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1.
Blood ; 130(6): 777-788, 2017 08 10.
Article in English | MEDLINE | ID: mdl-28596424

ABSTRACT

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL.


Subject(s)
Calgranulin B/immunology , Exosomes/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , NF-kappa B/immunology , Basigin/analysis , Basigin/immunology , Calgranulin B/analysis , Disease Progression , Exosomes/immunology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , NF-kappa B/analysis , Proteome/analysis , Proteome/immunology
2.
Rev Med Chil ; 147(12): 1553-1560, 2019 Dec.
Article in English | MEDLINE | ID: mdl-32186619

ABSTRACT

Background Prognosis of patients with Diffuse Large B Cell Lymphoma (DLBCL) is highly variable, and despite the use of modern immunochemotherapy regimens, almost 50% of patients will eventually relapse. Standard risk models, like the International Prognostic Index or the Revised International Prognostic Index (R_IPI) incorporate patient and tumor characteristics but do not consider variables related to host adaptive immunity which have been shown to be of significant prognostic value in non-Hodgkin lymphomas. Aim To analyze the prognostic significance of the absolute monocyte count at diagnosis in diffuse large-B-cell lymphoma in a retrospective setting. Material and Methods We reviewed data of 171 patients with DLBCL treated with Rituximab-based immunochemotherapy at two reference public Hospitals in Montevideo-Uruguay. The outcome measures were overall and relapse free survival. Results The absolute monocyte count, analyzed as a dichotomized variable predicted progression-free and overall survival in low risk patients according to the R-IPI score. Worse outcomes were observed in those with high monocyte count al diagnosis. Conclusions Absolute monocyte count could help in the identification of high-risk patients otherwise expected to have a good prognosis according to traditional scores.


Subject(s)
Leukocyte Count , Lymphoma, Large B-Cell, Diffuse/blood , Monocytes , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Female , Humans , Immunotherapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Young Adult
3.
Br J Haematol ; 182(4): 521-525, 2018 08.
Article in English | MEDLINE | ID: mdl-29953583

ABSTRACT

Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that did or did not express LPL mRNA. Our results show that LPL protein is differently located in CLL cells depending on whether it is incorporated from the extracellular medium in mutated CLL or generated de novo by leukaemic cells of unmutated patients. The specific quantification of endogenous LPL protein correlates with mRNA expression levels and mutational IGHV status, suggesting LPL protein as a possible reliable prognostic marker in CLL.


Subject(s)
Biomarkers, Tumor/biosynthesis , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Leukemic , Leukemia, Lymphocytic, Chronic, B-Cell/enzymology , Lipoprotein Lipase/biosynthesis , Neoplasm Proteins/biosynthesis , Aged , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Prognosis , RNA, Messenger/biosynthesis , RNA, Neoplasm/biosynthesis
4.
Rev Med Chil ; 141(7): 844-52, 2013 Jul.
Article in Spanish | MEDLINE | ID: mdl-24356732

ABSTRACT

BACKGROUND: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). AIM: To analyze the benefit of Rituxi-mab in overall survival (OS) of patients with NHL. MATERIAL AND METHODS: Review of medical record of 230 adult patients with a first episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. RESULTS: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). CONCLUSIONS: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Humans , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Neoplasm Staging , Prednisone/administration & dosage , Prognosis , Rituximab , Treatment Outcome , Vincristine/administration & dosage , Young Adult
5.
Cancer Cell ; 41(9): 1637-1649.e11, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37652007

ABSTRACT

A high percentage of patients with brain metastases frequently develop neurocognitive symptoms; however, understanding how brain metastasis co-opts the function of neuronal circuits beyond a tumor mass effect remains unknown. We report a comprehensive multidimensional modeling of brain functional analyses in the context of brain metastasis. By testing different preclinical models of brain metastasis from various primary sources and oncogenic profiles, we dissociated the heterogeneous impact on local field potential oscillatory activity from cortical and hippocampal areas that we detected from the homogeneous inter-model tumor size or glial response. In contrast, we report a potential underlying molecular program responsible for impairing neuronal crosstalk by scoring the transcriptomic and mutational profiles in a model-specific manner. Additionally, measurement of various brain activity readouts matched with machine learning strategies confirmed model-specific alterations that could help predict the presence and subtype of metastasis.


Subject(s)
Brain Neoplasms , Humans , Brain Neoplasms/genetics , Brain , Gene Expression Profiling , Machine Learning , Mutation
6.
Cells ; 11(3)2022 01 20.
Article in English | MEDLINE | ID: mdl-35159141

ABSTRACT

Parkinson's disease (PD) is the second-most common neurodegenerative disorder, whose physiopathology is still unclear. Moreover, there is an urgent need to discover new biomarkers and therapeutic targets to facilitate its diagnosis and treatment. Previous studies performed in PD models and samples from PD patients already demonstrated that metabolic alterations are associated with this disease. In this context, the aim of this study is to provide a better understanding of metabolic disturbances underlying PD pathogenesis. To achieve this goal, we used a Drosophila PD model based on inactivation of the DJ-1ß gene (ortholog of human DJ-1). Metabolomic analyses were performed in 1-day-old and 15-day-old DJ-1ß mutants and control flies using 1H nuclear magnetic resonance spectroscopy, combined with expression and enzymatic activity assays of proteins implicated in altered pathways. Our results showed that the PD model flies exhibited protein metabolism alterations, a shift fromthe tricarboxylic acid cycle to glycolytic pathway to obtain ATP, together with an increase in the expression of some urea cycle enzymes. Thus, these metabolic changes could contribute to PD pathogenesis and might constitute possible therapeutic targets and/or biomarkers for this disease.


Subject(s)
Drosophila Proteins , Parkinson Disease , Protein Deglycase DJ-1 , Animals , Disease Models, Animal , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Humans , Nerve Tissue Proteins/metabolism , Oxidative Stress/physiology , Parkinson Disease/metabolism , Protein Deglycase DJ-1/genetics , Protein Deglycase DJ-1/metabolism
7.
Cancers (Basel) ; 14(7)2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35406446

ABSTRACT

Clinical and molecular heterogeneity are hallmarks of chronic lymphocytic leukemia (CLL), a neoplasm characterized by accumulation of mature and clonal long-lived CD5 + B-lymphocytes. Mutational status of the IgHV gene of leukemic clones is a powerful prognostic tool in CLL, and it is well established that unmutated CLLs (U-CLLs) have worse evolution than mutated cases. Nevertheless, progression and treatment requirement of patients can evolve independently from the mutational status. Microenvironment signaling or epigenetic changes partially explain this different behavior. Thus, we think that detailed characterization of the miRNAs landscape from patients with different clinical evolution could facilitate the understanding of this heterogeneity. Since miRNAs are key players in leukemia pathogenesis and evolution, we aim to better characterize different CLL behaviors by comparing the miRNome of clinically progressive U-CLLs vs. stable U-CLLs. Our data show up-regulation of miR-26b-5p, miR-106b-5p, and miR-142-5p in progressive cases and indicate a key role for miR-26b-5p during CLL progression. Specifically, up-regulation of miR-26b-5p in CLL cells blocks TGF-ß/SMAD pathway by down-modulation of SMAD-4, resulting in lower expression of p21-Cip1 kinase inhibitor and higher expression of c-Myc oncogene. This work describes a new molecular mechanism linking CLL progression with TGF-ß modulation and proposes an alternative strategy to explore in CLL therapy.

8.
PLoS One ; 14(3): e0212819, 2019.
Article in English | MEDLINE | ID: mdl-30845148

ABSTRACT

Alginate is considered an exceptional biomaterial due to its hydrophilicity, biocompatibility, biodegradability, nontoxicity and low-cost in comparison with other biopolymers. We have recently demonstrated that the incorporation of 1% graphene oxide (GO) into alginate films crosslinked with Ca2+ cations provides antibacterial activity against Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, and no cytotoxicity for human keratinocyte HaCaT cells. However, many other reports in literature have shown controversial results about the toxicity of GO demanding further investigation. Furthermore, the synergic effect of GO with other divalent cations with intrinsic antibacterial and cytotoxic activity such as Zn2+ has not been explored yet. Thus, here, two commercially available sodium alginates were characterised and utilized in the synthesis of zinc alginate films with GO following the same chemical route reported for the calcium alginate/GO composites. The results of this study showed that zinc release, water sorption/diffusion and wettability depended significantly on the type of alginate utilized. Furthermore, Zn2+ and GO produced alginate films with increased water diffusion, wettability and opacity. However, neither the combination of GO with Zn2+ nor the use of different types of sodium alginates modified the antibacterial activity and cytotoxicity of the zinc alginates against these Gram-positive pathogens and human cells respectively.


Subject(s)
Alginates/pharmacology , Anti-Bacterial Agents/pharmacology , Biocompatible Materials/pharmacology , Graphite/pharmacology , Zinc/pharmacology , Anti-Bacterial Agents/chemistry , Biocompatible Materials/chemistry , Cell Line , Humans , Keratinocytes , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , Toxicity Tests , Wettability
10.
Leuk Lymphoma ; 57(6): 1363-6, 2016.
Article in English | MEDLINE | ID: mdl-26374395

ABSTRACT

The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6-12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL.


Subject(s)
Lymphoma, Non-Hodgkin/diagnosis , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Radiation Dosage , Radiation Effects , Sensitivity and Specificity , Tomography, X-Ray Computed/adverse effects , Tomography, X-Ray Computed/standards , Young Adult
11.
Rev. méd. Chile ; 147(12): 1553-1560, dic. 2019. tab, graf
Article in English | LILACS | ID: biblio-1094189

ABSTRACT

ABSTRACT Background Prognosis of patients with Diffuse Large B Cell Lymphoma (DLBCL) is highly variable, and despite the use of modern immunochemotherapy regimens, almost 50% of patients will eventually relapse. Standard risk models, like the International Prognostic Index or the Revised International Prognostic Index (R_IPI) incorporate patient and tumor characteristics but do not consider variables related to host adaptive immunity which have been shown to be of significant prognostic value in non-Hodgkin lymphomas. Aim To analyze the prognostic significance of the absolute monocyte count at diagnosis in diffuse large-B-cell lymphoma in a retrospective setting. Material and Methods We reviewed data of 171 patients with DLBCL treated with Rituximab-based immunochemotherapy at two reference public Hospitals in Montevideo-Uruguay. The outcome measures were overall and relapse free survival. Results The absolute monocyte count, analyzed as a dichotomized variable predicted progression-free and overall survival in low risk patients according to the R-IPI score. Worse outcomes were observed in those with high monocyte count al diagnosis. Conclusions Absolute monocyte count could help in the identification of high-risk patients otherwise expected to have a good prognosis according to traditional scores.


Antecedentes El pronóstico de pacientes con Linfoma Difuso de Células B Grandes (DLBCL) es muy variable y el 50% de los pacientes recae a pesar de uso de regímenes actualizados de inmuno-quimioterapia. Los modelos pronósticos clásicos como el International Prognostic Index o el Revised International Prognostic Index (R_IPI) incorporan características del paciente o del tumor pero no incorporan variables asociadas a la inmunidad adaptativa que tienen valor en linfomas no Hodgkin. Objetivo Analizar retrospectivamente el valor pronóstico del recuento absoluto de monocitos al momento del diagnóstico en pacientes con DLBCL. Material y Métodos Se revisó información de 171 pacientes con DLBCL tratados con inmuno-quimioterapia basada en rituximab en dos centros de referencia públicos de Montevideo, Uruguay. Las variables de resultado fueron la sobrevida global y libre de recaída. Resultados El recuento absoluto de monocitos, tratado como una variable dicotómica, predijo la sobrevida libre de recaída en pacientes de bajo riesgo, de acuerdo al puntaje R-IPI. El pronóstico fue peor en pacientes con altos recuentos al momento del diagnóstico. Conclusiones El recuento absoluto de monocitos puede identificar pacientes de alto riesgo, clasificados como de bajo riesgo por los puntajes tradicionales.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Monocytes , Lymphoma, Large B-Cell, Diffuse/blood , Leukocyte Count , Prognosis , Antineoplastic Combined Chemotherapy Protocols , Retrospective Studies , Lymphoma, Large B-Cell, Diffuse/drug therapy , Immunotherapy
13.
Rev. Urug. med. Interna ; 2(1): 25-31, abr. 2017. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1092309

ABSTRACT

Resumen: El síndrome hemofagocítico es una enfermedad infrecuente y grave caracterizada por un estado de hiperinflamación sistémica con sobreproducción de citocinas. Puede responder a causas genéticas (primario) o desencadenarse por infecciones, fármacos, neoplasias o enfermedades autoinmunes. Existen criterios diagnósticos establecidos. El tratamiento consiste en el bloqueo de la respuesta inflamatoria sistémica, asociado al tratamiento de la causa desencadenante cuando se halla. La mortalidad es alta y usualmente está en relación a la causa que gatilla el fenómeno. Se presenta un caso de sindrome hemofagocítico en paciente infectada por el virus de la inmunodeficiencia humana.


Abstract: Hemophagocytic syndrome is a rare and serious disease characterized by a state of systemic hyperinflammation with overproduction of cytokines. Can respond to genetic causes (primary) or be triggered by infections, drugs, tumors or autoimmune diseases. There are established diagnostic criteria. Treatment consists in blocking the inflammatory response associated with the treatment of the underlying cause when it is. Mortality is high and usually is related to the cause that triggers the phenomenon. We report a case of hemophagocytic syndrome in HIV-infected patient.

14.
Rev. méd. Urug ; 30(1): 30-36, 2014.
Article in Spanish | URUCAN | ID: bcc-4825

ABSTRACT

Introducción: rituximab es un anticuerpo monoclonal que se une específicamente al antígeno CD20 expresado en los linfocitos B. El uso de rituximab en el tratamiento de la trombocitopenia inmune refractaria no se encuentra aprobado en su ficha técnica. Objetivo: describir las características clínicas, la respuesta terapéutica y los aspectos vinculados a la seguridad con el uso de rituximab en los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas y revisar la evidencia sobre el beneficio clínico esperado en este grupo de pacientes. Material y método: se realizó un estudio descriptivo de los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas a quienes se les prescribió rituximab. Se realizó una búsqueda bibliográfica en PubMed sobre el uso de rituximab en este tipo de patología. Resultados: se trataron cuatro pacientes con trombocitopenia inmune refractaria con rituximab. Se obtuvo respuesta en tres de cuatro pacientes. La media de tiempo de respuesta fue 9,25 semanas. La respuesta se ha mantenido en los tres pacientes. No se registraron efectos adversos durante la perfusión de rituximab. La evidencia publicada se limita a estudios observacionales, en adultos, con pocos pacientes, habiendo mostrado respuestas favorables. Conclusiones: existen limitaciones en la evidencia sobre el tratamiento de la trombocitopenia inmune refractaria, pero rituximab constituye una alternativa efectiva. Es indispensable la integración clínica para monitorizar la efectividad y seguridad del uso de anticuerpos monoclonales, especialmente en indicaciones no aprobadas(AU)


Subject(s)
Humans , Thrombocytopenia/drug therapy , Thrombocytopenia/therapy , Bibliography, National , Uruguay
15.
Arch. med. interna (Montevideo) ; 37(1): 1-6, mar. 2015. graf, tab
Article in Spanish | LILACS | ID: lil-754168

