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2.
Medicine (Baltimore) ; 99(36): e22060, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899071

RESUMO

The phase III West Japan Oncology Group (WJOG) 4407G study showed noninferiority of folinic acid, bolus/continuous fluorouracil, and irinotecan plus bevacizumab to modified folinic acid, bolus/continuous fluorouracil, and oxaliplatin 6 plus bevacizumab in progression-free survival (PFS) as first-line chemotherapy for patients with metastatic colorectal cancer. The aim of this study was to evaluate the predictive and prognostic value of morphologic response in patients with colorectal liver metastases (CLM) as a post hoc analysis of the WJOG4407G study.Morphologic response was assessed by comparing contrast-enhanced computed tomography (CT) images at baseline and week 8. Three blinded radiologists evaluated CT images and classified their response as optimal, incomplete, or no response according to the morphologic criteria. Response evaluation criteria in solid tumors (RECIST) response, early tumor shrinkage (ETS), and depth of response (DpR) were also evaluated.Among 395 patients who were eligible for efficacy analysis in the WJOG4407G study, 70 patients had liver-limited disease. We finally evaluated 55 of these patients. Optimal morphologic response was identified in 19 of 55 patients (34.5%). The median PFS was 10.7 months for patients with optimal response and 10.1 months in those with incomplete/no response (log-rank, P = .96). The median overall survival (OS) was 26.2 and 35.5 months, respectively (log-rank, P = .062). According to univariate analysis, morphologic response was not associated with PFS or OS, whereas RECIST response was significantly associated with both PFS and OS, with ETS and DpR being associated with significantly longer PFS.Morphologic response might be neither a predictive nor a prognostic factor in patients with CLM undergoing chemotherapy containing bevacizumab, whereas RECIST response was significantly associated with both PFS and OS.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Antimetabólitos Antineoplásicos , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas/métodos , Irinotecano/uso terapêutico , Japão/epidemiologia , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Oxaliplatina/uso terapêutico , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X/métodos , Inibidores da Topoisomerase I/uso terapêutico , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico
3.
Nat Commun ; 11(1): 4261, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848136

RESUMO

Metastasis, the spread of malignant cells from a primary tumour to distant sites, causes 90% of cancer-related deaths. The integrin ITGB3 has been previously described to play an essential role in breast cancer metastasis, but the precise mechanisms remain undefined. We have now uncovered essential and thus far unknown roles of ITGB3 in vesicle uptake. The functional requirement for ITGB3 derives from its interactions with heparan sulfate proteoglycans (HSPGs) and the process of integrin endocytosis, allowing the capture of extracellular vesicles and their endocytosis-mediated internalization. Key for the function of ITGB3 is the interaction and activation of focal adhesion kinase (FAK), which is required for endocytosis of these vesicles. Thus, ITGB3 has a central role in intracellular communication via extracellular vesicles, proposed to be critical for cancer metastasis.


Assuntos
Neoplasias da Mama/metabolismo , Comunicação Celular/fisiologia , Vesículas Extracelulares/metabolismo , Integrina beta3/metabolismo , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Endocitose , Feminino , Quinase 1 de Adesão Focal/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Xenoenxertos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Células MCF-7 , Camundongos , Camundongos Nus , Modelos Biológicos , Metástase Neoplásica/patologia , Transplante de Neoplasias
4.
Medicine (Baltimore) ; 99(30): e21325, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791728

