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1.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675020

RESUMO

Lung cancer is a disease that in recent years has become one of the greatest threats to modern society. Every year there are more and more new cases and the percentage of deaths caused by this type of cancer increases. Despite many studies, scientists are still looking for answers regarding the mechanisms of lung cancer development and progression, with particular emphasis on the role of the immune system. The aim of this literature review was to present the importance of disorders of the immune system and the accompanying changes at the level of cell signaling in the pathogenesis of lung cancer. The collected results showed that in the process of immunopathogenesis of almost all subtypes of lung cancer, changes in the tumor microenvironment, deregulation of immune checkpoints and abnormalities in cell signaling pathways are involved, which contribute to the multistage and multifaceted carcinogenesis of this type of cancer. We, therefore, suggest that in future studies, researchers should focus on a detailed analysis of tumor microenvironmental immune checkpoints, and to validate their validity, perform genetic polymorphism analyses in a wide range of patients and healthy individuals to determine the genetic susceptibility to lung cancer development. In addition, further research related to the analysis of the tumor microenvironment; immune system disorders, with a particular emphasis on immunological checkpoints and genetic differences may contribute to the development of new personalized therapies that improve the prognosis of patients.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transdução de Sinais , Carcinogênese , Microambiente Tumoral/genética , Sistema Imunitário/metabolismo
2.
Molecules ; 25(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32353989

RESUMO

Naturally occurring coumarins are bioactive compounds widely used in Asian traditional medicine. They have been shown to inhibit proliferation, induce apoptosis, and/or enhance the cytotoxicity of currently used drugs against a variety of cancer cell types. The aim of our study was to examine the antiproliferative activity of different linear furanocoumarins on human rhabdomyosarcoma, lung, and larynx cancer cell lines, and dissolve their cellular mechanism of action. The coumarins were isolated from fruits of Angelica archangelica L. or Pastinaca sativa L., and separated using high-performance counter-current chromatography (HPCCC). The identity and purity of isolated compounds were confirmed by HPLC-DAD and NMR analyses. Cell viability and toxicity assessments were performed by means of methylthiazolyldiphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, respectively. Induction of apoptosis and cell cycle progression were measured using flow cytometry analysis. qPCR method was applied to detect changes in gene expression. Linear furanocoumarins in a dose-dependent manner inhibited proliferation of cancer cells with diverse activity regarding compounds and cancer cell type specificity. Imperatorin (IMP) exhibited the most potent growth inhibitory effects against human rhabdomyosarcoma and larynx cancer cell lines owing to inhibition of the cell cycle progression connected with specific changes in gene expression, including CDKN1A. As there are no specific chemotherapy treatments dedicated to laryngeal squamous cell carcinoma and rhabdomyosarcoma, and IMP seems to be non-toxic for normal cells, our results could open a new direction in the search for effective anti-cancer agents.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Furocumarinas/farmacologia , Neoplasias Laríngeas/patologia , Rabdomiossarcoma/patologia , Angelica archangelica/química , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Cromatografia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Citometria de Fluxo , Frutas/química , Humanos , L-Lactato Desidrogenase/metabolismo , Neoplasias Laríngeas/tratamento farmacológico , Pastinaca/química , Rabdomiossarcoma/tratamento farmacológico
3.
BMC Microbiol ; 17(1): 167, 2017 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28747178

RESUMO

BACKGROUND: Cationic antibacterial peptides (CAPs) and synthetic molecules mimicking the amphiphilic structure of CAPs, such as ceragenins, are promising compounds for the development of new antimicrobials. RESULTS: We tested the in vitro activity of ceragenins CSA-13 and CSA-131 against several anaerobic bacteria including Bacteroides spp. and Clostridium difficile. We compared results to the activity of cathelicidin LL-37, metronidazole and nanosystems developed by attachment of CSA-13 and CSA-131 to magnetic nanoparticles (MNPs). The antibacterial effect was tested using killing assay and modified CLSI broth microdilution assay. Ceragenins CSA-13 and CSA-131 displayed stronger bactericidal activity than LL-37 or metronidazole against all of the tested bacterial strains. Additionally CSA-131 revealed an enhanced ability to prevent the formation of Bacteroides fragilis and Propionibacterium acnes biofilms. CONCLUSIONS: These data confirmed that ceragenins display antimicrobial activity against a broad range of microorganisms including anaerobic bacteria and deserve further investigations as compounds serving to develop new treatment against anaerobic and mixed infections.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Bactérias Anaeróbias/crescimento & desenvolvimento , Nanopartículas de Magnetita/química , Pregnanos/farmacologia , Esteroides/farmacologia , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Pregnanos/química , Esteroides/química , Catelicidinas
4.
J Clin Med ; 13(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38792335

RESUMO

(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision.

