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1.
Recent Results Cancer Res ; 215: 147-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605228

RESUMO

The development of metastatic disease accounts for the vast majority of cancer-related deaths in solid tumor malignancies. Distant metastases primarily develop as a result of tumor cell dissemination through the circulatory system.


Assuntos
Neoplasias da Mama/patologia , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Humanos
2.
Recent Results Cancer Res ; 215: 231-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605232

RESUMO

In only few years, circulating tumor DNA (ctDNA) in breast cancer has moved from purely fundamental research to nearby daily use for treatment selection and drug-resistance assessment. Indeed, technical advances and widespread use of next-generation sequencing or digital PCR allowed for detection of very low amount of tumor DNA in bloodstream. The use of ctDNA as liquid biopsy able either to monitor tumor burden under treatment or to overcome tumor heterogeneity and identify potential targetable drivers. Time has come to define how ctDNA can be implemented for early or metastatic breast cancer management. Data from retrospective analyses of prospective trials have recently highlighted the potential advantages but also the limitations of ctDNA, in particular for patients under endocrine therapy.


Assuntos
Neoplasias da Mama , DNA Tumoral Circulante , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Metástase Neoplásica/patologia , Metástase Neoplásica/terapia
3.
Anticancer Res ; 39(10): 5653-5662, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570463

RESUMO

BACKGROUND/AIM: Factors influencing fulvestrant efficacy may be useful in selecting the optimal treatment regimen for postmenopausal Japanese women with metastatic/recurrent HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated progression-free and overall survival (PFS and OS) in 100 fulvestrant-treated patients according to metastatic site. RESULTS: Median PFS was significantly better in patients with non-visceral (bone and regional metastases; 22.8 months) vs. visceral metastasis (lung, liver, and other organs; 8.2 months; p=0.024), although median OS did not differ (p=0.922). Median PFS in patients with lung metastasis (20.8 months) and non-visceral metastasis (22.8 months) were comparable; patients with liver metastasis (6.1 months) and other organ metastases (3.7 months) had worse prognoses. CONCLUSION: Patients with non-visceral metastases had a better prognosis than those with visceral metastases. Fulvestrant induced a longer PFS in patients with non-visceral metastasis, and also in those with lung metastasis without liver or other organ involvement.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Fulvestranto/uso terapêutico , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/genética , Receptores de Superfície Celular/genética , Estudos Retrospectivos
4.
Cytogenet Genome Res ; 158(4): 205-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434093

RESUMO

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.


Assuntos
Inativação Gênica , Antígenos de Histocompatibilidade/genética , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Caderinas/biossíntese , Adesão Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/genética
5.
Anticancer Res ; 39(8): 4315-4324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366523

RESUMO

BACKGROUND/AIM: This study aimed to obtain accurate differential diagnosis (DDx) of multicentric carcinogenesis (MC) and intrahepatic metastasis (IM) in recurrent lesions of hepatocellular carcinoma. MATERIALS AND METHODS: A total of 79 patients who underwent re-hepatectomy (2000-2013) were examined. PCR was used to analyze 13 chromosomal microsatellite loci by PCR. On the basis of this genetic analysis, the recurrent lesions were diagnosed as IM, MC or not determined (ND). Subsequently, DDx was compared with types of resection and outcome. RESULTS: The recurrent lesions were diagnosed as IM in 33 patients, MC in 44, and ND in 2. The anatomical resection group included 14 IM lesions (28%) and 36 MC lesions (72%), while the non-anatomical resection group included 19 IM lesions (70%) and 8 MC lesions (30%) (p<0.001). CONCLUSION: Anatomical resection at initial hepatectomy may reduce the likelihood of IM recurrence, leading to a better outcome for patients with HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Metástase Neoplásica/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diagnóstico Diferencial , Feminino , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
6.
Medicine (Baltimore) ; 98(30): e16187, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348230

