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1.
Forensic Sci Int Genet ; 68: 102946, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39090852

RESUMO

The DNA Commission of the International Society for Forensic Genetics (ISFG) has developed a set of nomenclature recommendations for short tandem repeat (STR) sequences. These recommendations follow the 2016 considerations of the DNA Commission of the ISFG, incorporating the knowledge gained through research and population studies in the intervening years. While maintaining a focus on backward compatibility with the CE data that currently populate national DNA databases, this report also looks to the future with the establishment of recommended minimum sequence reporting ranges to facilitate interlaboratory comparisons, automated solutions for sequence-based allele designations, a suite of resources to support bioinformatic development, guidance for characterizing new STR loci, and considerations for incorporating STR sequences and other new markers into investigative databases.


Assuntos
Genética Forense , Repetições de Microssatélites , Terminologia como Assunto , Humanos , Genética Forense/métodos , Sociedades Científicas , Impressões Digitais de DNA , Bases de Dados de Ácidos Nucleicos
2.
JACC Clin Electrophysiol ; 10(8): 1840-1847, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38904577

RESUMO

BACKGROUND: Current therapies for pulmonary vein stenosis (PVS) or pulmonary vein total occlusion (PVTO) involving angioplasty and stenting are hindered by high rates of restenosis. OBJECTIVES: This study compares a novel approach of drug-coated balloon (DCB) angioplasty and stenting with the current standard of care in PVS or PVTO due to pulmonary vein isolation (PVI). METHODS: A retrospective single-center study analyzed patients with PVS or PVTO due to PVI who underwent either angioplasty and stenting (NoDCB group; December 2012-December 2016) or DCB angioplasty and stenting (DCB group; January 2018-January 2021). Multivariable Andersen-Gill regression analysis assessed the risk of restenosis and target lesion revascularization (TLR). RESULTS: The NoDCB group comprised 58 patients and 89 veins, with a longer median follow-up of 35 months, whereas the DCB group included 26 patients and 33 veins, with a median follow-up of 11 months. The DCB group exhibited more PVTO (NoDCB: 12.3%; DCB: 42.4%; P = 0.0001), with a smaller reference vessel size (NoDCB: 10.2 mm; DCB: 8.4 mm; P = 0.0004). Follow-up computed tomography was performed in 82% of NoDCB and 85% of DCB, revealing lower unadjusted rates of restenosis (NoDCB: 26%; DCB: 14.3%) and TLR (NoDCB: 34.2%; DCB: 10.7%) in the DCB group. DCB use was associated with a significantly lower risk of restenosis and TLR (HR: 0.003: CI: 0.00009-0.118; P = 0.002). CONCLUSIONS: The novel approach of DCB angioplasty followed by stenting is effective and safe and significantly reduces the risk of restenosis and reintervention compared with the standard of care in PVS or PVTO due to PVI.


Assuntos
Angioplastia com Balão , Estenose de Veia Pulmonar , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Angioplastia com Balão/métodos , Angioplastia com Balão/instrumentação , Resultado do Tratamento , Adulto , Idoso , Veias Pulmonares/cirurgia , Pneumopatia Veno-Oclusiva
3.
Int J Oncol ; 65(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38940351

RESUMO

Obesity is a chronic disease caused by the accumulation of excessive adipose tissue. This disorder is characterized by chronic low­grade inflammation, which promotes the release of proinflammatory mediators, including cytokines, chemokines and leptin. Simultaneously, chronic inflammation can predispose to cancer development, progression and metastasis. Proinflammatory molecules are involved in the recruitment of specific cell populations in the tumor microenvironment. These cell populations include myeloid­derived suppressor cells (MDSCs), a heterogeneous, immature myeloid population with immunosuppressive abilities. Obesity­associated MDSCs have been linked with tumor dissemination, progression and poor clinical outcomes. A comprehensive literature review was conducted to assess the impact of obesity­associated MDSCs on cancer in both preclinical models and oncological patients with obesity. A secondary objective was to examine the key role that leptin, the most important proinflammatory mediator released by adipocytes, plays in MDSC­driven immunosuppression Finally, an overview is provided of the different therapeutic approaches available to target MDSCs in the context of obesity­related cancer.


