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1.
Transplant Proc ; 49(2): 373-377, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28219601

RESUMO

Syndrome of inappropriate anti-diuretic hormone (SIADH) has been reported to be associated with systemic Strongyloides stercoralis. Here, we report a case of a stem cell transplant (SCT) recipient who developed severe SIADH secondary to systemic S Stercoralis. The SIADH resolved quickly after treating the systemic S Stercoralis with ivermectin. A systematic review of the literature was performed by PubMed, Scopus, and Cochrane database search. Only eight cases of S Stercoralis in allogeneic SCT recipients have been previously reported. To our knowledge, ours is the first reported case of SIADH secondary to S Stercoralis infection in an allogeneic SCT recipient. Prior to transplantation, even if asymptomatic, patients from endemic regions should be screened with strongyloides immunoglobulin (Ig)G serology. Pretransplantation eosinophilia should be evaluated by screening multiple stool samples for ova and parasites. Transplant candidates with positive serology or stool tests can be treated pretransplantation to eradicate infection. Patients at risk for S Stercoralis who develop nonspecific gastrointestinal complaints, rash, pulmonary infiltrates, or gram-negative bacteremia or meningitis may have S Stercoralis hyperinfection syndrome. Our case indicates that the development of SIADH may be an additional clue to this diagnosis. Appropriate diagnostic studies, including repeat stool and other body fluid sampling, should be expedited and ivermectin therapy initiated rapidly to prevent significant morbidity and mortality.


Assuntos
Duodenopatias/parasitologia , Síndrome de Secreção Inadequada de HAD/parasitologia , Infecções Oportunistas/complicações , Transplante de Células-Tronco , Strongyloides stercoralis , Estrongiloidíase/complicações , Idoso , Animais , Antinematódeos/efeitos adversos , Antinematódeos/uso terapêutico , Duodenopatias/tratamento farmacológico , Eosinofilia/parasitologia , Humanos , Imunoglobulina G/sangue , Ivermectina/uso terapêutico , Masculino , Infecções Oportunistas/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/parasitologia , Transplante Homólogo
2.
Leukemia ; 31(3): 697-704, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27654852

RESUMO

PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.


Assuntos
Vacinas Anticâncer/imunologia , Antígeno HLA-A2/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Peptídeos/imunologia , Biomarcadores , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Epitopos de Linfócito T/imunologia , Feminino , Antígeno HLA-A2/química , Humanos , Memória Imunológica , Imunofenotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Análise de Sobrevida , Especificidade do Receptor de Antígeno de Linfócitos T , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do Tratamento , Vacinação
3.
Bone Marrow Transplant ; 43(9): 685-92, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19011667

RESUMO

Lymphocyte and platelet recovery may influence outcomes of allo-SCT for treatment of AML. It is not clear, however, if this impact is independent of patient and transplant characteristics. To investigate this question, we evaluated the influence of pre- or post transplant factors on day +30 absolute lymphocyte count (ALC) and the speed of platelet engraftment. We studied 106 AML patients treated with fludarabine and melphalan reduced-intensity conditioning and allo-SCT. Twenty nine percent of patients were in CR at the initiation of the conditioning, 39% had active disease with circulating blasts and 32% had active disease without circulating blasts. The graft source was peripheral blood from a matched sibling donor in 55% and BM from a matched unrelated donor in 45%. Our data showed that the presence of circulating blasts before transplantation is significantly correlated with low post-SCT day +30 ALC and slow platelet engraftment. This finding suggests that the impact of early ALC and platelet recovery on transplant outcome may not be independent of disease status at transplantation.