RESUMO

BACKGROUND: Recently, many studies have been carried out to investigate the clinicopathological significance of E-cadherin expression in thyroid cancer. However, the results remained inconsistent. In the present study, we performed a meta-analysis to evaluate the associations of E-cadherin expression with susceptibility and clinicopathological characteristics of thyroid cancer. METHODS: Eligible studies were searched from Medicine, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The strength of associations between E-cadherin expression and susceptibility and clinicopathological features of thyroid cancer were assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Forty-six studies with 1700 controls and 2298 thyroid cancer patients were included for this meta-analysis. Pooled results indicated that E-cadherin expression was significantly associated with susceptibility of papillary cancer and follicular cancer (papillary cancer, ORs = 14.31, 95% CIs = 3.42-59.90; follicular cancer, ORs = 10.14, 95% CI = 4.52-22.75). Significant association between E-cadherin expression and thyroid cancer risk was also observed in the subgroup analysis based on control group (normal thyroid tissue, ORs = 28.28, 95% CI = 8.36-95.63; adjacent thyroid tissue, ORs = 8.83, 95% CI = 3.27-23.85; benign thyroid tissue, ORs = 43.96, 95% CI = 9.91-194.95). In addition, E-cadherin expression was significantly correlated with lymph node metastasis, differentiation, and tumor-node-metastasis (TNM) stage of thyroid cancer (lymph node metastasis, ORs = 3.21, 95% CI = 1.98-5.20; differentiation, ORs = 0.25, 95% CI = 0.07-0.82; TNM stage, ORs = 4.85, 95% CI = 2.86-8.25). CONCLUSIONS: The present study showed that E-cadherin expression was significantly associated with susceptibility and clinicopathological characteristics of thyroid cancer, which suggested that E-cadherin expression might be a potential predictive factor for clinical progression of thyroid cancer.


Assuntos
Adenocarcinoma Folicular/patologia , Caderinas/biossíntese , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/patologia , Humanos , Metástase Linfática , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Medição de Risco , Fatores de Risco
7.
Cancer Sci ; 110(8): 2442-2455, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148345

RESUMO

The human prolyl isomerase PIN1, best known for its association with carcinogenesis, has recently been indicated in the disease of pancreatic ductal adenocarcinoma (PDAC). However, the functions of PIN1 and the feasibility of targeting PIN1 in PDAC remain elusive. For this purpose, we examined the expression of PIN1 in cancer, related paracarcinoma and metastatic cancer tissues by immunohistochemistry and analyzed the associations with the pathogenesis of PDAC in 173 patients. The functional roles of PIN1 in PDAC were explored in vitro and in vivo using both genetic and chemical PIN1 inhibition. We showed that PIN1 was upregulated in pancreatic cancer and metastatic tissues. High PIN1 expression is significantly association with poor clinicopathological features and shorter overall survival and disease-free survival. Further stratified analysis showed that PIN1 phenotypes refined prognostication in PDAC. Inhibition of PIN1 expression with RNA interference or with all trans retinoic acid decreased not only the growth but also the migration and invasion of PDAC cells through regulating the key molecules of multiple cancer-driving pathways, simultaneously resulting in cell cycle arrest and mesenchymal-epithelial transition in vitro. Furthermore, genetic and chemical PIN1 ablation showed dramatic inhibition of the tumorigenesis and metastatic spread and then reduced the tumor burden in vivo. We provided further evidence for the use of PIN1 as a promising therapeutic target in PDAC. Genetic and chemical PIN1 ablation exerted potent antitumor effects through blocking multiple cancer-driving pathways in PDAC. More potent and specific PIN1 targeted inhibitors could be exploited to treat this aggressive cancer.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Peptidilprolil Isomerase de Interação com NIMA/genética , Metástase Neoplásica/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Animais , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Ductal Pancreático/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Neoplasias Pancreáticas/patologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
8.
Cancer Sci ; 110(8): 2493-2506, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215139