Assuntos
Progressão da Doença , Células Supressoras Mieloides , Neoplasias , Obesidade , Microambiente Tumoral , Humanos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Obesidade/complicações , Obesidade/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/etiologia , Microambiente Tumoral/imunologia , Animais , Leptina/metabolismo , Inflamação/imunologia , Inflamação/patologia
4.
Front Immunol ; 15: 1293931, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469299

RESUMO

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Biomarcadores , Linfócitos T CD8-Positivos/patologia , Células Matadoras Naturais/patologia , Lenalidomida/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/patologia , Resposta Patológica Completa
5.
Int J Mol Sci ; 25(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256268

RESUMO

Cancer is a complex disease that, despite advances in treatment and the greater understanding of the tumor biology until today, continues to be a prevalent and lethal disease. Chemotherapy, radiotherapy, and surgery are the conventional treatments, which have increased the survival for cancer patients. However, the complexity of this disease together with the persistent problems due to tumor progression and recurrence, drug resistance, or side effects of therapy make it necessary to explore new strategies that address the challenges to obtain a positive response. One important point is that tumor cells can interact with the microenvironment, promoting proliferation, dissemination, and immune evasion. Therefore, immunotherapy has emerged as a novel therapy based on the modulation of the immune system for combating cancer, as reflected in the promising results both in preclinical studies and clinical trials obtained. In order to enhance the immune response, the combination of immunotherapy with nanoparticles has been conducted, improving the access of immune cells to the tumor, antigen presentation, as well as the induction of persistent immune responses. Therefore, nanomedicine holds an enormous potential to enhance the efficacy of cancer immunotherapy. Here, we review the most recent advances in specific molecular and cellular immunotherapy and in nano-immunotherapy against cancer in the light of the latest published preclinical studies and clinical trials.


Assuntos
Imunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Apresentação de Antígeno , Evasão da Resposta Imune , Nanomedicina , Microambiente Tumoral
6.
Oncología (Guayaquil) ; 33(2): 162-171, 14 de agosto del 2023.
Artigo em Espanhol | LILACS | ID: biblio-1451581

RESUMO

Introducción: El cáncer de mama triple negativo (TNBC) se caracteriza por la ausencia de receptores hormonales estrogénicos y progesterona; así como, del receptor 2 del factor de crecimiento epidérmico humano (HER2). Los TNBC se asocian con altas tasas de recurrencia, metástasis rápidas, supervivencia deficiente y mayor mortalidad en comparación con otros subtipos histológicos de cáncer de mama. El objetivo de este estudio fue establecer la prevalencia del TNBC; Así también, las características clínicas, en pacientes atendidas en un centro oncológico de referencia en Bogotá. Metodología: Estudio retrospectivo descriptivo transversal observacional, donde se evaluó la frecuencia del cáncer de mama subtipo triple negativo, Asimismo, las variables clínicas. En mujeres atendidas en la Organización Clínica Bonnadona Prevenir S.A.S. en Barranquilla, Colombia en el periodo 2021-2022. Resultados: Se estudiaron 350 pacientes, de los cuales 61 pacientes (17.4%) presentaban el inmunofenotipo triple negativo. La edad promedio fue de 54.5 años, 74% eran multíparas, 85% brindaron lactancia materna, 70% eran postmenopáusicas y el estadio clínico más frecuente fue el IIIB. Conclusión: En el presente estudio el 57.35% de la población exhibió un estadio clínico avanzado en el momento del diagnóstico; así mismo, las características clínicas son congruentes con los reportes en la literatura.


Introduction: Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen, progesterone hormone receptors, and human epidermal growth factor receptor 2 (HER2). TNBC is associated with an increased recurrence rate, distant metastasis, poor survival, and higher mortality than other pathological breast cancer subtypes. The objective of this study was to establish the prevalence of TNBC, likewise, with the clinical characteristics, in patients treated in a reference cancer center in Bogotá. Methodology: A retrospective descriptive cross-sectional observational study, where the frequency of triple negative subtype breast cancer was evaluated, as well as clinical variables and gynecologic and obstetric history, women treated at the Organización Clínica Bonnadona Prevenir S.A.S. in Barranquilla, Colombia in the period 2021-2022. Results: 350 patients were studied, of which 61 (17.4%) presented the triple-negative immunophenotype. The average age was 54, 74% were multiparous, 85% were breastfed, 70% were menopausal, and the most frequent clinical stage was IIIB. Conclusion: In this study, 57.35% of the population exhibited an advanced clinical stage at the time of diagnosis; Likewise, the clinical characteristics are consistent with the reports in the literature.


