Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.246
Filtrar
2.
Adv Exp Med Biol ; 1268: 53-114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918214

RESUMO

Increasing scientific evidence supports the link between vitamin D and cancer risk. The active metabolite 1,25(OH)2D exerts its activity by binding to the vitamin D receptor (VDR), an intracellular receptor that mediates transcriptional activation and repression of target genes. The binding of 1,25(OH)2D to VDR is able to regulate hundreds of different genes. VDR is active in virtually all tissues including the colon, breast, lung, ovary, bone, kidney, parathyroid gland, pancreatic b-cells, monocytes, T lymphocytes, melanocytes, keratinocytes, and also cancer cells.The relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies.We have carried out a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies considering ethnicity as a key factor for heterogeneity.Up to December 2018, we identified 176 independent studies with data to assess the risk of breast, prostate, colorectal, skin (melanoma and non-melanoma skin cancer), lung, ovarian, kidney, bladder, gallbladder, esophageal, thyroid, head and neck, liver and pancreatic cancer, oral squamous cell carcinoma, non-Hodgkin lymphoma, multiple myeloma and sarcoma.Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1, Apa1, Cdx2), breast (Fok1, Bsm1, Taq1, Apa1, CdX2), colorectal (Fok1, Bsm1, Taq1, Apa1), and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites.Conflicting data have been reported for most malignancies, and at present, it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that other factors such as ethnicity, phenotype, 25(OH)D plasma levels, and UV radiation exposure play a role as confounding factors and introduce heterogeneity.To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with assessment of vitamin D status and stratified by ethnicity.


Assuntos
Neoplasias/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Humanos , Neoplasias/sangue , Vitamina D/sangue
3.
Medicine (Baltimore) ; 99(38): e22281, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957383

RESUMO

The regulation of the gene-regenerating family member 1 alpha (REG Iα) played important roles in cancer cell biology. However, the correlation between its gene product serum REG Iα and cancer has not been evaluated. In this observational study, 130 hospitalized patients from the department of internal medicine in Zhongda Hospital Southeast University were included and assigned to cancer or noncancer groups. History, clinical, and laboratory data were obtained. Serum REG Iα levels and alanine aminotransferase were found significantly higher in patients with cancer (P < .001 and P < .05 respectively). Logistic regression analysis indicated that REG Iα was an independent risk factor for cancer (P < .001). The area under the curve of REG Iα was 0.764 and the optimal cut-off point of REG Iα was 46.97 ng/mL. Besides, the cancer patients with metastasis had significantly higher serum REG Iα levels than those in nonmetastasis cancer group (P < .05). In conclusion, serum REG Iα was significantly elevated in patients with cancer, and it might be a potential biomarker in predicting cancer occurrence and development.


Assuntos
Biomarcadores Tumorais/sangue , Litostatina/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Anticancer Res ; 40(10): 5701-5706, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988895

RESUMO

BACKGROUND/AIM: The simultaneous increase of antioxidant CAT (catalase) enzyme and plasma MDA (malonidialdehyde) concentrations versus the numeric rating scale (NRS) pain score following surgery is unknown. Patients and Methods: The study included 114 patients with gallstone disease and 29 patients in the cancer group. RESULTS: Following surgery, the plasma CAT concentrations increased and plasma MDA concentrations decreased in all patients and especially in cancer patients. The linear mixed model time-effect was statistically significant in CAT and MDA (p<0.001 and p=0.02, respectively). In addition, a significant correlation between NRS pain score values and plasma MDA median concentrations in cancer patients was identified (r=0.430, p<0.001). CONCLUSION: The plasma MDA concentrations decreased and CAT concentrations increased significantly in all patients and especially in cancer patients following surgery. The simultaneous increase of antioxidant CAT enzyme with the decrease of plasma MDA may be an important ROS inhibiting mechanism to help patients return to normal antioxidant-oxidant status.


Assuntos
Catalase/sangue , Cálculos Biliares/sangue , Malondialdeído/sangue , Neoplasias/sangue , Dor/sangue , Antioxidantes/metabolismo , Feminino , Cálculos Biliares/patologia , Cálculos Biliares/cirurgia , Glutationa Peroxidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Neoplasias/cirurgia , Estresse Oxidativo/genética , Dor/patologia , Dor/cirurgia , Medição da Dor , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/sangue
5.
PLoS One ; 15(8): e0237793, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822383

