Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Transplante de Células-Tronco , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Genes bcl-2 , Genes myc , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Transplante de Células-Tronco/métodos , Transplante AutólogoRESUMO
BACKGROUND: Outcome of pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) is heterogeneous even after adjusting for clinico-pathological prognostic variables. The identification of additional prognostic or even predictive biomarkers is an unmet clinical need. PATIENTS AND METHODS: Forty patients with mucinous appendiceal tumors and PMP were clinically eligible and had evaluable tumor samples obtained after CRS and HIPEC. We carried out next-generations sequencing (NGS) of 50 gene's hotspot regions contained in the Hotspot Cancer Panel v2 using the Ion Torrent Personal Genome Machine platform (Life Technologies). RESULTS: KRAS and GNAS mutations were found in 72% and 52%, and their allelic frequency was below 10% in 55% and 43% of samples, respectively. KRAS and GNAS mutations were associated with worse progression-free survival (PFS) at univariate analysis (P = 0.006 and 0.011, respectively). At multivariate analysis, only KRAS mutations were independently associated with PFS (P = 0.012); GNAS mutations were not-being significantly associated with other poor prognostic features such as incomplete cytoreduction or KRAS mutations. Validation of results was carried out in an independent bi-institutional cohort of 25 patients and the prognostic effect of KRAS mutations was again confirmed in the multivariate model (P = 0.029). NGS approach allowed the discovery of other potentially druggable mutations such as those in PI3K, AKT, LKB1, FGFR3 and PDGFRA. CONCLUSIONS: Given the homogeneity of this series and the sensitivity of NGS in this low-cellularity tumor, we demonstrated for the first time a poor prognostic role of KRAS mutations.
Assuntos
Biomarcadores Tumorais/genética , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Pseudomixoma Peritoneal/genética , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipertermia Induzida , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/cirurgiaAssuntos
Criopreservação , Neoplasias , Bancos de Tecidos , Humanos , Itália , Bancos de Tecidos/normasAssuntos
Vilosidades Coriônicas/patologia , Malária Falciparum/patologia , Plasmodium falciparum/isolamento & purificação , Complicações Parasitárias na Gravidez/patologia , Adulto , Animais , Vilosidades Coriônicas/parasitologia , Doença Crônica , Feminino , Idade Gestacional , Humanos , Inflamação/parasitologia , Inflamação/patologia , Gravidez , Complicações Parasitárias na Gravidez/parasitologiaRESUMO
OBJECTIVE: To study the immunochemical distribution ofRantes chemokine and its correlation with HIV-p24 expression, in brains with HIV-related lesions. MATERIAL AND METHODS: 17 HIV-positive cases of HIV-related brain lesions, 7 HIV-positive cases without cerebral HIV-related lesions (5 with opportunistic brain diseases), and 7 HIV-negative cases as controls (4 with brain lesion) were selected. RESULTS: High expression of Rantes was observed in the cases with inflammatory brain lesions (22/24 HIV-positive and 2/7 HIV-negative patients). Positivity was observed in the diffuse and nodular microglial cells and lymphocytes. In the patients with HIV-related lesions, the presence of Rantes-stained microglia did not correlate with that of HIV-p24-positive cells. Positive astrocytes were only found in the HIV-positive patients. Multinucleated giant cells were always Rantes-negative. CONCLUSIONS: Our results seem to demonstrate the role of Rantes chemokine in inducing inflammatory brain perivascular and microglial reactions both in HIV-positive and -negative patients.