5.
J Clin Med ; 13(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38592328

RESUMO

Background: Non-small-cell lung cancer (NSCLC) is one of the most frequently diagnosed diseases among all types of lung cancer. Infectious diseases contribute to morbidity and mortality by delaying appropriate anti-cancer therapy in patients with NSCLC. Methods: The study aimed to evaluate the effectiveness of vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) in 288 newly diagnosed NSCLC patients. The analysis of the post-vaccination response was performed after vaccination by assessing the frequency of plasmablasts via flow cytometry and by assessing the concentration of specific anti-pneumococcal antibodies using enzyme-linked immunosorbent assays. Results: The results of the study showed that NSCLC patients responded to the vaccine with an increase in the frequencies of plasmablasts and antibodies but to a lesser extent than healthy controls. The immune system response to PCV13 vaccination was better in patients with lower-stage NSCLC. We found higher antibody levels after vaccination in NSCLC patients who survived 5 years of follow-up. Conclusions: We hope that our research will contribute to increasing patients' and physicians' awareness of the importance of including PCV13 vaccinations in the standard of oncological care, which will extend the survival time of patients and improve their quality of life.

6.
Front Oncol ; 14: 1341084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322415

RESUMO

Introduction: Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS. Conclusions: In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.

7.
Cancers (Basel) ; 15(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37894426

RESUMO

This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein-Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies.

8.
Diagnostics (Basel) ; 13(18)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37761256

RESUMO

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is a well-known oncogene with a high prevalence of mutation in breast cancer patients. The effect of the mutation is a deregulation in phosphatidylinositol 3-kinase-related pathways, and, consequently, in unrestricted cell growth and differentiation. With the advent of precision oncology, PIK3CA has emerged as a pivotal treatment target, culminating in the recent approval of alpelisib. Despite years of research on this genetic alteration, certain aspects of its influence on the prognosis of breast cancer remain ambiguous. The purpose of this analysis is to characterize the clinical picture of breast cancer patients with PIK3CA mutation in comparison to the PIK3CA-wild-type group. We examined 103 tumor samples from 100 breast cancer patients using a next-generation sequencing panel. Presence of the mutation was linked to an older age at diagnosis, a lower expression of Ki67 protein, a greater percentage of tumors expressing progesterone receptors, and a notably higher incidence of metastatic disease at presentation. No significant differences were identified in overall and progression-free survival between the two groups. Our findings enhance the understanding of how PIK3CA mutations shape the clinical and prognostic landscape for breast cancer patients.

9.
Cancers (Basel) ; 15(19)2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37835383

RESUMO

Estrogen receptor (ER) signaling is a critical regulator of cell proliferation, differentiation, and survival in breast cancer (BC) and other hormone-sensitive cancers. In this review, we explore the mechanism of ER-dependent downstream signaling in BC and the role of estrogens as growth factors necessary for cancer invasion and dissemination. The significance of the clinical implications of ER signaling in BC, including the potential of endocrine therapies that target estrogens' synthesis and ER-dependent signal transmission, such as aromatase inhibitors or selective estrogen receptor modulators, is discussed. As a consequence, the challenges associated with the resistance to these therapies resulting from acquired ER mutations and potential strategies to overcome them are the critical point for the new treatment strategies' development.

10.
Cancers (Basel) ; 15(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37835480

RESUMO

Primary immunodeficiencies (PIDs) and secondary immunodeficiencies (SIDs) are characterized by compromised immune function, rendering individuals susceptible to infections and potentially influencing cancer development. Epstein-Barr virus (EBV), a widespread herpesvirus, has been linked to cancer, particularly in those with weakened immune systems. This study aims to compare selected immune parameters, focusing on immune checkpoint molecules (PD-1/PD-L1, CTLA-4/CD86, CD200R/CD200), and EBV reactivation in patients with chronic lymphocytic leukemia (CLL, a representative of SIDs) and common variable immunodeficiency (CVID, a representative of PIDs). We performed a correlation analysis involving patients diagnosed with CLL, CVID, and a healthy control group. EBV reactivation was assessed using specific antibody serology and viral load quantification. Peripheral blood morphology, biochemistry, and immunophenotyping were performed, with emphasis on T and B lymphocytes expressing immune checkpoints and their serum concentrations. Our findings revealed elevated EBV reactivation markers in both CLL and CVID patients compared with healthy controls, indicating increased viral activity in immunodeficient individuals. Furthermore, immune checkpoint expression analysis demonstrated significantly altered percentages of T and B lymphocytes expressing PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200 in CLL and CVID patients. This suggests a potential interplay between immune checkpoint dysregulation and EBV reactivation in the context of immunodeficiency. In conclusion, our study underscores the intricate relationship between immune dysfunction, EBV reactivation, and immune checkpoint modulation in the context of immunodeficiency-associated cancers. The altered expression of immune checkpoints, along with heightened EBV reactivation, suggests a potential mechanism for immune evasion and tumor progression. These findings provide insights into the complex interactions that contribute to cancer development in immunocompromised individuals, shedding light on potential therapeutic targets for improved management and treatment outcomes. Further investigations are warranted to elucidate the underlying mechanisms and to explore potential interventions to mitigate cancer risk in these patient populations.