Assuntos
Humanos , Adulto , Fatores de Risco , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama , Epidemiologia
7.
Forensic Sci Int Genet ; 66: 102906, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37364481

RESUMO

The use of mitochondrial DNA (mtDNA) in the field of forensic genetics is widely spread mainly due to its advantages when identifying highly degraded samples. In this sense, massive parallel sequencing has made the analysis of the whole mitogenome more accessible, noticeably increasing the informativeness of mtDNA haplotypes. The civil war (1980-1992) in El Salvador caused many deaths and disappearances (including children) all across the country and the economic and social instability after the war forced many people to emigration. For this reason, different organizations have collected DNA samples from relatives with the aim of identifying missing people. Thus, we present a dataset containing 334 complete mitogenomes from the Salvadoran general population. To the best of our knowledge, this is the first publication of a nationwide forensic-quality complete mitogenome database of any Latin American country. We found 293 different haplotypes, with a random match probability of 0.0041 and 26.6 mean pairwise differences, which is similar to other Latin American populations, and which represent a marked improvement from the values obtained with just control region sequences. These haplotypes belong to 54 different haplogroups, being 91% of them of Native American origin. Over a third (35.9%) of the individuals carried at least a heteroplasmic site (excluding length heteroplasmies). Ultimately, the present database aims to represent mtDNA haplotype diversity in the general Salvadoran populations as a basis for the identification of people that disappeared during or after the civil war.


Assuntos
Genética Populacional , Genoma Mitocondrial , Criança , Humanos , El Salvador , DNA Mitocondrial/genética , Etnicidade/genética , Análise de Sequência de DNA , Haplótipos
8.
Int Rev Cell Mol Biol ; 375: 93-116, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36967155

RESUMO

Sarcomas are heterogeneous and aggressive malignant tumors with variable responses to current standard treatments being usually incurable for those patients with metastatic and unresectable diseases. The lack of curative strategies has led to develop new therapies in the treatment of sarcomas where the role of immune system is an evolving field. Most sarcomas often exhibit an immunosuppressive microenvironment, which reduces their capacity to trigger an immune response. Therefore, sarcomas are broadly considered as an "immune cold" tumor, although some studies have described a great immune heterogeneity across sarcoma subtypes. Sarcoma cells, like other tumors, evade their immune destruction through a variety of mechanisms, including expansion and recruitment of myeloid derived suppressor cells (MDSCs). MDSCs are immature myeloid cells that have been correlated with a reduction of the therapeutic efficacy, including immunotherapy, tumor progression and worst prognosis. Consequently, different strategies have been developed in recent years to target MDSCs in cancer treatments. This chapter discusses the role of MDSCs in sarcomas and their current potential as a therapeutic target in these malignancies.


Assuntos
Células Supressoras Mieloides , Neoplasias , Sarcoma , Humanos , Células Supressoras Mieloides/patologia , Neoplasias/patologia , Sarcoma/terapia , Sarcoma/patologia , Imunoterapia , Sistema Imunitário/patologia , Microambiente Tumoral
9.
Int J Mol Sci ; 24(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36982282

RESUMO

Breast cancer (BC) continues to be the most diagnosed tumor in women and a very heterogeneous disease both inter- and intratumoral, mainly given by the variety of molecular profiles with different biological and clinical characteristics. Despite the advancements in early detection and therapeutic strategies, the survival rate is low in patients who develop metastatic disease. Therefore, it is mandatory to explore new approaches to achieve better responses. In this regard, immunotherapy arose as a promising alternative to conventional treatments due to its ability to modulate the immune system, which may play a dual role in this disease since the relationship between the immune system and BC cells depends on several factors: the tumor histology and size, as well as the involvement of lymph nodes, immune cells, and molecules that are part of the tumor microenvironment. Particularly, myeloid-derived suppressor cell (MDSC) expansion is one of the major immunosuppressive mechanisms used by breast tumors since it has been associated with worse clinical stage, metastatic burden, and poor efficacy of immunotherapies. This review focuses on the new immunotherapies in BC in the last five years. Additionally, the role of MDSC as a therapeutic target in breast cancer will be described.


