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1.
Cancer Immunol Immunother ; 71(10): 2469-2483, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35254478

RESUMO

Dendritic cells (DCs) play a pivotal role in the homeostasis of the immune system. The tumor microenvironment impairs the proper function of DCs. The immunomodulatory properties of DCs in lung cancer are of interest. In the present study, we analysed DCs subsets and immune cells with the expression of immunomodulatory molecules: PD-1 and PD-L1 and co-stimulatory molecule CD80 in metastatic, non-metastatic lymph nodes (LNs) and peripheral blood (PB). LNs aspirates were obtained during the EBUS/TBNA procedure of 29 patients with primary lung cancer. The cells were analyzed by flow cytometry. We reported a higher percentage of DCs in the metastatic than in the non-metastatic LNs and the PB (0.709% vs. 0.166% vs. 0.043%, p < 0.0001). The proportions of PD-1 + , PD-L1 + and CD80 + DCs were higher in the metastatic LNs than in the non-metastatic ones. A higher proportion of regulatory DCs (DCregs) was found in the metastatic ones than in the non-metastatic LNs (22.5% vs. 3.1%, p = 0.0189). We report that DCs cells show increased expression of PD-1, PD-L1 and CD80 molecules that can interact with T lymphocytes. It can be assumed that mature DCs infiltrating metastatic LNs can develop into DCregs, which are involved in the suppression of anti-tumor response.


Assuntos
Antígeno B7-H1 , Neoplasias Pulmonares , Antígeno B7-1 , Antígeno B7-H1/metabolismo , Moléculas de Adesão Celular/metabolismo , Células Dendríticas , Humanos , Neoplasias Pulmonares/patologia , Linfonodos , Receptor de Morte Celular Programada 1 , Microambiente Tumoral
2.
Cent Eur J Immunol ; 47(4): 323-331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36817394

RESUMO

The number of argyrophilic nucleolus organizer regions (AgNOR) is related to the proliferative activity of cells and the degree of neoplastic transformation. The surface area of AgNOR depending on nuclear structure may be a predictor of tumor recurrence, while research into acute leukemias is scarce. The aim of the study was to determine whether the assessment of AgNOR parameters is useful in the differentiation of acute leukemias and, together with cytogenetic changes, would allow for a quick evaluation of the risk group. The AgNOR structures were analyzed in terms of the shape, surface area and distribution in bone marrow blast cells in patients with acute leukemias. We observed significant differences in the AgNOR structures, simple, compound and complex patterns between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Complex structures were more numerous in ALL than in AML patients. There were significant differences in the distribution of AgNOR configuration among various cytogenetic AML risk groups. We observed a significant difference in the mean number of AgNOR between ALL-T and ALL-B. We detected diversity in the AgNOR structures and pattern map in AML and ALL. Thus, presentation of a variety of AgNOR configurations is innovative and can be a useful method of differentiating patients with acute leukemia types and cytogenetic risk.

3.
Ann Hematol ; 98(9): 2197-2211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321454

RESUMO

Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs 44.8%; p < 0.0001). Outcome of bacterial infections was better in children (95.5% vs 91.4%; p = 0.0011). The IFD incidence (25.3% vs 6.3%; p < 0.0001) and outcome (88.0% vs 74.9%; p < 0.0001) were higher in children. The incidence of viral infections was higher in children after allo-HCT (56.3% vs 29.3%; p < 0.0001), and auto-HCT (6.6% vs 0.8%; p < 0.0001). Outcome of viral infections was better in children (98.6% vs 92.3%; p = 0.0096). Infection-related mortality was 7.8% in children and 18.4% in adults (p < 0.0001). No child after auto-HCT died of infection. Adult age, mismatched transplants, acute leukemia, chronic GVHD, CMV reactivation, infection with Gram-negatives, and duration of infection > 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas/epidemiologia , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/etiologia , Leucemia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Cent Eur J Immunol ; 44(4): 395-402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32140052

