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Association of Morphology and Immunophenotype in Diffuse Large B-Cell Lymphomas with Bone Marrow Infiltration in a Sample Mexican Population

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Open Journal of Pathology 2012年第2期2卷 29-37页

作者： Mónica-Belinda Romero-Guadarrama Fiacro Jiménez Ponce Armando Medina Cruz elsa lorena durán ramírez Icela Palma Lara Molecular and Celular Morphology Laboratory Escuela Superior de Medicina Instituto Politécnico Nacional and Morphology Department Facultad de Medicina Veterinaria y Zootecnia (UNAM) México City México Unidad de Patología del Hospital General de México Facultad de Medicina Universidad Nacional Autónoma de México (UNAM) México City México

Introduction: Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, is a large B-cell lymphoma with a diffuse growth pattern and aggressive clinical course. It is divided in subgroups according to its morphology, immunophenotype, and primary site. Dissemination to bone marrow occurs in 11% to 35% of cases and can be of concordant or discordant morphology. Objective: To examine the association, the type of bone marrow involvement in relation to the primary site, morphology, immunohistochemistry of DLBCLs and to determine the cases of Epstein-Barr virus positive DLBCLs. Materials and Methods: We reviewed lymph node and extranodal biopsies as well as the respective bone marrow biopsies in all cases of DLBCL diagnosed in the Hospital General de México during the period from 2002 to 2010. We used immunohystochemistry for immunophenotype identification (Hans’s algorithm) and an in-situ hybridization technique to detect presence of Epstein Barr encoded RnA (EBER). Results: We included 108 patients with a mean age of 51.9 years, 59 (55%) were men. DLBCL involved lymph nodes in 60% of cases and palatine tonsils in 13%. The centroblastic variant predominated (80%) and 58% originated from activated B-cells. Infiltration of bone marrow was present in 30% of cases and was discordant in 55% of these cases. Correlation between morphology and bone marrow infiltration was statistically significant (P = 0.0003). Presence of Epstein-Barr virus was demonstrated in 15% of patients older than 50 years. Conclusions: Dissemination to bone marrow occurred in 30% of cases and discordant involvement was most common. DLBCL originating from activated B-lymphocytes predominated and the most common extranodal sites were palatine tonsils, suggesting that our population has a clinical behavior similar to Asiatic populations.

关键词： Dissemination to Bone Marrow Diffuse Large B-Cell Lymphoma Immunophenotype

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Site-directed cysteine coupling of disulfide-containing non-antibody carrier proteins(THIOCAPs)

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Science China Materials 2023年第10期66卷 4109-4120页

作者： Ariana Rueda Julian I.Mendoza lorena Alba-Castellon Eloi Parladé Eric Voltà-durán David Paez Anna Avino ramon Eritja Esther Vázquez Antonio Villaverde ramón Mangues Ugutz Unzueta Institut d'Investigació Biomèdica Sant Pau(IIB Sant Pau) Sant Quintí 77-7908041 BarcelonaSpain Josep Carreras Leukaemia Research Institute(IJC Campus Sant Pau) 08041 BarcelonaSpain CIBER de Bioingeniería Biomateriales y NanomedicinaInstituto de Salud Carlos Ⅲ28029 MadridSpain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona08193 BellaterraSpain Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona08193 BellaterraSpain Department of Medical Oncology Hospital de la Santa Creu i Sant Pau.Barcelona08025 BarcelonaSpain CIBER de Enfermedades Raras(CIBERER) Instituto de Salud Carlos Ⅲ28029 MadridSpain Institute for Advanced Chemistry of Catalonia(IQAC) CSIC08034 BarcelonaSpain

The development of a new generation of nonantibody protein drug delivery systems requires site-directed conjugation strategies to produce homogeneous,reproducible and scalable *** that,the genetic addition of cysteine residues into solvent-exposed positions allows the thiol-mediated cysteine coupling of therapeutic drugs into protein-based ***,the high reactivity of unpaired cysteine residues usually reduces protein stability,consequently imposing the use of more methodologically demanding purification *** is especially relevant for disulfide-containing nanocarriers,as previously observed in ***,although many protein scaffolds and targeting ligands are also rich in disulfide bridges,the use of these methodologies over emerging non-antibody carrier proteins has been completely ***,we report the development of a simple and straightforward procedure for a onestep production and site-directed cysteine conjugation of disulfide-containing non-antibody thiolated carrier proteins(THIOCAPs).This method is validated in a fluorescent C-X-C chemokine receptor 4(CXCR4)-targeted multivalent nanocarrier containing two intramolecular disulfide bridges and one reactive cysteine residue strategically placed into a solvent-exposed position(THIO-T22-GFP-H6)for drug conjugation and in a humanized alternative intended for clinical applications(T22-HSnBT-H6).Thus,we produce very stable,homogeneous and fully functional antitumoral nanoconjugates(THIO-T22-GFP-H6-MMAE and T22-HSnBT-H6-MMAE)that selectively eliminate target cancer cells via ***,the developed methodology appears as a powerful tool for the rational engineering of emerging non-antibody,cell-targeted protein nanocarriers that contain disulfide bridges together with a solvent-exposed reactive cysteine(THIOCAP).This should pave the way for the development of a new generation of stable,homogeneous and efficient nanomedicines.

关键词： disulfide directed bridges

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