RESUMO

The present study aimed to retrospectively analyze the survival outcomes and prognostic factors for patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).Clinical data was collected from 691 patients with NPC receiving IMRT from January 2009 to August 2015. A survival analysis was performed and prognostic factors were analyzed using the Kaplan-Meier method, the Cox proportional hazards regression model, and the log-rank test.The median follow-up time was 62.8 months. Sixty-three patients experienced relapse, 44 cases (70%) of which occurred within 3 years. Six cases (9.5%) remained in remission for over 5 years. Seventy-two patients developed metastasis, 63 cases (87.5%) of which occurred within 3 years and only 1 case occurred after 5 years (1.3%). Five-year disease special survival (DSS), progression free survival, locoregional recurrence free survival, and distant metastasis free survival were 86.5%, 82.5%, 90.7%, and 89.4%, respectively in patients with NPC. Patients with stage III NPC with and without induction chemotherapy had 5-year DSS rates of 95.8% and 89.3%, respectively (P = .00). Patients with stage IVa NPC with and without induction chemotherapy had 5-year DSS rates of 73.1% and 68.9%, respectively (P = .04). The 5-year DSS rates of patients with stage III with or without concurrent chemotherapy were 92.8% and 85.5%, respectively (P = .04). The 5-year DSS rates of patients with stage IV with or without concurrent chemotherapy were 72.7% and 53.0% (P = .02).IMRT improves the survival rate of patients with NPC. Recurrence and metastasis mainly occur within 2 to 3 years after radiotherapy. Induction and concurrent chemotherapy improve the 5-year DSS of patients with locally advanced NPC.


Assuntos
Quimiorradioterapia/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Quimiorradioterapia/métodos , Feminino , Seguimentos , Humanos , Quimioterapia de Indução/métodos , Masculino , Carcinoma Nasofaríngeo/mortalidade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
5.
Life Sci ; 258: 118154, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735882

RESUMO

AIMS: Epithelial-to-mesenchymal transition (EMT) facilitates cell migration and invasion, and contributes to metastasis in bladder cancer. Within the perioperative period, anesthetic such as isoflurane have been found to affect cancer prognosis. In the study, we reported the tumor-promoting effect of isoflurane in bladder cancer. MATERIALS AND METHODS: Human bladder cancer cell lines T24 and BIU-87 were exposed to isoflurane at different concentrations. The immunofluorescent staining of Ki67, Annexin V-FITC/PI staining, Transwell invasion assays and wound-healing assays were performed to assess cell proliferation, apoptosis, invasion and migration. Expressions of EMT markers (E-cadherin, N-cadherin and Vimentin) and metastatic markers (Snail-1, Slug-1 and MMP-2/9) were determined by immunoblotting. Orthotopic tumor models and mice given tail vein injection of T24 cells were developed with or without 4-h exposure to 2% isoflurane. KEY FINDINGS: We found isoflurane promoted bladder cancer cell proliferation, invasion and migration but reduce apoptosis in a concentration-dependent manner. In addition, isoflurane was shown to increase HIF-1α and its nuclear accumulation in bladder cancer cells. HIF-1α knockdown inhibited bladder cancer cell proliferation and delayed EMT, which was reversed in the presence of 4-h exposure to 2% isoflurane. Likewise, we found isoflurane modulated ß-catenin/Notch1 pathways via HIF-1α. In vivo studies showed that isoflurane exposure accelerated formation of orthotopic bladder tumor and promoted hepatic metastases from carcinoma of the bladder. SIGNIFICANCE: Taken together, our study demonstrates that a frequently used anesthetic can exert a protumorigenic effect on bladder cancer. Isoflurane may serve as an important contributory factor to high recurrence following surgery.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Isoflurano/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/induzido quimicamente , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Receptor Notch1/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , beta Catenina/metabolismo
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): e0238207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841270