Assuntos
Neoplasias da Mama , Células Supressoras Mieloides , Neoplasias , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias/terapia , Imunoterapia , Microambiente Tumoral
10.
Cardiol Young ; 33(9): 1529-1535, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35997027

RESUMO

BACKGROUND: Despite high survival after bidirectional cavopulmonary anastomosis, a considerable number of patients suffer significant post-operative morbidities related to prolonged length of stay. METHODS: A single-center retrospective cohort study of all consecutive patients undergoing a first-time bidirectional cavopulmonary anastomosis from 2006 to 2019. RESULTS: Prolonged length of stay was defined as hospital stay greater than the 75th percentile for our cohort. Of 195 patients who met inclusion criteria, the median post-operative length of stay was 8 days (interquartile range, 4-15 days). Prolonged length of stay was defined as greater than 15 days. In multivariate analysis, greater than mild systemic atrioventricular valve regurgitation (odds ratio 3.7, 95% CI 1.05-13.068, p = 0.04), longer length of stay after the initial palliative procedure (odds ratio 1.028, 95% CI 1.004-1.05, p = 0.02), and pre-operative higher superior vena cava oxygen saturation (odds ratio 0.922, 95% CI 0.85-0.99, p = 0.04) maintained statistical significance as independent risk and protective factors for prolonged length of stay. A one-level increase in the severity of pre-operative systemic atrioventricular valve regurgitation was associated with a multiplicative change in the odds ratio of prolonged length of stay of 5.45 (p = 0.005) independent of the severity of systemic ventricular dysfunction. CONCLUSION: Pre-operative characteristics with greater than mild systemic atrioventricular valve regurgitation, longer length of stay after the initial palliative procedure, and lower superior vena cava oxygen saturation were associated with prolonged length of stay after a first-time bidirectional cavopulmonary anastomosis.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Humanos , Lactente , Tempo de Internação , Estudos Retrospectivos , Veia Cava Superior/cirurgia , Fatores de Risco , Cardiopatias Congênitas/cirurgia , Resultado do Tratamento , Artéria Pulmonar/cirurgia
11.
Int J Mol Sci ; 23(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36555171

RESUMO

Obesity, which is considered a pandemic due to its high prevalence, is a risk factor for many types of cancers, including lymphoma, through a variety of mechanisms by promoting an inflammatory state. Specifically, over the last few decades, obesity has been suggested not only to increase the risk of lymphoma but also to be associated with poor clinical outcomes and worse responses to different treatments for those diseases. Within the extensive range of proinflammatory mediators that adipose tissue releases, leptin has been demonstrated to be a key adipokine due to its pleotropic effects in many physiological systems and diseases. In this sense, different studies have analyzed leptin levels and leptin/leptin receptor expressions as a probable bridge between obesity and lymphomas. Since both obesity and lymphomas are prevalent pathophysiological conditions worldwide and their incidences have increased over the last few years, here we review the possible role of leptin as a promising proinflammatory mediator promoting lymphomas.


Assuntos
Leptina , Linfoma , Humanos , Leptina/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Adipocinas/metabolismo , Linfoma/metabolismo , Receptores para Leptina/metabolismo
12.
Cancers (Basel) ; 14(21)2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36358891

RESUMO

Ewing Sarcoma (EWS) is an aggressive bone and soft tissue tumor that mainly affects children, adolescents, and young adults. The standard therapy, including chemotherapy, surgery, and radiotherapy, has substantially improved the survival of EWS patients with localized disease. Unfortunately, this multimodal treatment remains elusive in clinics for those patients with recurrent or metastatic disease who have an unfavorable prognosis. Consistently, there is an urgent need to find new strategies for patients that fail to respond to standard therapies. In this regard, in the last decade, treatments targeting epigenetic dependencies in tumor cells and the immune system have emerged into the clinical scenario. Additionally, recent advances in nanomedicine provide novel delivery drug systems, which may address challenges such as side effects and toxicity. Therefore, therapeutic strategies stemming from epigenetics, immunology, and nanomedicine yield promising alternatives for treating these patients. In this review, we highlight the most relevant EWS preclinical and clinical studies in epigenetics, immunotherapy, and nanotherapy conducted in the last five years.

