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1.
Adv Exp Med Biol ; 1232: 169-176, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893407

RESUMO

Inhospitable conditions within the tumor microenvironment (TME) are a characteristic feature ('hallmark') of most solid malignancies. Regional tumor hypoxia is a primary deficiency since it plays a key role in malignant progression. Severe hypoxia is often associated with other detrimental conditions in the TME as a consequence of hypoxia-/HIF-1α-induced (with/without oncogene-direction and/or reciprocal interaction of cancer cells with TME cells) metabolic re-programming, exorbitant extracellular adenosine (ADO) generation and VEGF overexpression/VEGF-R activation. Re-programming of the tumor metabolism inter alia includes a 'selfish' upregulation of aerobic glycolysis/glycolytic flux ('Warburg effect'), a strongly enhanced glutaminolysis in tumor cells, ketogenesis in cancer-associated fibroblasts, and an acceleration of the tryptophan uptake/intensified catabolism yielding kynurenine, which can support the malignant phenotype. Aerobic glycolysis and glutaminolysis result in lactate accumulation (up to 40 mM), and together with the enhanced ketogenesis and CO2/carbonic acid production lead to extracellular acidosis (pHe < 6.8). These traits of the TME individually or collectively operate towards cancer progression via e.g. promotion of genetic instability and mutation, resistance to apoptosis, clonal selection, limitless cell survival and sustained proliferation, continuous angiogenesis and tumor growth, local invasion and distant metastasis, anti-tumor immunosuppression and resistance to therapy.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias , Hipóxia Tumoral , Microambiente Tumoral , Linhagem Celular Tumoral , Progressão da Doença , Glicólise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias/fisiopatologia , Fenótipo
2.
Zhonghua Wai Ke Za Zhi ; 58(1): 22-26, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31902165

RESUMO

The incidence of pancreatic cancer (PC) has continuously shown an upward trend all over the world. It remains one of the most challenging malignant tumors in clinical practice and is characterized by difficult diagnosis in early stages, low surgical resection rate and poor prognosis. Due to its significant genetic heterogeneity, there are notable individual differences in disease progression, clinical efficacy, sensitivity to chemoradiotherapy, and prognosis among PC patients. In-depth study is needed to reveal the molecular biological characteristics of different PC subtypes and their correlation with clinical manifestations and chemoradiotherapy sensitivity, which could contribute to develop corresponding targeted therapeutic strategies.It is not only the fundamental basis for the innovation of PC morphological classification to molecular subtyping, but also a prerequisite for achieving a shift in treatment mode from "standard therapeutic strategy for different diseases" to "treat the same disease with different strategies" .This article reviews several hot issues on the comprehensive diagnosis and treatment of PC in the era of targeted therapy and prospects its future development.


Assuntos
Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Quimiorradioterapia , Progressão da Doença , Humanos , Terapia de Alvo Molecular , Prognóstico , Radioterapia , Resultado do Tratamento
3.
Anticancer Res ; 40(1): 473-489, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892603

RESUMO

Melanoma is one of the most lethal types of skin cancer, with a poor prognosis once the disease enters metastasis. The efficacy of currently available treatment schemes for advanced melanomas is low, expensive, and burdened by significant side-effects. Therefore, there is a need to develop new treatment options. Skin cells are able to activate vitamin D via classical and non-classical pathways. Vitamin D derivatives have anticancer properties which promote differentiation and inhibit proliferation. The role of systemic vitamin D in patients with melanoma is unclear as epidemiological studies are not definitive. In contrast, experimental data have clearly shown that vitamin D and its derivatives have anti-melanoma properties. Furthermore, molecular and clinicopathological studies have demonstrated a correlation between defects in vitamin D signaling and progression of melanoma and disease outcome. Therefore, adequate vitamin D signaling can play a role in the treatment of melanoma.


