Browsing by Subject "Lymphoma"

Now showing 1 - 5 of 5
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    Aberrant expression of napsin A in a subset of malignant lymphomas
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Nam, Soo Jeong; Kim, Sehui; Kim, Ji Eun; Lim, Megan S.; Elenitoba-Johnson, Kojo S.J.; Kim, Chul Woo; Jeon, Yoon Kyung
    Background: Napsin A is commonly expressed in pulmonary adenocarcinomas and some renal cell carcinomas. However, napsin A expression in lymphoid neoplasms has never been reported. Methods: Glycoproteomic analyses of lymphoma-derived cell lines revealed napsin A expression in anaplastic large cell lymphoma (ALCL) cells. We thus investigated napsin A expression in lymphoid neoplasms. A variety of lymphomas (n=672) and histiocytic tumors (n=55) was immunostained for napsin A using patient tissues. Results: In reactive lymphoid tissues, only a few histiocytes were positive for napsin A. ALK-positive ALCLs most frequently expressed napsin A (34.4%, 11/32 cases) at a rate that was significantly higher compared with ALK-negative ALCL (8.6%, 3/35; P=0.015). Napsin A expression was also observed in 13.4% (20/149) of diffuse large B-cell lymphomas (DLBCL), 11.1% (15/134) of Hodgkin lymphomas, 4.9% (2/41) of follicular lymphomas, 6% (4/67) of peripheral T-cell lymphomas, and 3.8% (1/26) of plasma cell neoplasms. Otherwise, napsin A was not detected in any other types of lymphomas or histiocytic neoplasms. Napsin A expression in systemic ALCL was associated with a higher international prognostic index. ALCL and DLBCL patients with napsin A expression tended to have poor prognosis. Conclusion: These results demonstrated that napsin A is aberrantly expressed in a subset of lymphomas. The biological significance of napsin A in lymphomas warrants further study.
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    Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Berkova, Zuzana; Wang, Shu; Sehgal, Lalit; Pate, Keyur Pravinchandra; Prakash, Om; Samaniego, Felipe
    Growing evidence supports the involvement of human herpervirus 8, Kaposi’s sarcoma associated herpesvirus (KSHV), in the pathology of primary effusion lymphoma, multicentric Castleman’s disease, and Kaposi’s sarcoma, but the exact mechanism of KSHV contribution to the oncogenic process remains elusive. We studied transgenic mice expressing the ORF K1 of KSHV, whose position in the KSHV genome corresponds to known lymphoproliferative genes of other herpesviruses. K1 protein was previously shown to contain a constitutively active ITAM domain, involved in activation of Akt and pro-survival signaling, and to inhibit Fas-mediated apoptosis by interfering with binding of FasL. All this pointed to a possible role of K1 in the pathogenesis of KSHV-associated cancers. K1 transgenic mice (80-90%) developed lymphoid hyperplasia and splenomegaly at 8 and 10 months of age, 25% had confirmed diagnosis of lymphoma, and 50% developed abdominal and/or hepatic tumors by 18 months of age. Histological examination showed loss of splenic architecture and increased cellularity. Lymph nodes showed disrupted architecture with effaced follicles and other pathological changes, including signs of angiofollicular lymphoid hyperplasia. One of the livers showed signs of angiosarcoma. In summary, our histology results revealed pathological changes in K1 transgenic mice similar to lymphoma, Castleman’s disease, and angiosarcoma, suggesting that K1 may contribute to the development of KSHV-associated cancers.
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    Natural killer cell malignancies: clinicopathologic and molecular features
    (Murcia : F. Hernández, 2002) Siu, L.L.P.; Chan, John K.C.; Kwong, Y.L.
    Malignancies of natural killer (NK) cells h ave increasingly been recognized as distinct clinicopathological entities. The tumor cells are characterized by an immunophenotype of CD2+, surface CD3-, cytoplasmic CD3e+, and CD56+. The T cell receptor gene is in germline configuration, and a consistent association with Epstein-Barr virus is demonstrable. Pa t h o l o g i c a l l y, the tumor cells show variable cytological appearances, with frequent angioinvasion and angiocentricity associated with zonal necrosis. Clinically, most cases affect the nasal cavity or other parts of the upper aerodigestive tract, and are referred to as nasal NK cell lymphoma. A minority involve extranasal sites such as the skin, gastrointestinal tract and testis, and are often referred to as ex t r a n a s a l NK cell lymphoma. A particularly aggressive form presents fulminantly as disseminated disease, sometimes with a leukemic phase, and is referred to as aggressive NK cell lymphoma/leukemia. Cytogenetic and molecular analysis have shown DNA losses at chromosomes 6q, 11q, 13q and 17p to be recurrent aberrations in NK cell malignancies. Frequent DNA gains are also found in chromosomes 1p, 6p, 11q, 12q, 17q, 19p, 20q, and Xp. These regions of DNA losses and gains should be targets for further inve s t i gation in order to understand the molecular pathogenesis of this lymphoma. Finally, optimal treatment modalities need to be determined, as all subtypes of NK cell malignancies are associated with a poor prognosis.
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    Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): Effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease
    (Murcia : F. Hernández, 2003) Hayashi, K.; Joko, H.; Koirala, T.R.; Onoda, S.; Jin, Z.S.; Munemasa, M.; Ohara, N.; Oda, W.; Tanaka, T.; Oka, T.; Kondo, E.; Yoshino, T.; Takahashi, K.; Yamada, M.; Akagi, T.
    Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVPinduced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVPinduced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVPinduced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.
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    Tumoricidal potential of binary therapy in lymphoma: Role of DC-NK cross-talk and checkpoint inhibitors
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Chaudhary, Pratima; Yadav, Pragya; Manna, Partha Pratim; Biología Celular e Histología
    Lymphoma is a common type of cancer that occurs in humans. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype and is characterized by high clinical and biological heterogeneity. The tumor microenvironment (TME) in lymphoma is critical for the initiation, progression, and metastasis of tumors and influences the therapeutic efficiency of chemotherapy or immuno-therapy, including cell therapy or appropriate combinations of therapeutics. The role of effector immune cells in the development and progression of DLBCL is complex and involves reciprocal interactions between tumor cells, adaptive and innate immune cells, their soluble mediators, and structural components present in the TME. Recruitment of immune cells in the TME and their distinct effects on tumor progression and therapeutic outcomes in the presence of therapy have decisive effects on the outcome of therapy. In this review, we discuss the application and implications of binary therapy involving suboptimal-dose chemotherapy and adoptive cell therapy on the basis of our recent findings on γc cytokine-aided cross-talk between dendritic cells and natural killer cells in therapy against experimental murine lymphoma. This novel therapeutic protocol induces a healing response in experimental lymphoma by downregulating FOXP3 and programmed cell death protein 1. We discuss the various aspects of binary therapy covering multiple issues, including the participation of cell subsets and checkpoint inhibitors in the treatment of malignant lymphoma. These new therapies involve the induction of adoptive cell therapy through the passive transfer of immunologic effectors in addition to a suboptimal dose of adriamycin (doxorubicin hydrochloride) to increase the ability of the immune system to react against tumor antigens, inducing the destruction of tumor cells.