RESUMO

INTRODUCTION: M2 macrophages are predominant in the immune infiltrates of resected tumours, but little is known about macrophage phenotype in the local lung cancer environment, which may be evaluated by bronchoalveolar lavage fluid (BALF). AIM OF THE STUDY: To find differences between BALF from lung affected by cancer (clBALF) and hlBALF from the opposite, healthy lung, as a control, from the same patient, regarding their individual macrophage polarization and their correlation with IL-10 and TGF-ß. MATERIAL AND METHODS: Eighteen patients with confirmed lung cancer were investigated. Macrophage subtyping was performed by immunofluorescence with antibodies anti-CCR7 and CD163 (M1 and M2, respectively). RESULTS: We found five populations of macrophages: cells with a single reaction: only for CCR7+ or CD163+, a double reaction (CCR7+CD163+), cells with a stronger CD163 (CCR7lowCD163+), and cells with a stronger CCR7 (CCR7+CD163low). The main population in the clBALF was composed of cells with a phenotype similar to M2 (CCR7lowCD163+), while in the hlBALF the predominating phenotype was the one similar to M1 (CCR7+CD163low). The median proportion of TGF-ß1 concentration was higher in the clBALF and hlBALF supernatant than in the serum. CONCLUSIONS: In this study we confirmed the usefulness of the immunofluorescence method with CCR7 and CD163 in the evaluation of BALF macrophage polarization in lung cancer.

5.
Eur J Haematol ; 96(3): 236-44, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25912052

RESUMO

Internal tandem duplication (ITD) of the FLT3 gene (Fms-like tyrosine kinase 3) is the most commonly found mutation in acute myeloid leukemia (AML). The significance of FLT3-ITD at diagnosis was retrospectively estimated for allo-HSCT (allogeneic hematopoietic stem cell transplantation) outcomes in 140 patients, median age of 38, undergoing allo-HSCT after myeloablative conditioning in first complete remission of AML. FLT3-ITD was detected at AML diagnosis in 42/140 (30%) of included into this study patients. At 3 years, relapse incidence (RI) following allo-HSCT in AML patients with intermediate or normal karyotype was significantly higher in those FLT3-ITD positive than FLT3-ITD negative [52.9 vs. 20.4%, P = 0.002]. Additionally, patients with mild chronic graft-versus-host disease (cGvHD) had significantly lower RI compared to patients with moderate or severe grade cGvHD or those not experiencing cGvHD, respectively, 4.8 vs. 36.0 vs. 27.8%, P = 0.032. FLT3-ITD was harboring a poor prognosis in AML with intermediate or normal karyotype and significantly increased risk of relapse following allo-HSCT. It appears that allo-HSCT does not cure patients with FLT3-ITD, unless they develop symptoms of mild cGvHD and graft versus leukemia, which may decrease RI.


Assuntos
Duplicação Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Translocação Genética , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
6.
Future Oncol ; 11(1): 17-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24953672

RESUMO

Tyrosine kinase inhibitors are novel therapies targeting specific cellular signalling pathways. Sunitinib and sorafenib primarily block tyrosine kinase receptors involved in the progression of many tumours, including clear cell renal cell cancer (ccRCC). Although developed to target selected receptors, it is becoming apparent that they inhibit other kinases; this may result in the development of unexpected side effects. This is potentially dangerous as kinases on noncancerous cells are also inhibited. TKI off-target effects contributing to cardiotoxicity, hypothyroidism, hypertension, fatigue, hair depigmentation, hand-foot syndrome and gastrointestinal perforation have been described. We report three patients (3/412) treated with sunitinib and sorafenib who developed chronic myeloid leukaemia (CML) during treatment for ccRCC, proposing a molecular mechanism of tyrosine kinase inhibitors action on bone marrow cells that might be co-responsible for CML development.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Carcinoma de Células Renais/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Terapia de Alvo Molecular/efeitos adversos , Adulto , Idoso , Células da Medula Óssea/patologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/patologia , Humanos , Indóis/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Pirróis/efeitos adversos , Sorafenibe , Sunitinibe , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia
7.
Pol Merkur Lekarski ; 38(225): 164-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25815618