Assuntos
Progressão da Doença , Melanoma/patologia , Melanoma/terapia , Vitamina D/metabolismo , Ensaios Clínicos como Assunto , Humanos , Raios Ultravioleta
4.
Anticancer Res ; 40(1): 97-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892557

RESUMO

BACKGROUND/AIM: Chronic expanding hematoma is defined as a hematoma that gradually expands over 1 month or longer, is without neoplastic features on histological sections, and does not occur in the setting of coagulopathy. The pathogenetic mechanism behind its development is unknown, nor is anything known about its genetic features. CASE REPORT: A 49-year-old man noted a tender lump close to the right femoral trochanter. Examination of a core needle biopsy showed a fibrous capsule with fibrinoid material on one side. The patient underwent surgery with removal of a cystic, encapsulated structure with central bleeding and proliferating vessels in the fibrous capsule. The reactive fibroblasts were without any sign of atypia. Genetic analyses were performed on this chronic expanding hematoma. RESULTS: G-Banding analysis of short-term cultured cells from the chronic expanding hematoma yielded a karyotype with a single clonal chromosome abnormality: 46,XY,t(11;19)(q13;q13)[8]/46,XY[10]. RNA sequencing and examination of the sequencing data using five different programs did not identify fusion genes related to the translocation. CONCLUSION: The acquired translocation t(11;19)(q13;q13) suggested that chronic expanding hematoma is a neoplastic lesion. Since the translocation did not lead to any fusion genes, one can speculate that it causes deregulation of gene expression.


Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 19 , Estudos de Associação Genética , Predisposição Genética para Doença , Hematoma/diagnóstico , Hematoma/genética , Translocação Genética , Biópsia , Bandeamento Cromossômico , Doença Crônica , Progressão da Doença , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade
5.
Medicine (Baltimore) ; 99(1): e18461, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895777

RESUMO

This study was conducted to examine the effect of protective factors on the relationship between crisis episodes and depression in the elderly population in Taiwan.In this study, the Taiwan Longitudinal Study on Aging was used as basis for a cross-sectional secondary data analysis. After eliminating respondents below the age of 65 years and those with missing values, 2426 samples were collected. Predictive variables, such as crisis episodes, personal resources, family ties, social participation, and social support, were investigated, and the dependent variable of "depression status" was measured using the Center for Epidemiologic Studies Depression scale.According to the results of regression analysis, the protective factors of self-assessed health (ß = -0.290, P < .001), instrumental support (ß = -0.153, P < .001), financial satisfaction (ß = -0.126, P < .001), emotional support (ß = -0.101, P < .001), crisis episodes (ß = 0.087, P < .001), support satisfaction (ß = -0.081, P < .001), leisure participation (ß = -0.053, P < .05), family ties (ß = -0.048, P < .05), and community participation (ß = -0.042, P < .05) had a significant effect on depression status. Moreover, leisure participation had a moderating effect on the relationship between crisis episodes and depression (ß = -0.07, P < .01). In addition, according to path analysis results, family ties had a significant negative predictive power on depression (ß = -0.225, P < .001), as did social support (ß = -0.978, P < .001). The predictive power of crisis episodes on depression through social support was 0.197 (-0.201 × -0.978 = 0.197, P < .001), and it was -0.324 (-0.331 × -0.978 = -0.324, P < .001) through social participation, which indicated that social support plays a mediating role between crisis episodes and depression and between social participation and depression.Strengthening effective protective factors can improve the resilience of elderly people and enable them to cope with dilemmas rapidly and effectively when faced with crisis episodes as well as restore their health status and enjoy a satisfactory life.


Assuntos
Depressão/epidemiologia , Resiliência Psicológica , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Depressão/diagnóstico , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Masculino , Fatores de Proteção , Apoio Social , Taiwan/epidemiologia
6.
Anticancer Res ; 40(1): 229-238, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892571

RESUMO

BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.


Assuntos
Neoplasias da Mama/patologia , Curcumina/farmacologia , Progressão da Doença , Naftoquinonas/farmacologia , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/uso terapêutico , Matriz Extracelular/metabolismo , Feminino , Humanos , Células MCF-7 , Naftoquinonas/química , Invasividade Neoplásica , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Angiology ; 71(1): 62-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31088126