Assuntos
Hematopoese , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Células Neoplásicas Circulantes/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Plaquetas/fisiologia , Feminino , Sobrevivência de Enxerto , Humanos , Cinética , Linfócitos/fisiologia , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Carga Tumoral , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
4.
Bone Marrow Transplant ; 41(1): 63-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17934530

RESUMO

Post transplantation constrictive bronchiolitis (PTCB) is the most common pulmonary complication among long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT). It is a late manifestation of GVHD. Its treatment with high-dose systemic corticosteroids and other immunosuppressive regimens is associated with multiple side effects. Topical corticosteroids are used for the treatment of other manifestations of GVHD to minimize these side effects. We conducted a retrospective analysis of a series of adult patients to evaluate the efficacy of high-dose inhaled corticosteroids in the treatment of PTCB. Seventeen patients with new-onset airflow obstruction were diagnosed with PTCB. Their forced expiratory volume in 1 s (FEV1) declined from a median of 84% (range, 56-119) before HSCT to 53% (26-82) after HSCT. All patients received inhaled fluticasone propionate 500-940 microg two times daily. Symptoms of airway obstruction improved and FEV1 stabilized 3-6 months after treatment. We conclude that high-dose inhaled corticosteroids may be effective in the treatment of PTCB and propose a plausible mechanism of its action. A prospective evaluation of its efficacy is warranted.


Assuntos
Corticosteroides/administração & dosagem , Bronquiolite/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Administração por Inalação , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Bone Marrow Transplant ; 40(2): 125-36, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17530009

RESUMO

We analyzed the clinical factors associated with late cytomegalovirus (CMV) reactivation in a group of 269 consecutive recipients of allogeneic stem cell transplant (SCT) for hematological malignancies. Eighty-four subjects (31%) experienced late CMV reactivation, including 64 with prior early reactivation and 20 with isolated late reactivation. Multivariate analyses were conducted in patients with early CMV reactivation to identify factors associated with late recurrence. Important risk factors included lymphoid diagnosis, occurrence of graft-versus-host disease (GVHD), greater number of episodes of early reactivation, persistent day 100 lymphopenia and the use of a CMV-seronegative donor graft. We combined these risk factors in a predictive model to identify those at relatively low, intermediate and high risk. The low-risk group (15% cumulative incidence, CI) encompassed patients without early CMV reactivation, and subjects transplanted for a myeloid malignancy from a matched-related (MR) donor without subsequent acute GVHD. The high-risk patients (73% CI) met all of the following criteria: (1) received an MR graft but developed GVHD, or received a non-MR graft irrespective of GVHD; (2) had more than two episodes of early reactivation; and (3) received a CMV-seronegative graft and/or remained persistently lymphopenic at day 100 after SCT. The remaining patients had an intermediate incidence of 32%.


Assuntos
Infecções por Citomegalovirus/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/imunologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Fatores de Risco , Linfócitos T/imunologia , Fatores de Tempo , Transplante Homólogo
6.
Cytotherapy ; 8(2): 95-104, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16698683

RESUMO

BACKGROUND: The generation of AML-specific T-lymphocyte responses by leukemia-derived DC has been documented by multiple investigators and is being pursued clinically. An obstacle to widespread use of this strategy is that it has not been possible to generate leukemic DC from all patients, and an alternative approach is needed if the majority of leukemia patients are to receive therapeutic vaccination in conjunction with other treatment protocols. METHODS: In the present study, we generated DC from CD14-selected monocytes isolated from healthy donor PBPC and loaded them with a total cell lysate from AML patient blasts. RESULTS: Immature in vitro-derived DC exhibited robust phagocytic activity, and mature DC demonstrated high expression of CD80, CD83, CD86 and the chemokine receptor CCR7, important for DC migration to local lymph nodes. Mature, Ag-loaded DC were used as APC for leukemia-specific cytotoxic T-lymphocyte (CTL) induction and demonstrated cytotoxic activity against leukemic targets. CTL lysis was Ag-specific, with killing of both allogeneic leukemic blasts and autologous DC loaded with allogeneic AML lysate. HLA-matched controls were not lysed in our system. DISCUSSION: These data support further research into the use of this strategy as an alternative approach to leukemia-derived DC vaccination.