RESUMO

Polymyalgia rheumatica (PMR) is a common inflammatory disease in elderly people. We present a case of a 49-year-old woman diagnosed with PMR. The treatment with prednisone resulted in a rapid resolution of clinical symptoms. However, inflammatory markers remained elevated. Ultrasonography and computed tomography revealed the presence of a large splenic lesion. A cyst was suspected but, because of the high risk of splenic rupture, a splenectomy was performed. The histopathological examination revealed the presence of splenic marginal zone lymphoma. Inflammatory markers returned to normal after splenectomy. Prednisone was tapered but clinical symptoms of PMR reappeared after lowering the dose of prednisone <10 mg/day. Thus, treatment with methotrexate was started, which allowed for further tapering of prednisone.


Assuntos
Linfoma/complicações , Linfoma/diagnóstico , Polimialgia Reumática/etiologia , Neoplasias Esplênicas/complicações , Neoplasias Esplênicas/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Linfoma/patologia , Linfoma/cirurgia , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Prednisona/administração & dosagem , Recidiva , Esplenectomia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/cirurgia
8.
Pol Merkur Lekarski ; 36(211): 39-41, 2014 Jan.
Artigo em Polonês | MEDLINE | ID: mdl-24645577

RESUMO

Fibrocytes are bone-marrow derived mesenchymal progenitor cells. They express typical markers of leukocytes, hematopoietic stem cells and fibroblasts. They play a pivotal role in the tissue remodeling and fibrosis in both physiologic and pathologic settings. Fibrocytes are unique in that they are capable of differentiating into fibroblasts and myofibroblasts, as well as adipocytes. Circulating fibrocytes may play a role in pulmonary fibrosis and clinical outcomes. Recent data obtained from the clinical setting suggest that high numbers of circulating fibrocytes correlate with pulmonary function test parameters and disease activity in patients with different interstitial lung diseases. A greater understanding of the immunologic mediator that influence fibrocyte biology suggest new opportunities for therapeutic manipulation of these cells in fibrogenesis.


Assuntos
Fibroblastos/imunologia , Fibroblastos/patologia , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Diferenciação Celular , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/patologia , Humanos , Células-Tronco Mesenquimais/patologia , Prognóstico
9.
Contemp Oncol (Pozn) ; 18(5): 313-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25477752

RESUMO

Although multiple myeloma (MM) is still considered an incurable disease, the treatment philosophy is changing due to the introduction of novel agents. Standard treatment consists of an induction phase and autologous stem cell transplantation in patients under 65-70 years. Prolonged treatment (consolidation and/or maintenance) is being introduced in many countries. We present a review of clinical trials dedicated to consolidation treatment in multiple myeloma. Bortezomib, lenalidomide and carfilzomib in different combinations were tested in the trials mentioned below. Although they did not prolong overall survival, the data are very promising. Three very important large clinical trials are still in progress. The results might help to establish the actual value of consolidation treatment.