RESUMO

The prevalence of coronary intimal thickening (IT) was assessed in fetuses and pediatric population. We studied the coronary arteries of 63 hearts obtained from fetuses, infants, children, and adolescents, deceased from noncardiac disease or trauma. Histomorphometric analysis, planimetry, and immunohistochemical studies were conducted. Intimal thickening consisted of proliferation of smooth muscle cells and scarce monocytes embedded in amorphous deposits within the internal elastic membrane (IEM). Intermingled lesions of intimal hyperplasia and parietal nonstenotic plaques were also observed. Intimal thickening was found in 10% of 20 fetuses, in 33.3% of 18 infants, 73.3% of 15 children, and 100% of 10 adolescents. A significant correlation (r = 0.671, P < 0.001) was found between the extent of IT and age. The IEM was duplicated or interrupted in 43% of patients, showing a positive correlation with the degree of IT (P = 0.01). Intimal thickening was predominantly found near bifurcation sites in the left anterior descending coronary artery (55.6%) and in zones free of bifurcation in the right coronary artery (75%). In conclusion, the prevalence and extension of IT lesions are higher at older ages within a young population. Intimal thickening may be regarded as the first event occurring in coronary preatherosclerosis, preceding lipid deposition.


Assuntos
Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Coração Fetal/patologia , Neointima , Placa Aterosclerótica , Túnica Íntima/patologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Progressão da Doença , Feminino , Idade Gestacional , Humanos , Hiperplasia , Lactente , Recém-Nascido , Masculino
8.
Angiology ; 71(1): 70-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31446774

RESUMO

Both elevated resting heart rate (HR) and electrocardiographic left ventricular hypertrophy (ECG-LVH) are signs of a poor prognosis. Although elevated resting HR is a known risk factor for cardiovascular disease and target organ damage, the association between resting HR and the development of ECG-LVH is unclear. In the present study, 6860 subjects (4203 men, 2657 women, 19-89 years of age) without ECG-LVH at baseline were evaluated and followed for a mean duration of 3.7±1.4 years. During the follow-up period, 484 (7.1%) subjects developed ECG-LVH. Cox regression analysis revealed that each 10 beats/min increase in resting HR was associated with a 22% reduction in the development of ECG-LVH (95% confidence interval: 12%-30%, P < .0001) in men. While an increase in HR tended to be associated with the development of ECG-LVH in women, the relationship was not significant. In contrast to the concept that an elevated resting HR is a cardiovascular risk factor, these findings revealed that resting HR was negatively associated with the development of ECG-LVH in men.


Assuntos
Frequência Cardíaca , Hipertrofia Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Eletrocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
9.
Recent Results Cancer Res ; 215: 77-88, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605224

RESUMO

Circulating tumor cells (CTCs) provide valuable information about the molecular evolution of cancers, as they may initially respond and ultimately progress on therapy. As intact tumor cells isolated from the bloodstream, CTCs also enable assessment of heterogeneous subpopulations, and their analysis may include DNA, RNA, and protein biomarkers. New microfluidic cell isolation strategies greatly facilitate the challenge of enriching viable tumor cells from the billions of hematopoietic cells within a standard blood specimen. While counting and characterization of enriched CTCs have primarily relied on immunostaining for tumor cell-specific antigens, new RNA-based analytic platforms are providing new insight into the identity of CTCs and providing new tools for clinical applications. Single-cell RNA sequencing of CTCs reveals a high degree of heterogeneity among cancer cells from a single individual, while new digital RNA-based amplification platforms may now allow high-sensitivity and high-throughput quantitative scoring of CTCs for clinical applications. Here, we focus on transcriptomic analysis of CTCs and its relevance in understanding metastatic cancer progression and in developing diagnostic assays to monitor cancer.


Assuntos
Separação Celular/métodos , Neoplasias/genética , Neoplasias/patologia , Células Neoplásicas Circulantes , RNA Neoplásico/análise , Progressão da Doença , Humanos , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/metabolismo , RNA Neoplásico/genética
10.
Angiol Sosud Khir ; 25(4): 124-130, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31855209

