has biological important functions such as signaling cell death by suppressing peroxidation of membrane phospholipids. However, few studies exist on the expression and clinical relevance of GPX4 in malignant lymphomas such as diffuse large B-cell lymphoma. In this study, we assessed the expression of GPX4 immunohistochemically. GPX4 was expressed in 35.5% (33/93) cases of diffuse large B-cell lymphoma. The GPX4-positive group had poor overall survival (P = 0.0032) and progression-free survival (P = 0.0004) compared with those of the GPX4-negative group. In a combined analysis of GPX4 and 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, there was a negative correlation between GPX4 and 8-hydroxydeoxyguanosine (P = 0.0009). The GPX4-positive and 8-hydroxydeoxyguanosine-negative groups had a significantly worse prognosis than the other groups in both overall survival (P = 0.0170) and progression-free survival (P = 0.0005). These results suggest that the overexpression of GPX4 is an independent prognostic predictor in diffuse large B-cell lymphoma. Furthermore, in vitro analysis demonstrated that GPX4-overexpressing cells were resistant to reactive oxygen species-induced cell death (P = 0.0360). Conversely, GPX4-knockdown cells were sensitive to reactive oxygen species-induced cell death (P = 0.0111). From these data, we conclude that GPX4 regulates reactive oxygen species-induced cell death. Our results suggest a novel therapeutic strategy using the mechanism of ferroptosis, as well as a novel prognostic predictor of diffuse large B-cell lymphoma.

  8. Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Iñiguez-Ariza, Nicole M; Ryder, Mabel M; Hilger, Crystal R; Bible, Keith C

    2017-07-01

    Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy. A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015. Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib. This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required

  9. Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

    DEFF Research Database (Denmark)

    Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

    2016-01-01

    SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we...... prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD......57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia. These T cell populations were clonal in 20/20 patients and stably present...

  10. Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

    Science.gov (United States)

    DiBonaventura, Marco D; Wong, William; Shah-Manek, Bijal; Schulz, Mathias

    2018-01-01

    Background Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods Participating oncologists (N=95) in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor), collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male). The patients in our sample were older (median age of 60 vs 53 years), were more likely to be current smokers (12% vs 1%), had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0), and were less likely to have an adenocarcinoma histology (83% vs 96%) relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively) as was the disease control rate (89.9% vs 78.8%, respectively), though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0%) and dose reductions (3.4%) due to adverse events were uncommon in alectinib. Conclusion Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically diverse than patients in published trials. Real-world response rates were high and similar to those reported in clinical studies, though there is some variation by patient characteristics. Alectinib was well tolerated in clinical practice as reflected by the rates of discontinuation, dose reductions, and dose interruptions. PMID

  11. Preliminary study of steep pulse irreversible electroporation technology in human large cell lung cancer cell lines L9981

    Directory of Open Access Journals (Sweden)

    Song Zuoqing

    2013-01-01

    Full Text Available Our aim was to validate the effectiveness of steep pulse irreversible electroporation technology in human large cell lung cancer cells and to screen the optimal treatment of parameters for human large cell lung cancer cells. Three different sets of steep pulse therapy parameters were applied on the lung cancer cell line L9981. The cell line L9981 inhibition rate and proliferation capacity were detected by Vi-Cell vitality analysis and MTT. Steep pulsed irreversible electroporation technology for large cell lung cancer L9981 presents killing effects with various therapy parameters. The optimal treatment parameters are at a voltage amplitude of 2000V/cm, pulse width of 100μs, pulse frequency of 1 Hz, pulse number 10. With this group of parameters, steep pulse could have the best tumor cell-killing effects.

  12. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

    Science.gov (United States)

    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  13. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Mansour Ansari

    2017-01-01

    Full Text Available Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymphoma. Immunohistochemistry (IHC results showed that the tumor was positive for CD20, CD45, and Pax-5 and negative for BCL-2, cytokeratin, and S100. He had a normal bone marrow biopsy, abdominal, pelvic and chest CT scans. He had no B symptoms. The patient received 6 cycles of R-CHOP followed by radiotherapy (36 Gy to the pelvis. Six months after treatment, the patient is well and has returned to work. We have searched PubMed for primary diffuse large cell lymphoma. Primary diffuse large cell lymphoma of the bladder is best treated according to treatment for diffuse large cell lymphoma of other sites, which includes chemotherapy and radiotherapy. As seen in our review, primary diffuse large cell lymphoma of the bladder has a similar clinical course to diffuse large cell lymphoma of other sites.

  14. Severe vincristine-induced polyneuropathy in a teenager with anaplastic medulloblastoma and undiagnosed Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Aghajan, Yasmin; Yoon, Janet M; Crawford, John Ross

    2017-04-24

    Severe neuropathy is a known adverse effect of vincristine in patients with Charcot-Marie-Tooth disease (CMT). We present the case of a 16-year-old girl with anaplastic medulloblastoma treated with gross total resection and high-dose craniospinal radiation with adjuvant vincristine chemotherapy who developed acute-onset severe quadriplegia and vocal cord paralysis. Vincristine and radiation therapy were discontinued. Although her neuropathy slowly improved over several weeks, she developed metastatic extraneural medulloblastoma and died 5 months after diagnosis. Subsequent genetic testing revealed previously asymptomatic and undiagnosed CMT1A. Our case highlights the importance of early recognition of acute vincristine neurotoxicity that should raise suspicion of an underlying hereditary neuropathy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Ipilimumab and Local Radiation Therapy in Treating Patients With Recurrent Melanoma, Non-Hodgkin Lymphoma, Colon, or Rectal Cancer

    Science.gov (United States)

    2017-01-12

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Melanoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  16. Prostatic Adenocarcinoma with Concurrent Sertoli Cell Tumor in a Dog

    Science.gov (United States)

    Gill, C. W.

    1981-01-01

    A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7340923

  17. Characterization of primary cutaneous CD8+/CD30+ lymphoproliferative disorders.

    Science.gov (United States)

    Martires, Kathryn J; Ra, Seong; Abdulla, Farah; Cassarino, David S

    2015-11-01

    CD30 primary cutaneous lymphoproliferative diseases include both lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (PCALCL). The neoplastic cell of most primary CD30 lymphoproliferative disorders is CD4 positive. The terminology LyP "type D" has been used to describe a growing number of cases of LyP with a predominantly CD8 infiltrate. PCALCL with a CD8 phenotype has also been described, which presents a particularly difficult diagnostic and management challenge, given the difficulty in distinguishing it histologically from other cytotoxic lymphomas such as primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma and CD8 gamma/delta and natural killer/T-cell lymphoma. We report 7 additional cases of these rare cutaneous CD8/CD30 lymphoproliferative disorders. We also present a unique case of CD8/CD30 LyP with histologic similarities to LyP type B. In all 7 of our cases of CD8 LyP and CD8 anaplastic large cell lymphoma, we found focal to diffuse MUM-1 positivity. We propose that MUM-1 may represent an adjunctive marker for CD8 lymphoproliferative disease. Finally, we review the current literature on cases of CD8 LyP and PCALCL. For the 106 cases examined, we found similar clinical and histologic features to those reported for traditional CD4CD30 LyP and PCALCL.

  18. MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

    Directory of Open Access Journals (Sweden)

    Zi-Xun Yan

    2015-01-01

    Full Text Available MicroRNAs (miRs play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n=32, T-cell lymphoblastic lymphoma (n=16, peripheral T-cell lymphoma, not otherwise specified (n=45, anaplastic large cell lymphoma (n=15, and angioimmunoblastic T-cell lymphoma (n=22. Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies.

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

    Science.gov (United States)

    2017-09-27

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

  20. Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

    Science.gov (United States)

    Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

    2016-09-01

    Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

    Science.gov (United States)

    2017-05-28

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  2. Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

    Science.gov (United States)

    2018-06-13

    CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

  3. Large-scale generation of cell-derived nanovesicles

    Science.gov (United States)

    Jo, W.; Kim, J.; Yoon, J.; Jeong, D.; Cho, S.; Jeong, H.; Yoon, Y. J.; Kim, S. C.; Gho, Y. S.; Park, J.

    2014-09-01

    Exosomes are enclosed compartments that are released from cells and that can transport biological contents for the purpose of intercellular communications. Research into exosomes is hindered by their rarity. In this article, we introduce a device that uses centrifugal force and a filter with micro-sized pores to generate a large quantity of cell-derived nanovesicles. The device has a simple polycarbonate structure to hold the filter, and operates in a common centrifuge. Nanovesicles are similar in size and membrane structure to exosomes. Nanovesicles contain intracellular RNAs ranging from microRNA to mRNA, intracellular proteins, and plasma membrane proteins. The quantity of nanovesicles produced using the device is 250 times the quantity of naturally secreted exosomes. Also, the quantity of intracellular contents in nanovesicles is twice that in exosomes. Nanovesicles generated from murine embryonic stem cells can transfer RNAs to target cells. Therefore, this novel device and the nanovesicles that it generates are expected to be used in exosome-related research, and can be applied in various applications such as drug delivery and cell-based therapy.

  4. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  5. Photoluminescence in large fluence radiation irradiated space silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Hisamatsu, Tadashi; Kawasaki, Osamu; Matsuda, Sumio [National Space Development Agency of Japan, Tsukuba, Ibaraki (Japan). Tsukuba Space Center; Tsukamoto, Kazuyoshi

    1997-03-01

    Photoluminescence spectroscopy measurements were carried out for silicon 50{mu}m BSFR space solar cells irradiated with 1MeV electrons with a fluence exceeding 1 x 10{sup 16} e/cm{sup 2} and 10MeV protons with a fluence exceeding 1 x 10{sup 13} p/cm{sup 2}. The results were compared with the previous result performed in a relative low fluence region, and the radiation-induced defects which cause anomalous degradation of the cell performance in such large fluence regions were discussed. As far as we know, this is the first report which presents the PL measurement results at 4.2K of the large fluence radiation irradiated silicon solar cells. (author)

  6. Primary Intra-aortic Epstein-Barr Virus-Positive Large B-Cell Lymphoma Presenting as Aortic Mural Thrombosis: An Entity Distinct From Intravascular Large B-Cell Lymphoma.

    Science.gov (United States)

    Nakao, Ryuta; Sakashita, Aki; Omoto, Atsushi; Sato, Osamu; Hino, Yoko; Yanagisawa, Akio; Urata, Yoji

    2017-12-01

    Intravascular selective growth of neoplastic B lymphocytes is a characteristic finding of intravascular large B-cell lymphoma (IVLBCL). However, because neoplastic B cells of IVLBCL grow merely in the lumina of capillaries or small vessels, primary IVLBCL of the great vessels is considered exceptional. To our knowledge, only 2 primary B-cell lymphomas in the lumina of the vena cava have been reported. However, there has been no report of primary B-cell lymphoma with intra-aortic growth. We describe a novel manifestation of primary Epstein-Barr virus-positive large B-cell lymphoma mainly affecting the lumina of the aorta and its major branches in a 76-year-old man. He had a long-term fever that was refractory to antibiotics and aortic mural thrombosis with visceral embolization. Because he had no detectable mass suggesting a malignancy, it was difficult to diagnose while he was alive. He died without anticancer treatment, and the confirmed diagnosis was made at autopsy.

  7. Large mid-esophageal granular cell tumor: benign versus malignant

    Directory of Open Access Journals (Sweden)

    Prarthana Roselil Christopher

    2015-06-01

    Full Text Available Granular cell tumors are rare soft tissue neoplasms, among which only 2% are malignant, arising from nervous tissue. Here we present a case of a large esophageal granular cell tumor with benign histopathological features which metastasized to the liver, but showing on positron emission tomography-computerized tomography standardized uptake value suggestive of a benign lesion.

  8. Role of radiation therapy in large cell lymphoma

    International Nuclear Information System (INIS)

    Stryker, J.A.; Bartholomew, M.J.; Beatty, R.E.

    1990-01-01

    This paper compares the results of treatment for large cell lymphoma with use of radiation therapy (RT), chemotherapy (CT), or both. The authors retrospectively studied 142 patients with large cell lymphoma. Seventy-two has stage I or II disease and 70, stage III or IV; 37% had B symptoms. CT was used in 66 patients, RT in 22, both in 46, and surgery with or without RT or CT in eight. CT regimens were CHOP, 38 patients; C-MOPP/COPP, 25; CHOP-bleo/BACOP, 15; COP-BLAN-MEL, 8; M-BACOD, 8; COP/CVP, 5; COP-BLAM, 5; and other regimens, 12. Statistical analysis showed that age, stage B symptoms, and treatment were significant variables determining survival. In stages I and II, the 5-year survival rate with RT plus CT was 65%; with CT, 35%; and with RT, 9% (P = < .01)

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

    Science.gov (United States)

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

    2014-01-01

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

  10. Large area, low cost solar cell development and production readiness

    Science.gov (United States)

    Michaels, D.

    1982-01-01

    A process sequence for a large area ( or = 25 sq. cm) silicon solar cell was investigated. Generic cell choice was guided by the expected electron fluence, by the packing factors of various cell envelope designs onto each panel to provide needed voltage as well as current, by the weight constraints on the system, and by the cost goals of the contract.

  11. Silencing of Hsp27 and Hsp72 in glioma cells as a tool for programmed cell death induction upon temozolomide and quercetin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Jakubowicz-Gil, Joanna, E-mail: jjgil@poczta.umcs.lublin.pl [Department of Comparative Anatomy and Anthropology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin (Poland); Langner, Ewa [Department of Medical Biology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Bądziul, Dorota [Department of Comparative Anatomy and Anthropology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin (Poland); Wertel, Iwona [1st Department of Gynaecology, University School of Medicine, Staszica 16, 20-081 Lublin (Poland); Rzeski, Wojciech [Department of Medical Biology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Department of Immunology and Virology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin (Poland)

    2013-12-15

    The aim of the present study was to investigate whether silencing of Hsp27 or Hsp72 expression in glioblastoma multiforme T98G and anaplastic astrocytoma MOGGCCM cells increases their sensitivity to programmed cell death induction upon temozolomide and/or quercetin treatment. Transfection with specific siRNA was performed for the Hsp gene silencing. As revealed by microscopic observation and flow cytometry, the inhibition of Hsp expression was correlated with severe apoptosis induction upon the drug treatment studied. No signs of autophagy were detected. This was correlated with a decreased mitochondrial membrane potential, increased level of cytochrome c in the cytoplasm, and activation of caspase 3 and caspase 9. All these results suggest that the apoptotic signal was mediated by an internal pathway. Additionally, in a large percentage of cells treated with temozolomide, with or without quercetin, granules within the ER system were found, which was accompanied by an increased level of caspase 12 expression. This might be correlated with ER stress. Quercetin and temozolomide also changed the shape of nuclei from circular to “croissant like” in both transfected cell lines. Our results indicate that blocking of Hsp27 and Hsp72 expression makes T98G cells and MOGGCCM cells extremely vulnerable to apoptosis induction upon temozolomide and quercetin treatment and that programmed cell death is initiated by an internal signal. - Highlights: • Hsps gene silencing induced severe apoptosis upon temozolomide–quercetin treatment • Apoptosis in transfected glioma cells was initiated by internal signal • Programmed cell death was preceded by ER stress • Temozolomide–quercetin treatment changed nuclei shape in transfected glioma cells.

  12. Primary testicular diffuse large B-cell lymphoma: A case report

    Directory of Open Access Journals (Sweden)

    Muhammad Sadiq

    2017-12-01

    Full Text Available Primary testicular diffuse large-B cell lymphoma (DLBCL is an uncommon and aggressive disease with predominant manifestation in the older age. Herein, we report a case of 47-year-old male patient who presented with three months history of left testis swelling. The patient underwent unilateral (left radical orchiectomy. Histopathological examination revealed extensive involvement and replacement of testicular parenchyma by a tumor composed of large discohesive sheets of cells with pleomorphic, hyperchromatic nuclei and prominent nucleoli. Immunohistochemical (IHC staining showed reactivity for LCA & Pan B (CD20 and negativity for OCT 3/4, SALL4 and Inhibin. Moreover, Pan T (CD3 highlighted reactive T-cells. These features rendered the diagnosis of DLBCL of testis. The hybrid 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG positron emission tomography/computed tomography (PET/CT demonstrated two para-aortic FDG avid lymph nodes on the left side at the level of L2 vertebra. Presently, the patient has been planned for doxorubicin-based chemotherapy (i.e., cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP along with intrathecal Methroxate (MTX, which would presumably improve the prognosis. Our study would expand the pool of this uncommon tumor towards its better understanding. Keywords: Primary testicular lymphoma, Diffuse large-B cell lymphoma, Orchiectomy, Doxorubicin-based chemotherapy

  13. Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

    Science.gov (United States)

    Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

    2005-02-15

    The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

  14. MicroRNA profiling of primary cutaneous large B-cell lymphomas.

    Directory of Open Access Journals (Sweden)

    Lianne Koens

    Full Text Available Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs. However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT and primary cutaneous follicle center lymphoma (PCFCL are characterized by an activated B-cell (ABC-genotype and a germinal center B-cell (GCB-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL.

  15. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

  16. Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Wang

    2010-02-01

    Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

  17. 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)

    Timmermann, Beate; Kortmann, Rolf-Dieter; Kuehl, Joachim; Meisner, Christoph; Slavc, Irene; Pietsch, Thorsten; Bamberg, Michael

    2000-01-01

    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

  18. Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging

    International Nuclear Information System (INIS)

    Ishikawa, Hitoshi; Mitsuhashi, Norio; Niibe, Hideo

    2002-01-01

    Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p<0.01). Calcification detected in AC was usually multiple and/or gross (mean size: φ8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC. (author)

  19. A large multi-cell threshold gas Cerenkov counter

    International Nuclear Information System (INIS)

    Declais, Y.; Aubert, J.J.; Bassompierre, G.; Payre, P.; Thenard, J.M.; Urban, L.

    1980-08-01

    A large multi-cell threshold gas Cerenkov counter consisting of 78 cells has been built for use in a high energy muon scattering experiment at CERN (European Muon Collaboration). It is used with neon, nitrogen or a mixture of those two gases, allowing the pion threshold to be varied between 6 and 20 GeV/c. The sensitive region of the counter has a length of 4.0 m and entrance and exit windows of 1.1 x 2.4 m 2 and 2.4 x 5.0 m 2 , respectively

  20. Primary intravascular large B-cell lymphoma of pituitary

    Directory of Open Access Journals (Sweden)

    K R Anila

    2012-01-01

    Full Text Available A 68-year-old retired nurse, who was a known hypertensive on medication, presented with prolonged fever of 2-month duration without any clinical evidence of infection. On examination she had altered mental status. She also had other nonspecific complaints such as sleep disturbances, loss of weight, etc. On investigation, she was found to have anemia, thrombocytopenia, raised erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and lactate dehydrogenase (LDH values. She also had electrolyte imbalance. Radiological evaluation of brain showed mass lesion in the sella turcica, suggestive of pituitary adenoma. Biochemical evaluation showed hypopituitarism. Trans-sphenoidal biopsy was done. Based on histopathological and immunohistochemical findings a diagnosis of intravascular large B-cell lymphoma (IVLBCL of pituitary was made. Our patient′s condition deteriorated rapidly and she succumbed to her illness before therapy could be initiated. We are reporting this case because of the rare subtype of large B-cell lymphoma presenting at an extremely unusual primary site.

  1. Geophysics Under Pressure: Large-Volume Presses Versus the Diamond-Anvil Cell

    Science.gov (United States)

    Hazen, R. M.

    2002-05-01

    Prior to 1970, the legacy of Harvard physicist Percy Bridgman dominated high-pressure geophysics. Massive presses with large-volume devices, including piston-cylinder, opposed-anvil, and multi-anvil configurations, were widely used in both science and industry to achieve a range of crustal and upper mantle temperatures and pressures. George Kennedy of UCLA was a particularly influential advocate of large-volume apparatus for geophysical research prior to his death in 1980. The high-pressure scene began to change in 1959 with the invention of the diamond-anvil cell, which was designed simultaneously and independently by John Jamieson at the University of Chicago and Alvin Van Valkenburg at the National Bureau of Standards in Washington, DC. The compact, inexpensive diamond cell achieved record static pressures and had the advantage of optical access to the high-pressure environment. Nevertheless, members of the geophysical community, who favored the substantial sample volumes, geothermally relevant temperature range, and satisfying bulk of large-volume presses, initially viewed the diamond cell with indifference or even contempt. Several factors led to a gradual shift in emphasis from large-volume presses to diamond-anvil cells in geophysical research during the 1960s and 1970s. These factors include (1) their relatively low cost at time of fiscal restraint, (2) Alvin Van Valkenburg's new position as a Program Director at the National Science Foundation in 1964 (when George Kennedy's proposal for a Nation High-Pressure Laboratory was rejected), (3) the development of lasers and micro-analytical spectroscopic techniques suitable for analyzing samples in a diamond cell, and (4) the attainment of record pressures (e.g., 100 GPa in 1975 by Mao and Bell at the Geophysical Laboratory). Today, a more balanced collaborative approach has been adopted by the geophysics and mineral physics community. Many high-pressure laboratories operate a new generation of less expensive

  2. PIM kinases as potential therapeutic targets in a subset of peripheral T cell lymphoma cases.

    Directory of Open Access Journals (Sweden)

    Esperanza Martín-Sánchez

    Full Text Available Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL. The Proviral Integration site of Moloney murine leukemia virus (PIM kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs and pharmacologically (mainly with the pan-PIM inhibitor (PIMi ETP-39010 in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.

  3. Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

    Science.gov (United States)

    2018-05-21

    Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

  4. To the Large Nucleolar Bodies in Apoptotic Leukaemic Granulocytic Progenitors without Further Differentiation. Are Large Nucleoli Always Present in Proliferating Cells?

    Science.gov (United States)

    Smetana, K; Kuželová, K; Zápotocký, M; Hrkal, Z

    2017-01-01

    Large nucleoli have generally been believed to be present in less differentiated and proliferating cells including the malignant ones. Such nucleoli have also been considered to be active in the biosynthetic process and major cell developmental activities. In contrast, after cytostatic treatment, apoptotic leukaemic progenitors still containing nuclei did not exhibit substantial reduction of the nucleolar size but displayed decreased nucleolar biosynthetic activity. The present study was undertaken to provide more information on the large nucleoli in spontaneously occurring apoptotic leukaemic progenitors without further differentiation. Leukaemic progenitors of established cell lineages originating from leukaemic patients represented a very convenient model for such study. Some of them exhibit morphological signs of the spontaneously occurring apoptotic process. Since such signs are expressed by nuclear and cytoplasmic morphological variability, the present study dealt with spontaneously occurring apoptotic progenitors with preserved nuclei characterized by heavy chromatin condensation and occasional fragmentation. Based of nucleolar body and nuclear maximal diameter measurements it seems to be clear that the nucleolar size in these cells was not substantially reduced, contrary to that of the nucleus. However, large nucleolar bodies in spontaneously occurring apoptotic cells were characterized by markedly reduced biosynthetic activity, as expressed by the decreased number of nucleolar transcription markers such as nucleolar fibrillar centres. In conclusion, large nucleoli may be present not only in proliferating, but also in spontaneously occurring apoptotic cells.

  5. Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

    Science.gov (United States)

    Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

    2018-03-26

    In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with

  6. Cerebellar giant cell glioblastoma multiforme in an adult

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  7. Large gap plasma display cell with auxiliary electrodes: macro-cell experiments and two-dimensional modelling

    International Nuclear Information System (INIS)

    Ouyang, J T; Callegari, Th; Caillier, B; Boeuf, J-P

    2003-01-01

    In this paper we use a two-dimensional fluid model and a 'macroscopic' PDP cell to investigate the possibility of using large gap configurations with auxiliary electrodes to improve the efficiency of PDP discharge cells. The large gap allows operation in a transient positive column regime where energy is more efficiently deposited into xenon excitation, while the auxiliary electrodes are used to keep reasonable values of the operating voltage. Two types of auxiliary electrode configurations (floating and powered) are considered. The discharge characteristics and the discharge efficiency in exciting xenon are studied with simulations and by measuring the intensity of infrared emission from xenon and visible emission from neon in a macroscopic PDP cell. The results show that an efficient positive column regime can be achieved at reasonably low operating voltages when the auxiliary electrode configuration is carefully designed

  8. Posttransplantation primary cutaneous CD30 (Ki-1)-positive large-cell lymphoma.

    Science.gov (United States)

    Seçkin, D; Demirhan, B; Oğuz Güleç, T; Arikan, U; Haberal, M

    2001-12-01

    We describe the case of a 51-year-old female renal transplant recipient with primary cutaneous CD30-positive large-cell lymphoma of T-cell origin. Cutaneous T-cell lymphomas are rarely reported in organ transplant recipients, and we believe they should be considered in the differential diagnosis of cutaneous neoplastic and infectious diseases affecting this patient group.

  9. Osteoclastome-like giant cell thyroid carcinoma controlled by intensive radiation and adriamycin, in a patient with meningioma and multiple myeloma treated by radiation and cytoxan

    International Nuclear Information System (INIS)

    Vizel-Schwartz, M.

    1981-01-01

    The eighth cases of osteoclastome-like giant cell carcinoma of the thyroid, and the first one to be treated with adriamycin in addition to surgery and radiation, is reported. This rare variant of anaplastic thyroid carcinoma appeared in a patient operated on for meningioma and treated for multiple myeloma with cranial radiation and chronic administration of cytoxan

  10. Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xia, Yi; Xu-Monette, Z Y; Tzankov, A

    2017-01-01

    PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBC...

  11. Long-term survival in bronchogenic carcinoma with a solitary metastasis.

    Science.gov (United States)

    Shachor, J; Luria, H; Cordova, M; Bernheim, J; Griffel, B; Bruderman, I

    1986-03-01

    Partial resection of a huge anaplastic large cell carcinoma of the upper lobe of the right lung was performed in a 47-year-old patient in order to relieve symptoms of pulmonary hypertrophic osteoarthropathy. Several months later a solitary metastasis was noted in the muscles of the right forearm. The metastasis was resected and the forearm irradiated. The patient was further treated with injections of autologous tumour cell vaccine and BCG. Today, 7 years later, the patient is alive, without any signs of neoplastic disease.

  12. Investigation of an Aberrant Cell Voltage During the Filling of a Large Lithium Thionyl Chloride Cell

    Science.gov (United States)

    Thaller, Lawrence H.; Quinzio, Michael V.

    1997-01-01

    The investigation of an aberrant cell voltage during the filling of a large lithium thionyl chloride cell summary is at: an aberrant voltage trace was noted during the review of cell filling data; incident was traced to an interruption during filling; experimentation suggested oxidizable sites within the carbon electrode were responsible for the drop in voltage; the voltage anomaly could be reproduced by interrupting the filling of similar cells; and anomalous voltage dip was not due to a short.

  13. Actin and microtubule networks contribute differently to cell response for small and large strains

    Science.gov (United States)

    Kubitschke, H.; Schnauss, J.; Nnetu, K. D.; Warmt, E.; Stange, R.; Kaes, J.

    2017-09-01

    Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell’s response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (≤5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

  14. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Li, Ling; Byrd, John C

    2016-01-01

    CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its...

  15. Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type with significant T-cell immune response

    Directory of Open Access Journals (Sweden)

    Paul M. Graham, DO

    2018-05-01

    Full Text Available We report a case of histologically confirmed primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT that subsequently underwent spontaneous regression in the absence of systemic treatment. The case showed an atypical lymphoid infiltrate that was CD20+ and MUM-1+ and CD10–. A subsequent biopsy of the spontaneously regressed lesion showed fibrosis associated with a lymphocytic infiltrate comprising reactive T cells. PCDLBCL-LT is a cutaneous B-cell lymphoma with a poor prognosis, which is usually treated with chemotherapy. We describe a case of clinical and histologic spontaneous regression in a patient with PCDLBCL-LT who had a negative systemic workup but a recurrence over a year after his initial presentation. Key words: B cell, lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, regression

  16. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

    Directory of Open Access Journals (Sweden)

    Chia PL

    2014-11-01

    Full Text Available Puey Ling Chia,1 Paul Mitchell,1 Alexander Dobrovic,2–4 Thomas John1,2,4 1Department of Medical Oncology, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia; 2Ludwig Institute for Cancer Research, Austin Health, Victoria, Australia; 3Department of Pathology, University of Melbourne, Victoria, Australia; 4School of Cancer Medicine, La Trobe University, Victoria, Australia Abstract: Improved understanding of molecular drivers of carcinogenesis has led to significant progress in the management of lung cancer. Patients with non-small-cell lung cancer (NSCLC with anaplastic lymphoma kinase (ALK gene rearrangements constitute about 4%–5% of all NSCLC patients. ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment. There are now several newer ALK inhibitors, with the next generation of agents targeting resistance mutations. In this review, we will discuss the prevalence and clinical characteristics of ALK+ lung cancer, current treatment options, and future directions in the management of this subset of NSCLC patients. Keywords: anaplastic lymphoma kinase (ALK, gene rearrangements, lung cancer, kinase inhibitors, lung adenocarcinoma

  17. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  18. Profiling of diffuse large B-cell lymphoma by immunohistochemistry

    DEFF Research Database (Denmark)

    Sjö, Lene Dissing; Poulsen, Christian Bjørn; Hansen, Mads

    2007-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a frequent lymphoma subtype with a heterogeneous behavior and a variable response to conventional chemotherapy. This clinical diversity is believed to reflect differences in the molecular pathways leading to lymphomagenesis. In this study, we have analyzed...

  19. RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells.

    Science.gov (United States)

    Hesbacher, Sonja; Pfitzer, Lisa; Wiedorfer, Katharina; Angermeyer, Sabrina; Borst, Andreas; Haferkamp, Sebastian; Scholz, Claus-Jürgen; Wobser, Marion; Schrama, David; Houben, Roland

    2016-05-31

    The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.

  20. Intravascular Large B-Cell Lymphoma Presenting as Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Elham Vali Khojeini

    2014-01-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBL is a rare subtype of diffuse large B-cell lymphoma that resides in the lumen of blood vessels. Patients typically present with nonspecific findings, particularly bizarre neurologic symptoms, fever, and skin lesions. A woman presented with shortness of breath and a chest CT scan showed diffuse interstitial thickening and ground glass opacities suggestive of an interstitial lung disease. On physical exam she was noted to have splenomegaly. The patient died and at autopsy was found to have an IVLBL in her lungs as well as nearly all her organs that were sampled. Although rare, IVLBL should be included in the differential diagnosis of interstitial lung disease and this case underscores the importance of the continuation of autopsies.

  1. Lymphoma of the eyelid

    DEFF Research Database (Denmark)

    Svendsen, Frederik Holm; Heegaard, Steffen

    2017-01-01

    Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B......-cell lymphoma (18 cases-9%). T-cell lymphomas are most frequently mycosis fungoides (25 cases-13%), extranodal natural killer/T-cell, nasal-type lymphoma (12 cases-6%), and primary cutaneous anaplastic large-cell lymphoma (12 cases-6%). This distribution differs from the distribution of ocular adnexal lymphoma...... and that of cutaneous lymphoma. The majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and adolescents. Several subtypes have a male predominance, including peripheral T-cell lymphoma and Burkitt lymphoma. Only...

  2. Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.

    Science.gov (United States)

    Wallman, Lars; Åkesson, Elisabet; Ceric, Dario; Andersson, Per Henrik; Day, Kelly; Hovatta, Outi; Falci, Scott; Laurell, Thomas; Sundström, Erik

    2011-10-07

    Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes.

  3. Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

    LENUS (Irish Health Repository)

    Curry, Sarah

    2012-02-01

    The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

  4. Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

    Science.gov (United States)

    Alcántara-González, J; González-García, C; Fernández-Guarino, M; Jaén-Olasolo, P

    2014-01-01

    Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.

  5. Large-scale modeling of rain fields from a rain cell deterministic model

    Science.gov (United States)

    FéRal, Laurent; Sauvageot, Henri; Castanet, Laurent; Lemorton, JoëL.; Cornet, FréDéRic; Leconte, Katia

    2006-04-01

    A methodology to simulate two-dimensional rain rate fields at large scale (1000 × 1000 km2, the scale of a satellite telecommunication beam or a terrestrial fixed broadband wireless access network) is proposed. It relies on a rain rate field cellular decomposition. At small scale (˜20 × 20 km2), the rain field is split up into its macroscopic components, the rain cells, described by the Hybrid Cell (HYCELL) cellular model. At midscale (˜150 × 150 km2), the rain field results from the conglomeration of rain cells modeled by HYCELL. To account for the rain cell spatial distribution at midscale, the latter is modeled by a doubly aggregative isotropic random walk, the optimal parameterization of which is derived from radar observations at midscale. The extension of the simulation area from the midscale to the large scale (1000 × 1000 km2) requires the modeling of the weather frontal area. The latter is first modeled by a Gaussian field with anisotropic covariance function. The Gaussian field is then turned into a binary field, giving the large-scale locations over which it is raining. This transformation requires the definition of the rain occupation rate over large-scale areas. Its probability distribution is determined from observations by the French operational radar network ARAMIS. The coupling with the rain field modeling at midscale is immediate whenever the large-scale field is split up into midscale subareas. The rain field thus generated accounts for the local CDF at each point, defining a structure spatially correlated at small scale, midscale, and large scale. It is then suggested that this approach be used by system designers to evaluate diversity gain, terrestrial path attenuation, or slant path attenuation for different azimuth and elevation angle directions.

  6. REMOVAL OF FACIAL MELANOSARCOMA OF A WHITE TIGRESS (PANTHERA TIGRIS - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Indramani Nath

    2016-12-01

    Full Text Available An 18 years old white tigress “Kunti” developed a large ulcerated mass originating beneath the left lower eyelid along with clinical signs of lacrimation, irritation and thwarted vision. Surgical excision was performed under tranquilization to restore normalcy. Histopathological examination revealed presence of spindle shaped anaplastic cells containing abundant melanin pigments; which was suggestive of melanosarcoma. Obligation of proper surgical techniques and maintenance of adequate postoperative measures rewarded with uneventful recovery

  7. Magnetic resonance imaging of large chromophobe renal cell carcinomas

    International Nuclear Information System (INIS)

    Sasaguri, Kohei; Irie, Hiroyuki; Kamochi, Noriyuki; Nakazono, Takahiko; Yamaguchi, Ken; Uozumi, Jiro; Kudo, Sho

    2010-01-01

    The objective of this study was to clarify the magnetic resonance imaging (MRI) findings of large chromophobe renal cell carcinomas. Five patients diagnosed pathologically with chromophobe renal cell carcinoma are included. MRI findings were retrospectively evaluated for the tumor contour, uniformity and hypointensity of the rim of the tumor on T2-weighted images, ''micro-scopic fat'', enhancement degree and pattern on dynamic study, and necrosis in the tumor, among other findings. The tumor size ranged from 4.8 to 13.7 cm (mean 7.9 cm). The tumor contour was well defined in four patients. All but one tumor showed a hypointensity rim, and all tumors had a heterogeneous appearance on T2-weighted images. ''Microscopic fat'' was detected in one case. All tumors demonstrated low enhancement compared to that of the renal cortex. All tumors showed heterogeneous enhancement on postcontrast images. Necrosis was seen in four. Hemorrhage and renal vein thrombosis was seen in one. Chromophobe renal cell carcinomas of large size tend to have a heterogeneous appearance on post-contrast and T2-weighted images, a well-defined tumor contour with a hypointensity rim on T2-wighted images, and lower enhancement than that of the renal cortex. Tumor necrosis is easily apparent, and ''microscopic fat'' may be observed. (author)

  8. Magnetization of large polystyrene peptide beads for capturing and expanding cancer cells

    International Nuclear Information System (INIS)

    Marik, Jan; Lau, D.H.; Song Aimin; Wang Xiaobing; Liu Ruiwu; Lam, K.S.

    2003-01-01

    A method is described for preparation of large magnetic polystyrene beads coupled with peptide ligands for surface receptors of lung cancer cells. We have demonstrated the feasibility of using these magnetic peptide beads for capturing and enriching lung cancer cells spiked into blood. These magnetic peptide beads potentially can be used to efficiently isolate cancer cells from body fluids

  9. CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2018-01-25

    B Acute Lymphoblastic Leukemia; CD19 Positive; Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation; Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma of the Elderly; Minimal Residual Disease; Philadelphia Chromosome Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma; T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

  10. Synthesis on power electronics for large fuel cells: From power conditioning to potentiodynamic analysis technique

    International Nuclear Information System (INIS)

    De Bernardinis, Alexandre

    2014-01-01

    Highlights: • Active load for fuel cell managing electrical drive constraints: frequency and current ripple can be adjusted independently. • Multi-port resonant soft-switched topology for power management of a thirty kilowatt segmented PEM fuel cell. • Splitting current control strategy for power segmented PEM fuel cell in case of a segment is under fault. • Reversible Buck topology for large fuel cell with control of the fuel cell potential linked to current density nonlinearity. - Abstract: The work addressed in this paper deals with a synthesis on power electronic converters used for fuel cells. The knowledge gap concerns conceptually different electronic converter architectures for PEM (Proton Exchange Membrane) fuel cells able to perform three types of functionalities: The first one is the capacity of emulating an active load representative of electrical drive constraints. In that case, frequency and fuel cell current ripple can be set independently to investigate the dynamic behavior of the fuel cell. The second one is power conditioning applied to large high power and segmented fuel cell systems (“Large” represents several tens of cells and multi-kilowatt stacks), which is a non trivial consideration regarding the topological choices to be made for improving efficiency, compactness and ensure operation under faulty condition. A multi-port resonant isolated boost topology is analyzed enabling soft switching over a large operating range for a thirty kilowatt segmented fuel cell. A splitting current control strategy in case of a segment is under fault is proposed. Each considered converter topologies meet specific constraints regarding fuel cell stack design and power level. The third functionality is the ability for the power electronics to perform analysis and diagnosis techniques, like the cyclic voltammetry on large PEM fuel cell assemblies. The latter technique is an uncommon process for large fuel cell stacks since it is rather performed on

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

    Energy Technology Data Exchange (ETDEWEB)

    Dandekar, Prasad [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Harmer, Clive; Barbachano, Yolanda [Department of Clinical Research and Development, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher [Head and Neck-Thyroid Unit, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom); Newbold, Kate [Head and Neck/Thyroid Unit, Royal Marsden NHS Foundation Trust, Sutton, Surrey (United Kingdom); Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust, Chelsea, London (United Kingdom)

    2009-06-01

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

  12. MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility

    Directory of Open Access Journals (Sweden)

    Daniel Luxen

    2017-02-01

    Full Text Available Epigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH. Fifty-nine glioma tissue samples and seven glioma cell lines were examined for hypermethylation of the MTSS1 promotor, MTSS1 expression levels and gene dosage. GBM cell lines were treated with demethylating agents and interrogated for functional consequences of MTSS1 expression after transient transfection. Hypermethylation was significantly associated with IDH1/2 mutation. Comparative SNP analysis indicates higher incidence of loss of heterozygosity of MTSS1 in anaplastic astrocytomas and secondary glioblastomas as well as hypermethylation of the remaining allele. Reversal of promoter hypermethylation results in an increased MTSS1 expression. Cell motility was significantly inhibited by MTSS1 overexpression without influencing cell growth or apoptosis. Immunofluorescence analysis of MTSS1 in human astrocytes indicates co-localization with actin filaments. MTSS1 is down-regulated by DNA methylation in glioblastoma cell lines and is part of the G-CIMP phenotype in primary glioma tissues. Our data on normal astrocytes suggest a function of MTSS1 at focal contact structures with an impact on migratory capacity but no influence on apoptosis or cellular proliferation.

  13. Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation.

    Science.gov (United States)

    D'Aiuto, Leonardo; Zhi, Yun; Kumar Das, Dhanjit; Wilcox, Madeleine R; Johnson, Jon W; McClain, Lora; MacDonald, Matthew L; Di Maio, Roberto; Schurdak, Mark E; Piazza, Paolo; Viggiano, Luigi; Sweet, Robert; Kinchington, Paul R; Bhattacharjee, Ayantika G; Yolken, Robert; Nimgaonka, Vishwajit L; Nimgaonkar, Vishwajit L

    2014-01-01

    Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented opportunity to perform high-throughput screening of novel drugs for neurological and neurodegenerative diseases. Such screenings require a robust and scalable method for generating large numbers of mature, differentiated neuronal cells. Currently available methods based on differentiation of embryoid bodies (EBs) or directed differentiation of adherent culture systems are either expensive or are not scalable. We developed a protocol for large-scale generation of neuronal stem cells (NSCs)/early neural progenitor cells (eNPCs) and their differentiation into neurons. Our scalable protocol allows robust and cost-effective generation of NSCs/eNPCs from iPSCs. Following culture in neurobasal medium supplemented with B27 and BDNF, NSCs/eNPCs differentiate predominantly into vesicular glutamate transporter 1 (VGLUT1) positive neurons. Targeted mass spectrometry analysis demonstrates that iPSC-derived neurons express ligand-gated channels and other synaptic proteins and whole-cell patch-clamp experiments indicate that these channels are functional. The robust and cost-effective differentiation protocol described here for large-scale generation of NSCs/eNPCs and their differentiation into neurons paves the way for automated high-throughput screening of drugs for neurological and neurodegenerative diseases.

  14. The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas.

    Science.gov (United States)

    Ngo, Teri-T B; Peng, Tien; Liang, Xing-Jie; Akeju, Oluwaseun; Pastorino, Sandra; Zhang, Wei; Kotliarov, Yuri; Zenklusen, Jean C; Fine, Howard A; Maric, Dragan; Wen, Patrick Y; De Girolami, Umberto; Black, Peter McL; Wu, Wells W; Shen, Rong-Fong; Jeffries, Neal O; Kang, Dong-Won; Park, John K

    2007-04-18

    Malignant gliomas are generally resistant to all conventional therapies. Notable exceptions are anaplastic oligodendrogliomas with loss of heterozygosity on chromosome 1p (1p+/-). Patients with 1p+/- anaplastic oligodendroglioma frequently respond to procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine. Because the underlying biologic basis for this clinical finding is unclear, we evaluated differentially expressed 1p-encoded proteins in 1p+/- and 1p+/+ malignant glioma cell lines and then examined whether their expression was associated with outcome of patients with anaplastic oligodendroglioma. We used a comparative proteomic screen of A172 (1p+/-) and U251 (1p+/+) malignant glioma cell lines to identify differentially expressed 1p-encoded proteins, including stathmin, a microtubule-associated protein. 1p+/- and 1p+/+ anaplastic oligodendroglioma specimens from 24 patients were assessed for stathmin expression by immunohistochemistry. The relationship between stathmin expression and clinical outcome was assessed with Kaplan-Meier analyses. RNA inhibition and cDNA transfection experiments tested effects of stathmin under- and overexpression, respectively, on the in vitro and in vivo resistance of malignant glioma cells to treatment with nitrosourea. For in vivo resistance studies, 36 mice with intracranial and 16 mice with subcutaneous xenograft tumor implants were used (one tumor per mouse). Flow cytometry was used for cell cycle analysis. Immunoblotting was used to assess protein expression. All statistical tests were two-sided. Decreased stathmin expression in tumors was statistically significantly associated with loss of heterozygosity in 1p (Pnitrosourea-treated mice carrying xenograft tumors. Median survival of mice with stathmin+/- tumors was 95 days (95% CI = 68.7 to 121.3 days) and that of mice with stathmin+/+ tumors was 64 days (95% CI = 58.2 to 69.8 days) (difference = 31 days, 95% CI = 4.1 to 57.9 days; PNitrosoureas induced

  15. Evaluation of hollow fiber culture for large-scale production of mouse embryonic stem cell-derived hematopoietic stem cells.

    Science.gov (United States)

    Nakano, Yu; Iwanaga, Shinya; Mizumoto, Hiroshi; Kajiwara, Toshihisa

    2018-03-03

    Hematopoietic stem cells (HSCs) have the ability to differentiate into all types of blood cells and can be transplanted to treat blood disorders. However, it is difficult to obtain HSCs in large quantities because of the shortage of donors. Recent efforts have focused on acquiring HSCs by differentiation of pluripotent stem cells. As a conventional differentiation method of pluripotent stem cells, the formation of embryoid bodies (EBs) is often employed. However, the size of EBs is limited by depletion of oxygen and nutrients, which prevents them from being efficient for the production of HSCs. In this study, we developed a large-scale hematopoietic differentiation approach for mouse embryonic stem (ES) cells by applying a hollow fiber (HF)/organoid culture method. Cylindrical organoids, which had the potential for further spontaneous differentiation, were established inside of hollow fibers. Using this method, we improved the proliferation rate of mouse ES cells to produce an increased HSC population and achieved around a 40-fold higher production volume of HSCs in HF culture than in conventional EB culture. Therefore, the HF/organoid culture method may be a new mass culture method to acquire pluripotent stem cell-derived HSCs.

  16. PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro.

    Directory of Open Access Journals (Sweden)

    Lina Quan

    Full Text Available Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL is an aggressive malignancy that is largely resistant to current therapeutic regimens, and is an attractive target for immune-based therapies. Anti-programmed death-1 (PD-1 antibodies showed encouraging anti-tumor effects in both preclinical models and advanced solid and hematological malignancies, but its efficacy against EBV+DLBCL is unknown. Herein, we performed experiments using co-culture system with T cells and lymphoma cell lines including EBV+DLBCL and EBV-DLBCL [including germinal center B-cell like (GCB-DLBCL and non-GCB-DLBCL] in vitro. We show that lymphoma cells augmented the expression of PD-1 on T cells, decreased the proliferation of T cells, and altered the secretion of multiple cytokines. However, through PD-1 blockade, these functions could be largely restored. Notbaly, the effect of PD-1 blockade on antitumor immunity was more effective in EBV+DLBCL than that in EBV-DLBCL in vitro. These results suggest that T-cell exhaustion and immune escape in microenvironment is one of the mechanisms underlying DLBCL; and PD-1 blockade could present as a efficacious immunotherapeutic treatment for EBV+DLBCL.

  17. Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

    Energy Technology Data Exchange (ETDEWEB)

    Colomba, A [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Giuriato, S; Dejean, E [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Thornber, K [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Delsol, G [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Tronchère, H [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Meggetto, F [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Payrastre, B; Gaits-Iacovoni, F [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France)

    2011-06-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas.

  18. Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

    International Nuclear Information System (INIS)

    Colomba, A; Giuriato, S; Dejean, E; Thornber, K; Delsol, G; Tronchère, H; Meggetto, F; Payrastre, B; Gaits-Iacovoni, F

    2011-01-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

  19. Anaplasia and grading in medulloblastomas.

    Science.gov (United States)

    Eberhart, Charles G; Burger, Peter C

    2003-07-01

    The variable clinical outcomes of medulloblastoma patients have prompted a search for markers with which to tailor therapies to individuals. In this review, we discuss clinical, histological and molecular features that can be used in such treatment customization, focusing on how histopathological grading can impact both patient care and research on the molecular basis of CNS embryonal tumors. Medulloblastomas span a histological spectrum ending in overtly malignant large cell/anaplastic lesions characterized by increased nuclear size, marked cytological anaplasia, and increased mitotic and apoptotic rates. These "high-grade" lesions make up approximately one quarter of medulloblastomas, and recur and metastasize more frequently than tumors lacking anaplasia. We believe anaplastic change represents a type of malignant progression common to many medulloblastoma subtypes and to other CNS embryonal lesions as well. Correlation of these histological changes with the accumulation of genetic events suggests a model for the histological and molecular progression of medulloblastoma.

  20. Breast implant capsule-associated squamous cell carcinoma: a report of 2 cases.

    Science.gov (United States)

    Olsen, Daniel L; Keeney, Gary L; Chen, Beiyun; Visscher, Daniel W; Carter, Jodi M

    2017-09-01

    The use of prosthetic implants for breast augmentation has become commonplace. Although implants do not increase the risk of conventional mammary carcinoma, they are rarely associated with anaplastic large cell lymphoma. We report 2 cases of breast implant capsule-associated squamous cell carcinoma with poor clinical outcomes. Both patients (56-year-old woman and 81-year-old woman) had long-standing implants (>25 years) and presented with acute unilateral breast enlargement. In both cases, squamous cell carcinoma arose in (focally dysplastic) squamous epithelium-lined breast implant capsules and widely invaded surrounding breast parenchyma or chest wall. Neither patient had evidence of a primary mammary carcinoma or squamous cell carcinoma at any other anatomic site. Within 1 year, one patient developed extensive, treatment-refractory, locoregional soft tissue metastasis, and the second patient developed hepatic and soft tissue metastases and died of disease. There are 2 prior reported cases of implant-associated squamous cell carcinoma in the plastic surgery literature; one provides no pathologic staging or outcome information, and the second case was a capsule-confined squamous cell carcinoma. Together, all 4 cases share notable commonalities: the patients had long-standing breast implants and presented with acute unilateral breast pain and enlargement secondary to tumors arising on the posterior aspect of squamous epithelialized implant capsules. Because of both its rarity and its unusual clinical presentation, implant capsule-associated squamous cell carcinoma may be underrecognized. The aggressive behavior of the tumors in this series underscores the importance of excluding malignancy in patients with long-standing breast implants who present with acute unilateral breast pain and enlargement. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Primary Diffuse Large Cell Lymphoma of the Bladder: Case Report and Literature Review

    OpenAIRE

    Mansour Ansari; Hamid Nasrollahi; Majdaddin Rajaei; Maral Mokhtari; Seyed Hasan Hamedi; Mohammad Mohammadianpanah; Shapour Omidvari; Ahmad Mosalaei; Niloofar Ahmadloo

    2017-01-01

    Most bladder tumors are epithelial in origin. Nonepithelial cancers are rarely located in the bladder. Sarcomas are the most common malignancies among nonepithelial cancers. Primary bladder lymphoma is rare and mostly low grade. Here, we have reported a case of diffuse large cell lymphoma of the bladder. The patient, a 64-year-old man, had urinary frequency for 18 months. Abdominal sonography indicated a thick bladder wall and transurethral biopsy showed diffuse large cell lymp...

  2. Diffuse large B-cell lymphoma of the oral cavity

    International Nuclear Information System (INIS)

    Carlos Bortoluzzi, Marcelo

    2010-01-01

    The authors report a case of diffuse large B-cell lymphoma (DLBL) of the oral cavity. The patient was a 73-year-old white man who first presented at the Division of Stomatology with a large nodular mass in the hard palate and a nodular lesion in the upper lip, which were diagnosed as DLBL. The patient was treated with eight cycles of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), but the disease recurred 22 months after the end of the therapy. Both primary sites hard palate and upper lip were involved again and the patient was resubmitted to chemotherapy. (author)

  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. Primary cutaneous large B-cell lymphoma of scalp: Case report of a rare variant

    Directory of Open Access Journals (Sweden)

    Yasmeen Khatib

    2017-01-01

    Full Text Available Primary cutaneous large B-cell lymphoma (Bcl is defined as a lymphoma composed of large cells constituting more than 80% of the infiltrate and absence of extracutaneous involvement after staging investigations. In the new World Health Organization/European Organization for Research and Treatment of Cancer classification, cutaneous Bcls with large cells are of three types - primary cutaneous large Bcl leg type (PCLBCLLT, primary cutaneous follicle center lymphoma diffuse type (PCFCLDT, and primary cutaneous large Bcls other (PCLBCLO. These three different types are distinct in terms of their clinicopathological features and survival. The PCLBCLO has intermediate features between those of PCLBCLLT and PCFCLDT. We present a case of PCLBCLO in a 57-year-old male who presented with a scalp swelling. Ultrasonography examination was suggestive of a sebaceous cyst. Computed tomography scan revealed the presence of an ill-defined hyperdense region in the soft tissue of the scalp region extending into the deeper layers of the scalp. Fine-needle aspiration cytology (FNAC revealed the presence of atypical lymphoid cells. Diagnosis was confirmed by biopsy and immunohistochemistry. Patient received rituximab combined with doxorubicin, vincristine, cyclophosphamide, and prednisolone regimen with complete resolution of the lesion. We present this case for its rarity, the utility of FNAC in early diagnosis, and to discuss the differential diagnosis.