10.
Adv Clin Exp Med ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819940

RESUMO

BACKGROUND: The coronavirus pandemic has become the most critical global health threat of this century and the greatest challenge to the human population. The search for simple and quick diagnostic methods enabling the identification of patients infected with the SARS-CoV-2 virus may be a valuable method to track infection. OBJECTIVES: The aim of the study was the clinical and immunological characterization of patients by assessing the degrees of maturity of T lymphocytes from the 1st and 5th waves of coronavirus disease 2019 (COVID-19) in comparison to a healthy control group (HC). MATERIAL AND METHODS: We determined leukocyte and T lymphocyte subpopulations (recent thymic emigrant (RTE), naïve, effector, central memory and effector memory) in patients from the 1st COVID-19 wave (n = 23), the 5th COVID-19 wave (n = 38) and HC (n=20) using a panel of monoclonal antibodies using multiparameter flow cytometry. RESULTS: We observed a lower median proportion of lymphocytes and NK cells, and elevated percentage and number of neutrophils in patients from the 5th wave compared to the 1st. We found a reduced percentage of CD4+ effector memory cells in the 1st wave group compared to the 5th wave (14.1 vs 23.2, p < 0.05), and a higher percentage of RTE and naïve CD8+ cells in the 1st wave compared to the 5th wave (p < 0.05). The effector memory CD8+ cells were highest in the 5th wave compared to both 1st wave and HC patients (respectively, 35.1 vs 18.1 vs 19.3%, p < 0.05). The 5th wave group showed significantly more differences compared to HC. CONCLUSIONS: Our results showed a clear increase of effector cells with a simultaneous decrease in virgin T cells in the 5th COVID-19 infection. Monitoring lymphocyte subsets during infection allows assessment of the patient's immune status and of readiness of lymphocytes to respond to the immune response, and may be necessary to improve clinical outcomes.

11.
Anal Biochem ; 434(1): 78-83, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23146589

RESUMO

Lysosomal phospholipase A2 (group XV PLA2, LPLA2) is a lysosomal enzyme linked to drug-induced phospholipidosis. We developed phospholipid "smart probes" based on the conversion of a quenched fluorogenic substrate to a fluorescent product. Due to the preference of LPLA2 for phosphatidylglycerol, three fluorogenic phosphatidylglycerols were synthesized. Two fluorogenic phosphatidylglycerols were conjugated with one FAM (fluorescein amidite) group and one DABCYL [4-(4-dimethylaminophenylazo)-benzoyl] group; the third substrate consisted of two FAM groups conjugated at the sn-1 and sn-2 positions. The sn-1 ester linkage was replaced with an amide linkage. 1-FAM-2-DABCYL-PG was degraded by recombinant LPLA2 and mouse serum but not by the serum obtained from LPLA2-deficient mice when 1,2-dioleoyl-PG/1-FAM-2-DABCYL-PG liposomes were used. The formation of 1-FAM-lyso-PG generated from 1-FAM-2-DABCYL-PG in the presence of LPLA2 was quantitatively determined by fluorescent measurements. The 1-FAM-2-DABCYL-PG incorporated into 1,2-dioleoyl-phosphatidylcholine/sulfatide liposomes was used to evaluate the effect of the cationic amphiphilic drugs amiodarone and fluoxetine on LPLA2 activity. The IC(50) values of amiodarone and fluoxetine estimated by fluorescent measurement were 10 and 19µM, respectively. These results indicate that 1-FAM-2-DABCYL-PG is a specific substrate for LPLA2 and a useful reagent for the detection of LPLA2 activity from multiple sources.


Assuntos
Corantes Fluorescentes/química , Lisossomos/enzimologia , Fosfatidilgliceróis/metabolismo , Fosfolipases A2/análise , Espectrometria de Fluorescência , Animais , Fluoresceína/química , Lipossomos/química , Camundongos , Fosfatidilgliceróis/química , Fosfolipases A2/genética , Fosfolipases A2/metabolismo , Proteínas Recombinantes/análise , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Especificidade por Substrato , p-Dimetilaminoazobenzeno/análogos & derivados , p-Dimetilaminoazobenzeno/química
12.
Biomedicines ; 11(10)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37893102

RESUMO

The mechanisms underlying the immune response to coronavirus disease 2019 (COVID-19) and the recovery process have not been fully elucidated. The aim of the study was to analyze leukocyte subpopulations in patients at significant time points (at diagnosis, and 3 and 6 months after infection) selected according to the analysis of changes in the lungs by the CT classification system, considering the severity of the disease. The study groups consisted of severe and non-severe COVID-19 patients. There was a significant decrease in CD8+ T cells, NK and eosinophils, with an increasing percentage of neutrophils during hospitalization. We noticed lower levels of CD4 and CD8 T lymphocytes, eosinophils, basophils, and CD16+ monocytes and elevated neutrophil levels in severe patients relative to non-severe patients. Three months after infection, we observed higher levels of basophils, and after 6 months, higher CD4/CD8 ratios and T cell levels in the severe compared to non-severe group. Non-severe patients showed significant changes in the leukocyte populations studied at time of hospitalization and both within 3 months and 6 months of onset. The CT CSS classification with parameters of the flow cytometry method used for COVID-19 patients determined changes that proved useful in the initial evaluation of patients.

13.
Cancers (Basel) ; 15(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37958349

RESUMO

Macrophages play an important role in the suppression and activation of immune anti-cancer response, but little is known about dominant macrophage phenotype in the lung cancer environment, evaluated by bronchoalveolar lavage fluid (BALF). The aim of this study was to characterize macrophages in BALF from a lung affected by cancer (cBALF) and a healthy lung (hBALF) of the same patient regarding their individual macrophage polarization and selected cytokines profile. A total of 36 patients with confirmed lung cancer were investigated. Macrophages markers: CD206 CD163 CD80 CD86 CD40 CD45, Arginase-1, and CD68 were evaluated by flow cytometry. Cytokines (IL-1 RA, IL-6, IL-10, TNF-α, IL-1ß, IL-12, IL-23, and TGF-ß) profile was analyzed. There was higher median proportion of macrophages in Cbalf than in Hbalf. The population of macrophages presented immunophenotype: Ccd68+bright CD206+bright CD163+bright CD80+ CD86+ CD40+bright CD45+ cArginase+. We observed some trends in the expression of the analyzed antigens in clBALF and hlBLAF. The highest concentrations of IL-1RA and IL-6 were in Cbalf and Hbalf supernatant. There were the correlations between pro- and anti-inflammatory cytokines. The findings showed that macrophages include a diverse and plastic group with the presence of different antigens and cytokines, and determining the target phenotype is a complex and variable process.

14.
Cancers (Basel) ; 15(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37173954

RESUMO

Myelodysplastic syndromes (MDS) are common malignant disorders with a poor prognosis. It is necessary to search for new rapid diagnostic methods to detect MDS patients with cytogenetic changes. The aim of the study was to assess new hematological neutrophil- and monocyte- related parameters I then bone marrow of MDS patient with and without cytogenetic changes. A total of 45 patients with MDS, including 17 patients with cytogenetic changes, were examined. The study was conducted using the Sysmex XN-Series hematological analyzer. New neutrophil and monocyte parameters, such as immature granulocytes (IG), neutrophil reactivity intensity (NEUT-RI), neutrophil granularity intensity (NEUT-GI), neutrophil size (NE-FSC) and neutrophil/monocyte data relating to granularity, activity and volume (NE-WX/MO-WX, NE-WY/MO-WY, NE-WZ/MO-WZ, MO-X, MO-Y, MO-Z) were evaluated. We observed higher median proportions of NE-WX, NE-WY, NE-WZ, and IG counts in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The NE-FSC parameter was lower in MDS patients with cytogenetic changes than in patients without cytogenetic changes. The combination of new neutrophil parameters was found to be a new successful approach in distinguishing MDS patients with cytogenetic changes from patients without cytogenetic changes. It appears that there may be unique neutrophil parameter signatures associated with an underlying mutation.