RESUMO

Gallbladder cancer (GBC) is the most common malignancy of the bile duct and has a high mortality rate. Here, we demonstrated that BRD4 inhibitor JQ1 and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) synergistically inhibited the GBC cells in vitro and in vivo. Our results showed that cotreatment with JQ1 and SAHA significantly inhibited proliferation, cell viability and metastasis, and induced apoptosis and G2/M arrest in GBC cells, with only minor effects in benign cells. In vivo, tumor volumes and weights of GBC xenograft models were significantly decreased after treatment with JQ1 or SAHA; meanwhile, the cotreatment showed the strongest effect. Further study indicated that the above anticancer effects was associated with the downregulation of BRD4 and suppression of PI3K/AKT and MAPK/ERK pathways. These findings highlight JQ1 and SAHA as potential therapeutic agents and their combination as a promising therapeutic strategy for GBC.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Proteínas Nucleares/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Fase G2/efeitos dos fármacos , Neoplasias da Vesícula Biliar/patologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Vorinostat/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
9.
Adv Exp Med Biol ; 1136: 57-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31201716

RESUMO

Metastasis remains the leading cause of cancer-related deaths. To date, there are no specific treatments targeting disseminated disease. New therapeutic options will become available only if we enhance our understanding of mechanisms underlying metastatic spread. A large body of literature shows that the metastatic potential of tumor cells is strongly influenced by microenvironmental cues such as low oxygen (hypoxia). Clinically, hypoxia is a hallmark of most solid tumors and is associated with increased metastasis and poor survival in a variety of cancer types. Mechanistically, hypoxia influences multiple steps within the metastatic cascade and particularly impacts the interactions between tumor cells and host stroma at both primary and secondary sites. Here we review current evidence for a hypoxia-induced tumor secretome and its impact on metastatic progression. These studies have identified potential biomarkers and therapeutic targets that could be integrated into strategies for preventing and treating metastatic disease.


Assuntos
Metástase Neoplásica/patologia , Neoplasias/patologia , Hipóxia Tumoral , Microambiente Tumoral , Hipóxia Celular , Progressão da Doença , Humanos
10.
Adv Exp Med Biol ; 1136: 87-95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31201718

RESUMO

The hypoxic microenvironment is one of the major features of solid tumors, which regulates cell malignancy in multiple ways. As a response to hypoxia, a large number of target genes involved in cell growth, metabolism, metastasis and immunity are activated in cancer cells. Hypoxia-inducible factor 1 (HIF-1), as a heterodimeric DNA-binding complex, is comprised of a constitutively expressed HIF-1ß subunit and an oxygen sensitive HIF-1α subunit, thus, adapts to decreased oxygen availability as a transcriptional factor. HIF-1 regulates many genes involved in tumorigenesis. Here, we focus on cancer cell metabolism and metastasis regulated by hypoxia.


Assuntos
Metástase Neoplásica/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Hipóxia Tumoral , Hipóxia Celular , Regulação da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Oxigênio , Microambiente Tumoral
11.
Adv Exp Med Biol ; 1136: 97-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31201719

RESUMO

Metastasis is considered the latest stage of cancer development; however, metastasis occurs earlier than it can be detected. Metastatic sites are actively remodeled by secretory factors including growth factors, chemokines and cytokines, extracellular matrix (ECM) enzymes, and exosomes produced by the primary cancer tissues. Many of the associated-secretory factors are abundantly induced by inflammation and hypoxia. These secretory factors modify the ECM, immune composition, and blood vessel permeability of the future metastatic sites, a process termed 'metastatic niche formation.' In general, ECM is modified to enhance the attachment of other cell types or cancer cells to establish a growth-factor rich metastatic niche. Immune-suppressive cells such as tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) dominate the metastatic niche to allow metastatic cancer cells to bypass immune surveillance and propagate. Endothelial cell-to-cell junctions of blood vessels are loosened to enhance the penetrance of metastatic cancer cells to the metastatic sites. Different metastatic tissues have unique ECM constituents, resident immune cells, and anatomical positions linked with the circulatory system; therefore, many cancer types have their own metastatic pattern, and they favor metastasis to specific organs. Some of the remodeling events represent the earliest step of metastasis, even preceding the detachment of cancer cells from the primary tumor site. Understanding how the metastatic niche is formed is important for the development of drugs to prevent the earliest step of metastasis and advance our understanding of organotrophic metastasis. This review summarizes the major findings in the field of metastatic niche highlighting the role of hypoxia.