Assuntos
Células Dendríticas/imunologia , Leucemia Mieloide/imunologia , Células Th1/imunologia , Doença Aguda , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/fisiologia , Antígenos CD/imunologia , Células Cultivadas , Células Dendríticas/fisiologia , Humanos , Imunofenotipagem , Interferon gama/biossíntese , Interleucina-1/imunologia , Interleucina-6/imunologia , Leucemia/imunologia , Leucemia/metabolismo , Leucemia/patologia , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Modelos Lineares , Receptores de Lipopolissacarídeos/imunologia , Ativação Linfocitária/imunologia , Monócitos/citologia , Monócitos/imunologia , Fagocitose/imunologia , Receptores de Quimiocinas/imunologia , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Células Th1/citologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/imunologia
7.
Cytotherapy ; 4(4): 333-42, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12396833

RESUMO

The thymus is the primary site of T-cell production early in life, and has now been shown to continue to function in both healthy and immunocompromised individuals late into life. Positive and negative selection occurring in the thymus are two of the most important processes that govern the development and specificity of peripheral T cells, including their restriction to self HLA and their ability to respond in an alloreactive manner. In the chimeric state that follows successful allogeneic stem-cell transplants, the specificity of alloreactive cells may be governed by either host- or recipient-derived cellular elements, as well as maturing lymphoid cells, which are, in turn, derived from donor stem cells or host cells surviving transplant conditioning. The ability to measure recent thymic emigrants via the detection of T-cell receptor excision circles has facilitated studies of thymic function in immunodeficient individuals, including HIV-1 infected subjects and recipients of autologous or allogeneic stem-cell transplant (SCT). These studies have now demonstrated that thymic function is likely to play a beneficial role in immune reconstitution in these settings, but have yet to clearly demonstrate what clinical variables are the most important determinants of thymic persistence. It is also not yet clear how much the degree of thymic function following allogeneic SCT influences the alloreactive T-cell repertoire, although studies in animal models and early clinical studies suggest that GvHD results in thymic injury and dysfunction. Future studies will further clarify how thymic function shapes the repertoire of T cells that mediate alloreactivity, as well as protective pathogen-specific immune responses, following SCT. Finally, these studies will also demonstrate whether endogenous mediators of thymic function could be selectively applied to regulate post-SCT thymic function and alloreactivity.


Assuntos
Transplante de Células-Tronco , Linfócitos T/fisiologia , Timo/fisiologia , Animais , Homeostase , Humanos , Imunofenotipagem , Estrutura Molecular , Receptores de Antígenos de Linfócitos T/metabolismo , Timo/citologia , Transplante Homólogo
8.
J Infect Dis ; 183(8): 1285-9, 2001 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11262214

RESUMO

Clinical histories are reported for 2 patients treated with highly active antiretroviral therapy (HAART) who experienced multiple relapses of cytomegalovirus (CMV) retinitis, despite suppression of human immunodeficiency virus type 1 (HIV-1) viremia and improvement in CD4+ T cell counts (to >400 cells/microL). CMV-specific CD4+ T cell immune reconstitution was measured directly, using cytokine flow cytometry, which revealed persistent deficits in CMV-specific CD4+ T cell responses in both patients. CMV-specific T cells constituted 0.14% and 0.05% of the total CD4+ T cell count in these patients, which is significantly lower than the percentages for 34 control subjects (0.6%-46%; CD4+ T cell count range, 7-1039 cells/microL; P=.019). Deficits in pathogen-specific immune responses may persist in some individuals, despite suppression of HIV-1 replication and substantial increases in circulating CD4+ T cells after HAART, and such deficits may be associated with significant morbidity from opportunistic infections.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Linfócitos T CD4-Positivos/imunologia , Retinite por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Infecções por HIV/imunologia , HIV-1 , Infecções Oportunistas Relacionadas com a AIDS/virologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/virologia , Citocinas/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Valores de Referência
10.
Virology ; 279(2): 459-70, 2001 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-11162802