RESUMO

BACKGROUND: Although infrequent, distant metastasis from differentiated thyroid cancer is the main cause of mortality in patients and mostly involves the lung, bone, and brain. Distant metastases to other sites in differentiated thyroid cancer patients are rare, thus, the clinical course of unusual metastases has not been adequately researched. In the present study, the clinico-pathological findings and treatment outcomes of unusual metastases in differentiated thyroid cancer patients in Korea were evaluated. PATIENTS AND METHODS: We retrospectively reviewed the medical records of differentiated thyroid cancer patients with unusual metastases in four Korean tertiary hospitals (Chonnam National University Hwasun Hospital, Asan Medical Center, Busan National University Hospital, Severance Hospital). Unusual metastases were diagnosed using (1) cytology or histology and/or (2) imaging studies including fluorodeoxyglucose F 18 positron emission tomography/computed tomography and/or iodine 131 whole body scans with simultaneously elevated serum levels of thyroglobulin. The pathological findings of primary thyroid cancer, diagnostic method for unusual metastases, and treatment responses of unusual metastases were examined. RESULTS: In all, 25 unusual metastatic foci of 19 patients were analyzed; 13 patients (68.4%) had papillary thyroid carcinoma including 4 follicular variant papillary thyroid carcinomas. The median time interval between the first diagnosis of primary thyroid cancer and unusual metastases diagnosis was 110 months (11.0-138.0 months). Only 4 patients (21.1%) had synchronous unusual metastases and 6 patients (31.6%) were symptomatic. Unusual metastases included 19 metastases to solid organs (6 to kidney, 5 to liver, 4 to pancreas, 3 to adrenal gland, and 1 to ovary) and 6 to the skin and muscles. Unusual metastases were pathologically proven in 10 patients (52.6%) and 11 of 16 patients (68.8%) who received iodine 131 whole body scans had radioiodine-refractory differentiated thyroid cancer. Among 5 patients treated with tyrosine kinase inhibitors, 4 treated with lenvatinib showed stable disease or a partial response at the first treatment response. Six patients (31.6%) died due to disease progression during the median 20.0-month follow-up period (11.0-55.0 months). CONCLUSION: Unusual metastases from differentiated thyroid cancer are thought to be underestimated due to disease rarity and their metachronous nature with other distant metastases. The most of unusual metastases in differentiated thyroid cancer patients are existed with usual distant metastasis and clinical outcomes of those could not be significantly different from the prognosis of usual distant metastasis.


Assuntos
Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma Papilar/secundário , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/patologia , Metástase Neoplásica/terapia , Especificidade de Órgãos , Compostos de Fenilureia/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , República da Coreia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/terapia , Fatores de Tempo , Imagem Corporal Total
8.
Nature ; 585(7823): 113-118, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32814895

RESUMO

Cancer cells, including melanoma cells, often metastasize regionally through the lymphatic system before metastasizing systemically through the blood1-4; however, the reason for this is unclear. Here we show that melanoma cells in lymph experience less oxidative stress and form more metastases than melanoma cells in blood. Immunocompromised mice with melanomas derived from patients, and immunocompetent mice with mouse melanomas, had more melanoma cells per microlitre in tumour-draining lymph than in tumour-draining blood. Cells that metastasized through blood, but not those that metastasized through lymph, became dependent on the ferroptosis inhibitor GPX4. Cells that were pretreated with chemical ferroptosis inhibitors formed more metastases than untreated cells after intravenous, but not intralymphatic, injection. We observed multiple differences between lymph fluid and blood plasma that may contribute to decreased oxidative stress and ferroptosis in lymph, including higher levels of glutathione and oleic acid and less free iron in lymph. Oleic acid protected melanoma cells from ferroptosis in an Acsl3-dependent manner and increased their capacity to form metastatic tumours. Melanoma cells from lymph nodes were more resistant to ferroptosis and formed more metastases after intravenous injection than did melanoma cells from subcutaneous tumours. Exposure to the lymphatic environment thus protects melanoma cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood.


Assuntos
Ferroptose , Linfa/metabolismo , Melanoma/patologia , Metástase Neoplásica/patologia , Animais , Sobrevivência Celular , Coenzima A Ligases/metabolismo , Feminino , Ferroptose/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Ferro/metabolismo , Masculino , Melanoma/sangue , Melanoma/metabolismo , Camundongos , Metástase Neoplásica/tratamento farmacológico , Ácido Oleico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Análise de Componente Principal
10.
Medicine (Baltimore) ; 99(29): e20821, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702824

RESUMO

This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure.Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed.Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response (P = .002, .026, .007, respectively).Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antagonistas do Receptor de Estrogênio/uso terapêutico , Fulvestranto/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Pós-Menopausa/efeitos dos fármacos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Grupo com Ancestrais do Continente Asiático/etnologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Segurança , Tempo para o Tratamento , Resultado do Tratamento
11.
Nat Commun ; 11(1): 3568, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678085