Assuntos
Metástase Neoplásica/patologia , Neoplasias/patologia , Hipóxia Tumoral , Microambiente Tumoral , Humanos , Vigilância Imunológica
12.
Biochim Biophys Acta Rev Cancer ; 1872(1): 103-110, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152824

RESUMO

Plexin D1 belongs to a family of transmembrane proteins called plexins. It was characterized as a receptor for semaphorins and is known to be essential for axonal guidance and vascular patterning. Mutations in Plexin D1 have been implicated in pathologic conditions such as truncus arteriosus and Möbius syndrome. Emerging data show that expression of Plexin D1 is deregulated in several cancers; it can support tumor development by aiding in tumor metastasis and EMT; and conversely, it can act as a dependence receptor and stimulate cell death in the absence of its canonical ligand, semaphorin 3E. The role of Plexin D1 in tumor development and progression is thereby garnering research interest for its potential as a biomarker and as a therapeutic target. In this review, we describe its discovery, structure, mutations, role(s) in cancer, and therapeutic potential.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Síndrome de Möbius/genética , Metástase Neoplásica/genética , Neoplasias/genética , Biomarcadores Tumorais/genética , Humanos , Síndrome de Möbius/complicações , Síndrome de Möbius/terapia , Terapia de Alvo Molecular , Metástase Neoplásica/patologia , Neoplasias/complicações , Neoplasias/terapia , Transdução de Sinais/genética , Tronco Arterial/patologia
13.
Vet Clin North Am Small Anim Pract ; 49(5): 819-836, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31178200

RESUMO

Canine cutaneous mast cell tumors (MCTs) are among the most common canine cutaneous tumors, with highly variable biological behavior. This review describes in detail current approaches for cytologic and histologic diagnosis and prognosis, including advantages and limitations of cytologic and histologic grading and utilization of molecular markers, for example, Ki67, AgNORs, KIT expression, and c-Kit mutations, for a more accurate detection of aggressive MCTs. Furthermore, the current approach to evaluate surgical margins and spread to local lymph nodes is discussed.


Assuntos
Doenças do Cão/diagnóstico , Mastocitose Cutânea/veterinária , Animais , Biomarcadores Tumorais , Biópsia/métodos , Biópsia/veterinária , Doenças do Cão/patologia , Cães , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/patologia , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias/veterinária , Prognóstico
14.
Virchows Arch ; 475(3): 341-348, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31076902

RESUMO

Desmoplastic reaction (DR) involves the growth of fibrous or connective tissues around a tumor and has recently attracted attention as an indicator of malignant potential. Previous studies have confirmed that histological categorization of DR in the primary tumor is an independent prognostic factor in patients with colorectal liver metastases (CRLM). However, it remains unclear whether the DR status of the metastatic liver lesion (DRliver) is a useful prognostic factor. This pathological review evaluated records from 204 patients who underwent hepatectomy for CRLM at the National Defense Medical College Hospital in Japan. Each case's DRliver was classified as mature, intermediate, or immature based on the presence of keloid-like collagen and myxoid stroma in the metastatic liver lesion. This resulted in 12 cases of mature DRliver, 101 cases of intermediate DRliver, and 91 cases of immature DRliver. There was a significant correlation between the DR statuses of the primary tumor and the metastatic liver lesion (Spearman's rho = 0.3, P = 0.0001). The 5-year relapse-free survival rates after hepatectomy were 33.8% for mature/intermediate DRliver and 16.7% for immature DRliver (P = 0.0021). The 5-year overall survival rate after hepatectomy was higher in the mature/intermediate DRliver group (64.8%) than in the immature DRliver group (35.0%; P = 0.0012). The multivariate analysis confirmed that DRliver categorization could independently predict relapse-free survival and overall survival. In conclusion, DRliver categorization may be valuable for predicting prognosis after hepatectomy among patients with CRLM.


