RESUMEN

OBJECTIVE: Patients with epithelial ovarian cancers experience the highest fatality rates among all gynecological malignancies which require development of novel treatment strategies. Tumor cell necrosis was previously reported in a number of cancer cell lines following treatment with a p53-derived anti-cancer peptide called PNC-27. This peptide induces necrosis by transmembrane pore formation with HDM-2 protein that is expressed in the cancer cell membrane. We aimed to extend these studies further by investigating expression of membrane HDM-2 protein in ovarian cancer as it relates to susceptibility to PNC-27. PROCEDURES: Herein, we measured HDM-2 membrane expression in two ovarian cancer cell lines (SKOV-3 and OVCAR-3) and a non-transformed control cell line (HUVEC) by flow cytometric and western blot analysis. Immunofluorescence was used to visualize colocalization of PNC-27 with membrane HDM-2. Treatment effects with PNC-27 and control peptide were assessed using a MTT cell proliferation assay while direct cytotoxicity was measured by lactate dehydrogenase (LDH) release and induction of apoptotic markers; annexin V and caspase-3. RESULTS: HDM-2 protein was highly expressed and frequently detected in the membranes of SKOV-3 and OVCAR-3 cells; a prominent 47.6 kDa HDM-2 plasma membrane isoform was present in both cell lines whereas 25, 29, and 30 kDa isoforms were preferentially expressed in OVCAR-3. Notably, PNC-27 colocalized with HDM-2 in the membranes of both cancer cell lines that resulted in rapid cellular necrosis. In contrast, no PNC-27 colocalization and cytotoxicity was observed with non-transformed HUVEC demonstrating minimal expression of membrane HDM-2. CONCLUSIONS: Our results suggest that HDM-2 is highly expressed in the membranes of these ovarian cancer cell lines and colocalizes with PNC-27. We therefore conclude that the association of PNC-27 with preferentially expressed membrane HDM-2 isoforms results in the proposed model for the formation of transmembrane pores and epithelial ovarian cancer tumor cell necrosis, as previously described in a number of solid tissue and hematologic malignancies.

Asunto(s)

Neoplasias Ováricas/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/farmacología , Anexina A5/análisis , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Epitelial de Ovario/metabolismo , Caspasa 3/análisis , Línea Celular Tumoral , Membrana Celular/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , L-Lactato Deshidrogenasa/análisis , Necrosis/metabolismo , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo

RESUMEN

Extracts of Serjania lethalis A. St.-Hil leaves and stems were tested in order to identify potential agents against Leishmania amazonensis. The hexane fraction (HF) and dichloromethane subfractions (DDF and MDF) showed leishmanicidal effect. The anti-promastigote IC50 values were 10.29 (HF), 11.41 (DDF) and 28.33µg/mL (MDF); whereas those against amastigote were 7.2 (HF), 8.1 (DDF) and 6.5µg/mL (MDF). Among the fractions and subfractions assayed, only HF altered the cell cycle of the parasite, increasing 3-fold the number of cells in the sub-G0/G1 phase. HF also changed the parasite mitochondrial membrane potential (ΔΨm) and the percentage of annexin-V-propidium iodide positive promastigotes. Our evaluations of the IC50 values showed that HF, DDF and MDF decreased NO production in infected macrophages stimulated with IFN-γ and LPS. Moreover, HF increased the production of TNF-α in Leishmania infected macrophages. This paper reports for the first time the leishmanicidal activity of extracts and fractions of Serjania lethalis leaves and also characterizes its leishmanicidal and immunomodulatory properties.

Asunto(s)

Antiprotozoarios/farmacología , Leishmania mexicana/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Magnoliopsida/química , Extractos Vegetales/farmacología , Animales , Anexina A5/análisis , Fase G1/efectos de los fármacos , Hexanos/química , Inmunomodulación , Concentración 50 Inhibidora , Interferón gamma/inmunología , Leishmania mexicana/crecimiento & desarrollo , Leishmania mexicana/fisiología , Lipopolisacáridos/inmunología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/parasitología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Cloruro de Metileno/química , Ratones , Óxido Nítrico/biosíntesis , Extractos Vegetales/química , Hojas de la Planta/química , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis

RESUMEN

The dynamics of regulatory T cells in the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, negatively impacting on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTreg cell number associated to cell precursor exhaustion, partially avoided by glucocorticoid ablation- and IL-2 survival factor depletion. At the same time, tTregs accumulate within the CD4 single-positive compartment, exhibiting an increased Ki-67/Annexin V ratio compared to controls. Moreover, tTregs enhance after the infection the expression of signature markers (CD25, CD62L and GITR) and they also display alterations in the expression of migration-associated molecules (α chains of VLAs and chemokine receptors) such as functional fibronectin-driven migratory disturbance. Taken together, we provide data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is significantly affected. The evident loss of tTreg cell number may compromise the composition of tTreg peripheral pool, and such sustained alteration over time may be partially related to the immune dysregulation observed in the chronic phase of the disease.

Asunto(s)

Enfermedad de Chagas/patología , Linfocitos T Reguladores/inmunología , Timo/patología , Trypanosoma cruzi/inmunología , Animales , Anexina A5/análisis , Atrofia/patología , Modelos Animales de Enfermedad , Humanos , Antígeno Ki-67/análisis , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL

RESUMEN

We explored Group B Streptococcus (GBS)-induced apoptosis in human umbilical vein endothelial cells (HUVEC) and the role of phosphoramidon, a zinc metalloprotease inhibitor, in this process. GBS 90186 strain (serotype V, a blood isolate) and concentrated supernatant (CS) were used to investigate the viability and morphological alterations in HUVEC by Trypan blue uptake, electrophoresis in 2 % agarose gel and scanning electron microscopy assays. Apoptosis before and after phosphoramidon-treatment were verified by flow cytometry using annexin V-FITC labeling. Differences were considered significant when P < 0.05 using unpaired Student's t test. GBS and CS induced HUVEC death by apoptosis (76.5 and 32 %, respectively) with an increasing pro-apoptotic Bax expression and decreasing anti-apoptotic Bcl-2 expression. Caspase-3 was activated during GBS-induced endothelial apoptosis. Phosphoramidon reduced 89.3 and 100 % of GBS and CS cell death by apoptosis, respectively. Some GBS strains may induce cell death by apoptosis with involvement of metalloproteases and signaling through the intrinsic pathway of apoptosis, which may contribute to GBS survival during sepsis of adults and neonates.

Asunto(s)

Apoptosis , Células Endoteliales/microbiología , Células Endoteliales/fisiología , Glicopéptidos/metabolismo , Metaloproteasas/metabolismo , Inhibidores de Proteasas/metabolismo , Streptococcus agalactiae/enzimología , Anexina A5/análisis , Supervivencia Celular , Células Cultivadas , Electroforesis , Humanos , Metaloproteasas/antagonistas & inhibidores , Microscopía Electrónica , Coloración y Etiquetado/métodos , Azul de Tripano/metabolismo

RESUMEN

Macrophages (Mφ) and dendritic cells are the major target cell populations of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. Leishmania promastigotes have been shown to protect Mφ, neutrophils, and dendritic cells from both natural and induced apoptosis. Nevertheless, the effect of the infection with Leishmania amastigotes in the apoptosis of these cell populations has not been established, which results are very important since amastigotes persist in cells for many days and are responsible for sustaining infection in the host. As shown in this study, apoptosis of monocyte-derived dendritic cells (moDC) induced by treatment with camptothecin was downregulated by infection with L. mexicana amastigotes from 42.48 to 36.92% as detected by Annexin-V binding to phosphatidylserine. Also, the infection of moDC with L. mexicana amastigotes diminished the fragmentation of DNA as detected by terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling assay, and changes in cell morphology were analyzed by electron microscopy. The observed antiapoptotic effect was found to be associated with an 80% reduction in the presence of active caspase-3 in infected moDC. The capacity of L. mexicana amastigotes to delay apoptosis induction in the infected moDC may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.