RESUMO

AIM: The purpose of this study was to investigate the natural course of stenosis of the common carotid artery (CCA) after carotid endarterectomy, as well as the long-term outcomes of various methods of reconstruction of the internal carotid artery (ICA) in patients with extended atherosclerotic lesions. PATIENTS AND METHODS: Presented herein are the remote retrospective and prospective results of carotid endarterectomy in a total of 78 patients with concomitant atherosclerotic lesions of carotid arteries. Depending on the degree of CCA stenosis, the patients were divided into 2 groups. Group One (n=25): stenosis of the internal carotid artery (ICA) of more than 70% and haemodynamically insignificant (30-35% stenosis) but extended (from 3.0 to 5.0 cm (Q1, Me, Q3); 3.5 cm, 4.0 cm, 5.0 cm) stenosis of the CCA. These patients underwent carotid endarterectomy (CEA) from the ostium of the ICA, during which an atherosclerotic plaque was not completely removed from the CCA because the stenosis was extended but haemodynamically insignificant. Group Two (n=53): stenosis of the ICA of more than 70% and haemodynamically significant, extended (from 7.0 to 10.0 cm (Q1, Me, Q3); 7.5 cm, 8.0 cm, 9.0 cm) stenosis of the CCA. The patients of this group were subjected to various methods of operative intervention on the ICA and CCA: carotid endarterectomy (ECA) combined with open endarterectomy from the CCA with plasty using the primary suture (n=23); carotid endarterectomy and alloreconstruction of the CCA (n=10); simultaneous eversion endarterectomy from the ICA and CCA (n=20). The remote period of follow up of patients ranged from 14 to 24 months ((Q1, Me, Q3; 19 months, 22 months, 24 months). The differences were statistically insignificant (Mann-Whitney U-test, p=0.881). RESULTS: In the remote postoperative period, 32% of Group One patients after previously performed carotid endarterectomy were found to have an increase in the degree of stenosis of the CCA up to a haemodynamically significant one (70% and more), thus suggesting progression of the atherosclerotic process. In Group Two patients, after plasty of the CCA with the primary suture, 21.7% of patients were diagnosed as having restenosis of the reconstruction zone up to 30%, with no neurological deficit. 20% of patients after carotid endarterectomy and alloreconstruction of the CCA were diagnosed as having restenosis of the reconstruction zone more than 70% and acute impairment of cerebral circulation with a lethal outcome. The patients after simultaneous eversion endarterectomy form the ICA and CCA in the intraoperative and postoperative periods had neither restenosis of the reconstruction zone nor neurological deficit. CONCLUSION: 32% of patients after previously performed carotid endarterectomy with the presence of extended, but haemodynamically insignificant stenosis of the CCA (30-35% stenosis) in the postoperative period were found to have progression of the atherosclerotic lesion in the form of an increased degree of stenosis up to haemodynamically significant (more than 70%), thus requiring repeat reconstructive operation. Therefore, in patients presenting with concomitant atherosclerotic lesions of the carotid arteries it is appropriate to carry out operative intervention simultaneously on the ICA and CCA, which would make it possible to considerably improve the remote postoperative results of reconstructive interventions on the carotid basin in this cohort of patients. A comparative study of the outcomes of various methods of reconstruction of carotid arteries in patients with concomitant atherosclerotic lesions of the ICA and CCA demonstrated that simultaneous eversion endarterectomy from the ICA and CCA resulted in good postoperative parameters: absence of restenosis and neurological deficit in the remote period of follow up.


Assuntos
Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Primitiva/cirurgia , Artéria Carótida Interna/cirurgia , Endarterectomia das Carótidas/métodos , Artéria Carótida Primitiva/patologia , Artéria Carótida Interna/patologia , Estenose das Carótidas/cirurgia , Progressão da Doença , Humanos , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(10): 1179-1187, 2019 Oct 28.
Artigo em Chinês | MEDLINE | ID: mdl-31857514

RESUMO

Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease, mainly caused by polycystic kidney disease 1/2 (PKD1/2) gene mutation. The main manifestation is the formation of multiple progressive enlarged cysts in both kidneys, which can be accompanied by decreased glomerular filtration rate, hypertension, liver cyst and cerebral aneurysm. About 45% of patients will progress to end-stage renal failure before the age of 60. ADPKD gene sequencing can be chosen for suspicious patients with atypical clinical features, no positive family history, and inconspicuous imaging findings. In the ADPKD positive families, imaging examination is the main means of diagnosing ADPKD. Height-adjusted total kidney volume (htTKV) and kidney growth rate are commonly used to monitor ADPKD disease progression and prognosis. There is no effective treatment for ADPKD to stop its progress. Drugs such as tolvaptan and bosutinib can delay the renal disfunction and they have been applied to clinical therapy in Europe and America.


