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Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment

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World Journal of Gastroenterology 2014年第32期20卷 11054-11061页

作者： Carlo Visco Silvia Finotto Department of hematology and cell therapy San Bortolo Hospital

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade > 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with trans

关键词： Hepatitis C virus Non-Hodgkin lymphoma Liver Toxicity Diffuse large B-cell lymphoma Rituximab Cyclophosphamide Hydroxydaunorubicin Vincristine Prednisolone Immuno-chemotherapy Antiviral treatment

Stem cell-based regenerative opportunities for the liver: State of the art and beyond

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World Journal of Gastroenterology 2015年第43期21卷 12334-12350页

作者： Eleftheria Tsolaki Evangelia Yannaki Gene and cell therapy Center Hematology Department-BMT UnitGeorge Papanicolaou Hospital Department of Medicine University of Washington

The existing mismatch between the great demand for liver transplants and the number of available donor organs highlights the urgent need for alternative therapeutic strategies in patients with acute or chronic liver failure. The rapidly growing knowledge on stem cell biology and the intrinsic repair processes of the liver has opened new avenues for using stem cells as a cell therapy platform in regenerative medicine for hepatic diseases. An impressive number of cell types have been investigated as sources of liver regeneration: adult and fetal liver hepatocytes,intrahepatic stem cell populations,annex stem cells,adult bone marrow-derived hematopoietic stem cells,endothelial progenitor cells,mesenchymal stromal cells,embryonic stem cells,and induced pluripotent stem cells. All these highly different cell types,used either as cell suspensions or,in combination with biomaterials as implantable liver tissue constructs,have generated great promise for liver regeneration. However,fundamental questions still need to be addressed and critical hurdles to be overcome before liver cell therapy emerges. In this review,we summarize the state-of-the-art in the field of stem cell-based therapies for the liver along with existing challenges and future perspectives towards a successful liver cell therapy that will ultimately deliver its demanding goals.

关键词： Stem cells Liver regeneration Liver cirrhosis Acut

Antiviral therapy of hepatitis C as curative treatment of indolent B-cell lymphoma

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World Journal of Gastroenterology 2016年第38期22卷 8447-8458页

作者： Michele Merli Giuseppe Carli Luca Arcaini Carlo Visco Division of hematology University Hospital Ospedale di Circolo & Fondazione MacchiUniversity of Insubria Department of cell therapy and hematology San Bortolo Hospital Department of Molecular Medicine University of Pavia

The association of hepatitis C virus(HCV) and B-cell non-Hodgkin lymphomas(NHL) has been highlighted by several epidemiological and biological insights; however the most convincing evidence is represented by interventional studies demonstrating the capability of antiviral treatment(AT) with interferon(IFN) with or without ribavirin to induce the regression of indolent lymphomas, especially of marginal-zone origin. In the largest published retrospective study(100 patients) the overall response rate(ORR) after first-line IFN-based AT was 77%(44% complete responses) and responses were sustainable(median duration of response 33 mo). These results were confirmed by a recent metaanalysis on 254 patients, demonstrating an ORR of 73%. Moreover this analysis confirmed the highly significant correlation between the achievement of viral eradication sustained virological response(SVR) and hematological responses. Two large prospective studies demonstrated that AT is associated with improved survival and argue in favor of current guidelines' recommendation of AT as preferential first-line option in asymptomatic patients with HCV-associated indolent NHL. The recently approved direct-acting antiviral agents(DAAs) revolutionized the treatment of HCV infection, leading to SVR approaching 100% in all genotypes. Very preliminary data of IFN-free DAAs therapy in indolent HCV-positive NHL seem to confirm their activity in inducing lymphoma regression.

关键词： Non-hodgkin lymphomas Hepatitis C virus Antiviral therapy Interferon Ribavirin Sofosbuvir Direct-acting antiviral agents Marginal zone lymphomas

Rationale for the potential use of mesenchymal stromal cells in liver transplantation

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World Journal of Gastroenterology 2014年第44期20卷 16418-16432页

作者： Morgan Vandermeulen Céline Grégoire Alexandra Briquet Chantal Lechanteur Yves Beguin Olivier Detry Department of Abdominal Surgery and Transplantation CHU Liege University of Liege Department of hematology CHU Liege University of Liege Laboratory of cell and Gene therapy CHU Liege University of Liege

Mesenchymal stromal cells (MSCs) are multipotent and self-renewing cells that reside essentially in the bone marrow as a non-hematopoietic cell population, but may also be isolated from the connective tissues of most organs. MSCs represent a heterogeneous population of adult, fibroblast-like cells characterized by their ability to differentiate into tissues of mesodermal lineages including adipocytes, chondrocytes and osteocytes. For several years now, MSCs have been evaluated for their in vivo and in vitro immunomodulatory and ‘tissue reconstruction’ properties, which could make them interesting in various clinical settings, and particularly in organ transplantation. This paper aims to review current knowledge on the properties of MSCs and their use in pre-clinical and clinical studies in solid organ transplantation, and particularly in the field of liver transplantation. The first available clinical data seem to show that MSCs are safe to use, at least in the medium-term, but more time is needed to evaluate the potential adverse effects of long-term use. Many issues must be resolved on the correct use of MSCs. Intensive in vitro and pre-clinical research are the keys to a better understanding of the way that MSCs act, and to eventually lead to clinical success.