11.
Cancers (Basel) ; 14(3)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35158937

RESUMO

Infection with Epstein-Barr virus (EBV) worsens the prognosis in chronic lymphocytic leukemia (CLL), but the underlying mechanisms are not yet established. We intended to assess whether EBV affects the course of CLL by the deregulation of the CTLA-4/CD86 signaling pathway. We used polymerase chain reaction to measure the load of EBV DNA in the blood of 110 newly diagnosed patients with CLL. The expression of CTLA-4 and CD86 antigen on lymphocytes was assessed with flow cytometry. Additionally, CTLA-4 and CD86 serum concentrations were measured through enzyme-linked immunosorbent assays. Fifty-four percent of the patients had detectable EBV DNA [EBV(+)]. In EBV(+) patients the CTLA-4 and CD86 serum concentrations and their expressions on investigated cell populations were significantly higher than in EBV(-) patients. EBV load correlated positively with unfavorable prognostic markers of CLL and the expression of CTLA-4 on CD3+ lymphocytes (r = 0.5339; p = 0.027) and CD86 on CD19+ cells (r = 0.6950; p < 0.001). During a median follow-up period of 32 months EBV(+) patients were more likely to require treatment or have lymphocyte doubling (p < 0.001). Among EBV(+) but not EBV(-) patients, increased expressions of CTLA-4 lymphocytes were associated with elevated risks of progression. We propose that EBV coinfection may worsen prognosis in CLL patients, partly due to EBV-induced up-regulation of CTLA-4 expression.

12.
Am J Cancer Res ; 11(6): 2821-2837, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249430

RESUMO

Successful treatment of advanced larynx squamous cell carcinoma (LSCC) remains a challenge, mainly due to limited response to chemotherapy and the phenomenon of the drug resistance. Therefore, new chemotherapeutic solutions are needed. The aim of this study was to explore benefit of combined cisplatin (CDDP) and valproic acid (VPA) therapy in patients' derived LSCC cell lines. Cell viability assay was used to establish cellular response to the drug by isobolography followed by RNA sequencing (RNAseq) analysis. Danio rerio were used for in vivo studies. Depending on the cell line, we found that the combinations of drugs resulted in synergistic or antagonistic pharmacological interaction, which was accompanied by significant changes in genes expression profiles. The presented therapeutic scheme efficiently blocked tumor growth in an in vivo model, corresponding to the in vitro performed studies. Interestingly the RK5 cell line, upon the combined treatment acquired a molecular profile typically associated with epithelial to mesenchymal transition (EMT). Hence, our studies demonstrates that patient-specific personalized therapy of larynx cancer should be considered and the combination of cisplatin and valproic acid should be explored as a potential therapeutic strategy in the treatment of larynx cancer.

13.
Biomolecules ; 11(8)2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34439871

RESUMO

Ovarian cancer is a global problem that affects women of all ages. Due to the lack of effective screening tests and the usually asymptomatic course of the disease in the early stages, the diagnosis is too late, with the result that less than half of the patients diagnosed with ovarian cancer (OC) survive more than five years after their diagnosis. In this study, we examined the expression of TLR2 in the peripheral blood of 50 previously untreated patients with newly diagnosed OC at various stages of the disease using flow cytometry. The studies aimed at demonstrating the usefulness of TLR2 as a biomarker in the advanced stage of ovarian cancer. In this study, we showed that TLR2 expression levels were significantly higher in women with more advanced OC than in women in the control group. Our research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and thus in increasing survival in patients with confirmed ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Receptor 2 Toll-Like/sangue , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/metabolismo , Prognóstico
14.
Anticancer Res ; 41(2): 983-991, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517305