13.
Ann Pediatr Cardiol ; 15(2): 180-182, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246762

RESUMO

Patients with single right ventricle and tricuspid regurgitation have increased morbidity and mortality rates. The outcomes of surgical tricuspid valve repair and replacement are dismal. Although some centers prefer valve replacement with a bioprosthetic valve in the tricuspid position for the pediatric population, these valves have limited longevity and will eventually need to be replaced. Unfortunately, single ventricle patients are fragile and unlikely to tolerate a second replacement. Percutaneous valve-in-valve (ViV) implantation is an acceptable alternative with low morbidity and mortality. Studies have also shown acceptable short- and mid-term outcomes. We report a case of Melody ViV placement in the tricuspid position in a patient with hypoplastic left heart syndrome through the fenestration of a Fontan conduit.

14.
Cell Mol Life Sci ; 79(11): 546, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221013

RESUMO

The majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model.


Assuntos
Neuroblastoma , Rabdomiossarcoma , Proteínas ADAM/metabolismo , Humanos , Cadeias alfa de Integrinas , Integrinas , Metástase Neoplásica , Neuroblastoma/tratamento farmacológico , Rabdomiossarcoma/tratamento farmacológico
15.
Forensic Sci Int Genet ; 61: 102771, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36075175

RESUMO

The EuroForMix model has been extended to create a new open-source software called EFMrep which enables the combination of STR DNA mixture samples from different multiplexes. In addition to calculating combined likelihood ratios and carrying out deconvolution, the software also includes the capability to specify related unknown individuals. A graphical user interface has been implemented to ease the analysis for practitioners in real case work. The effect of combining multiple samples based on the PROVEDIt dataset was investigated, either from the same or different multiplexes. The information gain increases when more samples are combined. A head-to-head comparison against EuroForMix shows the benefit of a more general model. Guidelines are provided. A real case example was used to demonstrate how EFMrep could be used to combine multiple samples when a proposition includes kinship.


Assuntos
Impressões Digitais de DNA , Repetições de Microssatélites , Humanos , Funções Verossimilhança , DNA/genética , DNA/análise , Software
16.
Clin Cancer Res ; 28(17): 3658-3668, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35727601

RESUMO

PURPOSE: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma. PATIENTS AND METHODS: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29). RESULTS: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells. CONCLUSIONS: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Humanos , Lenalidomida/efeitos adversos , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Rituximab/uso terapêutico , Resultado do Tratamento
17.
Cancers (Basel) ; 14(6)2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35326620

RESUMO

Lymphoma is a neoplasm arising from B or T lymphocytes or natural killer cells characterized by clonal lymphoproliferation. This tumor comprises a diverse and heterogeneous group of malignancies with distinct clinical, histopathological, and molecular characteristics. Despite advances in lymphoma treatment, clinical outcomes of patients with relapsed or refractory disease remain poor. Thus, a deeper understanding of molecular pathogenesis and tumor progression of lymphoma is required. Epigenetic alterations contribute to cancer initiation, progression, and drug resistance. In fact, over the past decade, dysregulation of epigenetic mechanisms has been identified in lymphomas, and the knowledge of the epigenetic aberrations has led to the emergence of the promising epigenetic therapy field in lymphoma tumors. However, epigenetic aberrations in lymphoma not only have been found in tumor cells, but also in cells from the tumor microenvironment, such as immune cells. Whereas the epigenetic dysregulation in lymphoma cells is being intensively investigated, there are limited studies regarding the epigenetic mechanisms that affect the functions of immune cells from the tumor microenvironment in lymphoma. Therefore, this review tries to provide a general overview of epigenetic alterations that affect both lymphoma cells and infiltrating immune cells within the tumor, as well as the epigenetic cross-talk between them.