Assuntos
Encéfalo/metabolismo , Quimiocina CCL5/metabolismo , Infecções por HIV/metabolismo , Complexo AIDS Demência/metabolismo , Complexo AIDS Demência/patologia , Encéfalo/patologia , Infecções por HIV/patologia , Soronegatividade para HIV , Humanos , Imuno-Histoquímica , Estudos Retrospectivos , Distribuição TecidualRESUMO
OBJECTIVES: To evaluate the correlation between immunohistochemical positive patterns (globular and filamentous structures) of beta-amyloid precursor protein (beta-APP), used as a marker of axonal damage, and the different distribution of HIV p24 antigens, in three different brain areas of AIDS patients. METHODS: Eighteen AIDS patients with HIV-related brain lesions were included in the study. Forty-nine sections from basal ganglia, frontal cortex and hippocampus were selected. After microwave oven pre-treatment, the sections were incubated with anti-HIV p24 and anti-beta-APP monoclonal antibodies; the reactions were developed with peroxidase/3,3'diaminobenzidine. The positivity was graded by semi-quantitative scores. Double immunohistochemical staining was used to evaluate the co-localization of the antigens. RESULTS: HIV p24 immunohistochemistry was positive in 44 of 49 sections (89%), with a prevalence of interstitial positive cells and positive microglial nodules in 27 and 13 sections respectively. beta-APP-positive structures were demonstrated in 23 of 44 sections (52%) with HIV-related lesions, and were absent from the five sections without viral expression. Globular and filamentous lesions were observed in 21 of 23 sections and 10 of 23 lesions respectively. Moreover, a high grade of globular type lesion was related to an elevated presence of diffuse interstitial HIV p24-positive cells in basal ganglia; double immunohistochemical reactions demonstrated the co-localization of beta-APP globules and HIV p24 antigens. CONCLUSIONS: The data obtained confirm the coexpression of beta-APP and viral antigens in particular areas of the brain with HIV-related lesions; there is a strict correlation between beta-APP globules (indicating chronic cerebral damage) and the interstitial pattern of HIV p24 immunohistochemistry.
Assuntos
Síndrome da Imunodeficiência Adquirida/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Gânglios da Base/metabolismo , Lobo Frontal/metabolismo , Proteína do Núcleo p24 do HIV/metabolismo , HIV-1 , Hipocampo/metabolismo , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/patologia , Síndrome da Imunodeficiência Adquirida/virologia , Gânglios da Base/patologia , Gânglios da Base/virologia , Biomarcadores , Lobo Frontal/patologia , Lobo Frontal/virologia , Hipocampo/patologia , Hipocampo/virologia , Humanos , Itália/epidemiologia , Estudos RetrospectivosRESUMO
Microglial nodules associated with opportunistic and HIV-related lesions are frequently found in the brains of AIDS patients. However, in many cases, the causative agent is only presumptively suspected. We reviewed 199 brains of AIDS patients with micronodular lesions to clarify their etiology by immunohistochemistry (to Toxoplasma gondii, cytomegalovirus, herpes simplex virus I/II, varicella zoster virus and HIV-p24 core protein), PCR (for herpetic viruses and Mycobacterium tuberculosis) and electron microscopy. Productive HIV infection was observed in 110 cases (55.1%): 30 cases with Toxoplasma gondii encephalitis, 30 with cytomegalovirus encephalitis, eight with multiple cerebral diseases, while in the remaining 42 cases HIV was the only pathogenetic agent. Multinucleated giant cells (hallmark of HIV infection) were found in the MGNs of 85/110 cases with HIV-related lesions; the remaining 25 cases had only p24 positive cells but no multinucleated giant cells. In these latter cases the micronodular lesions had been initially attributed to the main opportunistic agent found in the brain, or defined as subacute encephalitis. Individual microglial nodules positive for an opportunistic pathogen were generally negative for HIV antigens. In 13 cases no opportunistic agent or HIV productive infection was found. In these cases, PCR and electron microscopy examination for HIV and other viral infections were negative. Our data suggest that HIV-immunohistochemistry should be used for the etiological diagnosis of micronodular lesions in AIDS brains, even in the presence of other pathogens. After extensive search, the etiology of the microglial nodules remains unknown in only a small percentage of cases.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Síndrome da Imunodeficiência Adquirida/patologia , Infecções do Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/patologia , Microglia/microbiologia , Microglia/patologia , Adulto , Idoso , Animais , Encéfalo/microbiologia , Encéfalo/patologia , Citomegalovirus/isolamento & purificação , Feminino , HIV/isolamento & purificação , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/microbiologia , Toxoplasmose Cerebral/patologiaRESUMO
The eradication of helminthic infections described by models of the Nåsell-Hirsch type is investigated. Simple criteria are proposed for comparing the efficiency of different modes of eradication.