RESUMO

BACKGROUND/AIM: Tumorigenesis and cancer progression might be driven by abnormal activation of growth factor receptors. Importantly, molecular changes in EGFR-dependent signaling is one of the most common characteristics of brain tumors. PATIENTS AND METHODS: HER1 and EGFRvIII variants in meningiomas and glioblastomas were evaluated at the RNA level. RESULTS: EGFRvIII was found in 18.6% of glioblastomas (GBM), whereas 25% of EGFRvIII positive tumors express wild-type EGFR as well. HER1 was over-expressed in benign meningiomas compared to glioblastomas, whereas HER1 expression in meningiomas differed significantly between sub-types of meningiomas. EGFRvIII and HER1 where positively correlated in glioblastomas. Yet, the patient overall survival did not differ between high- and low-HER1 expressing glioblastomas or between EGFRvIII positive and negative GBMs. CONCLUSION: HER1 may be considered as an independent factor for classification of benign meningiomas. The mRNA levels of HER1 or EGFRvIII should not be used as independent prognostic factors for patients with gliomas.


Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Receptores ErbB/genética , Feminino , Marcadores Genéticos , Humanos , Masculino , Neoplasias Meníngeas/genética , Meningioma/genética , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Regulação para Cima
15.
J Clin Med ; 9(6)2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32560392

RESUMO

Gastric cancer (GC) is one of the most commonly diagnosed malignancies and, unfortunately, still has a high mortality rate. Recent research points to CAR-T immunotherapy as a promising treatment for this disease. Using genetically engineered T cells designed to target a previously selected antigen, researchers are able to harness the natural anti-tumor activity of T cells. For therapy to be successful, however, it is essential to choose antigens that are present on tumor cells but not on healthy cells. In this review, we present an overview of the most important targets for CAR-T therapy in the context of GC, including their biologic function and therapeutic application. A number of clinical studies point to the following as important markers in GC: human epidermal growth factor receptor 2, carcinoembryonic antigen, mucin 1, epithelial cell adhesion molecule, claudin 18.2, mesothelin, natural-killer receptor group 2 member D, and folate receptor 1. Although these markers have been met with some success, the search for new and improved targets continues. Key among these novel biomarkers are the B7H6 ligand, actin-related protein 2/3 (ARP 2/3), neuropilin-1 (NRP-1), desmocollin 2 (DSC2), anion exchanger 1 (AF1), and cancer-related antigens CA-72-4 and CA-19-9.

16.
Front Oncol ; 10: 545078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33330023

RESUMO

BACKGROUND: The study aimed to identify the association between the lifestyle-related factors and the cancer-specific, or non-cancer-specific mortality, when accompanied by a competing risk. Two statistical methods were applied, i.e., cause-specific hazard (CSH), and sub-distribution hazard ratio (SHR). Their respective key advantages, relative to the actual study design, were addressed, as was overall application potential. METHODS: Source data from 4,584 residents (34.2% men), aged 45-64 years, were processed using two different families of regression models, i.e., CSH and SHR; principal focus upon the impact of lifestyle-related factors on the competing risk of cancer and non-cancer mortality. The results were presented as hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: Age, smoking status, and family history of cancer were found the leading risk factors for cancer death; the risk of non-cancer death higher in the elderly, and smoking individuals. Non-cancer mortality was strongly associated with obesity and hypertension. Moderate to vigorous physical activity decreased the risk of death caused by cancer and non-cancer causes. CONCLUSIONS: Specific, lifestyle-related factors, instrumental in increasing overall, and cancer-specific mortality, are modifiable through health-promoting, individually pursued physical activities. Regular monitoring of such health-awareness boosting pursuits seems viable in terms of public health policy making.

17.
Cells ; 9(4)2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316105

RESUMO

Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit-risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen.


Assuntos
Antígeno de Maturação de Linfócitos B/imunologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Imunoterapia Adotiva/métodos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Antígenos CD1d/imunologia , Antígeno de Maturação de Linfócitos B/metabolismo , Humanos , Cadeias beta de Integrinas/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Medição de Risco , Sindecana-1/imunologia , Sindecana-1/metabolismo
18.
Clin Interv Aging ; 15: 2301-2311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335389

RESUMO

BACKGROUND: Loss of fat-free mass (FFM) and gain in body fat (BF) are the key disability risk factors, also instrumental in perpetuating already existing functional disorders. Obesity construed in terms of body mass index (BMI) values, in view of undesirable gain in BF, is a risk factor for cardio-metabolic disorders. Both detrimental processes clearly evidence a scope of involutionary changes characteristic of an aging population, also standing for one of its greatest burdens. PURPOSE: The present study aimed to assess the changes in body composition (BC), in conjunction with the relationship between BF% and BMI, for defining overweight and obesity status in middle-aged and older adults, against the select indicator variables under study. MATERIALS AND METHODS: The study involved 4799 individuals (33.7% men), PONS Project participants, aged 43-64 years. BF% was measured with the aid of bioelectrical impedance analysis (BIA) method. Age-induced changes in BC were determined against BF%, fat mass (FM), FFM, BMI, fat mass index (FMI), and fat-free mass index (FFMI). The relationship between BF% and BMI was established with the aid of Bayesian regression models, adjusted for gender and age. RESULTS: In both genders, BF% increased with age at a similar annual rate. The reduction of FFM was noted mainly in men, which in conjunction with BF% gain ensured BMI stability. The increase in BF% in women with stable FFM affected an increase in BMI. Regardless of the BMI threshold, the anticipated (predicted) BF% increased with age in both genders. CONCLUSION: Monitoring of BC is of particular importance in older adults, in view of appreciably better characteristics of both the short- and long-term health predictors, as well as overall potential for developing specifically targeted, effective health interventions.


Assuntos
Tecido Adiposo/fisiologia , Envelhecimento/fisiologia , Índice de Massa Corporal , Sobrepeso/diagnóstico , Sobrepeso/fisiopatologia , Adulto , Teorema de Bayes , Composição Corporal , Estudos de Coortes , Estudos Transversais , Impedância Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia
19.
Clin Interv Aging ; 15: 161-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103918

RESUMO

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide; with age acknowledged as an independent cardiovascular risk factor (CRF) in adults. Appreciating the association between age and classic CRFs is believed to boost all potential benefits of prevention. PURPOSE: Assessment of the prevalence of single and clustered CRFs and their association with age. PATIENTS AND METHODS: The survey involved 4735 people (33.6% men) who were PONS project attendees aged 45-64. The study protocol comprised the Health Status Questionnaire, general medical examination, anthropometric measurements, and blood and urine sampling. The prevalence of single and clustered CRFs (hypertension, dyslipidemia, diabetes mellitus, and obesity) in the incrementally split age groups was calculated. The incidence rate of CRFs, against their absence, was determined by Poisson regression models with robust standard errors. RESULTS: The prevalence of CRFs was established in 90% of the respondents. Except dyslipidemia and ≥1 CRFs, prevalence of risk factors increased with age, although this trend was the weakest in men. In the total group, and in women, prevalence of dyslipidemia and ≥1 CRFs was unrelated to age, whereas in men, it was on the rise in the younger age groups. The incidence rate of CRFs was strongly related to age, and, with the exception of dyslipidemia, was higher in the older age groups. CONCLUSION: Cardiovascular risk factors are common in the adult population, while their prevalence and clustering are more prevalent in seniors. Apart from dyslipidemia, the risk of CRFs is appreciably age-related, and higher in seniors.


Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Obesidade/epidemiologia , Fatores Etários , Idoso , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Prevalência , Fatores de Risco
20.
J Clin Med ; 9(9)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911835

RESUMO

Modest weight loss enhances clinical control over cardiovascular disease (CVD) risk factors in overweight and obese individuals. This study aimed to assess the associations between individual weight loss and predefined criteria for clinical improvement in blood pressure, lipid levels, and glycemia. A two-year follow-up study involved 3388 (37.9% men) aged 45-64 years, BMI ≥ 25 kg/m2. Changes in body weight were calculated as a percentage of baseline weight; outcome variables: systolic (SBP), diastolic (DBP) blood pressure, high-density (HDL-C) and low-density (LDL-C) lipoproteins, fasting blood glucose (FBG), and triglycerides (TG) were construed as the differences between baseline and outcome values. Clinically significant improvement was defined as SBP/DBP reduction by 5 mm/Hg, FBG-20 mg/dL, LDL-C-10 mg/dL, TG-40 mg/dL, and HDL-C increase by 5 mg/dL. Apart from LDL-C, a modest 5%-10% weight loss was associated with clinically significantly improved outcomes. The incident rate ratios and 95% confidence intervals for clinical improvement of SBP were: 1.27 (1.14-1.40), DBP/1.30 (1.12-1.50), HDL/1.54 (1.18-2.02), and TG/1.69 (1.32-2.17). In the higher category of weight loss, associations were still manifest, although the results proved diagnostically challenging (low number of cases). Even though modest weight loss does enhance clinical control over CVD risk factors, offering regular medical guidance to patients is postulated to further boos the anticipated outcomes.

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