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1.
Gut ; 69(1): 7-17, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31672839

RESUMO

BACKGROUND AND AIM: The International Cancer of the Pancreas Screening Consortium met in 2018 to update its consensus recommendations for the management of individuals with increased risk of pancreatic cancer based on family history or germline mutation status (high-risk individuals). METHODS: A modified Delphi approach was employed to reach consensus among a multidisciplinary group of experts who voted on consensus statements. Consensus was considered reached if ≥75% agreed or disagreed. RESULTS: Consensus was reached on 55 statements. The main goals of surveillance (to identify high-grade dysplastic precursor lesions and T1N0M0 pancreatic cancer) remained unchanged. Experts agreed that for those with familial risk, surveillance should start no earlier than age 50 or 10 years earlier than the youngest relative with pancreatic cancer, but were split on whether to start at age 50 or 55. Germline ATM mutation carriers with one affected first-degree relative are now considered eligible for surveillance. Experts agreed that preferred surveillance tests are endoscopic ultrasound and MRI/magnetic retrograde cholangiopancreatography, but no consensus was reached on how to alternate these modalities. Annual surveillance is recommended in the absence of concerning lesions. Main areas of disagreement included if and how surveillance should be performed for hereditary pancreatitis, and the management of indeterminate lesions. CONCLUSIONS: Pancreatic surveillance is recommended for selected high-risk individuals to detect early pancreatic cancer and its high-grade precursors, but should be performed in a research setting by multidisciplinary teams in centres with appropriate expertise. Until more evidence supporting these recommendations is available, the benefits, risks and costs of surveillance of pancreatic surveillance need additional evaluation.


Assuntos
Carcinoma/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Pancreáticas/diagnóstico , Fatores Etários , Pesquisa Biomédica/métodos , Carcinoma/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Programas de Rastreamento/métodos , Neoplasias Pancreáticas/genética , Vigilância da População/métodos , Fatores de Risco
2.
Anticancer Res ; 39(10): 5789-5795, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570483

RESUMO

BACKGROUND/AIM: Pulmonary pleomorphic carcinoma (PPC) is rare, and few studies have reported its features. We assessed the clinicopathological features, surgical outcomes, oncogenic status and programmed death-ligand 1 (PD-L1) expression of PPC. PATIENTS AND METHODS: We retrospectively reviewed data from 22 consecutive patients who underwent resection of PPC between 2007 and 2017. RESULTS: The predominant tissue type of the epithelial component was adenocarcinoma in 15 patients (68%) and the others in 7 patients (32%), and the 3-year disease-free survival rate tended to be better in patients with an adenocarcinoma component compared to patients with another component (40.0% vs. 17.1%, p=0.059). PD-L1 expression was observed in all eight tumors whose PD-L1 status could be examined and high PD-L1 expression (≥50%) was frequent (5/8, 63%). CONCLUSION: A predominant adenocarcinoma epithelial component in PPC might be associated with better survival outcomes and high PD-L1 expression might be frequent in PPC.


Assuntos
Antígeno B7-H1/genética , Carcinoma/genética , Carcinoma/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Oncogenes/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
3.
Nature ; 574(7779): 532-537, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645730

RESUMO

The colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer1. However, our understanding of the earliest phases of colorectal neoplastic changes-which may occur in morphologically normal tissue-is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals. Signatures of multiple mutational processes were revealed; some of these were ubiquitous and continuous, whereas others were only found in some individuals, in some crypts or during certain periods of life. Probable driver mutations were present in around 1% of normal colorectal crypts in middle-aged individuals, indicating that adenomas and carcinomas are rare outcomes of a pervasive process of neoplastic change across morphologically normal colorectal epithelium. Colorectal cancers exhibit substantially increased mutational burdens relative to normal cells. Sequencing normal colorectal cells provides quantitative insights into the genomic and clonal evolution of cancer.