RESUMO

PURPOSE: It has been demonstrated that, for various types of cancer, the pretreatment albumin/alkaline phosphatase ratio (AAPR) was a prognostic factor. Therefore, in order to determine AAPR's prognostic effect on cancer, the meta-analysis was hereby performed. PATIENTS AND METHODS: The relevant studies conducted before November 10, 2019, were comprehensively searched in Web of Science, PubMed, and Embase. HRs(hazard ratios) with related 95%CIs(confidence intervals) were adopted to estimate AAPR's prognostic impact on overall survival (OS) & disease-free survival (DFS). RESULTS: Our meta-analysis involved thirteen cohort studies, which included 5,204 cases of 8 types. The results of this meta-analysis indicated that higher AAPR was corrected with better OS (pooled HR = 0.52; 95%CI = 0.47-0.58; P<0.001) and DFS (pooled HR = 0.55; 95%CI = 0.47-0.66; P<0.001). Subgroup analysis on OS was based on the cancer system, treatment methods, and cutoff value. Moreover, higher AAPR was statistically in associated with lighter infiltration (pooled OR = 0.79; 95%CI = 0.73-0.85; P<0.001), no lymph nodes metastasis (pooled OR = 0.89; 95%CI = 0.83-0.95; P = 0.001), and no distant metastasis (pooled OR = 0.92; 95%CI = 0.86-0.99; P = 0.028). CONCLUSION: Higher AAPR was related to better prognosis of cancer, and in cancer therapy, AAPR could be taken as a promising marker of prognosis. It might help physicians to select the most appropriate treatments by evaluating the current status of patients with cancer. Future multicenter prospective clinical trials were required to verify its applications.


Assuntos
Fosfatase Alcalina/sangue , Neoplasias/diagnóstico , Albumina Sérica/análise , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Humanos , Neoplasias/sangue , Neoplasias/terapia , Prognóstico
6.
Nature ; 585(7824): 283-287, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32814897

RESUMO

The risk of cancer and associated mortality increases substantially in humans from the age of 65 years onwards1-6. Nonetheless, our understanding of the complex relationship between age and cancer is still in its infancy2,3,7,8. For decades, this link has largely been attributed to increased exposure time to mutagens in older individuals. However, this view does not account for the established role of diet, exercise and small molecules that target the pace of metabolic ageing9-12. Here we show that metabolic alterations that occur with age can produce a systemic environment that favours the progression and aggressiveness of tumours. Specifically, we show that methylmalonic acid (MMA), a by-product of propionate metabolism, is upregulated in the serum of older people and functions as a mediator of tumour progression. We traced this to the ability of MMA to induce SOX4 expression and consequently to elicit transcriptional reprogramming that can endow cancer cells with aggressive properties. Thus, the accumulation of MMA represents a link between ageing and cancer progression, suggesting that MMA is a promising therapeutic target for advanced carcinomas.


Assuntos
Envelhecimento/metabolismo , Progressão da Doença , Ácido Metilmalônico/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias/patologia , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/genética , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Ácido Metilmalônico/sangue , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neoplasias/sangue , Neoplasias/genética , Fatores de Transcrição SOXC/metabolismo , Transdução de Sinais , Transcriptoma/genética , Fator de Crescimento Transformador beta/metabolismo
7.
PLoS One ; 15(8): e0237506, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790768

RESUMO

Circulating tumor cells (CTCs) invade blood vessels in solid tumors and promote metastases by circulating in the blood. CTCs are thus recognized as targets for liquid biopsy and can provide useful information for design of treatments. This diagnostic approach must consider not only the number of CTCs but also their molecular and genetic characteristics. For this purpose, use of devices that enrich CTCs independent of these characteristics and detectors that recognize various CTC characteristics is essential. In the present study, we developed a CTC detection system comprising ClearCell FX and ImageStream Mark II. We clarified the analytical performance of this system by evaluating recovery rate, lower limits of detection, and linearity. These parameters are critical for detecting rare cells, such as CTCs. We tested these parameters using three cell lines with different expression levels of the epithelial marker-epithelial cell adhesion molecule (EpCAM) and spiked these cells into whole-blood samples from healthy donors. The average recovery rate and lower limit of detection were approximately 40% and five cells/7.5 mL of whole blood, respectively. High linearity was observed for all evaluated samples. We also evaluated the ability of the system to distinguish between normal and abnormal cells based on protein expression levels and gene amplification and found that the system can identify abnormal cells using these characteristics. The CTC detection system thus displays the ability to distinguish specific characteristics of CTC, thereby providing valuable information for cancer treatment.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Molécula de Adesão da Célula Epitelial/metabolismo , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Tumorais Cultivadas
8.
Medicine (Baltimore) ; 99(32): e21575, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769903

RESUMO

BACKGROUND: Recent studies showed that Macrophage migration inhibitory factor (MIF) is overexpressed and closely associated with prognosis in cancer patients. The present study was systematically evaluated the prognostic significance of MIF expression in cancer patients. METHODS: PubMed, Cochrane library and Scopus were searched for eligible studies up to January 2020. Pooled hazard ratio with confidence interval (CI) was determined to assess the relationship between MIF expression and survival in cancer patients. RESULTS: A total of 8 studies comprising 847 cancer patients were included in this meta-analysis. For overall survival, the pooled hazard ratio was 2.23 (95% CI 1.67-2.99, P < .001). For disease-free survival, the pooled hazard ratio was 2.24 (95% CI 1.69-2.96, P < .001). The results suggested that high expression of MIF was significantly related to poor overall survival and disease-free survival in cancer patients. CONCLUSION: MIF expression could be a valuable prognostic factor in cancer patients.