关键词： Mesenchymal stem cells Organ transplantation Complication Immunosuppression Tolerance

Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang

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Cancer Biology & Medicine 2016年第2期13卷 248-259页

作者： Hong-Sheng Zhou Bing Z.Carter Michael Andreeff Section of Molecular hematology and therapy Department of Leukemia The University of Texas M.D.Anderson Cancer Center Department of hematology Nanfang Hospital Southern Medical University

Acute myeloid leukemia （AML） is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow （BM） niche is critical to the maintenance and retention of hematopoietic stem cells （HSC）, including leukemia stem cells （LSC）, and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

关键词： Bone marrow niche leukemia stem cell acute myeloid leukemia Yin and Yang

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How antithymocyte globulin,a polyclonal soup of the past century,when carefully dosed,has become crucial for hematopoietic stem cell transplantation with haplo-identical donors in the 21st century

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Science Bulletin 2021年第24期66卷 2445-2447页

作者： Norbert Claude Gorin Department of hematology and cell therapy Hopital Saint Antoine and Paris Sorbonne UniversityParis 75012France

Hematopoeitic stem cell transplantation(HSCT)using a haploidentical family donor(HAPLO)was long thought to be non-feasible,essentially because of HLA incompatibility leading to graft rejection,severe acute(aGVH)and chronic(cGVH)graft versus host disease(GVH),severe infections and unacceptable nonrelapse mortality(NRM).The group in Perugia in the last decade of the past century[1],was the first to be successful by initiating a positive selection of CD34+cells from peripheral blood stem cell(PBSC)collections,providing T cell depleted grafts with very high doses of CD34+cells to be *** combined with intensive conditioning regimen and profound immunosuppression,the Perugia group obtained the first demonstration of feasibility and *** later improved their results in acute myeloid leukemia(AML)by showing that a mismatch for natural killer(NK)cells in the killer-cell immunoglobulin-like receptor(KIR)-human leukocyte-antigen class I(HLA1)donor to recipient direction[2]decreased considerably the relapse incidence(RI).Unfortunately this approach was associated with severe infections,a high NRM and in addition was cumbersome and difficult to reproduce in other non-expert centers.

关键词：造血干细胞移植 acute doses

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Extramedullary plasmacytoma with the uvula as first affected site:A case report

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World Journal of Clinical Oncology 2025年第1期16卷 53-58页

作者： Jing Yang Hui Peng Sheng-Ke Tu Min Li Kui Song Department of hematology The First Affiliated Hospital of Jishou UniversityJishou 416000Hunan ProvinceChina Department of Pharmacy The First Affiliated Hospital of Jishou UniversityJishou 416000Hunan ProvinceChina

BACKGROUND Extramedullary plasmacytoma(EMP)represents one of the rarer forms of plasma cell malignancies,capable of impacting a variety of tissues and organs throughout the *** majority of EMP cases are predominantly found in the head and neck region,especially within the laryngopharynx,as well as in the gastrointestinal *** there have been documented instances of oropharyngeal involvement in EMP cases in the academic literature,it is important to note that EMP specifically affecting the uvula is exceedingly ***,it is noteworthy that over 60% of epithelial carcinomas in the upper respiratory tract and oropharynx tend to metastasize to the cervical lymph nodes,indicating a propensity for regional spread in these types of *** this context,we present a rare case of extramedullary plasmacytoma where the uvula served as the initially affected *** case emphasizes the need for heightened awareness among clinicians regarding such unusual comorbidities,as early recognition and diagnosis can significantly influence patient management and treatment *** addition,a review of the relevant literature is included to further educate and inform healthcare professionals about this rare presentation,ultimately aiming to enhance clinical understanding and improve patient care in similar *** SUMMARY A 51-year-old man was admitted to our hospital because of a slowly enlarging neck mass.A physical examination revealed a palpable left lymph node,and magnetic resonance imaging(MRI)of the oropharynx and the neck showed a soft tissue mass in the oropharynx and enlargement of multiple lymph nodes in the *** soft tissue mass was diagnosed as plasmacytoma by immunohistochemical *** immunoglobulins and bone marrow biopsy showed normal ***,we diagnosed that as EMP of the *** four cycles of adjuvant chemotherapy dominated by bortezomib,MRI reexamination showed a significant reduction of the mass

关键词： Extramedullary plasmacytoma Plasmacytoma Uvula Multiple myeloma Case report

“Clone-specific”antibody-drug conjugates:an innovative strategy in the treatment of T-cell cancers

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Signal Transduction and Targeted therapy 2024年第10期9卷 4149-4150页

作者： Dennis Jungherz Philipp Lückemeier Marco Herling Department of hematology Cellular TherapyHemostaseology and Infectious DiseasesUniversity of Leipzig Medical CenterLeipzigGermany

In a recent study published in Nature,Nichakawade et *** proof-of-principle data on innovative strategies to target and eliminate cancerous T-cells while sparing healthy T-lymphocytes,addressing the urgent clinical need posed by the mostly aggressive and treatment-refractory T-cell lymphomas.1 This research represents a significant milestone in overcoming major obstacles in immunotherapies for these cancers.

关键词： treatment eliminate mostly

Not just a combination: a fully-integrated strategy of cellular therapy for acute myeloid leukemia expressing CD7, a heretofore elusive target

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Science China Life Sciences 2024年

作者： Norbert-Claude Gorin Department of hematology and cell therapy EBMT Global Committee and Paris Office H?pital Saint Antoine APHP Paris Sorbonne University

Acute myeloid leukemia(AML) and its treatment have remained, for long, an area of slow but constant therapeutic progress as well as of permanent frustration. Chemotherapy has initially been and still is part of the ba...

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