18.
Oncogene ; 41(18): 2638-2650, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35354905

RESUMO

Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor with high susceptibility to metastasize. The underlying molecular mechanisms leading to EWS metastases remain poorly understood. Epigenetic changes have been implicated in EWS tumor growth and progression. Linking epigenetics and metastases may provide insight into novel molecular targets in EWS and improve its treatment. Here, we evaluated the effects of a selective G9a histone methyltransferase inhibitor (BIX01294) on EWS metastatic process. Our results showed that overexpression of G9a in tumors from EWS patients correlates with poor prognosis. Moreover, we observe a significantly higher expression of G9a in metastatic EWS tumor as compared to either primary or recurrent tumor. Using functional assays, we demonstrate that pharmacological G9a inhibition using BIX01294 disrupts several metastatic steps in vitro, such as migration, invasion, adhesion, colony formation and vasculogenic mimicry. Moreover, BIX01294 reduces tumor growth and metastases in two spontaneous metastases mouse models. We further identified the sialidase NEU1 as a direct target and effector of G9a in the metastatic process in EWS. NEU1 overexpression impairs migration, invasion and clonogenic capacity of EWS cell lines. Overall, G9a inhibition impairs metastases in vitro and in vivo through the overexpression of NEU1. G9a has strong potential as a prognostic marker and may be a promising therapeutic target for EWS patients.


Assuntos
Sarcoma de Ewing , Animais , Linhagem Celular Tumoral , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Histona Metiltransferases/metabolismo , Humanos , Camundongos , Recidiva Local de Neoplasia , Neuraminidase/metabolismo , Neuraminidase/uso terapêutico , Proteínas de Fusão Oncogênica/genética , Proteína Proto-Oncogênica c-fli-1/genética , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia
19.
Cardiol Young ; 32(12): 1952-1956, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35152927

RESUMO

BACKGROUND: Recurrent laryngeal nerve injury leading to vocal cord paralysis is a known complication of cardiothoracic surgery. Its occurrence during interventional catheterisation procedures has been documented in case reports, but there have been no studies to determine an incidence. OBJECTIVE: To establish the incidence of left recurrent laryngeal nerve injury leading to vocal cord paralysis after left pulmonary artery stenting, patent ductus arteriosus device closure and the combination of the procedures either consecutively or simultaneously. METHODS: Members of the Congenital Cardiovascular Interventional Study Consortium were asked to perform a retrospective analysis to identify cases of recurrent laryngeal nerve injury after the aforementioned procedures. Twelve institutions participated in the analysis. They also contributed the total number of each procedure performed at their respective institutions for statistical purposes. RESULTS: Of the 1337 patients who underwent left pulmonary artery stent placement, six patients (0.45%) had confirmed vocal cord paralysis. 4001 patients underwent patent ductus arteriosus device closure, and two patients (0.05%) developed left vocal cord paralysis. Patients who underwent both left pulmonary artery stent placement and patent ductus arteriosus device closure had the highest incidence of vocal cord paralysis which occurred in 4 of the 26 patients (15.4%). Overall, 92% of affected patients in our study population had resolution of symptoms. CONCLUSION: Recurrent laryngeal nerve injury is a rare complication of left pulmonary artery stent placement or patent ductus arteriosus device closure. However, the incidence is highest in patients undergoing both procedures either consecutively or simultaneously. Additional research is necessary to determine contributing factors that might reduce the risk of recurrent laryngeal nerve injury.


Assuntos
Permeabilidade do Canal Arterial , Traumatismos do Nervo Laríngeo Recorrente , Paralisia das Pregas Vocais , Humanos , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Traumatismos do Nervo Laríngeo Recorrente/complicações , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologia , Permeabilidade do Canal Arterial/epidemiologia , Permeabilidade do Canal Arterial/cirurgia , Permeabilidade do Canal Arterial/complicações , Incidência , Estudos Retrospectivos , Cateterismo/efeitos adversos
20.
Catheter Cardiovasc Interv ; 99(4): 1161-1164, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35018709

RESUMO

Device-related thrombosis and device-related endocarditis after atrial septal defect (ASD) transcatheter closure are extremely rare. It is known that COVID-19 infection could lead to a thrombotic microangiopathy-like phenomenon. We present the case of a 14-year-old female who developed fever and was found to have a thrombus on the right atrial side of the ASD closure device weeks after an asymptomatic COVID-19 infection and negative COVID-19 test 2 days before transcatheter ASD closure. Although there is no certainty that the thrombus was related to the prior COVID-19 infection, the possibility of an ongoing COVID-19-related hypercoagulable state should be entertained.


Assuntos
COVID-19 , Comunicação Interatrial , Dispositivo para Oclusão Septal , Trombose , Adolescente , COVID-19/complicações , Cateterismo Cardíaco , Feminino , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/terapia , Humanos , Desenho de Prótese , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/terapia , Fatores de Tempo , Resultado do Tratamento
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