Assuntos
Fatores Inibidores da Migração de Macrófagos/análise , Neoplasias/sangue , Prognóstico , Distribuição de Qui-Quadrado , Expressão Gênica/fisiologia , Humanos , Oxirredutases Intramoleculares/análise , Oxirredutases Intramoleculares/sangue , Oxirredutases Intramoleculares/fisiologia , Fatores Inibidores da Migração de Macrófagos/sangue , Fatores Inibidores da Migração de Macrófagos/fisiologia , Neoplasias/fisiopatologia
9.
Nat Commun ; 11(1): 3475, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694610

RESUMO

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.


Assuntos
DNA Tumoral Circulante/sangue , Detecção Precoce de Câncer/métodos , Neoplasias/sangue , Neoplasias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , China , Metilação de DNA , Epigenômica , Feminino , Marcadores Genéticos , Voluntários Saudáveis , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
11.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32675312

RESUMO

BACKGROUND: Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19. METHODS: We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome. RESULTS: Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-ß signatures. ACE2 positively correlated with macrophage subsets across tumor types. TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. CONCLUSIONS: We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neoplasias/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Serina Endopeptidases/metabolismo , Idoso , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Conjuntos de Dados como Assunto , Feminino , Microbioma Gastrointestinal/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Antígenos HLA/sangue , Antígenos HLA/imunologia , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/microbiologia , Neoplasias/patologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA-Seq
12.
Eur J Cancer ; 135: 62-65, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32544799

RESUMO

While confirmed cases of the deadly coronavirus disease 2019 (COVID-19) have exceeded 4.7 million globally, scientists are pushing forward with efforts to develop vaccines and treatments in an attempt to slow the pandemic and lessen the disease's damage. Although no proven effective therapies for treating patients with COVID-19 or for managing their complications currently exist, the rapidly expanding knowledge regarding severe acute respiratory syndrome coronavirus 2 and its interplay with hosts provides a significant number of potential drug targets and the potential to repurpose drugs already tested in other diseases. Herein, we report the biological rationale of immune-activating drugs and a brief summary of literature data on the potential therapeutic value of immune checkpoint inhibitors that have been recently tested beyond cancer treatment for their potential to restore cellular immunocompetence.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Fatores Imunológicos/farmacologia , Linfopenia/sangue , Linfopenia/tratamento farmacológico , Linfopenia/imunologia , Linfopenia/virologia , Neoplasias/sangue , Neoplasias/imunologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do Tratamento
13.
PLoS Med ; 17(6): e1003091, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511251

RESUMO

BACKGROUND: Anemia is the most common and serious cancer-related complication. This study aimed to evaluate the efficacy of administration of ferric carboxymaltose without erythropoiesis-stimulating agents for treating anemia in cancer patients. Moreover, we identified the biomarkers of hemoglobin response to predict the need for iron therapy. METHODS AND FINDINGS: We enrolled patients with solid cancers who were treated at a single institute (Samsung Medical Center, South Korea), from April 2015 to July 2017, in this prospective single-arm Phase II clinical trial. Patients received intravenous ferric carboxymaltose (1,000 mg) infusion on the first day (visit 1) of treatment. The primary end point was the number of hemoglobin responders, defined as patients with an increase in hemoglobin level ≥ 1.0 g/dL from the baseline, a hemoglobin level ≥ 11.0 g/dL, or both, within an 8-week observation period (week 3, 6, or 8). Secondary end points included changes in transferrin saturation and levels of soluble transferrin receptors, hepcidin, erythropoietin, interleukin-6, and C-reactive protein (CRP) at each visit. Of the 103 recruited patients, 92 were eligible for analysis. The mean patient age was 57.3 ± 12.5 years, and 54.3% of the patients were women. The most common diagnoses were breast cancer (n = 23, 25.1%), lung cancer (n = 21, 22.9%), gastrointestinal cancer (n = 20, 20.9%), and lymphoma (n = 16, 17.7%). A hemoglobin response was observed in 36 (39.1%), 53 (57.6%), and 61 (66.3%) patients in the third, fifth, and eighth weeks, respectively. The mean increase in hemoglobin levels from the baseline to the end of treatment was 1.77 ± 1.30 g/dL. Baseline values of hepcidin (p = 0.008), total iron binding capacity (p = 0.014), ferritin (p = 0.048), and CRP (p = 0.044) were significantly different between the responder and nonresponder groups. Multiple logistic regression analysis for baseline anemia-related biochemical variable significantly associated with the hemoglobin response showed that only baseline hepcidin level was a significant factor for hemoglobin response (odds ratio = 0.95, 95% confidence interval 0.90-1.0, p = 0.045). Hemoglobin responders had significantly lower hepcidin levels than nonresponders (mean [±standard deviation], 13.45 [±14.71] versus 35.22 [±40.470 ng/ml]; p = 0.007). However, our analysis had some limitations such as the different patient characteristics in the studies that were included, institutional differences in the measurement of hepcidin level, and missing data on long-term safety. Therefore, our findings need further validation. CONCLUSIONS: Intravenous ferric carboxymaltose (1,000 mg) monotherapy increases hemoglobin levels without serious adverse events in patients with cancer. Hepcidin is a useful biomarker for predicting iron requirement in cancer patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT02599012.