Assuntos
Colo/citologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Mutação , Sintomas Prodrômicos , Reto/citologia , Adenoma/genética , Adenoma/patologia , Idoso , Proteína Axina/genética , Carcinoma/genética , Carcinoma/patologia , Transformação Celular Neoplásica , Células Clonais/citologia , Células Clonais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Feminino , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco/citologia , Células-Tronco/metabolismo
4.
Nat Cell Biol ; 21(10): 1273-1285, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31548606

RESUMO

Chromosome translocation is a major cause of the onset and progression of diverse types of cancers. However, the mechanisms underlying this process remain poorly understood. Here, we identified a non-homologous end-joining protein, IFFO1, which structurally forms a heterotetramer with XRCC4. IFFO1 is recruited to the sites of DNA damage by XRCC4 and promotes the repair of DNA double-strand breaks in a parallel pathway with XLF. Interestingly, IFFO1 interacts with lamin A/C, forming an interior nucleoskeleton. Inactivating IFFO1 or its interaction with XRCC4 or lamin A/C leads to increases in both the mobility of broken ends and the frequency of chromosome translocation. Importantly, the destruction of this nucleoskeleton accounts for the elevated frequency of chromosome translocation in many types of cancer cells. Our results reveal that the lamin A/C-IFFO1-constituted nucleoskeleton prevents chromosome translocation by immobilizing broken DNA ends during tumorigenesis.


Assuntos
Carcinogênese/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades , Proteínas de Ligação a DNA/metabolismo , Lamina Tipo A/metabolismo , Translocação Genética , Animais , Carcinoma/genética , Cromossomos Humanos , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Células HEK293 , Humanos , Proteínas de Filamentos Intermediários/genética , Camundongos , Matriz Nuclear/metabolismo , Proteínas Associadas à Matriz Nuclear/química , Proteínas Associadas à Matriz Nuclear/metabolismo , Proteínas Associadas à Matriz Nuclear/fisiologia
5.
Braz J Med Biol Res ; 52(8): e8341, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365693

RESUMO

MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.


Assuntos
Carcinoma/patologia , Histona Desacetilases/metabolismo , MicroRNAs/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/patologia , Apoptose , Carcinogênese/genética , Carcinoma/genética , Carcinoma/metabolismo , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
6.
Gastroenterology ; 157(4): 949-966.e4, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31323292

RESUMO

In addition to the adenoma to carcinoma sequence, colorectal carcinogenesis can occur via the serrated pathway. Studies have focused on clarification of categories and molecular features of serrated polyps, as well as endoscopic detection and risk assessment. Guidelines from the World Health Organization propose assigning serrated polyps to categories of hyperplastic polyps, traditional serrated adenomas, and sessile serrated lesions (SSLs). Traditional serrated adenomas and SSLs are precursors to colorectal cancer. The serrated pathway is characterized by mutations in RAS and RAF, disruptions to the Wnt signaling pathway, and widespread methylation of CpG islands. Epidemiology studies of serrated polyps have been hampered by inconsistencies in terminology and reporting, but the prevalence of serrated class polyps is 20%-40% in average-risk individuals; most serrated polyps detected are hyperplastic. SSLs, the most common premalignant serrated subtype, and are found in up to 15% of average-risk patients by high-detecting endoscopists. Variations in rate of endoscopic detection of serrated polyps indicate the need for careful examination, with adequate bowel preparation and sufficient withdrawal times. Risk factors for SSLs include white race, family history of colorectal cancer, smoking, and alcohol intake. Patients with serrated polyps, particularly SSLs and traditional serrated adenomas, have an increased risk of synchronous and metachronous advanced neoplasia. Surveillance guidelines vary among countries, but SSLs and proximal hyperplastic polyps require special attention in assignment of surveillance interval-especially in light of concerns regarding incomplete detection and resection.


Assuntos
Pólipos Adenomatosos , Carcinoma , Pólipos do Colo , Neoplasias Colorretais , Terminologia como Assunto , Pólipos Adenomatosos/classificação , Pólipos Adenomatosos/epidemiologia , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/terapia , Biomarcadores Tumorais/genética , Carcinoma/classificação , Carcinoma/epidemiologia , Carcinoma/genética , Carcinoma/terapia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Pólipos do Colo/classificação , Pólipos do Colo/epidemiologia , Pólipos do Colo/genética , Pólipos do Colo/terapia , Neoplasias Colorretais/classificação , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Predisposição Genética para Doença , Variação Genética , Humanos , Fenótipo , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco
7.
J Cancer Res Clin Oncol ; 145(8): 1977-1986, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309300

RESUMO

CONTEXT: Parathyroid carcinoma (PC) is a rare endocrine malignancy with no approved systemic therapies for unresectable locally invasive or distant metastatic disease. Understanding the molecular changes in advanced PC can provide better understanding of this disease and potentially help directing targeted therapy. OBJECTIVE: To evaluate tumor-specific genetic changes using next-generation sequencing (NGS) panels. DESIGN: All patients with advanced PC were tested for hot-spot panels using NGS panels including a 50-gene panel, a 409-gene panel if the standard 50-gene panel (Ion Torrent, Life Technology) was negative or a FoundationOne panel. SETTING: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. PATIENTS OR OTHER PARTICIPANTS: 11 patients with advanced PC were selected to undergo molecular testing. MAIN OUTCOME MEASURE(S): Genetic profiles of advanced PC. RESULTS: Among the 11 patients, 4 patients had the 50-gene panel only, 6 had 409-gene panel after a negative 50-gene panel and 1 had FoundationOne. One patient who had 50-gene panel only also had his metastatic site (esophagus) of his tumor tested with FoundationOne. The most common mutations identified were in the PI3 K (PIK3CA, TSC1 and ATM) (4/11 patients) and TP53 (3/11) pathways. Genes not previously reported to be mutated in PC included: SDHA, TERT promoter and DICER1. Actionable mutations were found in 54% (6/11) of the patients. CONCLUSIONS: Mutational profiling using NGS panels in advanced PC has yielded important potentially targetable genetic alterations. Larger studies are needed to identify commonly mutated genes in advanced PC patients. Development of novel therapies targeting these cellular pathways should be considered.


Assuntos
Carcinoma/genética , Perfilação da Expressão Gênica , Técnicas de Diagnóstico Molecular/métodos , Monitorização Fisiológica/métodos , Neoplasias das Paratireoides/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/terapia , Análise Mutacional de DNA/métodos , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/tendências , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/terapia
9.
BMC Cancer ; 19(1): 604, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31216997

RESUMO

BACKGROUND: The prognosis of bladder urothelial carcinoma (BLCA) varies greatly among patients, and conventional pathological predictors are generally inadequate and often inaccurate to predict the heterogeneous behavior of BLCA. This study aims to investigate the prognostic value and function of TOP2A in BLCA. METHODS: TOP2A expression level was examined by RNA-sequencing, quantitative real time polymerase chain reaction and immunohistochemistry from 10, 40 and 209 BLCA samples, respectively. Public databases were analyzed for validation. Cell proliferation, migration, invasion assays were performed to explore potential functions of TOP2A in BLCA. Flow cytometry was performed for cell cycle and apoptosis analysis. Univariable and multivariable Cox regression models were performed to identify independent risk factors for the prognosis of BLCA. RESULTS: We found TOP2A was significantly upregulated in BLCA samples, especially for high-grade and advanced stage tumors, compared with matched normal epithelial tissue. Univariable COX regression analysis revealed high TOP2A expression was significantly associated with poorer cancer-specific, progression-free and recurrence-free survival, but not independently of clinical characteristics in the multivariable models. Knockdown of TOP2A remarkably inhibited the proliferation of BLCA cells and non-cancerous urothelial cells. Furthermore, migration and invasion capacity of BLCA cells were strongly suppressed after TOP2A knockdown. Moreover, flow cytometry suggested TOP2A had anti-apoptotic function, and knockdown of TOP2A could induce resistance to doxorubicin in J82 cells. CONCLUSIONS: In our study, TOP2A was overexpressed in BLCA and could serve as a prognostic biomarker for BLCA. Moreover, TOP2A is functionally important for the proliferation, invasion and survival of BLCA cells.