Assuntos
Fibroblastos Associados a Câncer/patologia , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibroblastos Associados a Câncer/metabolismo , Neoplasias Colorretais/classificação , Intervalo Livre de Doença , Feminino , Fibroblastos/patologia , Fibrose , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Células Estromais/patologia , Taxa de Sobrevida
15.
Folia Neuropathol ; 57(1): 72-79, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31038190

RESUMO

Glioblastoma, the most malignant astrocytic tumour, is associated with limited survival and thus rare metastases. We analysed a particularly interesting case - a 51-year-old male diagnosed within 2 years with primary and recurrent glioblastoma, isocitrate dehydrogenase (IDH)-wild type, as well as with numerous extra-central nervous system (CNS) metastatic foci. Genetic material obtained from primary and recurrent tumours, as well as from pulmonary metastasis was analysed and compared at a molecular level. Next generation sequencing (NGS) analysis revealed BRAFV600E mutation, detected only in 2-5% of glioblastomas, in both the primary tumour and pulmonary metastases. Importantly, this mutation provides a possible therapeutic option as it constitutes a target for clinically approved inhibitors. This case study not only demonstrates a molecular comparison of primary, recurrent and metastatic glioblastoma, but also emphasizes the need for precise molecular diagnostics, which may facilitate treatment choice, especially in tumours currently lacking efficient treatment.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , Metástase Neoplásica/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Lobo Temporal/patologia
16.
Int J Mol Sci ; 20(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052488

RESUMO

Background: Immune checkpoint inhibitors (ICI) have represented a revolution in the treatment of non-small-cell lung cancer (NSCLC). To improve these results, combined approaches are being tested. The addition of stereotactic ablative radiotherapy (SABR) to ICI seems promising. A systematic review was performed in order to assess the safety and efficacy of SABR-ICI combination. Material and Methods: MEDLINE databases from 2009 to March 3, 2019 were reviewed to obtain English language studies reporting clinical outcomes of the combination of ICI-SABR in NSCLC. 18 out of the 429 initial results fulfilled the inclusion criteria and were selected for review. Results: Eighteen articles, including six prospective studies, describing 1736 patients treated with an ICI-SABR combination fulfilled the selection criteria. The reported mean rates for local control and distant/abscopal response rates were 71% and 41%, respectively. Eleven studies reported progression-free survival and overall survival, with a mean of 4.6 and 12.4 months, respectively. Toxicity rates were consistent with the ones attributable to ICI treatment alone. Conclusions: The ICI-SABR combination has a good safety profile and achieves high rates of local control and greater chances of obtaining abscopal responses than SABR alone, with a relevant impact on PFS. More studies are needed to improve patient selection for an optimal benefit from this approach.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Metástase Neoplásica/radioterapia , Metástase Neoplásica/terapia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada/métodos , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Metástase Neoplásica/imunologia , Metástase Neoplásica/patologia , Radiocirurgia/métodos , Resultado do Tratamento
17.
Int J Mol Sci ; 20(10)2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31130715

RESUMO

The primary cause of mortality among patients with cancer is the progression of the tumor, better known as cancer invasion and metastasis. Cancer progression involves a series of biologically important steps in which the cross-talk between cancer cells and the cells in the surrounding environment is positioned as an important issue. Notably, angiogenesis is a key tumorigenic phenomenon for cancer progression. Cancer-related extracellular vesicles (EVs) commonly contribute to the modulation of a microenvironment favorable to cancer cells through their function of cell-to-cell communication. Vascular-related cells such as endothelial cells (ECs) and platelets activated by cancer cells and cancer-derived EVs develop procoagulant and proinflammatory statuses, which help excite the tumor environment, and play major roles in tumor progression, including in tumor extravasation, tumor cell microthrombi formation, platelet aggregation, and metastasis. In particular, cancer-derived EVs influence ECs, which then play multiple roles such as contributing to tumor angiogenesis, loss of endothelial vascular barrier by binding to ECs, and the subsequent endothelial-to-mesenchymal transition, i.e., extracellular matrix remodeling. Thus, cell-to-cell communication between cancer cells and ECs via EVs may be an important target for controlling cancer progression. This review describes the current knowledge regarding the involvement of EVs, especially exosomes derived from cancer cells, in EC-related cancer progression.