15.
Cancers (Basel) ; 15(13)2023 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-37444579

RESUMO

Fragility scales are intended to help in therapeutic decisions. Here, we asked if the fragility assessment in MM patients ≥ 75 years old qualified for treatment by the local physician correlates with the choice of treatment: a two- or three-drug regimens. Between 7/2018 and 12/2019, we prospectively enrolled 197 MM patients at the start of treatment from the 13 Polish Myeloma Group centers. The data to assess fragility were prospectively collected, but centrally assessed fragility was not disclosed to the local center. The activity of daily living (ADL) could be assessed in 192 (97.5%) and was independent in 158 (80.2%), moderately impaired in 23 (11.7%), and 11 (5.6%) in completely dependent. Patients with more than three comorbidities made up 26.9% (53 patients). Thus, according to the Palumbo calculator, 43 patients were in the intermediate fitness group (21.8%), and the rest belonged to the frailty group (153, 77.7%). Overall, 79.7% of patients (157) received three-drug regimens and 20.3% (40) received two-drug regimens. In each ECOG group, more than three out of four patients received three-drug regimens. According to the ADL scale, 82.3% of the independent 65.2% of moderately impaired, and 81.8% of the dependent received three-drug regimens. Out of 53 patients with at least four comorbidities, 71.7% received three-drug regimens, and the rest received two-drug regimens. Thirty-four patients from the intermediate fit group (79.0%), and 123 (79.9%) from the frail group received three-drug regimens. Early mortality occurred in 25 patients (12.7%). No one discontinued treatment due to toxicity. To conclude, MM patients over 75 are mainly treated with triple-drug regimens, not only in reduced doses, regardless of their frailty scores. However, the absence of prospective fragility assessment did not negatively affect early mortality and the number of treatment discontinuations, which brings into question the clinical utility of current fragility scales in everyday practice.

16.
Amino Acids ; 43(4): 1653-61, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22349763

RESUMO

A new approach for the separation of 6-aminoquinolyl-carbamyl (AQC)-derivatized amino acids has been proposed. The chromatography used ion-pairing mechanism to increase the method selectivity. Mobile phase was based on triethylamine buffer containing N,N-dimethyloctylamine as a modifier. A number of factors, buffer composition and pH, counterion concentration, temperature and acetonitrile gradient profile, were optimized to achieve final chromatographic conditions. With the presented analytical method, the separation and identification of 34 AQC-amino acids and amino compounds present in human plasma is possible. The results of validation proved the applicability of the method for quantification of 27 amino acids in biological samples. The ultrafiltration proposed as deproteinization procedure gave repeatable and reliable results for the amino acids under investigation. This method introduced in routine testing can be a suitable tool for amino acid profiling in plasma including all aspects of clinical application.


Assuntos
Aminoácidos/sangue , Aminoquinolinas/química , Carbamatos/química , Acetonitrilas , Aminoácidos/química , Soluções Tampão , Cromatografia Líquida de Alta Pressão , Etilaminas , Humanos , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Temperatura , Ultrafiltração
17.
Contemp Oncol (Pozn) ; 16(1): 90-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23788861

RESUMO

Kidney cancer, despite the constant upward trend in the incidence of this type of cancer (about 1.5-5.9% per year), is rather rare, representing approximately 2-3% of all adult cancers. Since recently, drugs based on so-called targeted therapy play a decisive role in the treatment of patients with metastatic kidney cancer. Prognostic and predictive factors can significantly contribute to prognosis assessment and the correct classification of patients to specific forms of causal treatment of kidney cancer. In addition to the most commonly used and widely known prognostic factors, grouped in the so-called Motzer model, new prognostic markers of this tumour are being sought. Preliminary reports indicate that there may be a promising role of factors that regulate the cell cycle and apoptosis, and agents from the group of hypoxia-induced proteins. The proliferation markers or proteins related to cellular adhesion can also be relevant. This article presents examples of markers from the first of the above groups of proteins, which on the basis of the performed analyses showed independent prognostic or predictive value in kidney cancer.

18.
Contemp Oncol (Pozn) ; 16(3): 250-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23788889

RESUMO

Malignant tumours of the kidneys are relatively rare tumours that occur in adults, although there has been a constant increase in the incidence of this cancer type in recent years. It occupies the 10(th) place in terms of the number of new cases of cancer in men and 14(th) place in women. Considerable progress in the treatment of renal cell carcinoma over the last years has forced researchers to look for new factors of potential prognostic or predictive value in this tumour type in order to clarify the selection of patients for optimal treatment. The drugs from the group of tyrosine kinase inhibitors have played a decisive role. So far, the Motzer model, grouping the prognostic factors, has been most commonly used in clinical practice. Based on the current research looking for new markers of prognostic or predictive value, these factors can be divided into cellular hypoxia-induced proteins and proteins regulating the cell cycle and the apoptosis process. In the second part of this study, hypoxia-inducible factors will be discussed.

19.
Am J Case Rep ; 23: e935141, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35332114

RESUMO

BACKGROUND Extramedullary hematopoiesis in organs outside the bone marrow most commonly occurs in the liver and spleen. This report is of a case of multifocal extramedullary and non-hepatosplenic extramedullary hematopoiesis a 43-year-old man with a history of congenital Eisenmenger syndrome. CASE REPORT We present the case of a 43-year-old patient with complex heart disease and full-blown Eisenmenger syndrome associated with ventricular septal defect, bicuspid right ventricle, and pulmonary hypertension. In July 2020, the patient began to report neurological symptoms in the form of lower-limb numbness and weakness of lower-limb strength, with additional increasing lower-limb edema. A CT scan of the abdomen and pelvis revealed a 63×102×103 mm soft-tissue mass in the pelvis, located behind the urinary bladder. Due to the suspicion of proliferative disease, mainly of the lymphatic system, a diagnostic trephine biopsy was performed first, but no tumor cell infiltration was found. Then, the patient was qualified for diagnostic surgery. During the operation, tumor sections were harvested. Histopathological examination of the tissue sections showed extramedullary hematopoiesis in the tumor lining. Hydroxycarbamide was used as first-line treatment. However, it was not effective in controlling clinical symptoms. Therefore, the patient was qualified for radiotherapy as a second-line palliative treatment. CONCLUSIONS This report presents a patient with cyanotic heart disease and extramedullary and non-hepatosplenic hematopoiesis presenting as masses that mimicked malignancy. In this case, palliative radiotherapy effectively reduced the symptoms due to the size of the mass lesion.


Assuntos
Complexo de Eisenmenger , Doenças Hematológicas , Hematopoese Extramedular , Adulto , Complexo de Eisenmenger/complicações , Humanos , Fígado , Masculino , Tomografia Computadorizada por Raios X
20.
Viruses ; 14(4)2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35458548

RESUMO

Monocytes play a role in viral biology, but little is known about the monocyte subpopulation in the course of COVID-19 disease. The aim of the study was the analysis of classical, intermediate and non-classical monocytes with expression of PD-L1 and CD62L, TIM-3 and CD86 molecules in peripheral blood (PB) to distinguish patients with SARS-CoV-2 infection from convalescent patients. The study group consisted of 55 patients with SARS-CoV-2 infection and 51 convalescent patients. The cells were analyzed by flow cytometry. The number and proportion of monocytes were lower in patients with COVID-19 than convalescent patients. We observed a lower proportion of non-classical monocytes in COVID-19 patients than convalescent ones. There was a higher proportion of PDL-1-positive intermediate monocytes in COVID-19 patients than convalescent ones. We noticed a higher geometric mean fluorescence intensity (GeoMean) of PD-L1 on intermediate monocytes in COVID-19 patients than convalescent patients, and a higher proportion of CD62L-positive monocytes in COVID-19 patients in comparison with convalescent ones. We found a higher GeoMean of CD62L on monocytes in COVID-19 patients than convalescent ones. Assessment of PD-L1- and CD62L-positive monocyte subsets may identify patients with a possible predisposition for rapid recovery. The monitoring of monocyte subsets in PB might be a useful test in COVID-19 patients.


Assuntos
Antígeno B7-H1 , COVID-19 , Selectina L , Monócitos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , COVID-19/genética , COVID-19/metabolismo , Citometria de Fluxo , Humanos , Selectina L/genética , Selectina L/metabolismo , Monócitos/metabolismo , SARS-CoV-2
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