Asunto(s)

Apoptosis , Células Dendríticas/inmunología , Células Dendríticas/parasitología , Leishmania mexicana/inmunología , Animales , Anexina A5/análisis , Electrones , Humanos , Evasión Inmune , Etiquetado Corte-Fin in Situ , Leishmania mexicana/patogenicidad

RESUMEN

The purpose of the present study was to examine the acute effects of resistance training (RT) on CD4⁺ and CD8⁺ T lymphocytes apoptosis (annexin V⁺) and migration (CX3CR1). Twelve subjects performed two RT sessions (3 sets of 9 exercises) with 1 min (Hyper-1) and 3 min (Hyper-3) of rest-interval length between sets and exercises. CD4⁺ and CD8⁺ cells count displayed no change following Hyper-1 and Hyper-3. There was an increase in the percentage of CD4⁺ positive for annexin V⁺ and CX3CR1⁺ immediately after and 24 h post Hyper-1. Percentage of CD4⁺ positive for annexin V⁺ increased 2 and 24 h post Hyper-3, and decreased after CXCR1⁺ for the same time-points. There was an increase in CD8⁺ positive for annexin V⁺ and CX3CR1⁺ immediately after, 2 and 24 h post Hyper-1 and Hyper-3, while no differences were found between Hyper-1 and Hyper-3. Acute RT increase the apoptosis and migration of CD4⁺ and CD8⁺ lymphocytes even 24h after exercise, with minimal effects of rest-interval length.

Asunto(s)

Apoptosis , Linfocitos T CD4-Positivos/fisiología , Linfocitos T CD8-positivos/fisiología , Movimiento Celular , Entrenamiento de Fuerza , Anexina A5/análisis , Anexina A5/inmunología , Antígenos de Superficie , Biomarcadores/análisis , Relación CD4-CD8 , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/inmunología , Receptor 1 de Quimiocinas CX3C , Femenino , Humanos , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Receptores de Quimiocina/análisis , Adulto Joven

RESUMEN

INTRODUCTION: Honey is a common household product with many medicinal uses described in traditional medicine. Only recently has its antioxidant properties and preventive effects against disease been highlighted. Chrysin is a natural flavone commonly found in honey that has been shown to be an antioxidant agent. In this study, we investigated the antiproliferative and apoptotic effects of honey and chrysin on cultured human prostate cancer cells. METHODS: Cells were cultured in RPMI medium and treated with different concentrations of honey and chrysin for three consecutive days. Cell viability was quantitated by the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The percentage of apoptotic cells was determined by flow cytometry using Annexin V-fluorescein isothiocyanate. RESULTS: The MTT assay revealed that both compounds had an antiproliferative effect on PC-3 cells in a dose- and time-dependent manner. The IC50 values for honey and chrysin against PC-3 cells were 2.5% and 24.5% after 48 h and 1.8% and 8.5% after 72 h, respectively. Chrysin induced apoptosis in PC-3 cells, as determined by flow cytometry. CONCLUSION: Our results suggest that honey has anti-proliferative effects on prostate cancer cells and the effects are mainly due to chrysin. Therefore, chrysin may be a potential compound for both cancer prevention and treatment. Further in vivo investigation is needed to support the use of chrysin in cancer therapy.

Asunto(s)

Apiterapia/métodos , Carcinoma/prevención & control , Flavonoides/farmacología , Neoplasias de la Próstata/prevención & control , Análisis de Varianza , Anexina A5/análisis , Antioxidantes/análisis , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Flavonoides/análisis , Citometría de Flujo , Humanos , Masculino , Factores de Tiempo

RESUMEN

The susceptibility of Trypanosoma cruzi epimastigotes to lysis by normal or immune sera in a complement-dependent reaction has been reported. Mouse immune sera depleted complement-induced damage in epimastigotes characterized by morphological changes and death. The purpose of this work was to study the mechanism of death in epimastigotes exposed to decomplemented mouse immune serum. Epimastigotes were maintained in RPMI medium. Immune sera were prepared in mice by immunization with whole crude epimastigote extracts. Viable epimastigotes were incubated with decomplemented normal or immune sera at 37 degrees C. By electron microscopy, agglutinated parasites showed characteristic patterns of membrane fusion between two or more parasites; this fusion also produced interdigitation of the subpellicular microtubules. Apoptosis was determined by flow cytometry using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and annexin V assays. Nuclear features were examined by 4'-,6-diamidino-2'-phenylindole diHCI cytochemistry that demonstrated apoptotic nuclear condensation. Caspase activity was also measured. TUNEL results showed that parasites incubated with decomplemented immune sera took up 26% of specific fluorescence as compared to 1.3% in parasites incubated with decomplemented normal sera. The Annexin-V-Fluos staining kit revealed that epimastigotes incubated with decomplemented immune sera exposed phosphatidylserine on the external leaflet of the plasma membrane. The incubation of parasites with immune sera showed caspase 3 activity. We conclude that specific antibodies are able to induce agglutination and apoptosis in epimastigotes, although the pathway is not elucidated.