Assuntos
Anemia/tratamento farmacológico , Compostos Férricos/uso terapêutico , Maltose/análogos & derivados , Anemia/induzido quimicamente , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Eritropoetina/sangue , Feminino , Compostos Férricos/administração & dosagem , Hemoglobinas/análise , Hepcidinas/sangue , Humanos , Infusões Intravenosas , Masculino , Maltose/administração & dosagem , Maltose/uso terapêutico , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Projetos Piloto , República da Coreia , Transferrina/análise , Resultado do Tratamento
14.
Nat Med ; 26(7): 1114-1124, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483360

RESUMO

In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10-5. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/sangue , DNA de Neoplasias/genética , Neoplasias/sangue , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Variações do Número de Cópias de DNA/genética , DNA de Neoplasias/sangue , Intervalo Livre de Doença , Feminino , Genoma Humano/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação/genética , Neoplasias/genética , Neoplasias/patologia , Carga Tumoral/genética , Sequenciamento Completo do Genoma
19.
Bull Cancer ; 107(7-8): 813-822, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32451070

RESUMO

Radiation induced lymphopenia is frequent and can be severe and durable. Although lymphocytes have long been known as highly radiosensitive cells, it is poorly characterized. Radiation-induced lymphopenia seems to affect lymphocyte subpopulations differently and seems to be influenced by radiation modalities. The depth and duration of lymphopenia depend on the location of the irradiation and the volumes of treatment. Importantly, radiation-induced lymphopenia has been associated with poorer prognosis in several tumor types. The knowledge about radiation-induced lymphopenia might lead to a rethinking of the modalities of radiotherapy and new approaches to restore lymphocytes counts.


Assuntos
Linfopenia/etiologia , Linfopenia/terapia , Linfócitos T/efeitos da radiação , Humanos , Subpopulações de Linfócitos/efeitos da radiação , Tecido Linfoide/efeitos da radiação , Neoplasias/sangue , Neoplasias/imunologia , Prognóstico , Tolerância a Radiação , Radioterapia/efeitos adversos , Radioterapia/métodos , Linfócitos T/fisiologia
20.
Thromb Haemost ; 120(5): 832-846, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369854

RESUMO

BACKGROUND: Low molecular weight heparins (LMWH) are often used as a first-line therapy for the prevention of thrombosis in cancer patients. Preclinical evidence from animal models suggests that LMWH may have antimetastatic properties. Clinical evidence of this effect is inconclusive. The objective of this systematic review is to evaluate the effect of LMWH on overall survival in patients with solid tumor malignancies. METHODS: MEDLINE, Embase, and The Cochrane Central Register of Controlled trials were searched from inception to November 26, 2018. We included randomized controlled trials that compared LMWH to placebo, a no-treatment arm, or a short-term prophylactic course of LMWH in adult patients with solid tumors. The primary outcome was overall survival. Secondary outcomes included progression-free survival, the occurrence of venous thromboembolism, and major bleeding events. The risk of bias was assessed in duplicate using the Cochrane Risk-of-Bias tool. RESULTS: Forty-five articles were included in the review. Overall, no difference in overall survival was observed between groups (risk ratio: 1.00; 95% confidence interval: 0.98-1.02; I2 = 36.5%). In our a priori defined subgroup analyses, the effect was not shown to vary by the type of LMWH, duration of LMWH use, length of study follow-up, comparator used in the study, or the setting in which the LMWH was administered. The majority of studies had an unclear risk of bias for at least one methodological criterion. CONCLUSION: Although LMWH is thought to possess antimetastatic properties and thus have the potential to improve survival in cancer patients, existing data do not support this hypothesis.


Assuntos
Anticoagulantes/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Neoplasias/tratamento farmacológico , Trombose/prevenção & controle , Anticoagulantes/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias/mortalidade , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Trombose/sangue , Trombose/diagnóstico , Trombose/mortalidade , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA