RESUMO
Severe COVID-19 patients present a clinical and laboratory overlap with other hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH). However, the underlying mechanisms of these conditions remain to be explored. Here, we investigated the transcriptome of 1596 individuals, including patients with COVID-19 in comparison to healthy controls, other acute inflammatory states (HLH, multisystem inflammatory syndrome in children [MIS-C], Kawasaki disease [KD]), and different respiratory infections (seasonal coronavirus, influenza, bacterial pneumonia). We observed that COVID-19 and HLH share immunological pathways (cytokine/chemokine signaling and neutrophil-mediated immune responses), including gene signatures that stratify COVID-19 patients admitted to the intensive care unit (ICU) and COVID-19_nonICU patients. Of note, among the common differentially expressed genes (DEG), there is a cluster of neutrophil-associated genes that reflects a generalized hyperinflammatory state since it is also dysregulated in patients with KD and bacterial pneumonia. These genes are dysregulated at the protein level across several COVID-19 studies and form an interconnected network with differentially expressed plasma proteins that point to neutrophil hyperactivation in COVID-19 patients admitted to the intensive care unit. scRNAseq analysis indicated that these genes are specifically upregulated across different leukocyte populations, including lymphocyte subsets and immature neutrophils. Artificial intelligence modeling confirmed the strong association of these genes with COVID-19 severity. Thus, our work indicates putative therapeutic pathways for intervention.
Assuntos
COVID-19 , Linfo-Histiocitose Hemofagocítica , Inteligência Artificial , COVID-19/complicações , COVID-19/genética , Criança , Humanos , Linfo-Histiocitose Hemofagocítica/complicações , Ativação de Neutrófilo , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptive transfer of in vitro expanded and activated cells, genetically engineered cells to contain chimeric antigen receptors (CAR-NKs), in vivo stimulation of NK cells (by cytokine therapy, checkpoint blockade therapies, etc.), and tumor-specific antibody-guided NK cells, among others. In this article, we review pivotal aspects of NK cells' biology and their contribution to immune responses against tumors, as well as providing a wide perspective on the many antineoplastic strategies using NK cells. Finally, we also discuss those approaches that have the potential to control glioblastoma-a disease that, currently, causes inevitable death, usually in a short time after diagnosis.
RESUMO
Dendritic cells (DCs) are the most efficient antigen-presenting cells and link the innate immune sensing of the environment to the initiation of adaptive immune responses, which may be directed to either acceptance or elimination of the recognized antigen. In cancer patients, though DCs would be expected to present tumor antigens to T lymphocytes and induce tumor-eliminating responses, this is frequently not the case. The complex tumor microenvironment subverts the immune response, blocks some effector mechanisms, and drives others to support tumor growth. Chronic inflammation in a tumor microenvironment is believed to contribute to the induction of such regulatory/tolerogenic response. Among the various mediators of the modulatory switch in chronic inflammation is the "antidanger signal" chaperone, heat shock protein 27 (Hsp27), that has been described, interestingly, to be associated with cell migration and drug resistance of breast cancer cells. Thus, here, we investigated the expression of Hsp27 during the differentiation of monocyte-derived DCs (Mo-DCs) from healthy donors and breast cancer patients and evaluated their surface phenotype, cytokine secretion pattern, and lymphostimulatory activity. Surface phenotype and lymphocyte proliferation were evaluated by flow cytometry, interferon- (IFN-) γ, and interleukin- (IL-) 10 secretion, by ELISA and Hsp27 expression, by quantitative polymerase chain reaction (qPCR). Mo-DCs from cancer patients presented decreased expression of DC maturation markers, decreased ability to induce allogeneic lymphocyte proliferation, and increased IL-10 secretion. In coculture with breast cancer cell lines, healthy donors' Mo-DCs showed phenotype changes similar to those found in patients' cells. Interestingly, patients' monocytes expressed less GM-CSF and IL-4 receptors than healthy donors' monocytes and Hsp27 expression was significantly higher in patients' Mo-DCs (and in tumor samples). Both phenomena could contribute to the phenotypic bias of breast cancer patients' Mo-DCs and might prove potential targets for the development of new immunotherapeutic approaches for breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Células Dendríticas/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Monócitos/metabolismo , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Reação em Cadeia da PolimeraseRESUMO
As cancer immunotherapy gains importance, the determination of a patient's ability to react to his/her tumor is unquestionably relevant. Though the presence of T cells that recognize specific tumor antigens is well established, the total frequency of tumor-reactive T cells in humans is difficult to assess, especially due to the lack of broad analysis techniques. Here, we describe a strategy that allows this determination, in both CD4 and CD8 compartments, using T cell proliferation induced by tumor cell-lysate pulsed dendritic cells as the readout. All 12 healthy donor tested had circulating CD4 and CD8 tumor cell-reactive T cells. The detection of these T cells, not only in the naïve but also in the memory compartment, can be seen as an evidence of tumor immunosurveillance in humans. As expected, breast cancer patients had higher frequencies of blood tumor-reactive T cells, but with differences among breast cancer subtypes. Interestingly, the frequency of blood tumor-reactive T cells in patients did not correlate to the frequency of infiltrating tumor-reactive T cells, highlighting the danger of implying a local tumor response from blood obtained data. In conclusion, these data add T cell evidence to immunosurveillance in humans, confirm that immune parameters in blood may be misleading and describe a tool to follow the tumor-specific immune response in patients and, thus, to design better immunotherapeutic approaches.
RESUMO
Cervical cancer is the last stage of a series of molecular and cellular alterations initiated with Human Papillomavirus (HPV) infection. The process involves immune responses and evasion mechanisms, which culminates with tolerance toward tumor antigens. Our objective was to understand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system as lesions progress to cancer. Locally, we observed higher cervical leukocyte infiltrate, reflected by the increase in the frequency of T lymphocytes, neutrophils and M2 macrophages, in cancer patients. We observed a strong negative correlation between the frequency of neutrophils and T cells in precursor and cancer samples, but not cervicitis. In 3D tumor cell cultures, neutrophils inhibited T cell activity, displayed longer viability and longer CD16 expression half-life than neat neutrophil cultures. Systemically, we observed higher plasma G-CSF concentration, higher frequency of immature low density neutrophils, and tolerogenic monocyte derived dendritic cells, MoDCs, also in cancer patients. Interestingly, there was a negative correlation between T cell activation by MoDCs and G-CSF concentration in the plasma. Our results indicate that neutrophils and G-CSF may be part of the immune escape mechanisms triggered by cervical cancer cells, locally and systemically, respectively.
Assuntos
Fator Estimulador de Colônias de Granulócitos/sangue , Evasão da Resposta Imune , Neutrófilos/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Dendríticas/imunologia , Feminino , Humanos , Macrófagos/imunologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Linfócitos T/imunologia , Adulto JovemRESUMO
Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose. This study presents LabMol-12, a new pyridinyl carboxamide derivative with antileishmanial and antichagasic activity, as a new hit for lung cancer treatment, which induces apoptosis dependent of caspases in NCI-H1299 lung cancer cells both in monolayer and 3D culture. Moreover, LabMol-12 allows a reduction of oxaliplatin dose when they are combined, thereby, it is a relevant strategy for reducing the side effects of oxaliplatin with the same response. Molecular modeling studies corroborated the biological findings and suggested that the combined therapy can provide a better therapeutically profile effects against NSCLC. All these findings support the fact that the combination of oxaliplatin and LabMol-12 is a promising drug combination for lung cancer.
Assuntos
Amidas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Piridinas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/patologia , Modelos Moleculares , Estrutura Molecular , Oxaliplatina , Relação Estrutura-AtividadeRESUMO
Mast cells (MCs) are tissue resident cells, rich in inflammatory mediators, involved in allergic reactions, and with an increasingly recognized role in immunomodulation. Dendritic cells (DCs), on the other hand, are central to the determination of immune response patterns, being highly efficient antigen-presenting cells that respond promptly to changes in their microenvironment. Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact with MC (MC-iDC) decreased HLA-DR but increased PD-L1 expression and stimulated regulatory T lymphocytes, which expresses FoxP3(+), secrete TGF-ß and IL-10, and suppress the proliferation of mitogen-stimulated naïve T lymphocytes. Furthermore, MC-iDC expressed higher levels of indoleamine-2,3-deoxigenase (IDO), a phenomenon that was blocked by treatment of MC with anti-PD-1 or by the treatment of DCs with anti-PD-L1 or anti-PD-L2, but not by blocking of H1 and H2 histamine receptors on DCs. Contact with MC also increased phosphorylated STAT-3 levels in iDCs. When a STAT-3 inhibitor, JSI-124, was added to the DCs before contact with MC, the MC-iDC recovered their ability to induce allogeneic T cell proliferation and did not increase their IDO expression.
RESUMO
Capsaicin, the primary pungent component of the chili pepper, has antitumor activity. Herein, we describe the activity of RPF151, an alkyl sulfonamide analogue of capsaicin, against MDA-MB-231 breast cancer cells. RPF151 was synthetized, and molecular modeling was used to compare capsaicin and RPF151. Cytotoxicity of RPF151 on MDA-MB-231 was also evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis, by flow cytometry, and Western blot analysis of cycle-related proteins were used to evaluate the antiproliferative mechanisms. Apoptosis was evaluated by phosphatidyl-serine externalization, cleavage of Ac-YVAD-AMC, and Bcl-2 expression. The production of reactive oxygen species was evaluated by flow cytometry. RPF151 in vivo antitumor effects were investigated in murine MDA-MB-231 model. This study shows that RPF151 downregulated p21 and cyclins A, D1, and D3, leading to S-phase arrest and apoptosis. Although RPF151 has induced the activation of TRPV-1 and TRAIL-R1/DR4 and TRAIL-2/DR5 on the surface of MDA-MB-231 cells, its in vivo antitumor activity was TRPV-1-independent, thus suggesting that RPF151 should not have the same pungency-based limitation of capsaicin. In silico analysis corroborated the biological findings, showing that RPF151 has physicochemical improvements over capsaicin. Overall, the activity of RPF151 against MDA-MB-231 and its lower pungency suggest that it may have a relevant role in cancer therapy.
Assuntos
Neoplasias da Mama/genética , Capsaicina/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Capsaicina/análogos & derivados , Capsaicina/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Modelos Moleculares , Proteínas de Neoplasias/genética , Ligação Proteica , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Lung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.
Assuntos
Antineoplásicos/administração & dosagem , Benzoxazóis/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Niacinamida/administração & dosagem , SorafenibeRESUMO
BACKGROUND: Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4(+)Foxp3(+) T cells. METHODOLOGY/PRINCIPAL FINDINGS: The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs), with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs) presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs) after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4(+) and CD8(+) T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4(+)Foxp3(+)IL-10(+) T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ), and an increase in the anti-inflammatory molecule IL-10. CONCLUSION/SIGNIFICANCE: This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4(+)Foxp3(+) T cells. Further characterization and validation of this phenomenon could support the use of SHEDs, directly or indirectly for immune modulation in the clinical practice.
Assuntos
Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Esfoliação de Dente/imunologia , Esfoliação de Dente/metabolismo , Antígenos CD1/metabolismo , Biomarcadores/metabolismo , Antígenos CD40/metabolismo , Diferenciação Celular , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/citologia , Fatores de Transcrição Forkhead/metabolismo , Glicoproteínas/metabolismo , Humanos , Imunomodulação , Interleucina-10/metabolismo , Ativação Linfocitária/imunologia , Monócitos/citologia , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoAssuntos
Imunoterapia , Neoplasias/imunologia , Anticorpos Monoclonais , Imunização , Imunoterapia Ativa , VacinasRESUMO
BACKGROUND: Patients with X-linked hyper-IgM syndrome (X-HIGM) due to CD40 ligand (CD40L) mutations are susceptible to fungal pathogens; however, the underlying susceptibility mechanisms remain poorly understood. OBJECTIVE: To determine whether monocyte-derived dendritic cells (DCs) from patients with X-HIGM exhibit normal responses to fungal pathogens. METHODS: DCs from patients and controls were evaluated for the expression of costimulatory (CD80 and CD86) and MHC class II molecules and for their ability to produce IL-12 and IL-10 in response to Candida albicans and Paracoccidioides brasiliensis. We also evaluated the ability of C albicans- and P brasiliensis-pulsed mature DCs to induce autologous T-cell proliferation, generation of T helper (T(H)) 17 cells, and production of IFN-γ, TGF-ß, IL-4, IL-5, and IL-17. RESULTS: Immature DCs from patients with X-HIGM showed reduced expression of CD80, CD86, and HLA-DR, which could be reversed by exogenous trimeric soluble CD40L. Most important, mature DCs from patients with X-HIGM differentiated by coculturing DCs with fungi secreted minimal amounts of IL-12 but substantial amounts of IL-10 compared with mature DCs from normal individuals. Coculture of mature DCs from X-HIGM patients with autologous T cells led to low IFN-γ production, whereas IL-4 and IL-5 production was increased. T-cell proliferation and IL-17 secretion were normal. Finally, in vitro incubation with soluble CD40L reversed the decreased IL-12 production and the skewed T(H)2 pattern response. CONCLUSION: Absence of CD40L during monocyte/DC differentiation leads to functional DC abnormalities, which may contribute to the susceptibility to fungal infections in patients with X-HIGM.
Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Células Dendríticas/metabolismo , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/imunologia , Paracoccidioides/imunologia , Paracoccidioidomicose/imunologia , Adolescente , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Antígeno B7-2/genética , Antígeno B7-2/metabolismo , Ligante de CD40/genética , Ligante de CD40/imunologia , Ligante de CD40/metabolismo , Candida albicans/patogenicidade , Candidíase/complicações , Candidíase/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células , Células Cultivadas , Criança , Pré-Escolar , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/patologia , Células Dendríticas/virologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Masculino , Mutação/genética , Paracoccidioides/patogenicidade , Paracoccidioidomicose/complicações , Paracoccidioidomicose/genética , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologiaRESUMO
Roots of Pfaffia paniculata have been well documented for multifarious therapeutic values and have also been used for cancer therapy in folk medicine. This study has been performed in a human breast tumor cell line, the MCF-7 cells. These are the most commonly used model of estrogen-positive breast cancer, and it has been originally established in 1973 at the Michigan Cancer Foundation from a pleural effusion taken from a woman with metastatic breast cancer. Butanolic extract of the roots of P. paniculata showed cytotoxic effect MCF-7 cell line, as determined with crystal violet assay, cellular death with acridine orange/ethidium bromide staining, and cell proliferation with immunocytochemistry of bromodeoxyuridine (BrdU). Subcellular alterations were evaluated by electron microscopy. Cells treated with butanolic extract showed degeneration of cytoplasmic components and profound morphological and nuclear alterations. The results show that this butanolic extract indeed presents cytotoxic substances, and its fractions merit further investigations.
Assuntos
Amaranthaceae , Neoplasias da Mama/ultraestrutura , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Amaranthaceae/química , Bromodesoxiuridina , Butanóis , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Imuno-Histoquímica , Microscopia Eletrônica de Transmissão , Raízes de Plantas/químicaRESUMO
CONTEXT: Sarcomatous differentiation, which represents transformation to high-grade malignancy, can occur in all histological types of renal malignancy. CASE REPORT: The authors report on the case of a 66-year-old woman with a right renal mass that was shown to be a clear cell carcinoma. She underwent radical nephrectomy and dendritic cell vaccination and, 3.5 years later, she developed retroperitoneal pure sarcomatous recurrence of the tumor. The authors speculate that the vaccination could have played some role in this differentiation or selection of the sarcomatous component of the primary tumor.
Assuntos
Vacinas Anticâncer/uso terapêutico , Carcinoma de Células Renais/patologia , Células Dendríticas , Neoplasias Renais/patologia , Neoplasias Retroperitoneais/secundário , Sarcoma/secundário , Idoso , Vacinas Anticâncer/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Células Dendríticas/imunologia , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia , RecidivaRESUMO
CONTEXT: Sarcomatous differentiation, which represents transformation to high-grade malignancy, can occur in all histogical types of renal malignancy. CASE REPORT: The authors report on the case of a 66-year-old woman with a right renal mass that was shown to be a clear cell carcinoma. She underwent radical nephrectomy and dendritic cell vaccination and, 3.5 years later, she developed retroperitoneal pure sarcomatous recurrence of the tumor. The authors speculate that the vaccination could have played some role in this differentiation or selection of the sarcomatous component of the primary tumor.
CONTEXTO: Diferenciação sarcomatosa, que representa evolução para malignidade de alto grau, pode ocorrer em todos os tipos histológicos de câncer renal. RELATO DE CASO: Os autores relatam o caso de uma mulher de 66 anos, com uma massa no rim esquerdo que se revelou um carcinoma de células renais. Após 3,5 anos da nefrectomia radical seguida de vacinação com células dendríticas, a paciente desenvolveu uma recorrência sarcomatosa pura no retroperitônio. Os autores especulam que a terapia com vacina de células dendríticas pode ter desempenhado algum papel na diferenciação ou seleção do componente sarcomatoso do tumor primário.
Assuntos
Humanos , Feminino , Idoso , Vacinas Anticâncer/uso terapêutico , Carcinoma de Células Renais/patologia , Células Dendríticas , Neoplasias Renais/patologia , Neoplasias Retroperitoneais/secundário , Sarcoma/secundário , Vacinas Anticâncer/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/cirurgia , Células Dendríticas/imunologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia , RecidivaRESUMO
BACKGROUND: The immune function is altered in jaundiced patients; here, the ability of their peripheral blood mononuclear cells to perform phagocytosis and to release H2O2 was analyzed. METHODS: Cells from 53 patients before surgery for relief of cholestasis, from 38 patients 1 week and from 15 patients 2 weeks after surgery were separated and cultured for 1 h in the presence of phorbol myristate acetate. H2O2 release was evaluated colorimetrically and phagocytosis by the ingestion of Escherichia coli in vitro. RESULTS: Before surgery for relief of cholestasis, the cells of the patients were unable to release H2O2, but, after surgery, an increasing percentage of patients had cells that were able to produce H2O2 (13% after 1 week; 33% after 2 weeks). This recovery did not correlate with bilirubinemia. When cultured for 1 week in the presence of normal or jaundiced plasma, regardless of collection time, cells of 12/12 patients released H2O2, but in lower levels if in the presence of jaundiced plasma. In contrast, H2O2 release by normal donor cells was enhanced in the presence of jaundiced plasma. Phagocytosis by cells of the patients was lower, but when present was associated with a significantly higher bactericidal activity. CONCLUSION: These significant, but reversible alterations of monocyte function in jaundiced patients might contribute to their enhanced susceptibility to surgical complications.
Assuntos
Peróxido de Hidrogênio/análise , Icterícia Obstrutiva/diagnóstico , Leucócitos/imunologia , Fagocitose/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Colestase/cirurgia , Feminino , Humanos , Icterícia Obstrutiva/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
O valor clínico dos marcadores tumorais séricos em câncer de pulmão é incerto. Objetivos: Avaliar a associação da concentração sérica de marcadores tumorais com a extensão da neoplasia e seu valor prognóstico. Casuística e método: Entre fevereiro de 1995 e setembro de 1997 foram estudados 103 pacientes, no Departamento de Cirurgia Torácica do Hospital do Câncer. Antes do tratamento os pacientes foram submetidos à coleta de sangue para dosagem da concentração do CEA, CYFRA21.1, CA15.3, CA19.9, CA72.4 e NSE. Resultados: O CYFRA21.1 foi o marcador mais freqüentemente elevado (55 por cento). Os pacientes com neoplasia avançada tiveram concentração sérica média do CEA (90,82 ± 329,08ng/ml), CYFRA21.1 (20,34 ± 58,42ng/ml) e CA15.3 (56,54 ± 86,81U/ml) significativamente superior às observadas nos tumores localizados, respectivamente, 10,24 ± 35,96ng/ml, 12,67 ± 25,23ng/ml e 22,22 ± 15,86U/ml. Mesmo considerando todos os marcadores deste estudo, apenas os pacientes com CEA elevado tiveram chance 5,6 vezes maior de ser portadores de neoplasia avançada, quando comparados com aqueles com CEA normal. A sobrevida foi influenciada pelo performance status (p = 0,001), extensão anatômica (p = 0,006), concentração aumentada do CEA (p = 0,043), mais que dois marcadores aumentados (p < 0,001) e tipo de tratamento (p < 0,001). O valor prognóstico da extensão da neoplasia atingiu o limite da significância (p = 0,052); entretanto, a presença de mais do que dois marcadores aumentados e a modalidade terapêutica tiveram valor prognóstico independente (respectivamente, p = 0,035 e p = 0,005). Conclusões: Nenhum dos marcadores tumorais séricos avaliados apresenta utilidade clínica no manejo dos pacientes com CNPCP.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Pulmonar de Células não Pequenas , Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/sangue , Análise de Sobrevida , PrognósticoRESUMO
O comportamento dos marcadores CA-72,4 e CYFRA-21.1 foi analisado em pacientes do Hospital a. C. Camargo. A dosagem dos níveis séricos de CA-72,4 foi realizada em 49 pacientes por ensaio automatizado de quimioluminescência e mostrou-se útil nos dois grupos de pacientes analisados, com tumores de esôfago e gástricos. Em ambos os casos, houve um aumento de sensibilidade quando se acrescentou a dosagem deste marcador à do antígeno carcinoembriônico (CEA) ou ao marcador CA-19.9. Foram mais sensíveis as associaçöes CA-72.4 e CA-19.9 para os tumores de esôfago, e CA-72.4 e CEA para tumores gástricos. Já o marcador CYFRA-21.1 foi analisado por radioimunoensaio em 102 doadores normais do banco de sangue do HACC e em 20 pacientes com tumores de pulmäo. Nestes últimos, o CYFRA-21.1 esteve alterado em 55 por cento dos casos. Desta forma, o marcador CYFRA-21.1 pode ser considerado, como a enolase neurônio-específica (NSE), uma ferramenta muito útil no seguimento de pacientes com tumores de pulmäo