  5. Molecular and in vivo characterization of cancer-propagating cells derived from MYCN-dependent medulloblastoma.

    Directory of Open Access Journals (Sweden)

    Zai Ahmad

    Full Text Available Medulloblastoma (MB is the most common malignant pediatric brain tumor. While the pathways that are deregulated in MB remain to be fully characterized, amplification and/or overexpression of the MYCN gene, which is has a critical role in cerebellar development as a regulator of neural progenitor cell fate, has been identified in several MB subgroups. Phenotypically, aberrant expression of MYCN is associated with the large-cell/anaplastic MB variant, which accounts for 5-15% of cases and is associated with aggressive disease and poor clinical outcome. To better understand the role of MYCN in MB in vitro and in vivo and to aid the development of MYCN-targeted therapeutics we established tumor-derived neurosphere cell lines from the GTML (Glt1-tTA/TRE-MYCN-Luc genetically engineered mouse model. A fraction of GTML neurospheres were found to be growth factor independent, expressed CD133 (a marker of neural stem cells, failed to differentiate upon MYCN withdrawal and were highly tumorigenic when orthotopically implanted into the cerebellum. Principal component analyzes using single cell RNA assay data suggested that the clinical candidate aurora-A kinase inhibitor MLN8237 converts GTML neurospheres to resemble non-MYCN expressors. Correlating with this, MLN8237 significantly extended the survival of mice bearing GTML MB allografts. In summary, our results demonstrate that MYCN plays a critical role in expansion and survival of aggressive MB-propagating cells, and establish GTML neurospheres as an important resource for the development of novel therapeutic strategies.

  6. Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-23

    Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

  7. Development of large engineered cartilage constructs from a small population of cells.

    Science.gov (United States)

    Brenner, Jillian M; Kunz, Manuela; Tse, Man Yat; Winterborn, Andrew; Bardana, Davide D; Pang, Stephen C; Waldman, Stephen D

    2013-01-01

    Confronted with articular cartilage's limited capacity for self-repair, joint resurfacing techniques offer an attractive treatment for damaged or diseased tissue. Although tissue engineered cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for the repair of large defects. As routine cell expansion methods tend to elicit negative effects on chondrocyte function, we have developed an approach to generate phenotypically stable, large-sized engineered constructs (≥3 cm(2) ) directly from a small amount of donor tissue or cells (as little as 20,000 cells to generate a 3 cm(2) tissue construct). Using rabbit donor tissue, the bioreactor-cultivated constructs were hyaline-like in appearance and possessed a biochemical composition similar to native articular cartilage. Longer bioreactor cultivation times resulted in increased matrix deposition and improved mechanical properties determined over a 4 week period. Additionally, as the anatomy of the joint will need to be taken in account to effectively resurface large affected areas, we have also explored the possibility of generating constructs matched to the shape and surface geometry of a defect site through the use of rapid-prototyped defect tissue culture molds. Similar hyaline-like tissue constructs were developed that also possessed a high degree of shape correlation to the original defect mold. Future studies will be aimed at determining the effectiveness of this approach to the repair of cartilage defects in an animal model and the creation of large-sized osteochondral constructs. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

  8. Mechanisms limiting the performance of large grain polycrystalline silicon solar cells

    Science.gov (United States)

    Culik, J. S.; Alexander, P.; Dumas, K. A.; Wohlgemuth, J. W.

    1984-01-01

    The open-circuit voltage and short-circuit current of large-grain (1 to 10 mm grain diameter) polycrystalline silicon solar cells is determined by the minority-carrier diffusion length within the bulk of the grains. This was demonstrated by irradiating polycrystalline and single-crystal (Czochralski) silicon solar cells with 1 MeV electrons to reduce their bulk lifetime. The variation of short-circuit current with minority-carrier diffusion length for the polycrystalline solar cells is identical to that of the single-crystal solar cells. The open-circuit voltage versus short-circuit current characteristic of the polycrystalline solar cells for reduced diffusion lengths is also identical to that of the single-crystal solar cells. The open-circuit voltage of the polycrystalline solar cells is a strong function of quasi-neutral (bulk) recombination, and is reduced only slightly, if at all, by grain-boundary recombination.

  9. Features and applications of the large capacity Li-MnO/sub 2/ cell

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Koichi; Takeuchi, Ken' ichi

    1987-04-10

    Recently, Litium cells are used for power source of wristwatches, pocket-computors and cameras. The large capacity Li-MnO/sub 2/ primary cell developed by Yuasa Battery Company features its prismatic shape with a completely-sealed construction and a large capacity up to 1300Ah in addition to its high energy density and small self-discharge inherent to this type of cell, and is used in various application where a maintenance-free property is required for a long period of time. This paper deals with characteristecs, structure, safety and application examples of this Li-MnO/sub 2/ cell. As application examples, power supplies for head lamps for mountaineering, buoys for oceanographic survey, back-up for computor-memories and back-up for emergency alarm, are mentioned. (10 figs, 1 tab, 3 photos)

  10. Large area, low cost space solar cells with optional wraparound contacts

    Science.gov (United States)

    Michaels, D.; Mendoza, N.; Williams, R.

    1981-01-01

    Design parameters for two large area, low cost solar cells are presented, and electron irradiation testing, thermal alpha testing, and cell processing are discussed. The devices are a 2 ohm-cm base resistivity silicon cell with an evaporated aluminum reflector produced in a dielectric wraparound cell, and a 10 ohm-cm silicon cell with the BSF/BSR combination and a conventional contact system. Both cells are 5.9 x 5.9 cm and require 200 micron thick silicon material due to mission weight constraints. Normalized values for open circuit voltage, short circuit current, and maximum power calculations derived from electron radiation testing are given. In addition, thermal alpha testing values of absorptivity and emittance are included. A pilot cell processing run produced cells averaging 14.4% efficiencies at AMO 28 C. Manufacturing for such cells will be on a mechanized process line, and the area of coverslide application technology must be considered in order to achieve cost effective production.

  11. Large scale tracking of stem cells using sparse coding and coupled graphs

    DEFF Research Database (Denmark)

    Vestergaard, Jacob Schack; Dahl, Anders Lindbjerg; Holm, Peter

    Stem cell tracking is an inherently large scale problem. The challenge is to identify and track hundreds or thousands of cells over a time period of several weeks. This requires robust methods that can leverage the knowledge of specialists on the field. The tracking pipeline presented here consists...

  12. Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

    Directory of Open Access Journals (Sweden)

    Milovanović Milena

    2017-06-01

    Full Text Available In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL, primary cutaneous follicle center lymphoma (PCFCL, primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT, and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O. The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP.

  13. Anaplasia and drug selection-independent overexpression of the multidrug resistance gene, MDR1, in Wilms' tumor.

    Science.gov (United States)

    Re, G G; Willingham, M C; el Bahtimi, R; Brownlee, N A; Hazen-Martin, D J; Garvin, A J

    1997-02-01

    One reason for the failure of chemotherapy is the overexpression of the multidrug resistance gene, MDR1. The product of this gene is the multidrug transporter P-glycoprotein, an ATP-dependent pump that extrudes drugs from the cytoplasm. Some tumors inherently express P-glycoprotein, whereas others acquire the ability to do so after exposure to certain chemotherapeutic agents, often by the mechanism of gene amplification. Classical Wilms' tumors (nephroblastoma) typically respond to therapy and have a good prognosis. On the contrary, anaplastic Wilms' tumors are generally refractory to chemotherapy. These anaplastic variants are rare (4.5% of all Wilms' tumors reported in the United States), aggressive, and often fatal forms of tumor, which are commonly thought to result from the progression of classical Wilms' tumors. To investigate the basis for this differential response to therapy, we examined a number of classical and anaplastic Wilms' tumors for the expression of the MDR1 gene by immunohistochemical and mRNA analysis. Classical Wilms' tumors consistently did not express P-glycoprotein except in areas of tubular differentiation, as in normal kidney. Similarly, two of three anaplastic tumors failed to show P-glycoprotein expression. In contrast, cultured cells derived from a third anaplastic tumor, W4, exhibited strong P-glycoprotein expression and were drug resistant in vitro. Southern analysis revealed that W4 cells contained a single copy of the MDR1 gene per haploid genome similar to normal cells, demonstrating that the overexpression of MDR1 was not caused by gene amplification. Transcriptional activation of the MDR1 gene would be in keeping with the concept that p53 might act as a transcriptional repressor of the MDR1 gene.

  14. Vav-1 expression correlates with NFkappaB activation and CD40-mediated cell death in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Hollmann, Annette; Aloyz, Raquel; Baker, Kristi

    2010-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with a variable response to therapy. We have previously shown that DLBCL cell lines differ in their susceptibility to CD40-mediated cell death, and that resistance to CD40-targeted antibodies correlated with increased expression...... as a potential marker to identify tumours likely to respond to CD40-targeted therapies. Copyright (c) 2010 John Wiley & Sons, Ltd....

  15. Aberrant methylation of cell-free circulating DNA in plasma predicts poor outcome in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Hansen, Jakob Werner; Kristensen, Søren Sommer

    2016-01-01

    BACKGROUND: The prognostic value of aberrant DNA methylation of cell-free circulating DNA in plasma has not previously been evaluated in diffuse large B cell lymphoma (DLBCL). The aim of this study was to investigate if aberrant promoter DNA methylation can be detected in plasma from DLBCL patients...

  16. The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

    Science.gov (United States)

    van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

    2017-03-01

    The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

  17. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F; Maitra, Anirban; Hicks, Jessica; Demarzo, Angelo M; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H; Wolfgang, Christopher L; Schulick, Richard D; Hruban, Ralph H; Tang, Laura H; Klimstra, David S; Iacobuzio-Donahue, Christine A

    2012-02-01

    Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

  18. Biochemical analysis of force-sensitive responses using a large-scale cell stretch device.

    Science.gov (United States)

    Renner, Derrick J; Ewald, Makena L; Kim, Timothy; Yamada, Soichiro

    2017-09-03

    Physical force has emerged as a key regulator of tissue homeostasis, and plays an important role in embryogenesis, tissue regeneration, and disease progression. Currently, the details of protein interactions under elevated physical stress are largely missing, therefore, preventing the fundamental, molecular understanding of mechano-transduction. This is in part due to the difficulty isolating large quantities of cell lysates exposed to force-bearing conditions for biochemical analysis. We designed a simple, easy-to-fabricate, large-scale cell stretch device for the analysis of force-sensitive cell responses. Using proximal biotinylation (BioID) analysis or phospho-specific antibodies, we detected force-sensitive biochemical changes in cells exposed to prolonged cyclic substrate stretch. For example, using promiscuous biotin ligase BirA* tagged α-catenin, the biotinylation of myosin IIA increased with stretch, suggesting the close proximity of myosin IIA to α-catenin under a force bearing condition. Furthermore, using phospho-specific antibodies, Akt phosphorylation was reduced upon stretch while Src phosphorylation was unchanged. Interestingly, phosphorylation of GSK3β, a downstream effector of Akt pathway, was also reduced with stretch, while the phosphorylation of other Akt effectors was unchanged. These data suggest that the Akt-GSK3β pathway is force-sensitive. This simple cell stretch device enables biochemical analysis of force-sensitive responses and has potential to uncover molecules underlying mechano-transduction.

  19. Microarray-based classification of diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Nielsen, Finn Cilius

    2005-01-01

    on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used......OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation...... for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1...

  20. Genetic and Functional Drivers of Diffuse LargeCell Lymphoma

    DEFF Research Database (Denmark)

    Reddy, Anupama; Zhang, Jenny; Davis, Nicholas S

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed...

  1. Development of polymers for large scale roll-to-roll processing of polymer solar cells

    DEFF Research Database (Denmark)

    Carlé, Jon Eggert

    Development of polymers for large scale roll-to-roll processing of polymer solar cells Conjugated polymers potential to both absorb light and transport current as well as the perspective of low cost and large scale production has made these kinds of material attractive in solar cell research....... The research field of polymer solar cells (PSCs) is rapidly progressing along three lines: Improvement of efficiency and stability together with the introduction of large scale production methods. All three lines are explored in this work. The thesis describes low band gap polymers and why these are needed....... Polymer of this type display broader absorption resulting in better overlap with the solar spectrum and potentially higher current density. Synthesis, characterization and device performance of three series of polymers illustrating how the absorption spectrum of polymers can be manipulated synthetically...

  2. Crizotinib for Untreated Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Morgan, Philip; Woolacott, Nerys; Biswas, Mousumi; Mebrahtu, Teumzghi; Harden, Melissa; Hodgson, Robert

    2017-09-01

    As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund. As part of this new appraisal, the company included a price discount patient access scheme (PAS). The Centre for Reviews and Dissemination and Centre for Health Economics Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company's submission and the ERG's review and summarises the resulting NICE guidance issued in August 2016. The main clinical-effectiveness data were derived from a multicentre randomised controlled trial-PROFILE 1014-that compared crizotinib with pemetrexed chemotherapy in combination with carboplatin or cisplatin in patients with untreated non-squamous ALK-positive NSCLC. In the trial, crizotinib demonstrated improvements in progression-free survival (PFS) and overall survival (OS). The company's economic model was a three-state 'area under the curve' Markov model. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be greater than £50,000 per quality-adjusted life-year (QALY) gained (excluding the PAS discount). The ERG assessment of the evidence submitted by the company raised a number of concerns. In terms of the clinical evidence, the OS benefit was highly uncertain due to the cross-over permitted in the trial and the immaturity of the data; only 26% of events had occurred by the data cut-off point. In the economic modelling, the most significant concerns related to the analysis

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology

    Science.gov (United States)

    Che, James; Yu, Victor; Dhar, Manjima; Renier, Corinne; Matsumoto, Melissa; Heirich, Kyra; Garon, Edward B.; Goldman, Jonathan; Rao, Jianyu; Sledge, George W.; Pegram, Mark D.; Sheth, Shruti; Jeffrey, Stefanie S.; Kulkarni, Rajan P.; Sollier, Elodie; Di Carlo, Dino

    2016-01-01

    Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. PMID:26863573

  5. Relapsed Diffuse Large B-Cell Lymphoma Treated by Reduced-Intensity Allogeneic Stem Cell Transplantation with Donor Lymphocyte Infusion

    International Nuclear Information System (INIS)

    Chudhry, Q.N.; Ahmed, P.; Ullah, K.; Satti, T.M.; Raza, S.; Mehmood, S.K.; Akram, M.; Ahmed, S.

    2010-01-01

    A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks post transplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years post transplant with his disease in complete remission. (author)

  6. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

    Science.gov (United States)

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  7. Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas.

    Science.gov (United States)

    Fanale, Michelle A; Horwitz, Steven M; Forero-Torres, Andres; Bartlett, Nancy L; Advani, Ranjana H; Pro, Barbara; Chen, Robert W; Davies, Andrew; Illidge, Tim; Uttarwar, Mayur; Lee, Shih-Yuan; Ren, Hong; Kennedy, Dana A; Shustov, Andrei R

    2018-05-10

    This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30 + peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789. © 2018 by The American Society of Hematology.

  8. The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2012-02-01

    Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

  9. Large Cell Neuroendocrine Cancer (LCNEC of uterine cervix

    Directory of Open Access Journals (Sweden)

    Gehanath Baral

    2009-01-01

    Full Text Available A rare type of cervical cancer was encountered as a neuroendocrine cancer of cervix. Clinically, the patient presented with bleeding per vagina. She refused biopsy in her first visit and did not come for follow up. However, after few months she came and since there was a polypoid growth from cervix, she was advised to undergo hysterectomy. Histopathologically, it was diagnosed as large cell type of neuroendocrine cancer. Multimodality systemic treatment was offered as per literature. Ibrahim Med. Coll. J. 2009; 3(1: 36-38

  10. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    Directory of Open Access Journals (Sweden)

    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  11. Flow-cytometric analysis of mouse embryonic stem cell lipofection using small and large DNA constructs.

    Science.gov (United States)

    McLenachan, Samuel; Sarsero, Joseph P; Ioannou, Panos A

    2007-06-01

    Using the lipofection reagent LipofectAMINE 2000 we have examined the delivery of plasmid DNA (5-200 kb) to mouse embryonic stem (mES) cells by flow cytometry. To follow the physical uptake of lipoplexes we labeled DNA molecules with the fluorescent dye TOTO-1. In parallel, expression of an EGFP reporter cassette in constructs of different sizes was used as a measure of nuclear delivery. The cellular uptake of DNA lipoplexes is dependent on the uptake competence of mES cells, but it is largely independent of DNA size. In contrast, nuclear delivery was reduced with increasing plasmid size. In addition, linear DNA is transfected with lower efficiency than circular DNA. Inefficient cytoplasmic trafficking appears to be the main limitation in the nonviral delivery of large DNA constructs to the nucleus of mES cells. Overcoming this limitation should greatly facilitate functional studies with large genomic fragments in embryonic stem cells.

  12. Xeno-Free and Defined Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells Functionally Integrate in a Large-Eyed Preclinical Model

    Directory of Open Access Journals (Sweden)

    Alvaro Plaza Reyes

    2016-01-01

    Full Text Available Human embryonic stem cell (hESC-derived retinal pigment epithelial (RPE cells could replace lost tissue in geographic atrophy (GA but efficacy has yet to be demonstrated in a large-eyed model. Also, production of hESC-RPE has not yet been achieved in a xeno-free and defined manner, which is critical for clinical compliance and reduced immunogenicity. Here we describe an effective differentiation methodology using human laminin-521 matrix with xeno-free and defined medium. Differentiated cells exhibited characteristics of native RPE including morphology, pigmentation, marker expression, monolayer integrity, and polarization together with phagocytic activity. Furthermore, we established a large-eyed GA model that allowed in vivo imaging of hESC-RPE and host retina. Cells transplanted in suspension showed long-term integration and formed polarized monolayers exhibiting phagocytic and photoreceptor rescue capacity. We have developed a xeno-free and defined hESC-RPE differentiation method and present evidence of functional integration of clinically compliant hESC-RPE in a large-eyed disease model.

  13. System design of a large fuel cell hybrid locomotive

    Science.gov (United States)

    Miller, A. R.; Hess, K. S.; Barnes, D. L.; Erickson, T. L.

    Fuel cell power for locomotives combines the environmental benefits of a catenary-electric locomotive with the higher overall energy efficiency and lower infrastructure costs of a diesel-electric. A North American consortium, a public-private partnership, is developing a prototype hydrogen-fueled fuel cell-battery hybrid switcher locomotive for urban and military-base rail applications. Switcher locomotives are used in rail yards for assembling and disassembling trains and moving trains from one point to another. At 127 tonnes (280,000 lb), continuous power of 250 kW from its (proton exchange membrane) PEM fuel cell prime mover, and transient power well in excess of 1 MW, the hybrid locomotive will be the heaviest and most powerful fuel cell land vehicle yet. This fast-paced project calls for completion of the vehicle itself near the end of 2007. Several technical challenges not found in the development of smaller vehicles arise when designing and developing such a large fuel cell vehicle. Weight, center of gravity, packaging, and safety were design factors leading to, among other features, the roof location of the lightweight 350 bar compressed hydrogen storage system. Harsh operating conditions, especially shock loads during coupling to railcars, require component mounting systems capable of absorbing high energy. Vehicle scale-up by increasing mass, density, or power presents new challenges primarily related to issues of system layout, hydrogen storage, heat transfer, and shock loads.

  14. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

    2013-01-01

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  15. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

    International Nuclear Information System (INIS)

    Diaz, Jason; Wang, Xin; Tsang, Sabrina H.; Jiao, Jing; You, Jianxin

    2014-01-01

    Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells

  16. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Jason; Wang, Xin; Tsang, Sabrina H. [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Jiao, Jing [Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 19104 (United States); You, Jianxin, E-mail: jianyou@mail.med.upenn.edu [Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2014-07-08

    Merkel Cell Polyomavirus (MCPyV) was recently discovered as a novel human polyomavirus that is associated with ~80% of Merkel Cell Carcinomas. The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. Phosphorylation plays a critical regulatory role for polyomavirus LT proteins, but no investigation of MCPyV LT phosphorylation has been performed to date. In this report mass spectrometry analysis reveals three unique phosphorylation sites: T271, T297 and T299. In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT’s ability to initiate replication from the viral origin. We test these mutants for their ability to bind, unwind, and act as a functional helicase at the viral origin. These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. Although the natural host cell of MCPyV has not yet been established, this work provides a foundation for understanding how LT activity is regulated and provides tools for better exploring this regulation in both natural host cells and Merkel cells.

  17. Ectopic production of beta-HCG by a maxillary squamous cell carcinoma.

    Science.gov (United States)

    Scholl, P D; Jurco, S; Austin, J R

    1997-12-01

    Paraneoplastic syndromes of the head and neck are rare. Hypercalcemia and leukocytosis have been described. The literature was reviewed, and a case of a squamous cell carcinoma of the maxilla producing beta human chorionic gonadotropin (beta-HCG) is presented. A 47-year-old white man with a T4N1M0 squamous cell carcinoma of the left maxilla was treated with a maxillectomy and neck dissection for an N1 positive neck. After completing his planned radiotherapy, he developed distant metastases, which included an axillary node that stained positive for human beta-HCG. Retrospective review of the primary specimen showed beta-HCG positivity in an anaplastic component of the tumor along with vascular invasion. The first case in the literature of a paraneoplastic syndrome with beta-HCG production in association with squamous cell carcinoma of the maxilla is presented. This case history fits the aggressive nature of beta HCG producing tumors elsewhere in the body.

  18. Flow-through electroporation based on constant voltage for large-volume transfection of cells.

    Science.gov (United States)

    Geng, Tao; Zhan, Yihong; Wang, Hsiang-Yu; Witting, Scott R; Cornetta, Kenneth G; Lu, Chang

    2010-05-21

    Genetic modification of cells is a critical step involved in many cell therapy and gene therapy protocols. In these applications, cell samples of large volume (10(8)-10(9)cells) are often processed for transfection. This poses new challenges for current transfection methods and practices. Here we present a novel flow-through electroporation method for delivery of genes into cells at high flow rates (up to approximately 20 mL/min) based on disposable microfluidic chips, a syringe pump, and a low-cost direct current (DC) power supply that provides a constant voltage. By eliminating pulse generators used in conventional electroporation, we dramatically lowered the cost of the apparatus and improved the stability and consistency of the electroporation field for long-time operation. We tested the delivery of pEFGP-C1 plasmids encoding enhanced green fluorescent protein into Chinese hamster ovary (CHO-K1) cells in the devices of various dimensions and geometries. Cells were mixed with plasmids and then flowed through a fluidic channel continuously while a constant voltage was established across the device. Together with the applied voltage, the geometry and dimensions of the fluidic channel determined the electrical parameters of the electroporation. With the optimal design, approximately 75% of the viable CHO cells were transfected after the procedure. We also generalize the guidelines for scaling up these flow-through electroporation devices. We envision that this technique will serve as a generic and low-cost tool for a variety of clinical applications requiring large volume of transfected cells. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

    2017-01-01

    Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

  20. Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Wasif Saif; Sapna Khubchandani; Marek Walczak

    2007-01-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis,including the gastrointestinal tract and bone marrow.However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma.The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma,based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient's abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation.Both cases responded well to chemotherapy.

  1. One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System

    Directory of Open Access Journals (Sweden)

    Joycelyn Lee

    2014-01-01

    Full Text Available Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin’s lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.

  2. Next-generation sequencing identifies deregulation of microRNAs involved in both innate and adaptive immune response in ALK+ ALCL.

    Directory of Open Access Journals (Sweden)

    Julia Steinhilber

    Full Text Available Anaplastic large cell lymphoma (ALCL is divided into two systemic diseases according to the expression of the anaplastic lymphoma kinase (ALK. We investigated the differential expression of miRNAs between ALK+ ALCL, ALK- ALCL cells and normal T-cells using next generation sequencing (NGS. In addition, a C/EBPβ-dependent miRNA profile was generated. The data were validated in primary ALCL cases. NGS identified 106 miRNAs significantly differentially expressed between ALK+ and ALK- ALCL and 228 between ALK+ ALCL and normal T-cells. We identified a signature of 56 miRNAs distinguishing ALK+ ALCL, ALK- ALCL and T-cells. The top candidates significant differentially expressed between ALK+ and ALK- ALCL included 5 upregulated miRNAs: miR-340, miR-203, miR-135b, miR-182, miR-183; and 7 downregulated: miR-196b, miR-155, miR-146a, miR-424, miR-503, miR-424*, miR-542-3p. The miR-17-92 cluster was also upregulated in ALK+ cells. Additionally, we identified a signature of 3 miRNAs significantly regulated by the transcription factor C/EBPβ, which is specifically overexpressed in ALK+ ALCL, including the miR-181 family. Of interest, miR-181a, which regulates T-cell differentiation and modulates TCR signalling strength, was significantly downregulated in ALK+ ALCL cases. In summary, our data reveal a miRNA signature linking ALK+ ALCL to a deregulated immune response and may reflect the abnormal TCR antigen expression known in ALK+ ALCL.

  3. Promoter methylation patterns in Richter syndrome affect stem-cell maintenance and cell cycle regulation and differ from de novo diffuse large B-cell lymphoma.

    Science.gov (United States)

    Rinaldi, Andrea; Mensah, Afua Adjeiwaa; Kwee, Ivo; Forconi, Francesco; Orlandi, Ester M; Lucioni, Marco; Gattei, Valter; Marasca, Roberto; Berger, Françoise; Cogliatti, Sergio; Cavalli, Franco; Zucca, Emanuele; Gaidano, Gianluca; Rossi, Davide; Bertoni, Francesco

    2013-10-01

    In a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to Richter syndrome (RS), usually a diffuse large B-cell lymphoma (DLBCL). We studied genome-wide promoter DNA methylation in RS and clonally related CLL-phases of transformed patients, alongside de novo DLBCL (of non-germinal centre B type), untransformed-CLL and normal B-cells. The greatest differences in global DNA methylation levels were observed between RS and DLBCL, indicating that these two diseases, although histologically similar, are epigenetically distinct. RS was more highly methylated for genes involved in cell cycle regulation. When RS was compared to the preceding CLL-phase and with untransformed-CLL, RS presented a higher degree of methylation for genes possessing the H3K27me3 mark and PRC2 targets, as well as for gene targets of TP53 and RB1. Comparison of the methylation levels of individual genes revealed that OSM, a stem cell regulatory gene, exhibited significantly higher methylation levels in RS compared to CLL-phases. Its transcriptional repression by DNA methylation was confirmed by 5-aza-2'deoxycytidine treatment of DLBCL cells, determining an increased OSM expression. Our results showed that methylation patterns in RS are largely different from de novo DLBCL. Stem cell-related genes and cell cycle regulation genes are targets of DNA methylation in RS. © 2013 John Wiley & Sons Ltd.

  4. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

    Energy Technology Data Exchange (ETDEWEB)

    Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

    2014-08-15

    Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

  5. Controlling Factors of Cell Design on Large-format Li-ion Battery Safety During Nail Penetration

    Directory of Open Access Journals (Sweden)

    Qing eWang

    2015-08-01

    Full Text Available In this paper we investigate the controlling design parameters of large-format Li-ion batteries on safety while undergoing nail penetration. We have identified three critical design parameters that control the safety during the nail penetration process: nail diameter, single sheet foil area, and cell capacity.Using commercial AutoLion software, we have investigated two typical design problems related to the selection of cell thickness and aspect ratio, namely: (1 the safety ramifications of increasing cell capacity via greater cell thickness for a fixed footprint, and (2 the effect of aspect ratio, or single sheet foil size, on safety at a given capacity. For a fixed footprint, our results indicate that the safety of the cell can be predicted by (Qcell Dnail^-0.5. For a given cell capacity, our results indicate that typically a larger single sheet foil area leads to a greater likelihood for thermal runaway due to its effect of making the heating more local in nature; however, for small cells (~ 5Ah and large nails (~ 20mm, the greater aspect ratio can lead to a safer cell, as the greater surface area strongly cools the global heating of the cell.

  6. Controlling Factors of Cell Design on Large-Format Li-Ion Battery Safety during Nail Penetration

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Qing; Shaffer, Christian Edward, E-mail: ceshaffer@ecpowergroup.com; Sinha, Puneet K. [EC Power, State College, PA (United States)

    2015-08-21

    In this paper, we investigate the controlling design parameters of large-format Li-ion batteries on safety while undergoing nail penetration. We have identified three critical design parameters that control the safety during the nail penetration process: nail diameter (D{sub nail}), single sheet foil area (A{sub foil}), and cell capacity (Q{sub cell}).Using commercial AutoLion™ software, we have investigated two typical design problems related to the selection of cell thickness and aspect ratio, namely, (1) the safety ramifications of increasing cell capacity via greater cell thickness for a fixed footprint and (2) the effect of aspect ratio, or single sheet foil size, on safety at a given capacity. For a fixed footprint, our results indicate that the safety of the cell can be predicted by (Q{sub cell} D{sub nail}{sup -0.5}). For a given cell capacity, our results indicate that typically a larger single sheet foil area leads to a greater likelihood for thermal runaway due to its effect of making the heating more local in nature; however, for small cells (~5 Ah) and large nails (~20 mm), the greater aspect ratio can lead to a safer cell, as the greater surface area strongly cools the global heating of the cell.

  7. Nucleoli in large (giant bi- and multinucleate cells after apoptosis-inducing photodynamic treatment

    Directory of Open Access Journals (Sweden)

    K Smetana

    2009-06-01

    Full Text Available The present experimental study was undertaken to provide information on nucleolar changes accompanying the apoptotic process in large or giant binucleate and multinucleate cells (LBMNCs. Such cells were present in a small but constant percentage in cultures of HL-60 cells. The apoptotic process was induced by photodynamic treatment (PDT by means of 5-aminolaevulinic acid (ALA as the precursor of the photosensitizer protoporphyrin IX and irradiation with broad spectrum blue light (BL. Nucleolar changes in LBMNCs were characterized by marked reduction or disappearance of silver stained particles representing AgNORs in nucleoli including the large ones. In addition, PDT also significantly reduced the number of nucleoli regardless of their size. These changes apparently reflected the decrease or cessation of nucleolar biosynthetic activities and resembled those which were previously observed in naturally maturing bone marrow megakaryocytes (Janoutová et al., 2001.

  8. 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

  9. Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

    LENUS (Irish Health Repository)

    Abdel Aziz, Mohamed T

    2011-05-05

    Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

  10. Prognosis of localized diffuse large B-cell lymphoma in younger patients

    DEFF Research Database (Denmark)

    Møller, Michael B; Christensen, Bjarne E; Pedersen, Niels T

    2003-01-01

    BACKGROUND: The International Prognostic Index (IPI) is widely used as a predictive model in diffuse large B-cell lymphoma (DLBCL) patients of all ages and stages. To determine the optimal IPI-based prognostic system at the time of diagnosis in younger patients with limited-stage DLBCL, the authors...

  11. Intratubular large cell hyalinizing Sertoli cell tumor of the testis presenting with prepubertal gynecomastia: a case report.

    Science.gov (United States)

    Tuhan, Hale; Abaci, Ayhan; Sarsık, Banu; Öztürk, Tülay; Olguner, Mustafa; Catli, Gonul; Anik, Ahmet; Olgun, Nur; Bober, Ece

    2017-08-01

    Intratubular large cell hyalinizing Sertoli cell neoplasia (ITLCHSCN) resulting from Sertoli cells of the testis are mainly reported in young adults and these are rarely seen in childhood. The most common presenting symptoms of the patients diagnosed with ITLCHSCN are gynecomastia, enlargement in the testicles, increase in growth velocity, and advanced bone age. Symptoms are basically resulting from increased aromatase enzyme activity in Sertoli cells. In this case report, an eight-and-a-half-year-old case presenting with complaint of bilateral gynecomastia since two years, showing no endocrine abnormality in laboratory during two years of follow-up, determined to have progression in bilateral gynecomastia, increase in testicular volumes, advanced bone age, increase in growth velocity in the clinical follow-up, and diagnosed with ITLCHSCN after testis biopsy was presented.

  12. Large-volume static compression using nano-polycrystalline diamond for opposed anvils in compact cells

    International Nuclear Information System (INIS)

    Okuchi, T; Sasaki, S; Ohno, Y; Osakabe, T; Odake, S; Kagi, H

    2010-01-01

    In order to extend the pressure regime of intrinsically low-sensitivity methods of measurement, such as neutron scattering and NMR, sample volume to be compressed in compact opposed-anvil cells is desired to be significantly increased. We hereby conducted a series of experiments using two types of compact cells equipped with enforced loading mechanisms. Super-hard nano-polycrystalline diamond (NPD) anvils were carefully prepared for large-volume compression in these cells. These anvils are harder, larger and stronger than single crystal diamond anvils, so that they could play an ideal role to accept the larger forces. Supported and unsupported anvil geometries were separately tested to evaluate this expectation. In spite of insufficient support to the anvils, pressures to 14 GPa were generated for the sample volume of > 0.1 mm 3 , without damaging the NPD anvils. These results demonstrate a large future potential of compact cells equipped with NPD anvils and enforced loading mechanism.

  13. High-Temperature-Short-Time Annealing Process for High-Performance Large-Area Perovskite Solar Cells.

    Science.gov (United States)

    Kim, Minjin; Kim, Gi-Hwan; Oh, Kyoung Suk; Jo, Yimhyun; Yoon, Hyun; Kim, Ka-Hyun; Lee, Heon; Kim, Jin Young; Kim, Dong Suk

    2017-06-27

    Organic-inorganic hybrid metal halide perovskite solar cells (PSCs) are attracting tremendous research interest due to their high solar-to-electric power conversion efficiency with a high possibility of cost-effective fabrication and certified power conversion efficiency now exceeding 22%. Although many effective methods for their application have been developed over the past decade, their practical transition to large-size devices has been restricted by difficulties in achieving high performance. Here we report on the development of a simple and cost-effective production method with high-temperature and short-time annealing processing to obtain uniform, smooth, and large-size grain domains of perovskite films over large areas. With high-temperature short-time annealing at 400 °C for 4 s, the perovskite film with an average domain size of 1 μm was obtained, which resulted in fast solvent evaporation. Solar cells fabricated using this processing technique had a maximum power conversion efficiency exceeding 20% over a 0.1 cm 2 active area and 18% over a 1 cm 2 active area. We believe our approach will enable the realization of highly efficient large-area PCSs for practical development with a very simple and short-time procedure. This simple method should lead the field toward the fabrication of uniform large-scale perovskite films, which are necessary for the production of high-efficiency solar cells that may also be applicable to several other material systems for more widespread practical deployment.

  14. [Radiological trap and oncological precautions in a patient who has undergone a permanent withdrawal of PIP breast implants].

    Science.gov (United States)

    Koutsomanis, A; Bruant-Rodier, C; Roedlich, M-N; Bretz-Grenier, M-F; Perrot, P; Bodin, F

    2015-12-01

    We report the case of a 57-year-old patient who presented radiological images similar to ruptured breast implants one year after the supposed withdrawal of the latter. This woman had benefited for the first time from cosmetic PIP breast implants in 2000. Early in 2014, she requested the removal of the implants without renewal because she was feeling pain and functional discomfort. A few months after the operation, she consulted for breast swelling in the upper pole of the breast. Radiological assessment showed liquid formations compatible with the presence of implants. At our request, the rereading of the MRI by the radiologist definitively concluded on a bilateral seroma within the persistent fibrous capsule. In the absence of symptoms, clinical monitoring had been decided. But at the recrudescence of anaplastic large cell lymphoma cases associated with breast implants, a cytological sampling was intended. In case of cytological abnormality or recurrence of the seroma, a surgical procedure should be performed. In conclusion, the removal of a breast implant without capsulectomy may result in the formation of a seroma whose images resemble those of an implant. It is always worthwhile to provide precise clinical data to the radiologist in order to help him to make informed interpretations. Every serous effusion in a breast lodge having contained a silicone implant must evoke the diagnosis of anaplastic large cell lymphoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. A monoclonal antibody against SV40 large T antigen (PAb416) does not label Merkel cell carcinoma.

    Science.gov (United States)

    Pelletier, Daniel J; Czeczok, Thomas W; Bellizzi, Andrew M

    2018-07-01

    Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective. Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches. The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma. © 2018 John Wiley & Sons Ltd.

  16. Deep RNA-Seq analysis reveals unexpected features of human prostate basal epithelial cells

    Directory of Open Access Journals (Sweden)

    Dingxiao Zhang

    2016-03-01

    Full Text Available Prostate cancer is the second leading cause of cancer-related deaths among American men [1]. The prostate gland mainly contains basal and luminal cells, which are constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, for the first time, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing (GSE67070 [2]. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development, and RNA processing. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. We also identified genes associated with patient clinical outcome. Therefore, we provide a gene expression resource for understanding human prostate epithelial lineages, and link the cell-type specific gene signatures to subtypes of prostate cancer development. Keywords: Prostate epithelial cells, Basal cells, Luminal cells, RNA-seq

  17. Randomized study: small cell anaplastic lung cancer treated by combination chemotherapy and adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Fox, R.M.; Woods, R.L.; Brodie, G.N.; Tattersall, M.H.N.

    1980-01-01

    Chemotherapy and primary site radiation therapy were compared to chemotherapy alone in a randomized study of 125 patients with small cell cancer of the lung. The sites of initial relapse, as well as disease free and overall survival were analyzed. Radiotherapy to the primary site reduced the rate of local relapse, but median survival was not prolonged in patients with either limited or extensive disease, when the radiation therapy-chemotherapy group was compared to the group that received chemotherapy alone

  18. A 3D Sphere Culture System Containing Functional Polymers for Large-Scale Human Pluripotent Stem Cell Production

    Directory of Open Access Journals (Sweden)

    Tomomi G. Otsuji

    2014-05-01

    Full Text Available Utilizing human pluripotent stem cells (hPSCs in cell-based therapy and drug discovery requires large-scale cell production. However, scaling up conventional adherent cultures presents challenges of maintaining a uniform high quality at low cost. In this regard, suspension cultures are a viable alternative, because they are scalable and do not require adhesion surfaces. 3D culture systems such as bioreactors can be exploited for large-scale production. However, the limitations of current suspension culture methods include spontaneous fusion between cell aggregates and suboptimal passaging methods by dissociation and reaggregation. 3D culture systems that dynamically stir carrier beads or cell aggregates should be refined to reduce shearing forces that damage hPSCs. Here, we report a simple 3D sphere culture system that incorporates mechanical passaging and functional polymers. This setup resolves major problems associated with suspension culture methods and dynamic stirring systems and may be optimal for applications involving large-scale hPSC production.

  19. Nutrient regulation by continuous feeding removes limitations on cell yield in the large-scale expansion of Mammalian cell spheroids.

    Directory of Open Access Journals (Sweden)

    Bradley P Weegman

    Full Text Available Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, β-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB, and continuously fed (CF SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications.

  20. Nutrient Regulation by Continuous Feeding Removes Limitations on Cell Yield in the Large-Scale Expansion of Mammalian Cell Spheroids

    Science.gov (United States)

    Weegman, Bradley P.; Nash, Peter; Carlson, Alexandra L.; Voltzke, Kristin J.; Geng, Zhaohui; Jahani, Marjan; Becker, Benjamin B.; Papas, Klearchos K.; Firpo, Meri T.

    2013-01-01

    Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, β-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB), and continuously fed (CF) SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications. PMID:24204645

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

    Czech Academy of Sciences Publication Activity Database

    Allegri, L.; Baldan, F.; Mio, F.; Puppin, C.; Russo, D.; Kryštof, Vladimír; Damante, G.

    2016-01-01

    Roč. 35, č. 4 (2016), s. 2413-2418 ISSN 1021-335X R&D Projects: GA ČR(CZ) GA15-15264S Institutional support: RVO:61389030 Keywords : mTOR * thyroid cancer * cell proliferation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.662, year: 2016

  2. Esophageal Large-Cell Neuroendocrine Carcinoma with Inconsistent Response to Treatment in the Primary and Metastatic Lesions

    Directory of Open Access Journals (Sweden)

    Takashi Tomiyama

    2018-05-01

    Full Text Available Esophageal large-cell neuroendocrine carcinoma (NEC is a rare malignant tumor that is characterized by high-grade malignancy and a poor prognosis. However, the rarity of esophageal NEC has prevented the development of an established treatment, and no reports have described a discrepancy in the effectiveness of cisplatin plus irinotecan between primary and metastatic lesions. A 43-year-old Japanese man was referred to our hospital with refractory epigastralgia. A previous gastrointestinal endoscopy had revealed a 50-mm type 2 tumor in the abdominal esophagus. The pathological findings indicated poorly differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a metastatic liver tumor. One cycle of fluorouracil and cisplatin was not effective, and endoscopy was repeatedly performed. The pathological findings indicated a large-cell malignant tumor with tumor cells that were positive for CD56, synaptophysin, and Ki-67 (> 80%. Based on a diagnosis of esophageal large-cell NEC with a metastatic liver tumor, the patient received cisplatin plus irinotecan biweekly. After 4 months, computed tomography revealed marked shrinkage of the metastatic tumor, but the patient complained of dysphagia. Endoscopy revealed enlargement of the primary tumor, which was then treated using radiotherapy plus fluorouracil and cisplatin. The primary tumor subsequently shrank, and the patient’s symptoms were relieved, but the metastatic tumor grew. Thus, chemoradiotherapy could be an option for managing a primary esophageal large-cell NEC that does not respond to chemotherapy alone. However, the possibility of an inconsistent response to therapy in primary and metastatic lesions should be considered.

  3. Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

    Science.gov (United States)

    Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

    2005-05-01

    In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

  4. Intravascular large B-cell lymphoma of the kidney: A case report

    Directory of Open Access Journals (Sweden)

    Jia Nan

    2011-09-01

    Full Text Available Abstract We report a 41-year-old Chinese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was admitted to Nanfang Hospital of Southern Medical University, Guangzhou, China with complaints of high spiking fever for a month and bilateral lower limb fatigue with difficulty ambulating for the past 5 months. She had renal dysfunction with a total urinary protein of 5.61 g/dL (56.1 g/L, serum albumin of 2.89 g/dL (28.9 g/L, urea nitrogen of 2.24 mg/dL (1.6 mmol/L, and serum creatinine of 0.54 mg/dL (48 μmol/L. Bone marrow biopsy revealed myeloproliferative disorder without abnormal myeloid or lymphocytic proliferation. Positron Emission Tomography-Computed Tomography (PET-CT showed marked bilateral swelling and enlargement of the renal parenchyma with splenic enlargement and involvement of multiple vertebrae. Percutaneous renal biopsy showed island-like accumulations of medium to large lymphoid cells in many areas of the interstitium, with round vesicular nuclei containing distinct basophilic nucleoli. Immunohistochemical analysis together with other supportive investigation confirmed the diagnosis of intravascular large B-cell lymphoma. Ten days later, she was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, leurocristime and prednisone for a week. Palliative radiotherapy DT 40Gy/20F with other supportive treatment was provided for metastatic foci in the medullary cavity of the sternum, T1-T7. The patient regained muscle strength in both lower limbs and was able to walk again after three weeks. The patient was discharged after hepatic and renal function and proteinuria values had returned to normal. Follow-up data shows the patient to be alive nine months after discharge.

  5. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

    Directory of Open Access Journals (Sweden)

    Azhar R Hussain

    Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  6. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Georg Lenz

    2015-05-01

    Full Text Available Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  7. Insights into the Molecular Pathogenesis of Activated B-Cell-like Diffuse Large B-Cell Lymphoma and Its Therapeutic Implications

    Energy Technology Data Exchange (ETDEWEB)

    Lenz, Georg [Translational Oncology, Department of Medicine A, Albert-Schweitzer Campus 1, University Hospital Münster, 48149 Münster (Germany); Cluster of Excellence EXC 1003, Cells in Motion, 48149 Münster (Germany)

    2015-05-22

    Within the last couple of years, the understanding of the molecular mechanisms that drive the pathogenesis of diffuse large B-cell lymphoma (DLBCL) has significantly improved. Large-scale gene expression profiling studies have led to the discovery of several molecularly defined subtypes that are characterized by specific oncogene addictions and significant differences in their outcome. Next generation sequencing efforts combined with RNA interference screens frequently identify crucial oncogenes that lead to constitutive activation of various signaling pathways that drive lymphomagenesis. This review summarizes our current understanding of the molecular pathogenesis of the activated B-cell-like (ABC) DLBCL subtype that is characterized by poor prognosis. A special emphasis is put on findings that might impact therapeutic strategies of affected patients.

  8. Implications of infiltrating immune cells within bone marrow of patients with diffuse large B-cell lymphoma.

    Science.gov (United States)

    Jeong, Juhyeon; Oh, Eun Ji; Yang, Woo Ick; Kim, Soo Jeong; Yoon, Sun Och

    2017-06-01

    The implications of infiltrating immune cells, especially T cells and macrophages, in the bone marrow (BM) microenvironment of patients with diffuse large B-cell lymphoma (DLBCL) have rarely been studied. We aimed to investigate the significance of infiltrating immune cells in the BM microenvironment as a prognostic factor for DLBCL patients. Using the initial pretreatment BM biopsy obtained from 198 DLBCL patients, we semiquantitatively evaluated CD3+ T cells, CD8+ T cells, and CD163+ macrophages that infiltrate into the paratrabecular and interstitial areas of BM by immunohistochemistry and analyzed their clinicopathological and prognostic implications. Levels of infiltrating CD3+ T cells, CD8+ T cells, and CD163+ macrophages were significantly higher in BM with DLBCL involvement (BMI-positive group) than in that without DLBCL involvement (BMI-negative group). Infiltration of CD8+ T cells significantly increased in cases with advanced Ann Arbor stage, elevated lactate dehydrogenase level, extranodal site involvement ≥2 sites, higher Eastern Cooperative Oncology Group performance status, and higher International Prognostic Index (IPI) risk. High levels of CD3+ T cells were significantly associated with age ≤60, and high levels of CD163+ macrophages were associated with advanced Ann Arbor stage and higher IPI risk. High infiltration of CD8+ T cells was significantly related to inferior overall and recurrence-free survival rate, even in the BMI-negative group. High infiltration of CD8+ T cells within the pretreatment BM was related to poor prognosis, and might be a useful prognostic factor of DLBCL patients. Therefore, evaluation of CD8+ T cells is helpful for predicting prognosis in initial pretreatment BM biopsy of DLBCL patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Differential distribution of inflammatory cells in large and small airways in smokers

    NARCIS (Netherlands)

    Battaglia, Salvatore; Mauad, Thais; van Schadewijk, Annemarie M.; Vignola, Antonia M.; Rabe, Klaus F.; Bellia, Vincenzo; Sterk, Peter J.; Hiemstra, Pieter S.

    2007-01-01

    BACKGROUND: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been

  10. Clinical Implications of Phosphorylated STAT3 Expression in de novo Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Ok, Chi Y; Chen, Jiayu; Xu-Monette, Ziju

    2014-01-01

    PURPOSE: Activated signal transducer and activator of transcription 3 (STAT3) regulates tumor growth, invasion, cell proliferation, angiogenesis, immune response, and survival. Data regarding expression of phosphorylated (activated) STAT3 in diffuse large B-cell lymphoma (DLBCL) and the impact of...

  11. MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma

    DEFF Research Database (Denmark)

    Mandrup, Charlotte; Petersen, Anders; Højfeldt, Anne Dirks

    MicroRNA expression in nodal and extranodal Diffuse Large B-cell Lymphoma   C. Mandrup1, A. Petersen1, A. D. Hoejfeldt1, H. F. Thomsen1, J. Madsen1, J. Dahlgaard1, P. Johansen2, A. Bukh1, K. Dybkaer1 and H. E Johnsen1. 1Department of Hematology, 2Pathological Institute, Aalborg Hospital, Aarhus...... University Hospital, Aalborg, Denmark Introduction: The aim of this project was to analyse microRNA (miRNA) expression in nodal and extranodal diffuse large B-cell lymphoma (DLBCL). Manifestation at diagnosis may be nodal and/or extranodal. At present, there are no known determinants for none...... of the manifestations, and no way to predict the potential progression from nodal to extranodal disease. miRNA are small regulatory RNA molecules with core function to repress/cleave sequence complementary mRNA targets. Abnormalities in miRNA genetics and expression are known to affect initiation and development...

  12. Origin of the high performance of perovskite solar cells with large grains

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jian; Shi, Tongfei, E-mail: tongfeishi@gmail.com; Li, Xinhua; Zhou, Bukang; Cao, Huaxiang; Wang, Yuqi [Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031 (China)

    2016-02-01

    Due to excellent carrier transport characteristics, CH{sub 3}NH{sub 3}PbI{sub 3} film made of large single crystal grains is considered as a key to improve upon already remarkable perovskite solar cell (PSC) efficiency. We have used a simple and efficient solvent vapor annealing method to obtain CH{sub 3}NH{sub 3}PbI{sub 3} films with grain size over 1 μm. PSCs with different grain size films have been fabricated and verified the potential of large grains for improving solar cells performance. Moreover, the larger grain films have shown stronger light absorption ability and more photon-generated carriers under the same illumination. A detailed temperature-dependent PL study has indicated that it originates from larger radius and lower binding energy of donor-acceptor-pair (DAP) in larger grains, which makes the DAP is easily to be separated and difficult to be recombine.

  13. Mixed Large Cell Neuroendocrine Carcinoma and Adenocarcinoma with Spindle Cell and Clear Cell Features in the Extrahepatic Bile Duct

    Directory of Open Access Journals (Sweden)

    John Wysocki

    2014-01-01

    Full Text Available Mixed adenoneuroendocrine carcinomas, spindle cell carcinomas, and clear cell carcinomas are all rare tumors in the biliary tract. We present the first case, to our knowledge, of an extrahepatic bile duct carcinoma composed of all three types. A 65-year-old man with prior cholecystectomy presented with painless jaundice, vomiting, and weight loss. CA19-9 and alpha-fetoprotein (AFP were elevated. Cholangioscopy revealed a friable mass extending from the middle of the common bile duct to the common hepatic duct. A bile duct excision was performed. Gross examination revealed a 3.6 cm intraluminal polypoid tumor. Microscopically, the tumor had foci of conventional adenocarcinoma (CK7-positive and CA19-9-postive surrounded by malignant-appearing spindle cells that were positive for cytokeratins and vimentin. Additionally, there were separate areas of large cell neuroendocrine carcinoma (LCNEC. Foci of clear cell carcinoma merged into both the LCNEC and the adenocarcinoma. Tumor invaded through the bile duct wall with extensive perineural and vascular invasion. Circumferential margins were positive. The patient’s poor performance status precluded adjuvant therapy and he died with recurrent and metastatic disease 5 months after surgery. This is consistent with the reported poor survival rates of biliary mixed adenoneuroendocrine carcinomas.

  14. Enhancing Performance of Large-Area Organic Solar Cells with Thick Film via Ternary Strategy.

    Science.gov (United States)

    Zhang, Jianqi; Zhao, Yifan; Fang, Jin; Yuan, Liu; Xia, Benzheng; Wang, Guodong; Wang, Zaiyu; Zhang, Yajie; Ma, Wei; Yan, Wei; Su, Wenming; Wei, Zhixiang

    2017-06-01

    Large-scale fabrication of organic solar cells requires an active layer with high thickness tolerability and the use of environment-friendly solvents. Thick films with high-performance can be achieved via a ternary strategy studied herein. The ternary system consists of one polymer donor, one small molecule donor, and one fullerene acceptor. The small molecule enhances the crystallinity and face-on orientation of the active layer, leading to improved thickness tolerability compared with that of a polymer-fullerene binary system. An active layer with 270 nm thickness exhibits an average power conversion efficiency (PCE) of 10.78%, while the PCE is less than 8% with such thick film for binary system. Furthermore, large-area devices are successfully fabricated using polyethylene terephthalate (PET)/Silver gride or indium tin oxide (ITO)-based transparent flexible substrates. The product shows a high PCE of 8.28% with an area of 1.25 cm 2 for a single cell and 5.18% for a 20 cm 2 module. This study demonstrates that ternary organic solar cells exhibit great potential for large-scale fabrication and future applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Reduction of Nup107 attenuates the growth factor signaling in the senescent cells

    International Nuclear Information System (INIS)

    Kim, Sung Young; Kang, Hyun Tae; Choi, Hae Ri; Park, Sang Chul

    2010-01-01

    Research highlights: → Decreased expression of Nup107 in aged cells and organs. → Depletion of Nup107 results in impaired nuclear translocation of p-ERK. → Depletion of Nup107 affects downstream effectors of ERK signaling. → Depletion of Nup107 inhibits cell proliferation of oligodendroglioma cells. -- Abstract: Hypo-responsiveness to growth factors is a fundamental feature of cellular senescence. In this study, we found markedly decreased level of Nup107, a key scaffold protein in nuclear pore complex assembly, in senescent human diploid fibroblasts as well as in organs of aged mice. Depletion of Nup107 by specific siRNA in young human diploid fibroblasts prevented the effective nuclear translocation of phosphorylated extracellular signal-regulated kinase (ERK) following epidermal growth factor (EGF) stimulation, and decreased the expression of c-Fos in consequence. The disturbances in ERK signaling in Nup107 depleted cells closely mirror the similar changes in senescent cells. Knockdown of Nup107 in anaplastic oligodendroglioma cells caused cell death, rather than growth retardation, indicating a greater sensitivity to Nup107 depletion in cancer cells than in normal cells. These findings support the notion that Nup107 may contribute significantly to the regulation of cell fate in aged and transformed cells by modulating nuclear trafficking of signal molecules.

  16. Reduction of Nup107 attenuates the growth factor signaling in the senescent cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Young; Kang, Hyun Tae; Choi, Hae Ri [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Sang Chul, E-mail: scpark@snu.ac.kr [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2010-10-08

    Research highlights: {yields} Decreased expression of Nup107 in aged cells and organs. {yields} Depletion of Nup107 results in impaired nuclear translocation of p-ERK. {yields} Depletion of Nup107 affects downstream effectors of ERK signaling. {yields} Depletion of Nup107 inhibits cell proliferation of oligodendroglioma cells. -- Abstract: Hypo-responsiveness to growth factors is a fundamental feature of cellular senescence. In this study, we found markedly decreased level of Nup107, a key scaffold protein in nuclear pore complex assembly, in senescent human diploid fibroblasts as well as in organs of aged mice. Depletion of Nup107 by specific siRNA in young human diploid fibroblasts prevented the effective nuclear translocation of phosphorylated extracellular signal-regulated kinase (ERK) following epidermal growth factor (EGF) stimulation, and decreased the expression of c-Fos in consequence. The disturbances in ERK signaling in Nup107 depleted cells closely mirror the similar changes in senescent cells. Knockdown of Nup107 in anaplastic oligodendroglioma cells caused cell death, rather than growth retardation, indicating a greater sensitivity to Nup107 depletion in cancer cells than in normal cells. These findings support the notion that Nup107 may contribute significantly to the regulation of cell fate in aged and transformed cells by modulating nuclear trafficking of signal molecules.

  17. Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting

    DEFF Research Database (Denmark)

    Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor

    2017-01-01

    Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal...... and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft...... enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat...

  18. Development of Large-Format Lithium-Ion Cells with Silicon Anode and Low Flammable Electrolyte

    Science.gov (United States)

    Wu, James J.; Hernandez-Lugo, D. M.; Smart, M. C.; Ratnakumar, B. V.; Miller, T. B.; Lvovich, V. F.; Lytle, J. K.

    2014-01-01

    NASA is developing safe, high energy and high capacity lithium-ion cell designs and batteries for future missions under NASAs Advanced Space Power System (ASPS) project. Advanced cell components, such as high specific capacity silicon anodes and low-flammable electrolytes have been developed for improving the cell specific energy and enhancing safety. To advance the technology readiness level, we have developed large-format flight-type hermetically sealed battery cells by incorporating high capacity silicon anodes, commercially available lithium nickel, cobalt, aluminum oxide (NCA) cathodes, and low-flammable electrolytes. In this report, we will present the performance results of these various battery cells. In addition, we will also discuss the post-test cell analysis results as well.

  19. EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.

    Science.gov (United States)

    Dong, Y U; Ren, Weihong; Qi, Jun; Jin, B O; Li, Ying; Tao, Huiqing; Xu, Ren; Li, Yanqing; Zhang, Qinxian; Han, Baohui

    2016-04-01

    Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies

  20. Rituximab and chemotherapy in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Sonet, Anne; Bosly, André

    2009-06-01

    Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

  1. Metastatic squamous cell non-small-cell lung cancer (NSCLC: disrupting the drug treatment paradigm with immunotherapies

    Directory of Open Access Journals (Sweden)

    Sarah L Scarpace

    2015-10-01

    Full Text Available Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR and anaplastic lymphoma kinase (ALK mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. Immunotherapies directed at the programmed cell death-1 receptor (PD-1 or its ligand (PD-L1 (nivolumab and pembrolizumab have demonstrated efficacy in both nonsquamous and squamous cell NSCLC. Because of their similar mechanism of action against the PD-L1/PD-1 pathway, both drugs have similar toxicity profiles related to immune-mediated adverse reactions that can generally be monitored and managed with oral corticosteroids. This paper provides an overview of drug therapy options for squamous cell NSCLC with a focus on the evidence and clinical application of the anti-PD1 therapies. A comparison of the dosing, administration, indications, and differences in the measurement of PD-L1 expression in the clinical trials of nivolumab and pembrolizumab is also provided.

  2. Organic solar cell modules for specific applications-From energy autonomous systems to large area photovoltaics

    International Nuclear Information System (INIS)

    Niggemann, M.; Zimmermann, B.; Haschke, J.; Glatthaar, M.; Gombert, A.

    2008-01-01

    We report on the development of two types of organic solar cell modules one for energy autonomous systems and one for large area energy harvesting. The first requires a specific tailoring of the solar cell geometry and cell interconnection in order to power an energy autonomous system under its specific operating conditions. We present an organic solar cell module with 22 interconnected solar cells. A power conversion efficiency of 2% under solar illumination has been reached on the active area of 46.2 cm 2 . A voltage of 4 V at the maximum power point has been obtained under indoor illumination conditions. Micro contact printing of a self assembling monolayer was employed for the patterning of the polymer anode. Large area photovoltaic modules have to meet the requirements on efficiency, lifetime and costs simultaneously. To minimize the production costs, a suitable concept for efficient reel-to-reel production of large area modules is needed. A major contribution to reduce the costs is the substitution of the commonly used indium tin oxide electrode by a cheap material. We present the state of the art of the anode wrap through concept as a reel-to-reel suited module concept and show comparative calculations of the module interconnection of the wrap through concept and the standard ITO-based cell architecture. As a result, the calculated overall module efficiency of the anode wrap through module exceeds the overall efficiency of modules based on ITO on glass (sheet resistance 15 Ω/square) and on foils (sheet resistance 60 Ω/square)

  3. Printable nanostructured silicon solar cells for high-performance, large-area flexible photovoltaics.

    Science.gov (United States)

    Lee, Sung-Min; Biswas, Roshni; Li, Weigu; Kang, Dongseok; Chan, Lesley; Yoon, Jongseung

    2014-10-28

    Nanostructured forms of crystalline silicon represent an attractive materials building block for photovoltaics due to their potential benefits to significantly reduce the consumption of active materials, relax the requirement of materials purity for high performance, and hence achieve greatly improved levelized cost of energy. Despite successful demonstrations for their concepts over the past decade, however, the practical application of nanostructured silicon solar cells for large-scale implementation has been hampered by many existing challenges associated with the consumption of the entire wafer or expensive source materials, difficulties to precisely control materials properties and doping characteristics, or restrictions on substrate materials and scalability. Here we present a highly integrable materials platform of nanostructured silicon solar cells that can overcome these limitations. Ultrathin silicon solar microcells integrated with engineered photonic nanostructures are fabricated directly from wafer-based source materials in configurations that can lower the materials cost and can be compatible with deterministic assembly procedures to allow programmable, large-scale distribution, unlimited choices of module substrates, as well as lightweight, mechanically compliant constructions. Systematic studies on optical and electrical properties, photovoltaic performance in experiments, as well as numerical modeling elucidate important design rules for nanoscale photon management with ultrathin, nanostructured silicon solar cells and their interconnected, mechanically flexible modules, where we demonstrate 12.4% solar-to-electric energy conversion efficiency for printed ultrathin (∼ 8 μm) nanostructured silicon solar cells when configured with near-optimal designs of rear-surface nanoposts, antireflection coating, and back-surface reflector.

  4. NPM-ALK mediates phosphorylation of MSH2 at tyrosine 238, creating a functional deficiency in MSH2 and the loss of mismatch repair

    International Nuclear Information System (INIS)

    Bone, K M; Wang, P; Wu, F; Wu, C; Li, L; Bacani, J T; Andrew, S E; Lai, R

    2015-01-01

    The vast majority of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ALCL) tumors express the characteristic oncogenic fusion protein NPM-ALK, which mediates tumorigenesis by exerting its constitutive tyrosine kinase activity on various substrates. We recently identified MSH2, a protein central to DNA mismatch repair (MMR), as a novel binding partner and phosphorylation substrate of NPM-ALK. Here, using liquid chromatography–mass spectrometry, we report for the first time that MSH2 is phosphorylated by NPM-ALK at a specific residue, tyrosine 238. Using GP293 cells transfected with NPM-ALK, we confirmed that the MSH2 Y238F mutant is not tyrosine phosphorylated. Furthermore, transfection of MSH2 Y238F into these cells substantially decreased the tyrosine phosphorylation of endogenous MSH2. Importantly, gene transfection of MSH2 Y238F abrogated the binding of NPM-ALK with endogenous MSH2, re-established the dimerization of MSH2:MSH6 and restored the sensitivity to DNA mismatch-inducing drugs, indicative of MMR return. Parallel findings were observed in two ALK+ALCL cell lines, Karpas 299 and SUP-M2. In addition, we found that enforced expression of MSH2 Y238F into ALK+ALCL cells alone was sufficient to induce spontaneous apoptosis. In conclusion, our findings have identified NPM-ALK-induced phosphorylation of MSH2 at Y238 as a crucial event in suppressing MMR. Our studies have provided novel insights into the mechanism by which oncogenic tyrosine kinases disrupt MMR

  5. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps.

    Science.gov (United States)

    Kuperstein, Inna; Cohen, David P A; Pook, Stuart; Viara, Eric; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

    2013-10-07

    Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.

  6. CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital.

    Science.gov (United States)

    Rattarittamrong, Ekarat; Norasetthada, Lalita; Tantiworawit, Adisak; Chai-Adisaksopha, Chatree; Nawarawong, Weerasak

    2013-11-01

    To determine the effectiveness and tolerability of the combination of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with the addition of etoposide (CHOEP-21) for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs). Between January 2009 and October 2011, patients aged 18 to 60 years with newly diagnosed nodal PTCLs at the Maharaj Nakorn Chiang Mai Hospital were enrolled to receive CHOEP-21 every three weeks for eight cycles. G-CSF prophylaxis was given to all patients. Twenty-four patients were enrolled. Twenty of them were male with a median age of 49 years. The majority of patients (66.7%) had PTCL, not otherwise specified (PTCL, NOS), and 95.8% of the patients were in stage III or IV. The overall response rate was 58% with 42% having complete response. The response rates were better among patients with ALK-negative anaplastic large cell lymphoma (ALCL; 100%) and angioimmunoblastic T-cell lymphoma (AITL; 85%) than those with PTCL, NOS (44%). With a median follow-up of 21 months, the patients had an estimated 2-year event-free survival, and an overall survival rate of 37.6% and 54.4%, respectively. The most common adverse effects were infection and hematologic toxicities that was manageable. Although CHOEP-21 induced favorable responses in patients with ALK-negative ALCL and AITL, the responses were not durable and further therapy is mandated in management of patients with nodal PTCL.

  7. High-Efficiency, Multijunction Solar Cells for Large-Scale Solar Electricity Generation

    Science.gov (United States)

    Kurtz, Sarah

    2006-03-01

    A solar cell with an infinite number of materials (matched to the solar spectrum) has a theoretical efficiency limit of 68%. If sunlight is concentrated, this limit increases to about 87%. These theoretical limits are calculated using basic physics and are independent of the details of the materials. In practice, the challenge of achieving high efficiency depends on identifying materials that can effectively use the solar spectrum. Impressive progress has been made with the current efficiency record being 39%. Today's solar market is also showing impressive progress, but is still hindered by high prices. One strategy for reducing cost is to use lenses or mirrors to focus the light on small solar cells. In this case, the system cost is dominated by the cost of the relatively inexpensive optics. The value of the optics increases with the efficiency of the solar cell. Thus, a concentrator system made with 35%- 40%-efficient solar cells is expected to deliver 50% more power at a similar cost when compare with a system using 25%-efficient cells. Today's markets are showing an opportunity for large concentrator systems that didn't exist 5-10 years ago. Efficiencies may soon pass 40% and ultimately may reach 50%, providing a pathway to improved performance and decreased cost. Many companies are currently investigating this technology for large-scale electricity generation. The presentation will cover the basic physics and more practical considerations to achieving high efficiency as well as describing the current status of the concentrator industry. This work has been authored by an employee of the Midwest Research Institute under Contract No. DE- AC36-99GO10337 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow

  8. Role of stem cells in large bowel carcinogenesis

    Directory of Open Access Journals (Sweden)

    N. A. Nefedova

    2015-01-01

    Full Text Available Сancer stem cells (CSC play a significant role in the development and progression of colorectal cancer. They are capable of self-senewal and multipotent differentiation. CSC can be formed from stem cells or mutant by dedifferentiation of crypt epithelial cells. Recently, much attention is paid to CSC in colon cancer, but very little has been published regarding their expression in colon polyps. In 2010 The World Health Organization attributed the so-called serrated lesions, including hyperplastic polyp, serrated sessile adenoma and traditional serrated adenoma to a group of precancerous lesions of the colon in addition to the classical tubular, villous and tubulo-villous adenomas. Despite the large number of publications devoted to the newly selected category, a full understanding of the processes involved in the formation of polyps and their progression into colon cancer, there is still no. Identification of CSC in colon polyps will assess their potential malignancy conduct adequate therapy, determine the amount of the operation and further treatment strategy. This in turn will contribute to the early detection and prevention of cancer. Identification of CSC, an assessment of their localization and distribution in tubular adenomas, serrated adenoma broad-based, traditional serrated adenoma and hyperplastic polyps allow to evaluate the potential of malignancy and prognosis for each of the polyps. In this regard, the definition of markers characteristic of colon CSC, is interesting not only from a scientific, but also from a practical point of view.

  9. A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

    Directory of Open Access Journals (Sweden)

    Daisuke Usuda

    2017-11-01

    Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

  10. AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Wang, Jinfen; Xu-Monette, Zijun Y; Jabbar, Kausar J

    2017-01-01

    AKT signaling is important for proliferation and survival of tumor cells. The clinical significance of AKT activation in diffuse large B-cell lymphoma (DLBCL) is not well analyzed. Here, we assessed expression of phosphorylated AKT (p-AKT) in 522 DLBCL patients. We found that high levels of p-AKT...

  11. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma.

    Science.gov (United States)

    Schmitz, Roland; Wright, George W; Huang, Da Wei; Johnson, Calvin A; Phelan, James D; Wang, James Q; Roulland, Sandrine; Kasbekar, Monica; Young, Ryan M; Shaffer, Arthur L; Hodson, Daniel J; Xiao, Wenming; Yu, Xin; Yang, Yandan; Zhao, Hong; Xu, Weihong; Liu, Xuelu; Zhou, Bin; Du, Wei; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Connors, Joseph M; Campo, Elias; Lopez-Guillermo, Armando; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa M; Tay Kuang Wei, Kevin; Zelenetz, Andrew D; Leonard, John P; Bartlett, Nancy L; Tran, Bao; Shetty, Jyoti; Zhao, Yongmei; Soppet, Dan R; Pittaluga, Stefania; Wilson, Wyndham H; Staudt, Louis M

    2018-04-12

    Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88 L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).

  12. Low-Temperature Soft-Cover Deposition of Uniform Large-Scale Perovskite Films for High-Performance Solar Cells.

    Science.gov (United States)

    Ye, Fei; Tang, Wentao; Xie, Fengxian; Yin, Maoshu; He, Jinjin; Wang, Yanbo; Chen, Han; Qiang, Yinghuai; Yang, Xudong; Han, Liyuan

    2017-09-01

    Large-scale high-quality perovskite thin films are crucial to produce high-performance perovskite solar cells. However, for perovskite films fabricated by solvent-rich processes, film uniformity can be prevented by convection during thermal evaporation of the solvent. Here, a scalable low-temperature soft-cover deposition (LT-SCD) method is presented, where the thermal convection-induced defects in perovskite films are eliminated through a strategy of surface tension relaxation. Compact, homogeneous, and convection-induced-defects-free perovskite films are obtained on an area of 12 cm 2 , which enables a power conversion efficiency (PCE) of 15.5% on a solar cell with an area of 5 cm 2 . This is the highest efficiency at this large cell area. A PCE of 15.3% is also obtained on a flexible perovskite solar cell deposited on the polyethylene terephthalate substrate owing to the advantage of presented low-temperature processing. Hence, the present LT-SCD technology provides a new non-spin-coating route to the deposition of large-area uniform perovskite films for both rigid and flexible perovskite devices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy

    OpenAIRE

    Nakashima, Yasuhiro; Shiratsuchi, Motoaki; Abe, Ichiro; Matsuda, Yayoi; Miyata, Noriyuki; Ohno, Hirofumi; Ikeda, Motohiko; Matsushima, Takamitsu; Nomura, Masatoshi; Takayanagi, Ryoichi

    2013-01-01

    Background Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of p...

  14. Large-scale Isolation of Highly Pure "Untouched" Regulatory T Cells in a GMP Environment for Adoptive Cell Therapy.

    Science.gov (United States)

    Haase, Doreen; Puan, Kia Joo; Starke, Mireille; Lai, Tuck Siong; Soh, Melissa Yan Ling; Karunanithi, Iyswariya; San Luis, Boris; Poh, Tuang Yeow; Yusof, Nurhashikin; Yeap, Chun Hsien; Phang, Chew Yen; Chye, Willis Soon Yuan; Chan, Marieta; Koh, Mickey Boon Chai; Goh, Yeow Tee; Bertin-Maghit, Sebastien; Nardin, Alessandra; Ho, Liam Pock; Rotzschke, Olaf

    2015-01-01

    Adoptive cell therapy is an emerging treatment strategy for a number of serious diseases. Regulatory T (Treg) cells represent 1 cell type of particular interest for therapy of inflammatory conditions, as they are responsible for controlling unwanted immune responses. Initial clinical trials of adoptive transfer of Treg cells in patients with graft-versus-host disease were shown to be safe. However, obtaining sufficient numbers of highly pure and functional Treg cells with minimal contamination remains a challenge. We developed a novel approach to isolate "untouched" human Treg cells from healthy donors on the basis of negative selection using the surface markers CD49d and CD127. This procedure, which uses an antibody cocktail and magnetic beads for separation in an automated system (RoboSep), was scaled up and adapted to be compatible with good manufacturing practice conditions. With this setup we performed 9 Treg isolations from large-scale leukapheresis samples in a good manufacturing practice facility. These runs yielded sufficient numbers of "untouched" Treg cells for immediate use in clinical applications. The cell preparations consisted of viable highly pure FoxP3-positive Treg cells that were functional in suppressing the proliferation of effector T cells. Contamination with CD4 effector T cells was cell types did not exceed 2% in the final product. Remaining isolation reagents were reduced to levels that are considered safe. Treg cells isolated with this procedure will be used in a phase I clinical trial of adoptive transfer into leukemia patients developing graft-versus-host disease after stem cell transplantation.

  15. Automated flow cytometric analysis across large numbers of samples and cell types.

    Science.gov (United States)

    Chen, Xiaoyi; Hasan, Milena; Libri, Valentina; Urrutia, Alejandra; Beitz, Benoît; Rouilly, Vincent; Duffy, Darragh; Patin, Étienne; Chalmond, Bernard; Rogge, Lars; Quintana-Murci, Lluis; Albert, Matthew L; Schwikowski, Benno

    2015-04-01

    Multi-parametric flow cytometry is a key technology for characterization of immune cell phenotypes. However, robust high-dimensional post-analytic strategies for automated data analysis in large numbers of donors are still lacking. Here, we report a computational pipeline, called FlowGM, which minimizes operator input, is insensitive to compensation settings, and can be adapted to different analytic panels. A Gaussian Mixture Model (GMM)-based approach was utilized for initial clustering, with the number of clusters determined using Bayesian Information Criterion. Meta-clustering in a reference donor permitted automated identification of 24 cell types across four panels. Cluster labels were integrated into FCS files, thus permitting comparisons to manual gating. Cell numbers and coefficient of variation (CV) were similar between FlowGM and conventional gating for lymphocyte populations, but notably FlowGM provided improved discrimination of "hard-to-gate" monocyte and dendritic cell (DC) subsets. FlowGM thus provides rapid high-dimensional analysis of cell phenotypes and is amenable to cohort studies. Copyright © 2015. Published by Elsevier Inc.

  16. Bioprinted Amniotic Fluid-Derived Stem Cells Accelerate Healing of Large Skin Wounds

    Science.gov (United States)

    Skardal, Aleksander; Mack, David; Kapetanovic, Edi; Atala, Anthony; Jackson, John D.; Yoo, James

    2012-01-01

    Stem cells obtained from amniotic fluid show high proliferative capacity in culture and multilineage differentiation potential. Because of the lack of significant immunogenicity and the ability of the amniotic fluid-derived stem (AFS) cells to modulate the inflammatory response, we investigated whether they could augment wound healing in a mouse model of skin regeneration. We used bioprinting technology to treat full-thickness skin wounds in nu/nu mice. AFS cells and bone marrow-derived mesenchymal stem cells (MSCs) were resuspended in fibrin-collagen gel and “printed” over the wound site. At days 0, 7, and 14, AFS cell- and MSC-driven wound closure and re-epithelialization were significantly greater than closure and re-epithelialization in wounds treated by fibrin-collagen gel only. Histological examination showed increased microvessel density and capillary diameters in the AFS cell-treated wounds compared with the MSC-treated wounds, whereas the skin treated only with gel showed the lowest amount of microvessels. However, tracking of fluorescently labeled AFS cells and MSCs revealed that the cells remained transiently and did not permanently integrate in the tissue. These observations suggest that the increased wound closure rates and angiogenesis may be due to delivery of secreted trophic factors, rather than direct cell-cell interactions. Accordingly, we performed proteomic analysis, which showed that AFS cells secreted a number of growth factors at concentrations higher than those of MSCs. In parallel, we showed that AFS cell-conditioned media induced endothelial cell migration in vitro. Taken together, our results indicate that bioprinting AFS cells could be an effective treatment for large-scale wounds and burns. PMID:23197691

  17. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Ye, Qing; Xu-Monette, Zijun Y; Tzankov, Alexandar

    2016-01-01

    Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2...... frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma...

  18. Unusually large unit cell of lipid bicontinuous cubic phase: towards nature's length scales

    Science.gov (United States)

    Kim, Hojun; Leal, Cecilia

    Lipid bicontinuous cubic phases are of great interest for drug delivery, protein crystallization, biosensing, and templates for directing hard material assembly. Structural modulations of lipid mesophases regarding phase identity and unit cell size are often necessary to augment loading and gain pore size control. One important example is the need for unit cells large enough to guide the crystallization of bigger proteins without distortion of the templating phase. In nature, bicontinuous cubic constructs achieve unit cell dimensions as high as 300 nm. However, the largest unit cell of lipid mesophases synthesized in the lab is an order of magnitude lower. In fact, it has been predicted theoretically that lipid bicontinuous cubic phases of unit cell dimensions exceeding 30 nm could not exist, as high membrane fluctuations would damp liquid crystalline order. Here we report non-equilibrium assembly methods of synthesizing metastable bicontinuous cubic phases with unit cell dimensions as high as 70 nm. The phases are stable for very long periods and become increasingly ordered as time goes by without changes to unit cell dimensions. We acknowledge the funding source as a NIH.

  19. Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent.

    Science.gov (United States)

    Park, Jin Myung; Lee, Sang Hyub; Chung, Kwang Hyun; Jang, Dong Kee; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Min; Paik, Woo Hyun

    2016-12-01

    Bilateral stent-in-stent (SIS) self-expandable metal stent placement is technically challenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent. Thirty-one patients who underwent bilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilar obstruction (Bismuth types II, III, IV) with different etiologies. Sixteen (51.6%) patients were male. The mean age of the patients was 67.0+/-14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma (58.1%) and gallbladder cancer (29.0%). Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence (MOC) than those with MOC (95.2% vs 60.0%, P=0.03). Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC (50.0% vs 19.0%, P=0.11). Median time to recurrent biliary obstruction was 188 days and median survival was 175 days. The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients.

  20. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Bernatsky, Sasha; Velásquez García, Héctor A; Spinelli, John; Gaffney, Patrick; Smedby, Karin E; Ramsey-Goldman, Rosalind; Wang, Sophia S.; Adami, Hans-Olov; Albanes, Demetrius; Angelucci, Emanuele; Ansell, Stephen M.; Asmann, Yan W.; Becker, Nikolaus; Benavente, Yolanda; Berndt, Sonja I.; Bertrand, Kimberly A.; Birmann, Brenda M.; Boeing, Heiner; Boffetta, Paolo; Bracci, Paige M.; Brennan, Paul; Brooks-Wilson, Angela R.; Cerhan, James R.; Chanock, Stephen J.; Clavel, Jacqueline; Conde, Lucia; Cotenbader, Karen H; Cox, David G; Cozen, Wendy; Crouch, Simon; De Roos, Anneclaire J.; De Sanjose, Silvia; Di Lollo, Simonetta; Diver, W. Ryan; Dogan, Ahmet; Foretova, Lenka; Ghesquières, Hervé; Giles, Graham G.; Glimelius, Bengt; Habermann, Thomas M.; Haioun, Corinne; Hartge, Patricia; Hjalgrim, Henrik; Holford, Theodore R.; Holly, Elizabeth A.; Jackson, Rebecca D.; Kaaks, Rudolph; Kane, Eleanor; Kelly, Rachel S.; Klein, Robert J.; Kraft, Peter; Kricker, Anne; Lan, Qing; Lawrence, Charles; Liebow, Mark; Lightfoot, Tracy; Link, Brian K.; Maynadie, Marc; McKay, James; Melbye, Mads; Molina, Thierry Jo; Monnereau, Alain; Morton, Lindsay M.; Nieters, Alexandra; North, Kari E.; Novak, Anne J.; Offit, Kenneth; Purdue, Mark P.; Rais, Marco; Riby, Jacques; Roman, Eve; Rothman, Nathaniel; Salles, Gilles; Severi, Gianluca; Severson, Richard K.; Skibola, Christine F.; Slager, Susan L.; Smith, Alex; Smith, Martyn T.; Southey, Melissa C.; Staines, Anthony; Teras, Lauren R.; Thompson, Carrie A.; Tilly, Hervé; Tinker, Lesley F.; Tjonneland, Anne; Turner, Jenny; Vajdic, Claire M.; Vermeulen, Roel C H; Vijai, Joseph; Vineis, Paolo; Virtamo, Jarmo; Wang, Zhaoming; Weinstein, Stephanie; Witzig, Thomas E.; Zelenetz, Andrew; Zeleniuch-Jacquotte, Anne; Zhang, Yawei; Zheng, Tongzhang; Zucca, Mariagrazia; Clarke, Ann E

    2017-01-01

    Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

  1. A method for medulloblastoma tumor differentiation based on convolutional neural networks and transfer learning

    Science.gov (United States)

    Cruz-Roa, Angel; Arévalo, John; Judkins, Alexander; Madabhushi, Anant; González, Fabio

    2015-12-01

    Convolutional neural networks (CNN) have been very successful at addressing different computer vision tasks thanks to their ability to learn image representations directly from large amounts of labeled data. Features learned from a dataset can be used to represent images from a different dataset via an approach called transfer learning. In this paper we apply transfer learning to the challenging task of medulloblastoma tumor differentiation. We compare two different CNN models which were previously trained in two different domains (natural and histopathology images). The first CNN is a state-of-the-art approach in computer vision, a large and deep CNN with 16-layers, Visual Geometry Group (VGG) CNN. The second (IBCa-CNN) is a 2-layer CNN trained for invasive breast cancer tumor classification. Both CNNs are used as visual feature extractors of histopathology image regions of anaplastic and non-anaplastic medulloblastoma tumor from digitized whole-slide images. The features from the two models are used, separately, to train a softmax classifier to discriminate between anaplastic and non-anaplastic medulloblastoma image regions. Experimental results show that the transfer learning approach produce competitive results in comparison with the state of the art approaches for IBCa detection. Results also show that features extracted from the IBCa-CNN have better performance in comparison with features extracted from the VGG-CNN. The former obtains 89.8% while the latter obtains 76.6% in terms of average accuracy.

  2. A case of cutaneous large B-cell lymphoma of the legs appearing as chronic venous ulceration

    Directory of Open Access Journals (Sweden)

    Marta Carlesimo

    2012-04-01

    Full Text Available We report here a case of a woman with a cutaneous large B-cell lymphoma of the legs. She had a plaque lesion, superficially ulcerated and necrotized with tumorous borders situated on the posterior side of the right leg and two red or bluish-red nodular lesions. A skin biopsy from both nodular and plaque lesion showed a diffuse infiltrate of atypical large B cells CD20+ and CD79a+, spanning epidermis, dermis and subcutaneous tissue. A therapeutic approach containing anti-CD20 monoclonal antibody (rituximab was suggested.

  3. Clinical results of BNCT for malignant brain tumors in children

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Kageji, Teruyoshi; Mizobuchi, Yoshifumi; Kumada, Hiroaki; Nakagawa, Yoshiaki

    2009-01-01

    It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

  4. NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Hayashi, Yoshihiro; Osanai, Makoto; Lee, Gang-Hong

    2015-10-01

    The NOTCH family of membranous receptors plays key roles during development and carcinogenesis. Since NOTCH2, yet not NOTCH1 has been shown essential for murine hepatogenesis, NOTCH2 rather than NOTCH1 may be more relevant to human hepatocarcinogenesis; however, no previous studies have supported this hypothesis. We therefore assessed the role of NOTCH2 in human hepatocellular carcinoma (HCC) by immunohistochemistry and cell culture. Immunohistochemically, 19% of primary HCCs showed nuclear staining for NOTCH2, indicating activated NOTCH2 signaling. NOTCH2-positive HCCs were on average in more advanced clinical stages, and exhibited more immature cellular morphology, i.e. higher nuclear-cytoplasmic ratios and nuclear densities. Such features were not evident in NOTCH1‑positive HCCs. In human HCC cell lines, abundant NOTCH2 expression was associated with anaplasia, represented by loss of E-cadherin. When NOTCH2 signaling was stably downregulated in HLF cells, an anaplastic HCC cell line, the cells were attenuated in potential for in vitro invasiveness and migration, as well as in vivo tumorigenicity accompanied by histological maturation. Generally, inverse results were obtained for a differentiated HCC cell line, Huh7, manipulated to overexpress activated NOTCH2. These findings suggested that the NOTCH2 signaling may confer aggressive behavior and immature morphology in human HCC cells.

  5. Orbital diffuse large B-cell lymphoma with combined variable immunodeficiency.

    Science.gov (United States)

    Parikh, Vishal S; Jagadeesh, Deepa; Fernandez, James M; Hsi, Eric D; Singh, Arun D

    2017-10-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency manifesting as a reduction in the level of total immunoglobulin (Ig) G, a reduction in the level of either IgA or IgM, poor response to polysaccharide vaccine, and usually frequent infections. The association of CVID with an increased risk of malignancy, specifically lymphoma, is well known. A 63-year-old female with a past medical history significant for CVID presented with a 1-month history of dull, left eye pain with proptosis, hypoglobus, and left upper lid fullness without a discrete palpable mass. Magnetic resonance imaging (MRI) of the orbits revealed a diffuse infiltrating orbital mass superonasally with extension into the superior rectus muscle, medial rectus muscle, and optic nerve up to the orbital apex and ethmoid sinus. A superonasal orbital biopsy with a caruncular approach was performed and demonstrated a sparse lymphoid infiltrate that was suggestive for a large B-cell neoplasm. Positron emission tomography (PET) scan demonstrated a hypermetabolic right lymph node, anterior to the right submandibular gland, which was biopsied and histopathology confirmed diffuse large B-cell lymphoma (DLBCL). Our patient achieved a very good response to chemotherapy with minimal residual disease on PET scan at the end of treatment. She attained a complete remission after radiation therapy. In conclusion, patients with new orbital and adnexa masses in the setting of a primary immunodeficiency can have an aggressive malignancy such as DLBCL and early diagnosis and systemic treatment carries a good prognosis.

  6. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)

    DEFF Research Database (Denmark)

    Marzec, Michal; Zhang, Qian; Goradia, Ami

    2008-01-01

    The mechanisms of malignant cell transformation caused by the oncogenic, chimeric nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially understood, with most of the previous studies focusing mainly on the impact of NPM/ALK on cell survival and proliferation. Here we report th...

  7. ITO with embedded silver grids as transparent conductive electrodes for large area organic solar cells

    DEFF Research Database (Denmark)

    Patil, Bhushan Ramesh; Mirsafaei, Mina; Cielecki, Pawel Piotr

    2017-01-01

    In this work, development of semi-transparent electrodes for efficient large area organic solar cells (OSCs) has been demonstrated. Electron beam evaporated silver grids were embedded in commercially available ITO coatings on glass, through a standard negative photolithography process, in order...... patterns. Solution processed bulk heterojunction OSCs based on PTB7:[70]PCBM were fabricated on top of these electrodes with cell areas of 4.38 cm2, and the performance of these OSCs was compared to reference cells fabricated on pure ITO electrodes. The Fill Factor of the large-scale OSCs fabricated on ITO...... with embedded Ag grids was enhanced by 18 % for the line grids pattern and 30 % for the square grids pattern compared to that of the reference OSCs. The increase in the Fill Factor was directly correlated to the decrease in the series resistance of the OSCs. The maximum power conversion efficiency (PCE...

  8. Intravascular Large B-Cell Lymphoma Presenting with Diffuse Gallbladder Wall Thickening: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sayf Al-Katib

    2018-01-01

    Full Text Available Intravascular large B-cell lymphoma is a rare subtype of extranodal diffuse B-cell lymphoma characterized by proliferation of neoplastic cells within the lumen of small and medium sized vessels. Clinical and imaging findings are nebulous as the intravascular subtype of lymphoma can involve a multitude of organs. Involvement of the gallbladder is extremely uncommon, and imaging findings can be easily confused for more prevalent pathologies. We report a case of intravascular large B-cell lymphoma in an 83-year-old male and review clinical presentation and imaging findings on CT, ultrasound, hepatobiliary iminodiacetic acid (HIDA scan, and MRI. It is important for the radiologist to know about this disease as the imaging findings are atypical of other types of lymphoma, and this may lead to a delay in diagnosis and treatment.

  9. Large-size, high-uniformity, random silver nanowire networks as transparent electrodes for crystalline silicon wafer solar cells.

    Science.gov (United States)

    Xie, Shouyi; Ouyang, Zi; Jia, Baohua; Gu, Min

    2013-05-06

    Metal nanowire networks are emerging as next generation transparent electrodes for photovoltaic devices. We demonstrate the application of random silver nanowire networks as the top electrode on crystalline silicon wafer solar cells. The dependence of transmittance and sheet resistance on the surface coverage is measured. Superior optical and electrical properties are observed due to the large-size, highly-uniform nature of these networks. When applying the nanowire networks on the solar cells with an optimized two-step annealing process, we achieved as large as 19% enhancement on the energy conversion efficiency. The detailed analysis reveals that the enhancement is mainly caused by the improved electrical properties of the solar cells due to the silver nanowire networks. Our result reveals that this technology is a promising alternative transparent electrode technology for crystalline silicon wafer solar cells.

  10. Primary diffuse large B cell lymphoma arising from a leiomyoma of the uterine corpus.

    Science.gov (United States)

    Zhao, Lianhua; Ma, Qiang; Wang, Qiushi; Zeng, Ying; Luo, Qingya; Xiao, Hualiang

    2016-01-20

    Primary diffuse large B cell lymphoma (DLBCL) of the uterus is rare, and primary DLBCL arising from a uterine leiomyoma (collision tumor) has not been reported in the literature. We describe the clinical, histological, immunohistochemical, and molecular features of primary DLBCL arising from a leiomyoma in the uterine corpus. A 73-year-old female patient had a uterine mass for 23 years. An ultrasound scan revealed marked enlargement of the uterus, measuring 18.2 × 13 × 16.3 cm, with a 17.6 × 10.9 × 11.6 cm hypoechoic mass in the uterine corpus. The tumors consisted of medium- to large-sized cells exhibiting a diffuse pattern of growth with a well-circumscribed leiomyoma. The neoplastic cells strongly expressed CD79α, CD20 and PAX5. Molecular analyses indicated clonal B-cell receptor gene rearrangement. To the best of our knowledge, no previous cases of primary DLBCL arising from a leiomyoma have been reported. It is necessary to differentiate a diagnosis of primary DLBCL arising from a leiomyoma from that of leiomyoma with florid reactive lymphocytic infiltration (lymphoma-like lesion). Careful analysis of clinical, histological, immunophenotypic, and genetic features is required to establish the correct diagnosis.

  11. In Vitro Large Scale Production of Human Mature Red Blood Cells from Hematopoietic Stem Cells by Coculturing with Human Fetal Liver Stromal Cells

    Directory of Open Access Journals (Sweden)

    Jiafei Xi

    2013-01-01

    Full Text Available In vitro models of human erythropoiesis are useful in studying the mechanisms of erythroid differentiation in normal and pathological conditions. Here we describe an erythroid liquid culture system starting from cord blood derived hematopoietic stem cells (HSCs. HSCs were cultured for more than 50 days in erythroid differentiation conditions and resulted in a more than 109-fold expansion within 50 days under optimal conditions. Homogeneous erythroid cells were characterized by cell morphology, flow cytometry, and hematopoietic colony assays. Furthermore, terminal erythroid maturation was improved by cosculturing with human fetal liver stromal cells. Cocultured erythroid cells underwent multiple maturation events, including decrease in size, increase in glycophorin A expression, and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to 80% of the cells. Importantly, they possessed the capacity to express the adult definitive β-globin chain upon further maturation. We also show that the oxygen equilibrium curves of the cord blood-differentiated red blood cells (RBCs are comparable to normal RBCs. The large number and purity of erythroid cells and RBCs produced from cord blood make this method useful for fundamental research in erythroid development, and they also provide a basis for future production of available RBCs for transfusion.

  12. Reconsideration of the indication of Ga-67 scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Takanashi, Toshiyasu; Komatani, Akio; Yamaguchi, Koichi (Yamagata Univ. (Japan))

    1984-11-01

    In order to establish proper indication of Ga-67 scintigraphy, its actual utilization in our hospital was reviewed. Although a large number of Ga-67 scintigraphy over 500 cases a year had been done, the clinical efficacy was found in limited conditions such as small cell carcinoma of the lung, malignant lymphoma, anaplastic carcinoma of the thyroid and abscess. In the other conditions, Ga-67 scintigraphy had little significance clinically and was not effective for seeking metastasis. Based on such situations, we emphasized that the indication of Ga-67 scintigraphy should be more limited under the better understanding of its characteristics.

  13. Increased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance

    OpenAIRE

    Mazzawi, Tarek; Gundersen, Doris Irene; Hausken, Trygve; El-Salhy, Magdy

    2015-01-01

    The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA i...

  14. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  15. Simplicity at the cost of predictive accuracy in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Biccler, Jorne Lionel; Eloranta, Sandra; Brown, Peter de Nully

    2018-01-01

    The international prognostic index (IPI) and similar models form the cornerstone of clinical assessment in newly diagnosed diffuse large B-cell lymphoma (DLBCL). While being simple and convenient to use, their inadequate use of the available clinical data is a major weakness. In this study, we co...

  16. Global hypomethylation is an independent prognostic factor in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Wedge, Eileen; Hansen, Jakob Werner; Garde, Christian

    2017-01-01

    Global hypomethylation has been linked to disease progression in several cancers, but has not been reported for Diffuse Large B Cell Lymphoma (DLBCL). This study aimed to assess global methylation in DLBCL and describe its prognostic value. Mean LINE1 methylation, a validated surrogate measure...... for global methylation, was measured in DNA from 67 tumor biopsies. Additionally, cell-free circulating DNA (cfDNA) in plasma samples from 74 patients was tested to assess the feasibility of global hypomethylation as a biomarker in liquid biopsies. LINE1 methylation was assessed using a commercially...

  17. Eosinophils may play regionally disparate roles in influencing IgA(+) plasma cell numbers during large and small intestinal inflammation.

    Science.gov (United States)

    Forman, Ruth; Bramhall, Michael; Logunova, Larisa; Svensson-Frej, Marcus; Cruickshank, Sheena M; Else, Kathryn J

    2016-05-31

    Eosinophils are innate immune cells present in the intestine during steady state conditions. An intestinal eosinophilia is a hallmark of many infections and an accumulation of eosinophils is also observed in the intestine during inflammatory disorders. Classically the function of eosinophils has been associated with tissue destruction, due to the release of cytotoxic granule contents. However, recent evidence has demonstrated that the eosinophil plays a more diverse role in the immune system than previously acknowledged, including shaping adaptive immune responses and providing plasma cell survival factors during the steady state. Importantly, it is known that there are regional differences in the underlying immunology of the small and large intestine, but whether there are differences in context of the intestinal eosinophil in the steady state or inflammation is not known. Our data demonstrates that there are fewer IgA(+) plasma cells in the small intestine of eosinophil-deficient ΔdblGATA-1 mice compared to eosinophil-sufficient wild-type mice, with the difference becoming significant post-infection with Toxoplasma gondii. Remarkably, and in complete contrast, the absence of eosinophils in the inflamed large intestine does not impact on IgA(+) cell numbers during steady state, and is associated with a significant increase in IgA(+) cells post-infection with Trichuris muris compared to wild-type mice. Thus, the intestinal eosinophil appears to be less important in sustaining the IgA(+) cell pool in the large intestine compared to the small intestine, and in fact, our data suggests eosinophils play an inhibitory role. The dichotomy in the influence of the eosinophil over small and large intestinal IgA(+) cells did not depend on differences in plasma cell growth factors, recruitment potential or proliferation within the different regions of the gastrointestinal tract (GIT). We demonstrate for the first time that there are regional differences in the requirement of

  18. Hierarchical imaging: a new concept for targeted imaging of large volumes from cells to tissues.

    Science.gov (United States)

    Wacker, Irene; Spomer, Waldemar; Hofmann, Andreas; Thaler, Marlene; Hillmer, Stefan; Gengenbach, Ulrich; Schröder, Rasmus R

    2016-12-12

    Imaging large volumes such as entire cells or small model organisms at nanoscale resolution seemed an unrealistic, rather tedious task so far. Now, technical advances have lead to several electron microscopy (EM) large volume imaging techniques. One is array tomography, where ribbons of ultrathin serial sections are deposited on solid substrates like silicon wafers or glass coverslips. To ensure reliable retrieval of multiple ribbons from the boat of a diamond knife we introduce a substrate holder with 7 axes of translation or rotation specifically designed for that purpose. With this device we are able to deposit hundreds of sections in an ordered way in an area of 22 × 22 mm, the size of a coverslip. Imaging such arrays in a standard wide field fluorescence microscope produces reconstructions with 200 nm lateral resolution and 100 nm (the section thickness) resolution in z. By hierarchical imaging cascades in the scanning electron microscope (SEM), using a new software platform, we can address volumes from single cells to complete organs. In our first example, a cell population isolated from zebrafish spleen, we characterize different cell types according to their organelle inventory by segmenting 3D reconstructions of complete cells imaged with nanoscale resolution. In addition, by screening large numbers of cells at decreased resolution we can define the percentage at which different cell types are present in our preparation. With the second example, the root tip of cress, we illustrate how combining information from intermediate resolution data with high resolution data from selected regions of interest can drastically reduce the amount of data that has to be recorded. By imaging only the interesting parts of a sample considerably less data need to be stored, handled and eventually analysed. Our custom-designed substrate holder allows reproducible generation of section libraries, which can then be imaged in a hierarchical way. We demonstrate, that EM

  19. FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas

    DEFF Research Database (Denmark)

    Brown, P J; Wong, K K; Felce, S L

    2016-01-01

    The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II......) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes......, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (PABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone...

  20. Primary central nervous system diffuse large B-cell lymphoma shows an activated B-cell-like phenotype with co-expression of C-MYC, BCL-2, and BCL-6.

    Science.gov (United States)

    Li, Xiaomei; Huang, Ying; Bi, Chengfeng; Yuan, Ji; He, Hong; Zhang, Hong; Yu, QiuBo; Fu, Kai; Li, Dan

    2017-06-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well. Nineteen cases of primary central nervous system DLBCL were stratified according to immunostaining algorithms of Hans, Choi and Meyer (Tally) and we investigated the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53. The Epstein-Barr virus and Borna disease virus infection were also detected. Among nineteen cases, most (15-17 cases) were assigned to the activated B-cell-like subtype, highly expression of C-MYC (15 cases, 78.9%), BCL-2 (10 cases, 52.6%), BCL-6 (15 cases, 78.9%). Unfortunately, two cases were positive for PD-L1 while PD-L2 was not expressed in any case. Two cases infected with BDV but no one infected with EBV. In conclusion, most primary central nervous system DLBCLs show an activated B-cell-like subtype characteristic and have multiple expressions of C-MYC, BCL-2, BCL-6 protein, these features might be significant factor to predict the outcome and guide treatment of PCNS-DLBCLs. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. A Case of Successful Remission of Extensive Primary Gastric Diffuse Large B Cell Lymphoma: Radiologic, Endoscopic and Pathologic Evidence

    Directory of Open Access Journals (Sweden)

    Mike M. Bismar

    2014-04-01

    Full Text Available Though rare amongst stomach neoplasms, primary gastric diffuse large B cell lymphoma is one of the commonest extranodal non-Hodgkin lymphomas. If left untreated, it can have a devastating progression and life-threatening consequences. We present the case of a successfully treated large antral ulcer confirmed to be large B cell lymphoma as evidenced by radiologic, endoscopic and histopathologic findings. A brief discussion about the types of gastric lymphoma, their Helicobacter pylori relation and therapeutic modalities follows.

  2. Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for prime-time?

    Science.gov (United States)

    Pailler, Emma; Faugeroux, Vincent; Oulhen, Marianne; Catelain, Cyril; Farace, Françoise

    2017-08-01

    In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis. Here we introduce the clinical needs in this disease that mainly consist of the diagnosis of epidermal growth factor receptor ( EGFR ) activating alterations and anaplastic lymphoma kinase ( ALK ) rearrangement. We present the proof-of-concept studies that explore the detection of these genetic alterations in CTCs from NSCLC patients. Finally, we discuss steps that are still required before CTCs are routinely used for diagnosis of EGFR -mutations and ALK -rearrangements in this disease.

  3. The role of printing techniques for large-area dye sensitized solar cells

    International Nuclear Information System (INIS)

    Mariani, Paolo; Vesce, Luigi; Di Carlo, Aldo

    2015-01-01

    The versatility of printing technologies and their intrinsic ability to outperform other techniques in large-area deposition gives scope to revolutionize the photovoltaic (PV) manufacturing field. Printing methods are commonly used in conventional silicon-based PVs to cover part of the production process. Screen printing techniques, for example, are applied to deposit electrical contacts on the silicon wafer. However, it is with the advent of third generation PVs that printing/coating techniques have been extensively used in almost all of the manufacturing processes. Among all the third generation PVs, dye sensitized solar cell (DSSC) technology has been developed up to commercialization levels. DSSCs and modules can be fabricated by adopting all of the main printing techniques on both rigid and flexible substrates. This allows an easy tuning of cell/module characteristics to the desired application. Transparency, colour, shape, layout and other DSSC’s features can be easily varied by changing the printing parameters and paste/ink formulations used in the printing process. This review focuses on large-area printing/coating technologies for the fabrication of DSSCs devices. The most used and promising techniques are presented underlining the process parameters and applications. (paper)

  4. Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

    Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

  5. The role of printing techniques for large-area dye sensitized solar cells

    Science.gov (United States)

    Mariani, Paolo; Vesce, Luigi; Di Carlo, Aldo

    2015-10-01

    The versatility of printing technologies and their intrinsic ability to outperform other techniques in large-area deposition gives scope to revolutionize the photovoltaic (PV) manufacturing field. Printing methods are commonly used in conventional silicon-based PVs to cover part of the production process. Screen printing techniques, for example, are applied to deposit electrical contacts on the silicon wafer. However, it is with the advent of third generation PVs that printing/coating techniques have been extensively used in almost all of the manufacturing processes. Among all the third generation PVs, dye sensitized solar cell (DSSC) technology has been developed up to commercialization levels. DSSCs and modules can be fabricated by adopting all of the main printing techniques on both rigid and flexible substrates. This allows an easy tuning of cell/module characteristics to the desired application. Transparency, colour, shape, layout and other DSSC’s features can be easily varied by changing the printing parameters and paste/ink formulations used in the printing process. This review focuses on large-area printing/coating technologies for the fabrication of DSSCs devices. The most used and promising techniques are presented underlining the process parameters and applications.