RESUMO

Dissemination of transformed cells is a key process in metastasis. Despite its importance, how transformed cells disseminate from an intact tissue and enter the circulation is poorly understood. Here, we use a fully developed tissue, Drosophila midgut, and describe the morphologically distinct steps and the cellular events occurring over the course of RasV12-transformed cell dissemination. Notably, RasV12-transformed cells formed the Actin- and Cortactin-rich invasive protrusions that were important for breaching the extracellular matrix (ECM) and visceral muscle. Furthermore, we uncovered the essential roles of the mechanosensory channel Piezo in orchestrating dissemination of RasV12-transformed cells. Collectively, our study establishes an in vivo model for studying how transformed cells migrate out from a complex tissue and provides unique insights into the roles of Piezo in invasive cell behavior.


Assuntos
Proteínas de Drosophila/metabolismo , Canais Iônicos/metabolismo , Mecanotransdução Celular , Invasividade Neoplásica/patologia , Proteínas ras/metabolismo , Animais , Membrana Basal/metabolismo , Membrana Basal/patologia , Transformação Celular Neoplásica , Modelos Animais de Doenças , Drosophila , Proteínas de Drosophila/genética , Vesículas Extracelulares/metabolismo , Trato Gastrointestinal/patologia , Genes ras , Canais Iônicos/genética , Metástase Neoplásica/patologia , Podossomos/metabolismo , Proteínas ras/genética
12.
Cancer Immunol Immunother ; 69(9): 1673-1697, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32500231

RESUMO

The tumor microenvironment (TME) not only facilitates cancer progression from the early formation to distant metastasis, but also it differs itself from time to time alongside the tumor evolution. Tumor-associated macrophages (TAMs), whether as pre-existing tissue-resident macrophages or recruited monocytes, are an inseparable part of this microenvironment. As their parents are broadly classified into a dichotomic, simplistic M1 and M2 subtypes, TAMs also exert paradoxical and diverse phenotypes as they are settled in different regions of TME and receive different microenvironmental signals. Briefly, M1 macrophages induce an inflammatory precancerous niche and flame the early oncogenic mutations, whereas their M2 counterparts are reprogrammed to release various growth factors and providing an immunosuppressive state in TME as long as abetting hypoxic cancer cells to set up a new vasculature. Further, they mediate stromal micro-invasion and co-migrate with invasive cancer cells to invade the vascular wall and neural sheath, while another subtype of TAMs prepares suitable niches much earlier than metastatic cells arrive at the target tissues. Accordingly, at the neoplastic transformation, during the benign-to-malignant transition and through the metastatic cascade, macrophages are involved in shaping the primary, micro-invasive and pre-metastatic TMEs. Whether their behavioral plasticity is derived from distinct genotypes or is fueled by microenvironmental cues, it could define these cells as remarkably interesting therapeutic targets.


Assuntos
Carcinogênese/patologia , Macrófagos/patologia , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Neoplasias/patologia , Animais , Humanos , Microambiente Tumoral/fisiologia
13.
Medicine (Baltimore) ; 99(21): e20165, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481285

RESUMO

Soft tissue sarcoma (STS) of the extremities are a rare tumor. Metastases develop in about 40%-50% of patients, most of whom die from their disease. We sought to identify potential risk factors associated with metastatic diseases upon presentation for patients with STS and established a reliable nomogram model to predict distant metastasis of STS at presentation. The current study retrospectively analyzed 3884 STS of the extremities or trunk patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Based on patient registration, all patients were randomly allocated to training sets and validation sets (2:1). Then, univariate and binary logistic regression analysis was used to determine the significantly correlated predictors of metastasis. Finally, the nomogram model was established, using these predictors and validated it. 311 (8.21%) of the cases experienced distant metastatic disease was present at the time of presentation. The nomogram was developed from age, histology subtype, primary site, tumor size, grade and depth. Encouragingly, the nomogram showed favorable calibration with C-index 0.790 in the training set and 0.801 in validation set. The DCA showed that the novel model was clinically useful. This nomogram model had a high precision to predict the metastasis of soft tissue sarcoma of the extremities. We expect this model could be used in different clinical consultation and established risk assessment.