Assuntos
Rim Policístico Autossômico Dominante , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Rim , Tolvaptan
12.
Medicine (Baltimore) ; 98(50): e18194, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852075

RESUMO

OBJECTIVE: To date, there are several published studies on the value of IDH-1 (isocitrate dehydrogenase-1) mutation and MGMT (O6-Methylguanine-DNA methyltransferas) promoter methylated status on the diagnosis of pseudoprogression (PSP) and true tumor progression after or within chemo-radiotherapy of high grade glioma (HGG). We performed a meta-analysis about the significant value of these 2 molecular markers on the diagnosis of PsP in high- grade glioma. METHODS: We searched the eligible studies from PubMed, Medline, Embase, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wan Fang Database. The relevant studies published before October 2018 were identified. ORs (odds ratios) with 95%CIs (confidence intervals) were used to evaluate the value using fixed- or random-effect model. RESULTS: Thirteen studies about MGMT promoter methylated status and 4 studies about IDH-1 mutations were found eligible for this present meta-analysis. Significant value of MGMT promoter methylation status (OR = 4.02, 95%CI = 2.76-5.87, P < .001) and IDH-1 mutations (OR = 12.78, 95%CI = 3.86-42.35, P < .001) were observed. CONCLUSIONS: This meta-analysis provided evidences that MGMT promoter methylation status and IDH-1 mutations could distinguish PSP from true tumor progression.


Assuntos
Neoplasias Encefálicas/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , DNA de Neoplasias/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação , Estadiamento de Neoplasias , Proteínas Supressoras de Tumor/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/metabolismo , Metilação de DNA , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , DNA de Neoplasias/metabolismo , Progressão da Doença , Glioma/diagnóstico , Glioma/metabolismo , Humanos , Isocitrato Desidrogenase/metabolismo , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor/metabolismo
13.
Medicine (Baltimore) ; 98(50): e18241, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852089

RESUMO

T helper 17 (Th17) cells are related to the progression of aortic dissection. This study aimed to determine whether circulating Th17 levels are associated with the prognosis of acute Stanford type B aortic dissection (STBAD) after thoracic endovascular aortic repair (TEVAR).A cohort study was performed and STBAD patients (n = 140) received TEVAR were enrolled, the circulating Th17 levels were measured and the patients were divided into low and high Th17 groups, and 36 months of follow-up was performed. The data for mortality, survival outcomes, heart structure and function changes, aortic regurgitation prevalence, and aortic remodeling outcomes were recorded.Lower mortality and fewer complications were observed in the low Th17 group than in the high Th17 group in the third year of follow-up. In addition, the low Th17 group exhibited better cardiac remodeling and cardiac function when compared with that in the high Th17 group in the second to third year after TEVAR. Aortic reflux was improved in both groups but was more pronounced in the low Th17 group. During follow-up, the true lumen of the proximal thoracic aorta at the level of the celiac trunk in both the low and high Th17 groups continuously enlarged and was more pronounced in the low Th17 group.Circulating Th17 cells were related to cardiac and aortic remodeling and prognosis during STBAD after TEVAR. Anti-inflammatory therapy may be useful for STBAD patients who have undergone TEVAR.


Assuntos
Aneurisma Dissecante/sangue , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/sangue , Procedimentos Endovasculares/métodos , Células Th17/patologia , Remodelação Vascular , Doença Aguda , Adulto , Aneurisma Dissecante/diagnóstico , Aneurisma Dissecante/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Angiografia por Tomografia Computadorizada , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo
14.
Medicine (Baltimore) ; 98(51): e18321, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860983

RESUMO

Oral lichen planus (OLP) exhibits variations in severity and response to corticosteroid therapy. This study aims to assess the histopathological features of OLP at the time of diagnosis and their relationship in response to corticosteroid therapy.In this retrospective study, OLP patients were selected if a histopathological report was available. Data were collected regarding patients' demographics and medical history. Clinical and histological data were also obtained. The outcomes were histopathological findings, clinical form of OLP, number of exacerbations per year, and the response to corticosteroid therapy.In this study, 100 OLP patients were enrolled. Basal layer hydropic degeneration and band-like subepithelial lymphocytes infiltrate were observed in all patients. Plasma cells, identified in 62% of OLP patients, were significantly associated with fewer disease exacerbations and better response to corticosteroid treatment.Identifying histopathological features that may affect the clinical course would be clinically helpful in tailoring patient management.