RESUMO

Data from murine models of chronic viral infection suggest that CD4+ T-cell responses to viral pathogens are important in sustaining the number and/or function of CD8+ cytotoxic T-cell (CTL) effectors. In this study, we used cytokine flow cytometry (CFC), staining with HLA-A*0201-peptide tetramers, and peptide stimulation with epitopic peptides to study functional CD4+ and CD8+ T-cell responses to cytomegalovirus (CMV) in human subjects coinfected with CMV and the human immunodeficiency virus, type 1 (HIV-1). We show that strong CD4+ and CD8+ T-cell responses to CMV antigens are sustained over time in HIV-1-infected individuals. Those who maintain a strong CD4+ T-cell response to CMV are also likely to maintain higher frequencies of CD8+ T cells capable of binding to HLA-A*0201-CMV pp65 (A2-pp65) tetramers as well as responses to pp65 peptide stimulation with effector cytokine production. These data support the hypothesis that declines in frequencies of CD4+ T-cell responses to CMV are associated with an inability to sustain high levels of CMV-specific CD8+ T-cell responses in HIV-1-infected subjects. These declines may precede the onset of CMV-associated end organ disease.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Infecções por HIV/imunologia , HIV-1 , Anticorpos Antivirais/sangue , Antígenos Virais/farmacologia , Doença Crônica , Citomegalovirus/imunologia , Infecções por Citomegalovirus/complicações , Feminino , Citometria de Fluxo , Infecções por HIV/complicações , Infecções por HIV/virologia , Antígenos HLA-A/análise , Humanos , Contagem de Linfócitos , Masculino , Fosfoproteínas/farmacologia , Estudos Prospectivos , Proteínas da Matriz Viral/farmacologia
11.
J Exp Med ; 190(4): 479-86, 1999 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-10449519

RESUMO

The understanding of human thymic function and evaluation of its contribution to T cell homeostasis are matters of great importance. Here we report the development of a novel assay to quantitate the frequency and diversity of recent thymic emigrants (RTEs) in the peripheral blood of humans. Such cells were defined by the presence of T cell receptor (TCR) rearrangement deletion circles (DCs), episomal byproducts of TCR-beta V(D)J rearrangement. DCs were detected in T cells in the thymus, cord blood, and adult peripheral blood. In the peripheral blood of adults aged 22 to 76 years, their frequency was highest in the CD4(+)CD45RA(+) CD62L(+) subpopulation of naive T cells. TCR DCs were also observed in other subpopulations of peripheral blood T cells, including those with the CD4(+)CD45RO(-)CD62L(+) and CD4(+)CD45RO(+)CD62L(+) phenotypes. RTEs were observed to have more than one Vbeta rearrangement, suggesting that replenishment of the repertoire in the adult is at least oligoclonal. These results demonstrate that the normal adult thymus continues to contribute, even in older individuals, a diverse set of new T cells to the peripheral circulation.


Assuntos
Envelhecimento/imunologia , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Subpopulações de Linfócitos T/imunologia , Timo/imunologia , Adulto , Idoso , Animais , Antígenos CD4 , Sangue Fetal/citologia , Citometria de Fluxo , Humanos , Selectina L , Antígenos Comuns de Leucócito , Camundongos , Pessoa de Meia-Idade , Fenótipo , Deleção de Sequência
12.
Nat Med ; 4(8): 953-6, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9701250

RESUMO

Recent studies of subjects infected with human immunodeficiency virus (HIV-1) have produced conflicting results about the extent of reconstitution possible in the CD4+ lymphocyte repertoire after highly active antiretroviral therapy (HAART). The effect of HAART on the incidence of opportunistic infections will probably depend on reconstitution of antigen-specific CD4+ lymphocyte responses to important pathogens, including cytomegalovirus (CMV), the leading cause of blindness in AIDS. Several studies have demonstrated an important role for CD4+ lymphocytes in controlling CMV replication in vitro and in clinical studies. It is now possible to quantitate antigen-specific CD4+ lymphocyte responses by flow cytometry. Using this method, we studied CMV-specific CD4+ lymphocyte responses in individuals infected with HIV-1 with and without a history of active CMV-associated end organ disease (EOD), and in those with quiescent CMV EOD after ganciclovir therapy and HAART. The presence of active CMV-associated EOD strongly correlated with loss of CMV-specific lymphocyte responses (P = 0.0004). In contrast, patients with no history of CMV-associated EOD and most patients with quiescent EOD after HAART demonstrated strong CMV-specific CD4+ lymphocyte responses. These data indicate that the loss of CMV-specific CD4+ lymphocyte responses in individuals infected with HIV-1 who have active CMV EOD may be restored after ganciclovir therapy and HAART, which provides evidence for functional immune reconstitution to an important pathogen.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/imunologia , Ganciclovir/uso terapêutico , HIV-1 , Contagem de Linfócito CD4/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Células Cultivadas , Estudos de Coortes , Citometria de Fluxo , Humanos , Estudos Longitudinais , Ativação Linfocitária
13.
J Immunol ; 158(2): 544-9, 1997 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-8992966

RESUMO

Infection by HIV-1 has been associated with perturbations in the TCR V beta repertoire, suggesting the involvement of a superantigen. Among the hallmarks of superantigens is the capacity to delete T cells bearing specific TCR V beta families in the developing thymus. To verify the presence of a superantigen in HIV-1, we analyzed the SCID-hu Thy/Liv TCR V beta repertoire within CD4+CD8+, CD4+CD8-, or CD4-CD8+ thymocytes subsets by flow cytometry using a panel of Abs recognizing about 60% of the TCR repertoire following injection of SEB or infection by two different HIV-1 isolates. Seven days following SEB injection, thymocyte subsets bearing TCR V beta 3, V beta 12, V beta 17, and V beta 20, but not V beta 5 or V beta 8 , were deleted relative to mock-injected mice. In contrast, no changes were observed in the TCR V beta repertoire in CD4+CD8+, CD4+CD8-, or CD4-CD8+ thymocyte subsets after infection with HIV-1. The T cell depletion caused by HIV-1 infection is most likely not mediated by an HIV-encoded superantigen.


Assuntos
Deleção Clonal/efeitos dos fármacos , Deleção Clonal/imunologia , Enterotoxinas/farmacologia , HIV-1/patogenicidade , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Staphylococcus aureus/imunologia , Superantígenos/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Animais , Quimera , HIV-1/imunologia , Humanos , Camundongos , Camundongos SCID , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Subpopulações de Linfócitos T/virologia
14.
J Acquir Immune Defic Syndr Hum Retrovirol ; 13(3): 215-26, 1996 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-8898666

RESUMO

Primary malignant lymphomatous effusions arising in individuals infected with the human immunodeficiency virus, type 1 (HIV-1) represent a rare subset of HIV-associated lymphomas. Previous studies have demonstrated that the malignant cells are monoclonal (as defined by rearrangement of the immunoglobulin gene), express cell surface CD38, and are infected with Epstein-Barr virus (EBV) and human herpes virus, type 8 (HHV-8). Despite these detailed molecular and immunophenotypic studies, clinical information on this disease entity is scant, prompting us to review the clinical features of eight cases seen at our institutions. All eight patients had total peripheral CD4+ lymphocytes < 200/microliter and presented with complaints related to body cavity distension. Routine laboratory values were nondiagnostic and yielded no prognostic information. Only two patients could tolerate and thus received chemotherapy with no obvious impact on their clinical course. The mean overall survival after diagnosis was 60 days (range 6-166 days). Four patients were examined at autopsy. The primary malignant lymphomatous effusion either was the immediate cause of death or contributed significantly to the death of only two. All four patients examined post mortem, however, had lymphomatous infiltration of serosal surfaces adjacent to the site of the primary malignant effusion. Molecular and immunologic studies performed on the malignant cells and effusion fluids revealed universal expression of cell surface CD38 and the presence of HHV-8 gene sequences, but in contrast with previous studies, only four had rearranged immunoglobulin genes or EBV present: IL-6 and IL-10 levels in the malignant effusion fluids were markedly elevated. In summary, this rare subset of HIV-associated lymphomas in our eight patients arose late in the course of HIV-associated disease, had a rapid clinical course, and was molecularly heterogeneous. A pathogenetic role for HHV-8 alone in this disease process is strengthened by our observation of four cases lacking EBV but containing HHV-8.