Assuntos
Metástase Neoplásica/patologia , Nomogramas , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Adulto , Estudos de Casos e Controles , Extremidades/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Análise de Sobrevida
14.
Medicine (Baltimore) ; 99(24): e20223, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541449

RESUMO

INTRODUCTION: At present, there is no uniform consensus on the treatment of brain metastases from esophageal cancer. The studies on the treatment of brain metastases from esophageal cancer by radiotherapy combined with temozolomide (TMZ) are even rarer. PATIENT CONCERNS: A 69-year-old woman was admitted to our hospital for brain metastases from esophageal cancer after thoracic irradiation. DIAGNOSES: Magnetic resonance imaging of the head showed a round, heterogeneous metastatic tumor in the left parietal lobe. Brain magnetic resonance imaging showed edema around brain metastasesInterventions: After radiotherapy plus TMZ in this patient's head, the brain metastatic tumor was significantly decreased. OUTCOMES: At the end of radiotherapy, and 1 and 2 months after the end of radiotherapy, the metastatic tumor continued to shrink, and no obvious side effects were observed. LESSONS: This study suggests that radiotherapy plus TMZ might be a feasible option for brain metastases from esophageal cancer.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Esofágicas/patologia , Temozolomida/uso terapêutico , Administração Oral , Assistência ao Convalescente , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Terapia Combinada/métodos , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Metástase Neoplásica/patologia , Radioterapia/métodos , Temozolomida/administração & dosagem , Resultado do Tratamento
16.
Nature ; 583(7814): 133-138, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32528174

RESUMO

Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1-3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4-6. However, the functional role and clinical importance of NET-DNA in metastasis in patients with cancer remain unclear. Here we show that NETs are abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs can predict the occurrence of liver metastases in patients with early-stage breast cancer. NET-DNA acts as a chemotactic factor to attract cancer cells, rather than merely acting as a 'trap' for them; in several mouse models, NETs in the liver or lungs were found to attract cancer cells to form distant metastases. We identify the transmembrane protein CCDC25 as a NET-DNA receptor on cancer cells that senses extracellular DNA and subsequently activates the ILK-ß-parvin pathway to enhance cell motility. NET-mediated metastasis is abrogated in CCDC25-knockout cells. Clinically, we show that the expression of CCDC25 on primary cancer cells is closely associated with a poor prognosis for patients. Overall, we describe a transmembrane DNA receptor that mediates NET-dependent metastasis, and suggest that targeting CCDC25 could be an appealing therapeutic strategy for the prevention of cancer metastasis.


Assuntos
Neoplasias da Mama/patologia , DNA/metabolismo , Armadilhas Extracelulares/genética , Proteínas de Membrana/metabolismo , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neutrófilos/metabolismo , Actinina/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Proteínas de Membrana/genética , Camundongos , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
17.
Medicine (Baltimore) ; 99(20): e20159, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443331

RESUMO

Postoperative delirium (PD), characterized by acute onset of global impairment in consciousness and cognition, is a common complication following major surgeries and is often associated with adverse outcomes. Because of the multiple comorbidities of the patient along with extensive nature of the surgery, patients undergoing surgery for bone metastases may be prone to developing PD. However, no study exists regarding PD in patients who undergo surgery for bone metastases.Two hundred seventy six patients with mean age of 64 years (range, 16-94) who underwent surgery for bone metastases were reviewed. The diagnosis of PD was made by the psychiatrist, according to fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Possible perioperative clinic-pathologic factors that may be associated with the development of PD were investigated.Among the 276 patients, 9% (n = 25) developed PD. On multivariate logistic regression analysis, history of psychiatric disorders (odds ratio [OR] = 9.63; 95% confidence interval [CI] 1.78-21.74, P = .004), high preoperative serum C-reactive protein (CRP) level (OR = 1.17; 95% CI 1.06-1.29, P = .001), low preoperative serum albumin level (OR = 0.13; 95% CI 0.03-0.48, P = 0.002), and high dose of opioid analgesics received in the immediate postoperative period (OR = 1.05; 95% CI 1.01-1.07, P = .001) were independently associated with the development of PD. Patients with PD had lower survival (log rank, P = .001) than patients without PD.Incidence of PD is considerable in patients undergoing surgery for bone metastases. History of psychiatric disorders, preoperative serum albumin and CRP levels, and the dose of postoperative opioid analgesics are associated with the development of PD.