Assuntos
Glucocorticoides/uso terapêutico , Líquen Plano Bucal/tratamento farmacológico , Líquen Plano Bucal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tecido Conjuntivo/metabolismo , Progressão da Doença , Relação Dose-Resposta a Droga , Epitélio/metabolismo , Epitélio/patologia , Feminino , Fibrina/metabolismo , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Plasmócitos/metabolismo , Estudos Retrospectivos , Linfócitos T/metabolismo
15.
Cell Physiol Biochem ; 53(S1): 63-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860207

RESUMO

Mitochondria play a central role in cancer development, by contributing to most of the classical hallmarks of cancer, including sustained proliferation, metabolic re-programming, apoptosis resistance, invasion and induction of angiogenesis [1]. In addition, mitochondria affect also the function of anti- and pro-tumoral immune cells in the tumor microenvironment. Mitochondria harbor a plethora of regulated ion channels whose function is related to ion/ metabolite transport and to fine-tuning of mitochondrial membrane potential as well as of reactive oxygen species release. As a consequence, growing evidence link ion channels located both in the outer and inner mitochondrial membranes to several cancer hallmarks. The present review summarizes our recent knowledge about the participation and role of mitochondrial channels leading to acquisition of cancer hallmarks and thus to cancer progression.


Assuntos
Canais Iônicos/metabolismo , Mitocôndrias/patologia , Neoplasias/patologia , Animais , Apoptose , Proliferação de Células , Progressão da Doença , Humanos , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Membranas Mitocondriais/patologia , Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia
16.
Medicine (Baltimore) ; 98(51): e18016, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860952

RESUMO

INTRODUCTION: Breast metastases from primary colorectal carcinoma are extremely rare, with only 45 cases being reported previously. Since the most common malignancy in the breast and axilla is primary breast cancer regardless of cancer history, non-hematologic metastases may be misdiagnosed initially. Nevertheless, differentiating breast metastases from primary breast cancer is crucial because of their differences in prognosis and management. PATIENT CONCERNS: We present a case of a 44-year-old Asian woman who noticed a new right breast lump after undergoing surgery and chemotherapy for her primary sigmoid colon cancer. DIAGNOSIS: Image and immunohistochemistry findings were consistent with breast metastasis from primary colorectal adenocarcinoma. INTERVENTIONS: The patient underwent breast tumor excision and reinitiated chemotherapy. OUTCOMES: The patient's disease progressed despite the interventions. She passed away 7 months after the detection of breast metastasis. CONCLUSION: When a new breast lesion is detected in patients with colorectal cancer history, the physician should consider the possibility of breast metastasis due to the poor prognosis. If a biopsy is necessary, cancer history should be provided to the clinicians to prevent incorrect pathological interpretation. In establishing the diagnosis, certain immunohistochemical markers have been shown to be sensitive and specific in previously reported cases. The combination of tumor excision and chemotherapy was the most common strategy in managing this condition with inconsistent clinical outcomes.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Mama/secundário , Neoplasias da Mama/terapia , Mastectomia Segmentar/métodos , Neoplasias do Colo Sigmoide/patologia , Adenocarcinoma/cirurgia , Biópsia por Agulha , Neoplasias da Mama/diagnóstico por imagem , Quimioterapia Adjuvante , Colectomia/métodos , Terapia Combinada , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Biópsia Guiada por Imagem/métodos , Imuno-Histoquímica , Neoplasias do Colo Sigmoide/diagnóstico por imagem , Neoplasias do Colo Sigmoide/terapia , Tomografia Computadorizada por Raios X/métodos
17.
Medicine (Baltimore) ; 98(51): e18110, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860959

RESUMO

OBJECTIVE: To study the potential diagnostic value of plasma miR-200c-3p, miR-100-5p, and miR-1826 levels in knee osteoarthritis (KOA). METHODS: Real-time quantitative PCR (RT-PCR) was used to measure the expression levels of serum miR-200c-3p, miR-100-5p, and miR-1826 in 150 KOA patients and 150 control controls. In addition, the levels of DNMT3A, ZEB1, MMP13, and CTNNB1 mRNAs in the synovial fluid were also measured by RT-PCR. RESULTS: The expression levels of miR-100-5p, miR-200c-3p, and miR-1826 in the synovial fluid of 150 KOA patients were significantly lower than those in 54 controls (P < .001). In the synovial fluid, the miR-100-5p and DNMT3A mRNA levels, miR-100-5p and ZEB1 mRNA levels, miR-200c-3p and MMP13 mRNA levels, and miR-1826 and CTNNB1 mRNA levels were all negatively correlated (r = -0.83, -0.81, -0.83, -0.58, respectively). The AUCs of the diagnosis for KOA using the plasma levels of miR-200c-3p, miR-100-5p, and miR-1826 were 0.755, 0.845, and 0.749, respectively. CONCLUSION: The plasma levels of miR-200c-3p, miR-100-5p, and miR-1826 are of potentially high value in the diagnosis of KOA.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/genética , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Western Blotting , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Prognóstico , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real/métodos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais
19.
Clin Exp Rheumatol ; 37 Suppl 121(6): 98-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856935

RESUMO

OBJECTIVES: The aim of this multicentre study was to understand patients' needs and to evaluate the oral ulcer activity with the Composite Index (CI), according to different treatment modalities in Behçet's syndrome (BS). METHODS: BS patients (n=834) from 12 centres participated in this cross-sectional study. Oral ulcer activity (active vs. inactive) and the CI (0: inactive vs. 1-10 points: active) were evaluated during the previous month. The effects of treatment protocols [non-immunosuppressive: non-IS vs. immunosuppressive: (ISs)], severity (mild vs. severe), disease duration (<5 years vs. ≥5 years) and smoking pattern (non-smoker vs. current smoker) were analysed for oral ulcer activity. RESULTS: Oral ulcer activity was observed in 65.1% of the group (n=543). In both genders, the activity was higher in mild disease course with non-IS treatment group compared to severe course with ISs (p<0.05). As a resistant group, patients with mild disease course whose mucocutaneous symptoms were unresponsive to non-IS medications were treated with ISs in a limited period and achieved the highest CI scores in females. Oral ulcer activity and poor CI score were associated with disease duration less than 5 years compared to others in male patients (p<0.05). CONCLUSIONS: Oral ulcer activity pattern is affected by both the combination of disease course, treatment protocols and disease duration. CI scores reflected the oral clinical activity and CI might be a candidate scale to evaluate the efficacy of treatments during the follow-up of oral ulcer activity in BS.


Assuntos
Síndrome de Behçet , Imunossupressores/uso terapêutico , Úlceras Orais , Síndrome de Behçet/classificação , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Úlceras Orais/classificação , Recidiva , Índice de Gravidade de Doença
20.
Cancer Immunol Immunother ; 68(12): 1995-2004, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31690954

RESUMO

Glioblastoma is a highly prevalent and aggressive form of primary brain tumor. It represents approximately 56% of all the newly diagnosed gliomas. Macrophages are one of the major constituents of tumor-infiltrating immune cells in the human gliomas. The role of immunosuppressive macrophages is very well documented in correlation with the poor prognosis of patients suffering from breast, prostate, bladder and cervical cancers. The current study highlights the correlation between the tumor-associated macrophage phenotypes and glioma progression. We observed an increase in the pool of M2 macrophages in high-grade gliomas, as confirmed by their CD68 and CD163 double-positive phenotype. In contrast, less M1 macrophages were noticed in high-grade gliomas, as evidenced by the down-regulation in the expression of CCL3 marker. In addition, we observed that higher gene expression ratio of CD163/CCL3 is associated with glioma progression. The Kaplan-Meier survival plots indicate that glioma patients with lower expression of M2c marker (CD163), and higher expression of M1 marker (CCL3) had better survival. Furthermore, we examined the systemic immune response in the peripheral blood and noted a predominance of M2 macrophages, myeloid-derived suppressor cells and PD-1+ CD4 T cells in glioma patients. Thus, the study indicates a high gene expression ratio of CD163/CCL3 in high-grade gliomas as compared to low-grade gliomas and significantly elevated frequency of M2 macrophages and PD-1+ CD4 T cells in the blood of tumor patients. These parameters could be used as an indicator of the early diagnosis and prognosis of the disease.


Assuntos
Neoplasias Encefálicas/imunologia , Linfócitos T CD4-Positivos/patologia , Glioblastoma/imunologia , Macrófagos/imunologia , Células Supressoras Mieloides/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Neoplasias Encefálicas/mortalidade , Carcinogênese , Quimiocina CCL3/metabolismo , Citocinas/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glioblastoma/mortalidade , Humanos , Tolerância Imunológica , Imunidade Humoral , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Superfície Celular/metabolismo , Análise de Sobrevida , Células Th2/imunologia
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