Assuntos
Antígenos CD , Infecções por HIV/complicações , HIV-1 , Linfoma/epidemiologia , Linfoma/etiologia , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Adulto , Antígenos de Diferenciação/análise , Líquido Ascítico/citologia , Líquido Ascítico/imunologia , Líquido Ascítico/virologia , Autopsia , Southern Blotting , Contagem de Linfócito CD4 , Progressão da Doença , Herpesvirus Humano 4/genética , Herpesvirus Humano 8/genética , Humanos , Switching de Imunoglobulina , Interleucina-10/análise , Interleucina-6/análise , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/virologia , Linfoma/diagnóstico , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , N-Glicosil Hidrolases/análise , Reação em Cadeia da Polimerase , Células Tumorais Cultivadas
15.
J Natl Cancer Inst ; 84(7): 523-7, 1992 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-1545442

RESUMO

BACKGROUND: Transforming growth factor-beta 1 (TGF-beta 1), a potent growth modulator produced by a variety of tumor cells, as well as by platelets, has pleiotropic effects on cell-extracellular matrix interactions and may influence tumor cell invasion and metastasis. PURPOSE: Our purpose was to characterize the effects of TGF-beta 1 on the adhesion, motility, and invasiveness of a metastatic human pulmonary carcinoma (A549 cell line) in vitro. METHODS: A549 cells were seeded onto type I collagen gels, and invasion over a 9-day period was measured in the presence or absence of TGF-beta 1 (0.1-10 ng/mL). In addition, cell adhesion to substrata coated with type I collagen (1-100 nM) as well as haptotactic migration through filters coated with type I collagen (100 micrograms/mL) were measured following a 24-hour treatment with TGF-beta 1 (1-10 ng/mL). RESULTS: TGF-beta 1 stimulated the invasion of A549 cells into type I collagen gels in a dose-dependent manner. Both the number of cells entering the gel and the depth of invasion into the gel were increased. In addition, the effects of TGF-beta 1 were blocked in a dose-dependent manner by a purified polyclonal IgG against TGF-beta 1 but not by normal rabbit IgG. A549 cell invasion was accompanied by dramatic changes in A549 cell morphology that included the appearance of numerous long pseudopodia, consistent with a change in the motile behavior of these cells. TGF-beta 1 stimulated by approximately fourfold the haptotactic migration of A549 cells on polycarbonate filters coated with type I collagen. The TGF-beta 1-mediated increase in invasion and motility was accompanied by a fourfold increase in A549 cell adhesion to type I collagen. CONCLUSIONS: The results suggest that TGF-beta 1 can influence cellular recognition of extracellular matrix components and can modulate cellular adhesion and migration on these components, leading to increased invasive potential. IMPLICATIONS: Given the wide-spread tissue distribution of TGF-beta 1 and its secretion by a variety of tumor cells as well as by platelets, TGF-beta 1 may be an important autocrineparacrine regulator of the invasive phenotype in vivo.


Assuntos
Adenocarcinoma/fisiopatologia , Neoplasias Pulmonares/fisiopatologia , Fator de Crescimento Transformador beta/farmacologia , Adenocarcinoma/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Colágeno , Filtração , Humanos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Células Tumorais Cultivadas
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