Assuntos
Células Endoteliais/patologia , Vesículas Extracelulares/patologia , Neoplasias/patologia , Animais , Progressão da Doença , Exossomos/patologia , Humanos , Metástase Neoplásica/patologia , Neoplasias/irrigação sanguínea , Neovascularização Patológica/patologia
18.
Anticancer Res ; 39(5): 2553-2559, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092452

RESUMO

BACKGROUND/AIM: This study aimed to evaluate the therapeutic effect of enzalutamide (ENZ) or abiraterone acetate (ABI) on bone metastasis in castration-resistant prostate cancer (CRPC), using bone scan index (BSI). MATERIALS AND METHODS: Treatment outcomes for 31 patients who had undergone ENZ or ABI treatment were examined for CRPC with bone metastases. Cox proportional-hazards regression models were used to investigate the association between overall survival (OS) and clinical characteristics. RESULTS: Median OS after ENZ or ABI treatment was 29 months. Considering the flare phenomenon, BSI in 17 (55%) patients decreased following treatment. In multivariate analysis, low baseline BSI value and a decrease in BSI following treatment were associated with longer OS (hazard ratio [HR]=8.009; p=0.35 and HR=7.025; p=0.045*, respectively). CONCLUSION: Low BSI value before ENZ/ABI treatment and a decrease in BSI following ENZ or ABI treatment are independent predictors of longer OS. BSI could be useful for risk assessment of CRPC patients with bone metastases.


Assuntos
Neoplasias Ósseas/diagnóstico , Metástase Neoplásica/diagnóstico , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Cintilografia/métodos , Acetato de Abiraterona/administração & dosagem , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/patologia , Feniltioidantoína/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia
19.
Semin Ophthalmol ; 34(3): 182-187, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135259

RESUMO

Purpose: To describe the clinical features, treatment, and outcomes of conjunctival melanoma in Asian Indians. Methods: Retrospective study of 42 patients. Results: The mean age at presentation of conjunctival melanoma was 43 years (median, 45 years; range, 9-78 years). There were 20 (48%) males and 22 (52%) females. Nineteen patients (45%) had a known history of a preexisting pigmented conjunctival lesion. Bulbar conjunctiva (n = 28; 67%) was the most common tumor epicenter, and medial ocular surface quadrant (n = 15; 36%) was more commonly involved. The mean tumor basal diameter was 12 mm (median, 10 mm; range, 4-30 mm), and the mean tumor thickness was 4 mm (median, 2 mm; range, 1-30 mm). Majority of the patients had a pigmented tumor (n = 33; 79%). The tumors arose de novo (n = 17, 41%) or were associated with conjunctival nevus (n = 9; 21%) or primary acquired melanosis (n = 16, 38%). Wide excisional biopsy, adjunctive cryotherapy, and amniotic membrane grafting were performed in 27 (71%) patients, 11 (29%) underwent orbital exenteration, and 4 were lost to follow-up prior to definitive treatment. Over a mean follow-up period of 24 months (median, 9 months; range, <1 to 136 months), four (11%) patients had tumor recurrence, seven (18%) had locoregional lymph node metastasis, and four (11%) developed systemic metastasis and died due to metastatic disease. Conclusion: Conjunctival melanoma predominantly occurs in middle-aged Asian Indians and is associated with a high rate of systemic metastasis and death.


Assuntos
Neoplasias da Túnica Conjuntiva , Melanoma , Adolescente , Adulto , Distribuição por Idade , Idoso , Âmnio/transplante , Grupo com Ancestrais do Continente Asiático , Criança , Neoplasias da Túnica Conjuntiva/epidemiologia , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/cirurgia , Neoplasias da Túnica Conjuntiva/terapia , Crioterapia/métodos , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Distribuição por Sexo , Adulto Jovem
20.
Crit Rev Oncol Hematol ; 138: 24-28, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31092381

RESUMO

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.


Assuntos
Metástase Neoplásica/radioterapia , Neoplasias da Próstata/radioterapia , Radioterapia/métodos , Consenso , Humanos , Masculino , Metástase Neoplásica/patologia , Prognóstico , Neoplasias da Próstata/patologia , Radiocirurgia/métodos
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