Assuntos
Neoplasias Ósseas/cirurgia , Delírio/etiologia , Metástase Neoplásica/patologia , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Neoplasias Ósseas/secundário , Proteína C-Reativa/análise , Cognição/efeitos dos fármacos , Cognição/fisiologia , Comorbidade , Delírio/epidemiologia , Delírio/mortalidade , Delírio/psicologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
18.
Zhonghua Zhong Liu Za Zhi ; 42(4): 331-335, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375450

RESUMO

Objective: To investigate the clinicopathological characteristics and outcomes of a series of ovarian metastases of pancreatic ductal adenocarcinoma. Methods: Data of clinical manifestation, pathological characteristic, treatment and follow-up result from ten patients with ovarian metastases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed. Results: The median age of onset was 46 years (38~79 years). The primary tumors were located in the body and tail of the pancreas in 8 cases. Bilateral ovarian metastasis occurred in 8 patients at the time of diagnosis. The median time from patients with clinical symptom to ovarian metastases was 2.5 months (0~12 months). Peritoneal metastasis was found in all of 10 cases. Nine cases were accompanied by CA125 elevation. The major features of metastatic carcinoma in the ovary were cystic-solid appearance (8 cases) and mucinous adenocarcinoma (6 cases) with no obvious immunohistochemical features in pathological observation. All patients underwent palliative ovariectomy at onset, and one patient underwent primary tumor resection simultaneously. Seven patients received chemotherapy. The median survival time of the 10 patients was 10.3 months. Conclusions: Ovarian metastases of pancreatic ductal adenocarcinoma are easily misdiagnosed. The final diagnosis depends on clinical manifestations, imaging and histopathological observation. Ovariectomy may be associated with better outcome.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Tumor de Krukenberg/patologia , Metástase Neoplásica/patologia , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/mortalidade , Adulto , Idoso , Antígeno Ca-125/sangue , Carcinoma Ductal Pancreático/mortalidade , China/epidemiologia , Feminino , Humanos , Tumor de Krukenberg/mortalidade , Tumor de Krukenberg/secundário , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/secundário , Ovário/patologia , Estudos Retrospectivos
20.
J Cancer Res Clin Oncol ; 146(9): 2351-2358, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32356176

RESUMO

PURPOSE: SBRT demonstrated to increase survival in oligometastatic patients. Nevertheless, little is known regarding the natural history of oligometastatic disease (OMD) and how SBRT may impact the transition to the polymetastatic disease (PMD). METHODS: 97 liver metastases in 61 oligometastatic patients were treated with SBRT. Twenty patients (33%) had synchronous oligometastases, 41 (67%) presented with metachronous oligometastases. Median number of treated metastases was 2 (range 1-5). RESULTS: Median follow-up was 24 months. Median tPMC was 11 months (range 4-17 months). Median overall survival (OS) was 23 months (range 16-29 months). Cancer-specific survival predictive factors were having further OMD after SBRT (21 months versus 15 months; p = 0.00), and local control of treated metastases (27 months versus 18 months; p = 0.031). Median PFS was 7 months (range 4-12 months). Patients with 1 metastasis had longer median PFS as compared to those with 2-3 and 4-5 metastases (14.7 months versus 5.3 months versus 6.5 months; p = 0.041). At the last follow-up, 50/61 patients (82%) progressed, 16 of which (26.6%) again as oligometastatic and 34 (56%) as polymetastatic. CONCLUSION: In the setting of oligometastatic disease, SBRT is able to delay the transition to the PMD. A proportion of patients relapse as oligometastatic and can be eventually evaluated for a further SBRT course. Interestingly, those patients retain a survival benefit as compared to those who had PMD. Further studies are needed to explore the role of SBRT in OMD and to identify treatment strategies able to maintain the oligometastatic state.


Assuntos
Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Metástase Neoplásica/patologia , Metástase Neoplásica/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Radiocirurgia/métodos
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