Asunto(s)

Anticuerpos Antiprotozoarios/inmunología , Apoptosis , Proteínas del Sistema Complemento/inmunología , Trypanosoma cruzi/inmunología , Animales , Anexina A5/análisis , Caspasa 3/análisis , Femenino , Etiquetado Corte-Fin in Situ , Ratones , Viabilidad Microbiana , Microscopía Electrónica , Trypanosoma cruzi/química , Trypanosoma cruzi/ultraestructura

RESUMEN

OBJECTIVE: To investigate the presence of caspase-3 and Bcl-2 concentration in human endometrial tissue throughout the menstrual cycle, and study the effect of nitric oxide (NO) on cell proliferation and apoptosis during culture. DESIGN: Expression of caspase-3 and Bcl-2 concentration in endometrial explants, and examination of L-arginine (L-Arg) effect on epithelial and stromal cell proliferation and apoptosis in vitro. SETTING: Prospective study.Twenty-seven eumenorrheic women (37 +/- 1.2 years). INTERVENTION(S): Endometrial samples were obtained with Pipelle suction curette from the corpus of the uterus. MAIN OUTCOME MEASURE(S): Apoptosis (annexin V-FITC binding), Bcl-2 concentration (ELISA), caspase-3 (immunohistochemistry), cell proliferation (spectrophotometric assay), and gene expression (RT-PCR). RESULT(S): Caspase-3 was detected by immunoassay in epithelial tissue throughout the menstrual cycle and in stroma during secretory phase. The Bcl-2 concentration was similar in endometrial homogenates obtained throughout the menstrual cycle, but L-Arg decreased Bcl-2 only in endometrium from the proliferative phase. In epithelial cells, NO increased apoptosis by 2.1 +/- 0.2-fold, augmented mRNA expression of Bax, and reduced expression of Bcl-2 compared with basal cultures. In stromal cells, NO increased cell proliferation in a dose-dependent manner, an effect that was blocked by a NO synthase inhibitor. CONCLUSION(S): These data indicate that NO has a differential regulatory function on endometrial cell survival, as indicated by the results on stromal cell proliferation and epithelial cell apoptosis during culture, which suggests paracrine interactions between both cell types.

Asunto(s)

Endometrio/citología , Ciclo Menstrual/fisiología , Óxido Nítrico/fisiología , Adulto , Anexina A5/análisis , Anexina A5/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Caspasa 3 , Caspasas/metabolismo , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endometrio/efectos de los fármacos , Endometrio/fisiología , Inhibidores Enzimáticos/farmacología , Células Epiteliales/citología , Células Epiteliales/metabolismo , Femenino , Humanos , Técnicas In Vitro , Óxido Nítrico/farmacología , Proteínas Proto-Oncogénicas/efectos de los fármacos , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2 , omega-N-Metilarginina/farmacología

RESUMEN

BACKGROUND: PBSC transplant provides 10 times more T cells than BMT However, the incidence and severity of acute GvHD is similar among recipients of both types of transplants. Studies in mouse models suggest that the similar clinical outcome in BMT and PBSCT is due to differences in the lymphokine profiles. METHODS: PBMC, PBMC from G-CSF mobilized donors (G-PBMC)and BM mononuclear cells (BM-MC) were analyzed by flow cytometry and ELISA to detect gamma-IFN and IL-4 production. Hematoxylin and eosin staining was used to identify morphology and annexin/propidium-iodide was used for apoptosis assays. RESULTS: We show decreased production of gamma-interferon (85%) and IL-4 (60%) in G-PBMC when compared with either PBMC or BM-MCT cells on ex vivo assays. Surprisingly, 85% of fresh G-PBMC is composed of low-density granulocytes (LDG), which undergo apoptosis after 48 h in culture. At this same time, gamma-IFN production from G-PBMC T cell was reverted. In vitro, G-CSF converts granulocytes into LDGs, able to inhibit T-cell function by H2O2 production, and not through immune-deviation towards a Th2-type phenotype. DISCUSSION: We show that the estimated numbers of Th1 and Th2 cells infused in BMT and PBSCT do not differ significantly. These findings are discussed with reference to the relatively low incidence of acute GvHD in PBSCT shown in the literature. We suggest that these results might depend on the high number of granulocytes and progenitors infused. The potential use of granulocytes as immunosupressive short-term therapy is now being investigated by our group using a mouse experimental model.

Asunto(s)

Granulocitos/fisiología , Trasplante de Células Madre de Sangre Periférica , Linfocitos T/fisiología , Acetato de Tetradecanoilforbol/análogos & derivados , Anexina A5/análisis , Antígenos CD/análisis , Apoptosis/fisiología , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/fisiología , Trasplante de Médula Ósea , Complejo CD3/análisis , Catalasa/farmacología , Recuento de Células , Citometría de Flujo , Factor Estimulante de Colonias de Granulocitos/farmacología , Granulocitos/citología , Granulocitos/efectos de los fármacos , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Humanos , Peróxido de Hidrógeno/metabolismo , Interferón gamma/análisis , Interleucina-4/análisis , Ionomicina/farmacología , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/fisiología , Leucosialina , Prueba de Cultivo Mixto de Linfocitos , Activación Neutrófila/efectos de los fármacos , Activación Neutrófila/fisiología , Sialoglicoproteínas/análisis , Linfocitos T/química , Linfocitos T/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo

RESUMEN

BACKGROUND: Atopic dermatitis is an inflammatory dysfunction in whose physiopathology the lymphocytes T play an important role in the regulation of the inflammatory process. OBJECTIVE: To determine and to characterize the role of apoptosis of lymphocytes in patients with moderate to severe atopic dermatitis before and after treatment with transfer factor. MATERIAL AND METHODS: Fifteen patients with moderate to severe atopic dermatitis in a range of age from 5 to 45 were included in the study. Fifteen healthy subjects were taken as a control group. In all subjects it was determined the apoptosis of the lymphocytes by means of annexin and TUNEL techniques, as well as the expression of CD95 cells. The 15 patients with atopic dermatitis received treatment with transfer factor in stepped dose as follows: 1 U/day/5 doses, 1 U/week/3 doses, 1 U/15 days/2 doses, 1 U/30 days, until completing three months. At the end of this period new determinations were done to measure apoptosis of lymphocytes and PMN. At the beginning and at the end assessments of the severity in relation to the scale SCORAD were made. RESULTS: By means of both techniques no significant difference was found in the percentage of apoptotic lymphocytes between patients and control subjects. Differences of the expression of CD95 between patients and control subjects before and after treatment were not significant. There was a significant difference (p < 0.01) of severity from the beginning to the end of treatment with transfer factor in patients with atopic dermatitis. CONCLUSION: No significant differences of apoptosis of lymphocytes were found in patients with atopic dermatitis who received treatment and control subjects, neither before not after the treatment with transfer factor. It was verified the decrease in the severity of the symptoms related to the treatment with transfer factor.

Asunto(s)

Apoptosis , Dermatitis Atópica/terapia , Linfocitos T/patología , Factor de Transferencia/uso terapéutico , Adolescente , Adulto , Anexina A5/análisis , Niño , Preescolar , Dermatitis Atópica/patología , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Masculino , Neutrófilos/patología , Rinitis Alérgica Estacional/patología , Rinitis Alérgica Estacional/terapia , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Receptor fas/análisis

RESUMEN

Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the susceptibility to apoptosis.

Asunto(s)

Apoptosis , Leucemia Linfocítica Crónica de Células B/patología , Linfocitos/patología , Anciano , Anciano de 80 o más Años , Anexina A5/análisis , Linfocitos T CD8-positivos/patología , Ciclo Celular , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/inmunología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Región Organizadora del Nucléolo