  6. DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Loo, Suet Kee; Ab Hamid, Suzina Sheikh; Musa, Mustaffa; Wong, Kah Keng

    2018-01-01

    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) 0.8) with DNMT1 expression and significantly downregulated (log fold-change <-1.35; p<0.05) following DNMT1 silencing in HT cells. These results suggest the involvement of DNMT1 in the activation of cell cycle and DNA replication in DLBCL cells. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. Chidamide Combined With R-GDP in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

    Science.gov (United States)

    2017-12-12

    Chidamide; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasm by Histology; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Rituximab; Gemcitabine; Cisplatin; Dexamethasone; HDAC Inhibitor

  8. CD79B limits response of diffuse large B cell lymphoma to ibrutinib.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Won Seog; Ryu, Kyungju; Kim, Seok Jin; Park, Chaehwa

    2016-01-01

    Blockage of B cell receptor signaling with ibrutinib presents a promising clinical approach for treatment of B-cell malignancies. However, many patients show primary resistance to the drug or develop secondary resistance. In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib. CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance. Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK. Combination of the AKT inhibitor or the MAPK inhibitor with ibrutinib resulted in circumvention of both primary and acquired resistance in ABC-DLBCL. Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.

  9. Anaplasia in pilocytic astrocytoma predicts aggressive behavior.

    Science.gov (United States)

    Rodriguez, Fausto J; Scheithauer, Bernd W; Burger, Peter C; Jenkins, Sarah; Giannini, Caterina

    2010-02-01

    The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.

  10. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

    OpenAIRE

    Chettiankandy, Tabita Joy; Tupkari, Jagdish Vishnu; Kumar, Keshav; Ahire, Manisha Sandeep

    2016-01-01

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Burkitt's lymphoma (BL), is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typica...

  11. Reducing cell-to-cell spacing for large-format lithium ion battery modules with aluminum or PCM heat sinks under failure conditions

    International Nuclear Information System (INIS)

    Coleman, Brittany; Ostanek, Jason; Heinzel, John

    2016-01-01

    Highlights: • Finite element analysis to evaluate heat sinks for large format li-ion batteries. • Solid metal heat sink and composite heat sink (metal filler and wax). • Transient simulations show response from rest to steady-state with normal load. • Transient simulations of two different failure modes were considered. • Significance of spacing, material properties, interface quality, and phase change. - Abstract: Thermal management is critical for large-scale, shipboard energy storage systems utilizing lithium-ion batteries. In recent years, there has been growing research in thermal management of lithium-ion battery modules. However, there is little information available on the minimum cell-to-cell spacing limits for indirect, liquid cooled modules when considering heat release during a single cell failure. For this purpose, a generic four-cell module was modeled using finite element analysis to determine the sensitivity of module temperatures to cell spacing. Additionally, the effects of different heat sink materials and interface qualities were investigated. Two materials were considered, a solid aluminum block and a metal/wax composite block. Simulations were run for three different transient load profiles. The first profile simulates sustained high rate operation where the system begins at rest and generates heat continuously until it reaches steady state. And, two failure mode simulations were conducted to investigate block performance during a slow and a fast exothermic reaction, respectively. Results indicate that composite materials can perform well under normal operation and provide some protection against single cell failure; although, for very compact designs, the amount of wax available to absorb heat is reduced and the effectiveness of the phase change material is diminished. The aluminum block design performed well under all conditions, and showed that heat generated during a failure is quickly dissipated to the coolant, even under the

  12. Role of Radiation Therapy in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

    DEFF Research Database (Denmark)

    Ng, Andrea K; Yahalom, Joachim; Goda, Jayant S

    2018-01-01

    Approximately 30% to 40% of patients with diffuse large B-cell lymphoma (DLBCL) will have either primary refractory disease or relapse after chemotherapy. In transplant-eligible patients, those with disease sensitive to salvage chemotherapy will significantly benefit from high-dose therapy with a...

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

    Directory of Open Access Journals (Sweden)

    Ahmed Idbaih

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

  14. Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by Genetic Analysis and a Patient-Derived Xenograft Study

    Directory of Open Access Journals (Sweden)

    Stuart L. Cramer

    2018-01-01

    Full Text Available Therapy for rhabdomyosarcoma (RMS has generally been limited to combinations of conventional cytotoxic agents similar to regimens originally developed in the late 1960s. Recently, identification of molecular alterations through next-generation sequencing of individual tumor specimens has facilitated the use of more targeted therapeutic approaches for various malignancies. Such targeted therapies have revolutionized treatment for some cancer types. However, malignancies common in children, thus far, have been less amenable to such targeted therapies. This report describes the clinical course of an 8-year-old female with embryonal RMS having anaplastic features. This patient experienced multiple relapses after receiving various established and experimental therapies. Genomic testing of this RMS subtype revealed mutations in BCOR, ARID1A, and SETD2 genes, each of which contributes to epigenetic regulation and interacts with or modifies the activity of histone deacetylases (HDAC. Based on these findings, the patient was treated with the HDAC inhibitor vorinostat as a single agent. The tumor responded transiently followed by subsequent disease progression. We also examined the efficacy of vorinostat in a patient-derived xenograft (PDX model developed using tumor tissue obtained from the patient’s most recent tumor resection. The antitumor activity of vorinostat observed with the PDX model reflected clinical observations in that obvious areas of tumor necrosis were evident following exposure to vorinostat. Histologic sections of tumors harvested from PDX tumor-bearing mice treated with vorinostat demonstrated induction of necrosis by this agent. We propose that the evaluation of clinical efficacy in this type of preclinical model merits further evaluation to determine if PDX models predict tumor sensitivity to specific agents and/or combination therapies.

  15. Epstein-Barr virus-positive diffuse large B-cell lymphoma in children: a disease reminiscent of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly.

    Science.gov (United States)

    Uccini, Stefania; Al-Jadiry, Mazin F; Scarpino, Stefania; Ferraro, Daniela; Alsaadawi, Adel R; Al-Darraji, Amir F; Moleti, Maria Luisa; Testi, Anna Maria; Al-Hadad, Salma A; Ruco, Luigi

    2015-05-01

    Pediatric Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is a rare disease in nonimmunocompromised hosts. In a review of 231 cases of malignant lymphoma (87 Hodgkin lymphoma and 144 non-Hodgkin lymphoma) occurring in Iraqi children, 7 cases (5% of NHLs) were classified as EBV+ DLBCL. Six children presented with nodal disease, and 1 presented with extranodal localization (bone). In all cases, the disease was at an advanced clinical stage (III/IV). Evidence of immunodeficiency (Evans syndrome and selective IgA deficiency) was observed in a single case. Two cases were "monomorphic" with immunoblastic histology, and 5 cases were "polymorphic" with histologic aspects reminiscent of nodular lymphocyte-predominant Hodgkin lymphoma (2 cases) and of CD30+ classical Hodgkin lymphoma (3 cases). In all cases, tumor cells were EBV infected (EBER+/LMP-1+), were medium-large B-cells (CD20+/CD79a+/PAX-5+/BOB-1+/OCT-2+) of non-germinal center (non-GC) origin (CD10-/MUM-1+), and had high proliferative activity (50%-70%). Chromosomal translocations involving BCL2, MYC, and IGH genes were not observed. IGH monoclonality could be demonstrated in 3 of 3 investigated cases. Six cases of EBV-negative DLBCL (4% of NHL) were present in the same series. All had monomorphic histology with centroblastic/immunoblastic morphology; 3 cases were of GC type and 3 of non-GC type. Our findings indicate that in Iraq, DLBCLs are 9% of NHLs. Moreover, 2 different types of the disease do exist; the EBV-positive cases, with strong histologic and immunohistochemical resemblance with EBV+ DLBCL of the elderly, and the EBV-negative cases, which are similar to the pediatric DLBCL usually observed in Western populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Alteration of the gene expression profile of T-cell receptor αβ-modified T-cells with diffuse large B-cell lymphoma specificity.

    Science.gov (United States)

    Zha, Xianfeng; Yin, Qingsong; Tan, Huo; Wang, Chunyan; Chen, Shaohua; Yang, Lijian; Li, Bo; Wu, Xiuli; Li, Yangqiu

    2013-05-01

    Antigen-specific, T-cell receptor (TCR)-modified cytotoxic T lymphocytes (CTLs) that target tumors are an attractive strategy for specific adoptive immunotherapy. Little is known about whether there are any alterations in the gene expression profile after TCR gene transduction in T cells. We constructed TCR gene-redirected CTLs with specificity for diffuse large B-cell lymphoma (DLBCL)-associated antigens to elucidate the gene expression profiles of TCR gene-redirected T-cells, and we further analyzed the gene expression profile pattern of these redirected T-cells by Affymetrix microarrays. The resulting data were analyzed using Bioconductor software, a two-fold cut-off expression change was applied together with anti-correlation of the profile ratios to render the microarray analysis set. The fold change of all genes was calculated by comparing the three TCR gene-modified T-cells and a negative control counterpart. The gene pathways were analyzed using Bioconductor and Kyoto Encyclopedia of Genes and Genomes. Identical genes whose fold change was greater than or equal to 2.0 in all three TCR gene-redirected T-cell groups in comparison with the negative control were identified as the differentially expressed genes. The differentially expressed genes were comprised of 33 up-regulated genes and 1 down-regulated gene including JUNB, FOS, TNF, INF-γ, DUSP2, IL-1B, CXCL1, CXCL2, CXCL9, CCL2, CCL4, and CCL8. These genes are mainly involved in the TCR signaling, mitogen-activated protein kinase signaling, and cytokine-cytokine receptor interaction pathways. In conclusion, we characterized the gene expression profile of DLBCL-specific TCR gene-redirected T-cells. The changes corresponded to an up-regulation in the differentiation and proliferation of the T-cells. These data may help to explain some of the characteristics of the redirected T-cells.

  17. The germacranolide sesquiterpene lactone neurolenin B of the medicinal plant Neurolaena lobata (L.) R.Br. ex Cass inhibits NPM/ALK-driven cell expansion and NF-κB-driven tumour intravasation.

    Science.gov (United States)

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

    2015-08-15

    The t(2;5)(p23;q35) chromosomal translocation results in the expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes gives rise to anaplastic large cell lymphomas (ALCL). In search of new therapy options the dichloromethane extract of the ethnomedicinal plant Neurolaena lobata (L.) R.Br. ex Cass was shown to inhibit NPM/ALK expression. Therefore, we analysed whether the active principles that were recently isolated and found to inhibit inflammatory responses specifically inhibit growth of NPM/ALK+ ALCL, leukaemia and breast cancer cells, but not of normal cells, and the intravasation through the lymphendothelial barrier. ALCL, leukaemia and breast cancer cells, and normal peripheral blood mononuclear cells (PBMCs) were treated with isolated sesquiterpene lactones and analysed for cell cycle progression, proliferation, mitochondrial activity, apoptosis, protein and mRNA expression, NF-κB and cytochrome P450 activity, 12(S)-HETE production and lymphendothelial intravasation. In vitro treatment of ALCL by neurolenin B suppressed NPM/ALK, JunB and PDGF-Rβ expression, inhibited the growth of ALCL cells late in M phase, and induced apoptosis via caspase 3 without compromising mitochondrial activity (as a measure of general exogenic toxicity). Moreover, neurolenin B attenuated tumour spheroid intravasation probably through inhibition of NF-κB and CYP1A1. Neurolenin B specifically decreased pro-carcinogenic NPM/ALK expression in ALK+ ALCL cells and, via the inhibition of NF-kB signalling, attenuated tumour intra/extravasation into the lymphatics. Hence, neurolenin B may open new options to treat ALCL and to manage early metastatic processes to which no other therapies exist. Copyright © 2015 Elsevier GmbH. All rights reserved.

  18. Investigation of Low-Cost Surface Processing Techniques for Large-Size Multicrystalline Silicon Solar Cells

    OpenAIRE

    Cheng, Yuang-Tung; Ho, Jyh-Jier; Lee, William J.; Tsai, Song-Yeu; Lu, Yung-An; Liou, Jia-Jhe; Chang, Shun-Hsyung; Wang, Kang L.

    2010-01-01

    The subject of the present work is to develop a simple and effective method of enhancing conversion efficiency in large-size solar cells using multicrystalline silicon (mc-Si) wafer. In this work, industrial-type mc-Si solar cells with area of 125×125 mm2 were acid etched to produce simultaneously POCl3 emitters and silicon nitride deposition by plasma-enhanced chemical vapor deposited (PECVD). The study of surface morphology and reflectivity of different mc-Si etched surfaces has also been d...

  19. Cloning, Stem Cells, and the Current National Debate: Incorporating Ethics into a Large Introductory Biology Course

    Science.gov (United States)

    Fink, Rachel D.

    2002-01-01

    Discussing the ethical issues involved in topics such as cloning and stem cell research in a large introductory biology course is often difficult. Teachers may be wary of presenting material biased by personal beliefs, and students often feel inhibited speaking about moral issues in a large group. Yet, to ignore what is happening "out there"…

  20. GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Okjae Lim

    Full Text Available Ex vivo-expanded, allogeneic natural killer (NK cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP conditions. After a single step of magnetic depletion of CD3(+ T cells, the depleted peripheral blood mononuclear cells (PBMCs were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(-CD16(+CD56(+ NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.

  1. Increased Chromogranin A Cell Density in the Large Intestine of Patients with Irritable Bowel Syndrome after Receiving Dietary Guidance

    Directory of Open Access Journals (Sweden)

    Tarek Mazzawi

    2015-01-01

    Full Text Available The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA in 13 IBS patients. Thirteen control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on controls and patients (at baseline and at 3–9 months after receiving guidance. Biopsy samples from the colon and rectum were immunostained for CgA and quantified by computerized image analysis. The densities of CgA cells in the total colon (mean ± SEM among the controls and the IBS patients before and after receiving dietary guidance were 83.3±10.1, 38.6±3.7, and 64.7±4.2 cells/mm2, respectively (P=0.0004, and were unchanged in the rectum. In conclusion, the increase in CgA cell density after receiving dietary guidance may reflect a change in the densities of the large intestinal endocrine cells causing an improvement in the IBS symptoms.

  2. Vapor and healing treatment for CH3NH3PbI3-xClx films toward large-area perovskite solar cells

    Science.gov (United States)

    Gouda, Laxman; Gottesman, Ronen; Tirosh, Shay; Haltzi, Eynav; Hu, Jiangang; Ginsburg, Adam; Keller, David A.; Bouhadana, Yaniv; Zaban, Arie

    2016-03-01

    Hybrid methyl-ammonium lead trihalide perovskites are promising low-cost materials for use in solar cells and other optoelectronic applications. With a certified photovoltaic conversion efficiency record of 20.1%, scale-up for commercial purposes is already underway. However, preparation of large-area perovskite films remains a challenge, and films of perovskites on large electrodes suffer from non-uniform performance. Thus, production and characterization of the lateral uniformity of large-area films is a crucial step towards scale-up of devices. In this paper, we present a reproducible method for improving the lateral uniformity and performance of large-area perovskite solar cells (32 cm2). The method is based on methyl-ammonium iodide (MAI) vapor treatment as a new step in the sequential deposition of perovskite films. Following the MAI vapor treatment, we used high throughput techniques to map the photovoltaic performance throughout the large-area device. The lateral uniformity and performance of all photovoltaic parameters (Voc, Jsc, Fill Factor, Photo-conversion efficiency) increased, with an overall improved photo-conversion efficiency of ~100% following a vapor treatment at 140 °C. Based on XRD and photoluminescence measurements, We propose that the MAI treatment promotes a ``healing effect'' to the perovskite film which increases the lateral uniformity across the large-area solar cell. Thus, the straightforward MAI vapor treatment is highly beneficial for large scale commercialization of perovskite solar cells, regardless of the specific deposition method.Hybrid methyl-ammonium lead trihalide perovskites are promising low-cost materials for use in solar cells and other optoelectronic applications. With a certified photovoltaic conversion efficiency record of 20.1%, scale-up for commercial purposes is already underway. However, preparation of large-area perovskite films remains a challenge, and films of perovskites on large electrodes suffer from non

  3. Enrichment of circulating tumor cells from a large blood volume using leukapheresis and elutriation: proof of concept.

    Science.gov (United States)

    Eifler, Robert L; Lind, Judith; Falkenhagen, Dieter; Weber, Viktoria; Fischer, Michael B; Zeillinger, Robert

    2011-03-01

    The aim of this study was to determine the applicability of a sequential process using leukapheresis, elutriation, and fluorescence-activated cell sorting (FACS) to enrich and isolate circulating tumor cells from a large blood volume to allow further molecular analysis. Mononuclear cells were collected from 10 L of blood by leukapheresis, to which carboxyfluorescein succinimidyl ester prelabeled CaOV-3 tumor cells were spiked at a ratio of 26 to 10⁶ leukocytes. Elutriation separated the spiked leukapheresates primarily by cell size into distinct fractions, and leukocytes and tumor cells, characterized as carboxyfluorescein succinimidyl ester positive, EpCAM positive and CD45 negative events, were quantified by flow cytometry. Tumor cells were isolated from the last fraction using FACS or anti-EpCAM coupled immunomagnetic beads, and their recovery and purity determined by fluorescent microscopy and real-time PCR. Leukapheresis collected 13.5 x 10⁹ mononuclear cells with 87% efficiency. In total, 53 to 78% of spiked tumor cells were pre-enriched in the last elutriation fraction among 1.6 x 10⁹ monocytes. Flow cytometry predicted a circulating tumor cell purity of ~90% giving an enrichment of 100,000-fold following leukapheresis, elutriation, and FACS, where CaOV-3 cells were identified as EpCAM positive and CD45 negative events. FACS confirmed this purity. Alternatively, immunomagnetic bead adsorption recovered 10% of tumor cells with a median purity of 3.5%. This proof of concept study demonstrated that elutriation and FACS following leukapheresis are able to enrich and isolate tumor cells from a large blood volume for molecular characterization. Copyright © 2010 International Clinical Cytometry Society.

  4. Large format lithium ion pouch cell full thermal characterisation for improved electric vehicle thermal management

    Science.gov (United States)

    Grandjean, Thomas; Barai, Anup; Hosseinzadeh, Elham; Guo, Yue; McGordon, Andrew; Marco, James

    2017-08-01

    It is crucial to maintain temperature homogeneity in lithium ion batteries in order to prevent adverse voltage distributions and differential ageing within the cell. As such, the thermal behaviour of a large-format 20 Ah lithium iron phosphate pouch cell is investigated over a wide range of ambient temperatures and C rates during both charging and discharging. Whilst previous studies have only considered one surface, this article presents experimental results, which characterise both surfaces of the cell exposed to similar thermal media and boundary conditions, allowing for thermal gradients in-plane and perpendicular to the stack to be quantified. Temperature gradients, caused by self-heating, are found to increase with increasing C rate and decreasing temperature to such an extent that 13.4 ± 0.7% capacity can be extracted using a 10C discharge compared to a 0.5C discharge, both at -10 °C ambient temperature. The former condition causes an 18.8 ± 1.1 °C in plane gradient and a 19.7 ± 0.8 °C thermal gradient perpendicular to the stack, which results in large current density distributions and local state of charge differences within the cell. The implications of these thermal and electrical inhomogeneities on ageing and battery pack design for the automotive industry are discussed.

  5. Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Shimada M

    2017-06-01

    Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

  6. Effects of cell asymmetry on the performance of a large heterogeneous critical assembly

    International Nuclear Information System (INIS)

    Scholtyssek, W.; Humbert, G.; Martini, M.; Norvez, G.

    1981-09-01

    Calculations were performed to investigate asymmetry effects observed in the RACINE reference configuration. The perturbation sources -material shifts in fissile rodlet cells- were identified and influences on various experimental parameters were estimated. Improvements of the relatively simple methods used in this work could lead to applications, considering similar effects, in project calculations for large power reactor cores

  7. Merkel Cell Polyomavirus Small T Antigen Induces Cancer and Embryonic Merkel Cell Proliferation in a Transgenic Mouse Model.

    Science.gov (United States)

    Shuda, Masahiro; Guastafierro, Anna; Geng, Xuehui; Shuda, Yoko; Ostrowski, Stephen M; Lukianov, Stefan; Jenkins, Frank J; Honda, Kord; Maricich, Stephen M; Moore, Patrick S; Chang, Yuan

    2015-01-01

    Merkel cell polyomavirus (MCV) causes the majority of human Merkel cell carcinomas (MCC) and encodes a small T (sT) antigen that transforms immortalized rodent fibroblasts in vitro. To develop a mouse model for MCV sT-induced carcinogenesis, we generated transgenic mice with a flox-stop-flox MCV sT sequence homologously recombined at the ROSA locus (ROSAsT), allowing Cre-mediated, conditional MCV sT expression. Standard tamoxifen (TMX) administration to adult UbcCreERT2; ROSAsT mice, in which Cre is ubiquitously expressed, resulted in MCV sT expression in multiple organs that was uniformly lethal within 5 days. Conversely, most adult UbcCreERT2; ROSAsT mice survived low-dose tamoxifen administration but developed ear lobe dermal hyperkeratosis and hypergranulosis. Simultaneous MCV sT expression and conditional homozygous p53 deletion generated multi-focal, poorly-differentiated, highly anaplastic tumors in the spleens and livers of mice after 60 days of TMX treatment. Mouse embryonic fibroblasts from these mice induced to express MCV sT exhibited anchorage-independent cell growth. To examine Merkel cell pathology, MCV sT expression was also induced during mid-embryogenesis in Merkel cells of Atoh1CreERT2/+; ROSAsT mice, which lead to significantly increased Merkel cell numbers in touch domes at late embryonic ages that normalized postnatally. Tamoxifen administration to adult Atoh1CreERT2/+; ROSAsT and Atoh1CreERT2/+; ROSAsT; p53flox/flox mice had no effects on Merkel cell numbers and did not induce tumor formation. Taken together, these results show that MCV sT stimulates progenitor Merkel cell proliferation in embryonic mice and is a bona fide viral oncoprotein that induces full cancer cell transformation in the p53-null setting.

  8. In vitro radiation and chemotherapy sensitivity of established cell lines of human small cell lung cancer and its large cell morphological variants

    International Nuclear Information System (INIS)

    Carney, D.N.; Mitchell, J.B.; Kinsella, T.J.