ABSTRACT

Introducción: El Trasplante Autólogo de Progenitores Hematopoyéticos forma parte del tratamiento de pacientes con Linfoma No Hodgkin (LNH) agresivos en respuesta parcial y recaída. Objetivos: evaluar las respuestas y sobrevida en los pacientes con LNH agresivos trasplantados en Hospital Británico. Material y Métodos: estudio retrospectivo de pacientes con LNH agresivos que se trasplantaron entre el 1/01/1995 y el 1/07/2013. Total 65 pacientes. Resultados: el 95% logró una Remisión Completa post Auto-TPH y el 5% una Remisión Parcial. Con una mediana de seguimiento de 74 meses (5-219), la mediana de SG no se ha alcanzado. La media estimada es de 145 meses (122-169) con una SG a 5 años de 71% y a 10 años es de 60%. La mediana de SLE no se ha alcanzado, a 5 años es de 60% y a 10 años es de 58%. Conclusiones: el trasplante Autólogo de Progenitores Hematopoyéticos es una herramienta terapéutica útil. Los resultados de nuestro grupo son comparables a los reportados por grupos internacionales con una baja mortalidad relacionada al procedimiento.


Introduction: Autologous Hematopoietic Stem Cell Transplantation is part of the treatment of patients with aggressive lymphomas in partial response or relapsed. Objectives: To evaluate the responses and survival in aggressive NHL patients transplanted in Hospital Británico. Material and Methods: Retrospective study of patients with aggressive NHL that were transplanted into... between 01/01/1995 and 07/01/2013. Total 65 patients. Results: 95% achieved a complete remission after Auto-SCT and 5% partial remission. With a median follow up of 74 months (5-219), the median OS has not been reached. The estimated mean is 145 months (122-169) with a 5-year OS of 71% and 60% at 10 years. The median DFS has not been reached, at 5 years is 60 % and at 10 years is 58 %. Conclusions: Autologous Hematopoietic Stem Cell Transplantation is a useful therapeutic tool. The results of our group are comparable to those reported by international groups with low procedure-related mortality.

16.
Rev Med Chile ; 141: 844-852, 2013.
Article in Spanish | URUCAN | ID: bcc-4765

ABSTRACT

Background: The most common types of non-Hodgkin lymphoma (NHL) arediffuse large B cell (DLBCL) and follicular (FL). Aim: To analyze the benefit of Rituximab in overall survival (OS) of patients with NHL. Material and Methods: Review of medical record of 230 adult patients with a first episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. Results:The overall response (OR) was 64% with 39% complete remissions (CR) inDLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favorof R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85% with 54% CR. With CHOP-like the OR was 59% with 18% CR. The OS at 24 and 36 monthsin patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66% respectively. The progression freesurvival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p =0,043). Conclusions: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL(AU)


Subject(s)
Humans , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Bibliography, National , Uruguay
17.
Rev. méd. Urug ; 29(2): 118-122, 2013. tab
Article in Spanish | URUCAN | ID: bcc-4661

ABSTRACT

La leucemia aguda linfoblástica tiene una incidencia global de 1,7/100.000 habitantes/año y es la enfermedad oncológica más frecuente en la infancia. La presentación con dolores óseos y articulares es frecuente en los adolescentes y niños, con una incidencia reportada de 1/3 de los casos.Se describen tres casos de leucemia aguda linfoblástica diagnosticados en la Cátedra de Hematología del Hospitalde Clínicas con debut bajo forma de artritis. Esta forma conlleva en general un retraso en el diagnóstico debido aun bajo índice de sospecha(AU)


Subject(s)
Humans , Male , Female , Adolescent , Adult , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Arthritis , Bibliography, National , Uruguay
18.
Rev. méd. Urug ; 30(1): 30-6, mar. 2014. tab
Article in Spanish | LILACS | ID: lil-737568

ABSTRACT

Introducción: rituximab es un anticuerpo monoclonal que se une específicamente al antígeno CD20 expresado en los linfocitos B. El uso de rituximab en el tratamiento de la trombocitopenia inmune refractaria no se encuentra aprobado en su ficha técnica. Objetivo: describir las características clínicas, la respuesta terapéutica y los aspectos vinculados a la seguridad con el uso de rituximab en los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas y revisar la evidencia sobre el beneficio clínico esperado en este grupo de pacientes. Material y método: se realizó un estudio descriptivo de los pacientes con trombocitopenia inmune refractaria asistidos en la Cátedra de Hematología del Hospital de Clínicas a quienes se les prescribió rituximab. Se realizó una búsqueda bibliográfica en PubMed sobre el uso de rituximab en este tipo de patología. Resultados: se trataron cuatro pacientes con trombocitopenia inmune refractaria con rituximab. Se obtuvo respuesta en tres de cuatro pacientes. La media de tiempo de respuesta fue 9,25 semanas. La respuesta se ha mantenido en los tres pacientes. No se registraron efectos adversos durante la perfusión de rituximab. La evidencia publicada se limita a estudios observacionales, en adultos, con pocos pacientes, habiendo mostrado respuestas favorables. Conclusiones: existen limitaciones en la evidencia sobre el tratamiento de la trombocitopenia inmune refractaria, pero rituximab constituye una alternativa efectiva. Es indispensable la integración clínica para monitorizar la efectividad y seguridad del uso de anticuerpos monoclonales, especialmente en indicaciones no aprobadas...


Subject(s)
Humans , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Thrombocytopenia/therapy
19.
Br. J. Haematol ; 182(4): [5 p.], 2018.
Article in English | URUCAN | ID: bcc-5210

ABSTRACT

Lipoprotein lipase (LPL) mRNA expression in chronic lymphocytic leukaemia (CLL) is associated with an unmutated immunoglobulin profile and poor clinical outcome. We evaluated the subcellular localization of LPL protein in CLL cells that did or did not express LPL mRNA. Our results show that LPL protein is differently located in CLL cells depending on whether it is incorporated from the extracellular medium in mutated CLL or generated de novo by leukaemic cells of unmutated patients. The specific quantification of endogenous LPL protein correlates with mRNA expression levels and mutational IGHV status, suggesting LPL protein as a possible reliable prognostic marker in CLL (AU)


Subject(s)
Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Flow Cytometry , Prognosis , Bibliography, National , Uruguay
20.
Rev. méd. Chile ; 141(7): 844-852, jul. 2013. ilus
Article in Spanish | LILACS | ID: lil-695765

ABSTRACT

Background: The most common types of non-Hodgkin lymphoma (NHL) are diffuse large B cell (DLBCL) and follicular (FL). Aim: To analyze the benefit ofRituxi-mab in overall survival (OS) of patients with NHL. Material and Methods: Review of medical record of 230 adult patients with afirst episode of NHL admitted between 2002 and 2011. We included 67 patients with DLBCL and 36 patients with FL. Results: The overall response (OR) was 64% with 39% complete remissions (CR) in DLBCL treated with CHOP-like and 100% with 89% CR with R-CHOP. The median OS with CHOP-like was 21 months versus not attained R-CHOP (p = 0.016). There was a statistically significant difference in median event-free survival (EvFS) in favor of R-CHOP: not attained versus 8.3 months for CHOP-like (log rank (p = 0.002)). In FL, the OR in patients treated with R-CHOP or R-CHOP-like was 85%) with 54% CR. With CHOP-like the OR was 59%> with 18% CR. The OS at 24 and 36 months in patients treated with R-CHOP or R-CHOP-like was 83 and 65%. The figures for patients treated with CHOP-like were 80 and 66%> respectively. The progression free survival (PFS) was 21 months with CHOP-like versus not attained with R-QT (p = 0,043). Conclusions: When Rituximab was added to CHOP, there was a higher CR, EvFS and OS in DLBCL and higher CR and PFS in FL.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Neoplasm Staging , Prednisone/administration & dosage , Prognosis , Treatment Outcome , Vincristine/administration & dosage
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