    1983-01-01

    The in vitro response to radiation and chemotherapeutic drugs of cell lines established from 7 patients with small cell (SC) lung cancer were tested using a soft agarose clonogenic assay. Five cell lines retained the typical morphological and biochemical amine precursor uptake decarboxylation characteristics of SC, while two cell lines had undergone ''transformation'' to large cell (LC) morphological variants with loss of amine precursor uptake decarboxylation cell characteristics of SC. The radiation survival curves for the SC lines were characterized by D0 values ranging from 51 to 140 rads and extrapolation values (n) ranging from 1.0 to 3.3. While the D0 values of the radiation survival curves of the LC variants were similar (91 and 80 rads), the extrapolation values were 5.6 and 11.1 In vitro chemosensitivity testing of the cell lines revealed an excellent correlation between prior treatment status of the patient and in vitro sensitivity or resistance. No correlation was observed between in vitro chemosensitivity and radiation response. These data suggest that transformation of SC to LC with loss of amine precursor uptake and decarboxylation characteristics is associated with a marked increase in radiation resistance (n) in vitro. The observation of a 2- to 5-fold increase in survival of the LC compared to the SC lines following 200 rads suggests that the use of larger daily radiation fractions and/or radiation-sensitizing drugs might lead to a significantly greater clinical response in patients with LC morphology. This clinical approach may have a major impact on patient response and survival

  9. Ionizing Radiation Deregulates the MicroRNA Expression Profile in Differentiated Thyroid Cells.

    Science.gov (United States)

    Penha, Ricardo Cortez Cardoso; Pellecchia, Simona; Pacelli, Roberto; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

    2018-03-01

    Ionizing radiation (IR) is a well-known risk factor for papillary thyroid cancer, and it has been reported to deregulate microRNA expression, which is important to thyroid carcinogenesis. Therefore, this study investigated the impact of IR on microRNA expression profile of the normal thyroid cell line (FRTL-5 CL2), as well as its effect on radiosensitivity of thyroid cancer cell lines, especially the human anaplastic thyroid carcinoma cell line (8505c). The global microRNA expression profile of irradiated FRTL-5 CL2 cells (5 Gy X-ray) was characterized, and data were confirmed by quantitative real-time polymerase chain reaction evaluating the expression of rno-miR-10b-5p, rno-miR-33-5p, rno-miR-128-1-5p, rno-miR-199a-3p, rno-miR-296-5p, rno-miR-328a-3p, and rno-miR-541-5p in irradiated cells. The miR-199a-3p and miR-10b-5p targets were validated by quantitative real-time polymerase chain reaction, Western blot, and luciferase target assays. The effects of miR-199a-3p and miR-10b-5p on DNA repair were determined by evaluating the activation of the protein kinases ataxia-telangiectasia mutated, ataxia telangiectasia, and Rad3-related and the serine 39 phosphorylation of variant histone H2AX as an indirect measure of double-strand DNA breaks in irradiated FRTL-5 CL2 cells. The impact of miR-10b-5p on radiosensitivity was analyzed by cell counting and MTT assays in FRTL-5 CL2, Kras-transformed FRTL-5 CL2 (FRTL KiKi), and 8505c cell lines. The results reveal that miR-10b-5p and miR-199a-3p display the most pronounced alterations in expression in irradiated FRTL-5 CL2 cells. Dicer1 and Lin28b were validated as targets of miR-10b-5p and miR-199a-3p, respectively. Functional studies demonstrate that miR-10b-5p increases the growth rate of FRTL-5 CL2 cells, while miR-199a-3p inhibits their proliferation. Moreover, both of these microRNAs negatively affect homologous recombination repair, reducing activated ataxia-telangiectasia mutated and Rad3-related protein levels

  10. Common pediatric cerebellar tumors: correlation between cell densities and apparent diffusion coefficient metrics.

    Science.gov (United States)

    Koral, Korgün; Mathis, Derek; Gimi, Barjor; Gargan, Lynn; Weprin, Bradley; Bowers, Daniel C; Margraf, Linda

    2013-08-01

    To test whether there is correlation between cell densities and apparent diffusion coefficient (ADC) metrics of common pediatric cerebellar tumors. This study was reviewed for issues of patient safety and confidentiality and was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center and was compliant with HIPAA. The need for informed consent was waived. Ninety-five patients who had preoperative magnetic resonance imaging and surgical pathologic findings available between January 2003 and June 2011 were included. There were 37 pilocytic astrocytomas, 34 medulloblastomas (23 classic, eight desmoplastic-nodular, two large cell, one anaplastic), 17 ependymomas (13 World Health Organization [WHO] grade II, four WHO grade III), and seven atypical teratoid rhabdoid tumors. ADCs of solid tumor components and normal cerebellum were measured. Tumor-to-normal brain ADC ratios (hereafter, ADC ratio) were calculated. The medulloblastomas and ependymomas were subcategorized according to the latest WHO classification, and tumor cellularity was calculated. Correlation was sought between cell densities and mean tumor ADCs, minimum tumor ADCs, and ADC ratio. When all tumors were considered together, negative correlation was found between cellularity and mean tumor ADCs (ρ = -0.737, P correlation between cellularity and ADC ratio. Negative correlation was found between cellularity and minimum tumor ADC in atypical teratoid rhabdoid tumors (ρ = -0.786, P correlation was found between cellularity and mean tumor ADC and ADC ratio. There was no correlation between the ADC metrics and cellularity of the pilocytic astrocytomas, medulloblastomas, and ependymomas. Negative correlation was found between cellularity and ADC metrics of common pediatric cerebellar tumors. Although ADC metrics are useful in the preoperative diagnosis of common pediatric cerebellar tumors and this utility is generally attributed to differences in cellularity of tumors

  11. A laser microsurgical method of cell wall removal allows detection of large-conductance ion channels in the guard cell plasma membrane

    Science.gov (United States)

    Miedema, H.; Henriksen, G. H.; Assmann, S. M.; Evans, M. L. (Principal Investigator)

    1999-01-01

    Application of patch clamp techniques to higher-plant cells has been subject to the limitation that the requisite contact of the patch electrode with the cell membrane necessitates prior enzymatic removal of the plant cell wall. Because the wall is an integral component of plant cells, and because cell-wall-degrading enzymes can disrupt membrane properties, such enzymatic treatments may alter ion channel behavior. We compared ion channel activity in enzymatically isolated protoplasts of Vicia faba guard cells with that found in membranes exposed by a laser microsurgical technique in which only a tiny portion of the cell wall is removed while the rest of the cell remains intact within its tissue environment. "Laser-assisted" patch clamping reveals a new category of high-conductance (130 to 361 pS) ion channels not previously reported in patch clamp studies on plant plasma membranes. These data indicate that ion channels are present in plant membranes that are not detected by conventional patch clamp techniques involving the production of individual plant protoplasts isolated from their tissue environment by enzymatic digestion of the cell wall. Given the large conductances of the channels revealed by laser-assisted patch clamping, we hypothesize that these channels play a significant role in the regulation of ion content and electrical signalling in guard cells.

  12. Iron Malabsorption in a Patient With Large Cell Lymphoma Involving the Duodenum

    Science.gov (United States)

    1992-01-01

    hemoglobin. The lymphomas (5-7). The presenting symptoms mimic chest radiograph in May demonstrated an anterior me- those of celiac disease and include...compounded the anemia in a pa- tion in celiac disease were reversible by the institution tient with diffuse large cell lymphoma involving the of a gluten...etiologies (usually 2-3 h) is expected in patients who are iron (e.g., celiac disease , pancreatic insufliciency). however, deficient and have normal

  13. CD4+ T cell-mediated cytotoxicity is associated with MHC class II expression on malignant CD19+ B cells in diffuse large B cell lymphoma.

    Science.gov (United States)

    Zhou, Yong; Zha, Jie; Lin, Zhijuan; Fang, Zhihong; Zeng, Hanyan; Zhao, Jintao; Luo, Yiming; Li, Zhifeng; Xu, Bing

    2018-01-15

    Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4 + T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19 + cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19 + cells than patients who did not show recurrence. Examining cytotoxic CD4 + T cells show that DLBCL patients presented significantly elevated frequencies of granzyme A-, granzyme B-, and/or perforin-expressing cytotoxic CD4 + T cells. Also, frequency of cytotoxic CD4 + T cells in DLBCL patients was positively correlated with the MHC II expression level. Subsequently, the cytotoxic potential of CD4 + T cells against autologous CD19 + cells was investigated. We found that the cytotoxic potential of CD4 + T cells was highest in MHC II-high, intermediate in MHC II-mid, and lowest in MHC II-low patients. The percentage of MHC II-expressing viable CD19 + cells presented a significant reduction after longer incubation with cytotoxic CD4 + T cells, suggesting that cytotoxic CD4 + T cells preferentially eliminated MHC II-expressing CD19 + cells. Blocking MHC II on CD19 + cells significantly reduced the cytolytic capacity of CD4 + T cells. Despite these discoveries, the frequency of cytotoxic CD4 + T cells did not predict the clinical outcome of DLBCL patients. Together, these results demonstrated that cytotoxic CD4 + T cells presented an MHC II-dependent cytotoxic potential against autologous CD19 + cells and could potentially represent a future treatment option for DLBCL. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

    Science.gov (United States)

    Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

    2017-09-01

    Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Role of Dicer1 in thyroid cell proliferation and differentiation.

    Science.gov (United States)

    Penha, Ricardo Cortez Cardoso; Sepe, Romina; De Martino, Marco; Esposito, Francesco; Pellecchia, Simona; Raia, Maddalena; Del Vecchio, Luigi; Decaussin-Petrucci, Myriam; De Vita, Gabriella; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

    2017-01-01

    DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.

  16. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  17. ITO with embedded silver grids as transparent conductive electrodes for large area organic solar cells

    Science.gov (United States)

    Patil, Bhushan R.; Mirsafaei, Mina; Piotr Cielecki, Paweł; Fernandes Cauduro, André Luis; Fiutowski, Jacek; Rubahn, Horst-Günter; Madsen, Morten

    2017-10-01

    In this work, development of semi-transparent electrodes for efficient large area organic solar cells (OSCs) has been demonstrated. Electron beam evaporated silver grids were embedded in commercially available ITO coatings on glass, through a standard negative photolithography process, in order to improve the conductivity of planar ITO substrates. The fabricated electrodes with embedded line and square patterned Ag grids reduced the sheet resistance of ITO by 25% and 40%, respectively, showing optical transmittance drops of less than 6% within the complete visible light spectrum for both patterns. Solution processed bulk heterojunction OSCs based on PTB7:[70]PCBM were fabricated on top of these electrodes with cell areas of 4.38 cm2, and the performance of these OSCs was compared to reference cells fabricated on pure ITO electrodes. The Fill Factor (FF) of the large-scale OSCs fabricated on ITO with embedded Ag grids was enhanced by 18% for the line grids pattern and 30% for the square grids pattern compared to that of the reference OSCs. The increase in the FF was directly correlated to the decrease in the series resistance of the OSCs. The maximum power conversion efficiency (PCE) of the OSCs was measured to be 4.34%, which is 23% higher than the PCE of the reference OSCs. As the presented method does not involve high temperature processing, it could be considered a general approach for development of large area organic electronics on solvent resistant, flexible substrates.

  18. Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Kania, P W; Ino, Y

    2000-01-01

    In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data fr...

  19. Study of solid and liquid behavior in large copper flotation cells (130 m2) using radioactive tracers

    International Nuclear Information System (INIS)

    Diaz, F.; Jimenez, O.; Yianatos, J.; Contreras, F.

    2013-01-01

    The behavior of the solid and liquid phases, in large flotation cells, was characterized by means of the radioactive tracer technique. The use of radioactive tracers enabled the identification of the Residence Time Distribution, of floatable and non-floatable solid, from continuous (on-line) measuring at the output streams of the flotation cells. For this study, the proper radioactive tracers were selected and applied in order to characterize the different phases; i.e. for liquid phase Br-82 as Ammonium Bromide, for floatable solid recovered in the concentrate Cu-64, and for non-floatable solid in three particle size classes (coarse: >150 μm, intermediate: 45 μm, and fine: <45 μm), Na-24. The experimental results confirmed the strong effect of particle size on the Residence Time Distribution, and mean residence time of solids in larger flotation cells, and consequently in flotation hydrodynamics. From a hydrodynamic point of view, the experimental data confirmed that a single mechanical flotation cells, of large size, can deviate significantly from perfect mixing. The experimental work was developed in a 130 m3 industrial flotation cell of the rougher circuit at El Teniente Division, Codelco-Chile. (authors)

  20. The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model.

    Science.gov (United States)

    Lu, Jiaxiong; Guan, Shan; Zhao, Yanling; Yu, Yang; Woodfield, Sarah E; Zhang, Huiyuan; Yang, Kristine L; Bieerkehazhi, Shayahati; Qi, Lin; Li, Xiaonan; Gu, Jerry; Xu, Xin; Jin, Jingling; Muscal, Jodi A; Yang, Tianshu; Xu, Guo-Tong; Yang, Jianhua

    2017-08-01

    Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Pulse power requirements for large aperture optical switches based on plasma electrode Pockels cells

    International Nuclear Information System (INIS)

    Rhodes, M.A.; Taylor, J.

    1992-06-01

    We discuss very large-aperture optical switches (greater than 30 x 30 cm) as an enabling technology for inertial confinement fusion drivers based on multipass laser amplifiers. Large-scale laser fusion drivers such as the Nova laser have been based on single-pass amplifier designs in part because of the unavailability of a suitable large-aperture switch. We are developing an optical switch based on a Pockels cell employing plasma-electrodes. A plasma-electrode Pockels cell (PEPC) is a longitudinal-mode Pockels cell in which a plasma discharge is formed on each side of an electro-optic crystal (typically KDP or deuterated KDP, often designated KD*P). The plasmas formed on either side of the crystal act as transparent electrodes for a switching-pulse and are intended to allow uniform charging of the entire crystal. The switching-pulse is a nominally rectangular high-voltage pulse equal to the half-wave voltage V x ( 8 kV for KD*P or 17 kV for KDP) and is applied across the crystal via the plasma-electrodes. When the crystal is charged to V x , the polarization of an incoming, linearly polarized, laser beam is rotated by 90 degree. When used in conjunction with an appropriate, passive polarizer, an optical switch is thus realized. A switch with a clear aperture of 37 x 37 cm is now in construction for the Beamlet laser which will serve as a test bed for this switch as well as other technologies required for an advanced NOVA laser design. In this paper, we discuss the unique power electronics requirements of PEPC optical switches

  2. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  3. Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström’s macroglobulinaemia

    Directory of Open Access Journals (Sweden)

    Radojković Milica

    2011-01-01

    Full Text Available Introduction. Waldenström’s macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström’s macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström’s macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. Case Outline. A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström’s macroglobulinaemia. Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström’s macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. Conclusion. The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenström’s macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors.

  4. Large, but not small, antigens require time- and temperature-dependent processing in accessory cells before they can be recognized by T cells

    DEFF Research Database (Denmark)

    Buus, S; Werdelin, O

    1986-01-01

    We have studied if antigens of different size and structure all require processing in antigen-presenting cells of guinea-pigs before they can be recognized by T cells. The method of mild paraformaldehyde fixation was used to stop antigen-processing in the antigen-presenting cells. As a measure...... of antigen presentation we used the proliferative response of appropriately primed T cells during a co-culture with the paraformaldehyde-fixed and antigen-exposed presenting cells. We demonstrate that the large synthetic polypeptide antigen, dinitrophenyl-poly-L-lysine, requires processing. After an initial......-dependent and consequently energy-requiring. Processing is strongly inhibited by the lysosomotrophic drug, chloroquine, suggesting a lysosomal involvement in antigen processing. The existence of a minor, non-lysosomal pathway is suggested, since small amounts of antigen were processed even at 10 degrees C, at which...

  5. [Prostatic granulomas revealing a peripheral T-cell lymphoma].

    Science.gov (United States)

    Foguem, C; Curlier, E; Rouamba, M-M; Regent, A; Philippe, P

    2009-02-01

    The presence of granulomas on tissue biopsie has been reported in a wide range of disorders. The clinical presentation and the diagnostic work-up of granulomatosis can be difficult as it is illustrated in the following report. A 59-year-old patient was referred in 2002 for a granulomatous prostatitis. Physical examination was normal. Except for the increase of prostate-specific antigen (which motivated a biopsy), the laboratory results were normal. Thoracic CT-scan disclosed mediastinal lymph nodes. A minor salivary gland biopsy was consistent with the diagnosis of sarcoidosis. In 2004, the patient presented an epidermal necrolysis, and in 2005 the deterioration of general status raised suspicion of a lymphoproliferative disorder. Liver and bone marrow biopsies revealed a granulomatous process. Despite steroid therapy, the patient died. Autopsy discloses a anaplasic T cell lymphoma. This report illustrates the relationship between sarcoidosis and lymphoma as a mode of presentation, a complication, or an accidental but misleading association? The association between anaplastic lymphoma and sarcoidosis is exceptional.

  6. Less initial rejoining of X-ray-induced DNA double-strand breaks in cells of a small cell (U-1285) compared to a large cell (U-1810) lung carcinoma cell line

    International Nuclear Information System (INIS)

    Cedervall, B.; Sirzea, F.; Brodin, O.; Lewensohn, R.

    1994-01-01

    Cells of a small cell lung carcinoma cell line, U-1285, and an undifferentiated large cell lung carcinoma cell line, U-1810, differ in radiosensitivity in parallel to the clinical radiosensitivity of the kind of tumors from which they are derived. The surviving fraction at 2 Gy (SF2) was 0.25 that of U-1285 cells and 0.88 that of U-1810 cells. We investigated the induction of DNA double-strand breaks (DSBs) by X rays and DSB rejoining in these cell lines. To estimate the number of DSBs we used a model adapted for pulsed-field gel electrophoresis (PFGE). The induction levels were of the same magnitude. These levels of induction do not correlate with radiosensitivity as measured by cell survival assays. Rejoining of DSBs after doses in the range of 0.50 Gy was followed for 0,15,30,60 and 120 min. We found a difference in the velocity of repair during the first hour after irradiation which is parallel to the differences in radiosensitivity. Thus U-1810 cells exhibit a fast component of repair, with about half of the DSBs being rejoined during the first 15 min, whereas U-1285 cells lack such a fast component, with only about 5% of the DSBs being rejoined after the same time. In addition there was a numerical albeit not statistical difference at 120 min, with more residual DSBs in the U-1285 cells compared to the U-1810 cells. 36 refs., 5 figs

  7. Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

    Directory of Open Access Journals (Sweden)

    Laura A Heaps

    2017-08-01

    Full Text Available Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE. The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats.

  8. Large-Cell Neuroendocrine Carcinoma of the Esophagus: A Case from Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Hadi Kuriry

    2015-10-01

    Full Text Available Neuroendocrine carcinomas of the esophagus are very rare, and the majority are high grade (poorly differentiated. They occur most frequently in males in their sixth and seventh decades of life. There have been no concrete data published on clinical features or on prognosis. We report a case of large-cell neuroendocrine carcinoma of the esophagus in a 66-year-old Saudi female with progressive dysphagia and weight loss. Upper endoscopy revealed an esophageal ulcerated mass.

  9. Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene

    International Nuclear Information System (INIS)

    Presta, Ivan; Filetti, Sebastiano; Russo, Diego; Arturi, Franco; Ferretti, Elisabetta; Mattei, Tiziana; Scarpelli, Daniela; Tosi, Emanuele; Scipioni, Angela; Celano, Marilena; Gulino, Alberto

    2005-01-01

    Recovery of iodide uptake in thyroid cancer cells by means of obtaining the functional expression of the sodium/iodide symporter (NIS) represents an innovative strategy for the treatment of poorly differentiated thyroid cancer. However, the NIS gene expression alone is not always sufficient to restore radioiodine concentration ability in these tumour cells. In this study, the anaplastic thyroid carcinoma ARO cells were stably transfected with a Pax8 gene expression vector. A quantitative RT-PCR was performed to assess the thyroid specific gene expression in selected clones. The presence of NIS protein was detected by Western blot and localized by immunofluorescence. A iodide uptake assay was also performed to verify the functional effect of NIS induction and differentiation switch. The clones overexpressing Pax8 showed the re-activation of several thyroid specific genes including NIS, Pendrin, Thyroglobulin, TPO and TTF1. In ARO-Pax8 clones NIS protein was also localized both in cell cytoplasm and membrane. Thus, the ability to uptake the radioiodine was partially restored, associated to a high rate of efflux. In addition, ARO cells expressing Pax8 presented a lower rate of cell growth. These finding demonstrate that induction of Pax8 expression may determine a re-differentiation of thyroid cancer cells, including a partial recovery of iodide uptake, fundamental requisite for a radioiodine-based therapeutic approach for thyroid tumours

  10. Very late relapse in diffuse large B-cell lymphoma represents clonally related disease and is marked by germinal center cell features

    NARCIS (Netherlands)

    de Jong, Daphne; Glas, Annuska M.; Boerrigter, Lucie; Hermus, Marie-Christine; Dalesio, Otilia; Willemse, Els; Nederlof, Petra M.; Kersten, Marie José

    2003-01-01

    Patients with diffuse large B-cell lymphoma (DLBCL) rarely show relapse after 4 years of complete remission (CR). In this study, we addressed the following questions: (1) Does late-relapsing DLBCL represent clonally related disease or a second malignancy; and (2) is there a characteristic biologic

  11. Stimulation of proteoglycans by IGF I and II in microvessel and large vessel endothelial cells

    International Nuclear Information System (INIS)

    Bar, R.S.; Dake, B.L.; Stueck, S.

    1987-01-01

    Endothelial cells were cultured from bovine capillaries and pulmonary arteries, and the effect of insulinlike growth factor (IGF) I and II (multiplication-stimulating activity) and insulin on the synthesis of proteoglycans was determined. IGF I and II stimulated 35 SO 4 incorporation into proteoglycans in a dose-dependent manner in both microvessel and pulmonary artery endothelial cells with maximum threefold increases. In pulmonary artery cells, the IGFs caused a general stimulation of all classes of glycosaminoglycan-containing proteoglycans. In microvessel endothelial cells, the IGFs appeared to preferentially increase heparan sulfate-containing proteoglycans. Insulin, at concentrations up to 10 -6 M, had no effect on the synthesis of proteoglycans in either microvessel or pulmonary arterial endothelial cells. Thus, the IGFs stimulate the synthesis of proteoglycans in both microvessel and large vessel endothelial cells, a property that is not mimicked by insulin. Because vascular endothelial cells are bathed by IGFs in vivo, such IGF-mediated functions are likely to be significant in both the normal physiology of vascular endothelium and in disease states such as diabetes mellitus

  12. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures

    DEFF Research Database (Denmark)

    Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander

    2013-01-01

    Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclo...

  13. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

  14. Clinicopathological study of primary gastric lymphoma

    International Nuclear Information System (INIS)

    Al-Shehabi, Zubeir A.; Saleh, Rana S.; Zezafon, Hassan B.

    2007-01-01

    Objective was to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas that was reclassified according to the new World Health Organization classification of lymphoid neoplasms. We reviewed the morphological and immunohistochemical features of 28 patients with gastric lymphomas, diagnosed in the Department of pathology at the University Hospital of Tishreen University, Lattakia, Syria, during the period 1994-2003. Specimens were obtained from endoscopic and surgical biopsies. The immunohistochemical study was performed to analyze the immunophenotype of these lymphomas. Patients were aged 17-71 years. There was a slight predominance of females (male to female ratio, 13:15). Seventeen of the patients had tumors mainly located in the gastric antrum. Histologically, the most common lymphoma was of mucosa-associated lymphoid tissue (MALT) type (20 patients), also with diffuse large B-cell lymphoma (7 patients) and anaplastic large cell lymphoma (one patient). Our study demonstrates the different patterns of gastric lymphomas in Lattakia, Syria during a 10-year period in 28 Syrian patients, and reveals that the most primary gastric lymphomas are B-cell MALT lymphomas. (author)

  15. Homotypic Cell Cannibalism and Cannibalism Index-A Four Year Study in Inltrating Ductal Carcinoma Breast

    Directory of Open Access Journals (Sweden)

    Alok Mohan

    2016-01-01

    Full Text Available Background: Homotypic cell cannibalism is a hallmark of malignant lesions. It serves as an emerging indicator of both the anaplastic grade and invasiveness. Aim and Objectives: The present study was conducted to correlate tumour cytological grade with the incidences of cell cannibalism. Material and Methods: Three stained smears per case were submitted for cytological grading. The smears were then submitted for visually counting the number of examples of cell cannibalism and the cannibalism index was calculated. Results: Seventy cytological diagnosed cases of breast malignancies were assessed for the presence of cell cannibalism. The results were correlated with the cytological grade of carcinoma. The study revealed that cell cannibalism was encountered in 68.57% cases of breast carcinoma. 44.4% of grade I, 71.4% of grade II and 100% of grade III tumours grade. It was observed that grade I tumours had mean cannibalism per smear of 1.62/1000 tumour cells smear, grade II mean cannibalism per smear of 2.50/ 1000 tumour cells and grade III mean cannibalism per smear 4.90/1000 tumour cells. Tumour diathesis and metastasis were also found more in cannibalism positive cases. Conclusion: The phenomenon of cell cannibalism was encountered more in high grade tumours. Thus it can be designated as an emerging marker of anaplasia and aggressive tumour behaviour

  16. Controversies on Hodgkin's disease and anaplastic large cell lymphoma. Hematopathology Study Group of the Società Italiana di Anatomia Patologica.

    Science.gov (United States)

    Pileri, S

    1994-01-01

    Just one year ago the Italian Society of Pathology (S.I.A.P.) created a Study Group which included members of the most active Italian hematopathology teams. Prof. Pasquale Calapso was asked to chair the Group and Prof. Stefano Pileri to take care of secretarial duties. The aim of the Group is to spread hematopathologic knowledge among young pathologists and to promote activities that can contribute to updating Italian pathologists on topics of both speculative and diagnostic interest. The first Workshop of the S.I.A.P. Hematopathology Group was held at the Palazzo dei Congressi in Bologna, November 20, 1993. About 150 pathologists from all over Italy took part in the meeting, which consisted of two sections devoted to: a) discussion of the boundaries between Hodgkin's disease and non-Hodgkin's lymphomas, and b) a case seminar illustrating the impact of immunohistochemistry in the diagnosis of bone-marrow biopsy. The first section included 5 presentations and a Round Table chaired by Prof. Luciano Fiore-Donati. Below, the contributors to this section summarize the content of their presentations, which were aimed at answering specific questions the Organizers had put to them.

  17. Intravascular large B-cell lymphoma presenting with anasarca-type edema and acute renal failure.

    Science.gov (United States)

    Bilgili, Serap Gunes; Yılmaz, Deniz; Soyoral, Yasemin Usul; Karadag, Ayse Serap; Bayram, Irfan

    2013-09-01

    Intravascular lymphoma (IVL) is a rare extra nodal subtype (usually of B-cell origin) presenting with infiltration of large neoplastic lymphocytes into lumina of blood vessels, leading to vascular occlusion. The early diagnosis is very crucial, however it is usually diagnosed postmortem investigation in most of the cases. A 56-year-old female presented with elevated creatinine level, and anasarca-type edema that superimposed with hard, indurated, erythematous plaques extending to inguinal region, abdomen, anterior aspect of chest, and face. B-cell IVL was confirmed with skin biopsy. The patient had some degree of clinical improvement following chemotherapy. B-cell IVL presenting with anasarca edema was not previously reported in the literature. Even if its rarity, IVL should be considered in the differential diagnosis of renal failure with anasarca edema.

  18. Prognostic impact of germinal center-associated proteins and chromosomal breakpoints in poor-risk diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    van Imhoff, Gustaaf W.; Boerma, Evert-Jan G.; van der Holt, Bronno; Schuuring, Ed; Verdonck, Leo F.; Kluin-Nelemans, Hanneke C.; Kluin, Philip M.

    2006-01-01

    Purpose Outcome of diffuse large B-cell lymphoma (DLBCL) with a germinal center B-cell (GCB) expression profile is superior to that of non-GCB DLBCL. This conclusion is mainly derived from patients with mixed international prognostic index (IPI) risk profiles treated with CHOP-like therapy

  19. Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

    Science.gov (United States)

    Mino-Kenudson, Mari

    2017-10-01

    In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

  20. [Diffuse large B-cell lymphoma complicated with drug-induced vasculitis during administration of pegfilgrastim].

    Science.gov (United States)

    Ito, Yuta; Noda, Kentaro; Aiba, Keisuke; Yano, Shingo; Fujii, Tsunehiro

    A 59-year-old female with diffuse large B-cell lymphoma was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimen. In addition, we administered pegfilgrastim for treating chemotherapy-induced febrile neutropenia. She complained of fever and neck and chest pain a few days after pegfilgrastim administration during the third and fourth courses of R-CHOP. Radiological imaging revealed an inflammation of large vessels, which led to the diagnosis of drug-associated vasculitis. We confirmed that vasculitis observed in this case was caused by pegfilgrastim administration because similar symptoms appeared with both injections of pegfilgrastim.