Assuntos
Carcinoma/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células , DNA Topoisomerases Tipo II/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose/genética , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sequência de RNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
10.
Zhongguo Fei Ai Za Zhi ; 22(6): 329-335, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31196365

RESUMO

BACKGROUND: Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor. METHODS: Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital (PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted. RESULTS: A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough (41/46, 89.1%) and expectoration (35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation (87.0%), patchy consolidation (84.8%), and multiple ground-glass nodules (84.8%). Multiple cystic changes (40%) and cavitation (13%) were also quite frequent. Ipsilateral and contralateral intrapulmonary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days (95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy (TBLB) combined with bronchoalveolar lavage (BAL) had a diagnostic yield of 80.9% (17/21). Sputum cytology had a diagnostic yield of 45% (9/20). Twenty-six cases were invasive mucinous adenocarcinoma (26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8% (6/38) of patients and ALK rearrangement was detected in 3.0% (1/33) of patients. The median overall survival for these patients was 522 d (95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival (HR=0.155, P=0.002,2). The median overall survival was 547 d (95%CI: 492-602 d) with chemotherapy and 331 d (95%CI: 22-919) without chemotherapy. CONCLUSIONS: Diagnosis of pneumonic-type carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/genética , Carcinoma/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X
11.
Nat Commun ; 10(1): 2450, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164648

RESUMO

Tumor-associated myeloid cells regulate tumor growth and metastasis, and their accumulation is a negative prognostic factor for breast cancer. Here we find calcium/calmodulin-dependent kinase kinase (CaMKK2) to be highly expressed within intratumoral myeloid cells in mouse models of breast cancer, and demonstrate that its inhibition within myeloid cells suppresses tumor growth by increasing intratumoral accumulation of effector CD8+ T cells and immune-stimulatory myeloid subsets. Tumor-associated macrophages (TAMs) isolated from Camkk2-/- mice expressed higher levels of chemokines involved in the recruitment of effector T cells compared to WT. Similarly, in vitro generated Camkk2-/- macrophages recruit more T cells, and have a reduced capability to suppress T cell proliferation, compared to WT. Treatment with CaMKK2 inhibitors blocks tumor growth in a CD8+ T cell-dependent manner, and facilitates a favorable reprogramming of the immune cell microenvironment. These data, credential CaMKK2 as a myeloid-selective checkpoint, the inhibition of which may have utility in the immunotherapy of breast cancer.


Assuntos
Neoplasias da Mama/imunologia , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/imunologia , Carcinoma/imunologia , Neoplasias Mamárias Animais/imunologia , Células Mieloides/imunologia , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linfócitos T CD8-Positivos/imunologia , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Proliferação de Células , Quimiocinas/imunologia , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Macrófagos/imunologia , Macrófagos/metabolismo , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Células Mieloides/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/metabolismo , Evasão Tumoral/genética
12.
Mol Med Rep ; 20(1): 393-400, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115553

RESUMO

Various genomic and epigenetic modifications that occur during the development of cancer act as potential biomarkers for early diagnosis and treatment. Previous studies have demonstrated abnormal expression of the claudin (CLDN) tight junction (TJ) proteins in numerous types of human cancer. Reverse transcription­quantitative polymerase chain reaction and western blotting were employed to investigate variations in the expression of the CLDN TJ proteins in laryngeal non­neoplastic tissues and laryngeal squamous carcinoma tissues. It was revealed that CLDN2, CLDN4, CLDN5, CLDN6, CLDN9, CLDN11 and CLDN12 were undetectable in laryngeal squamous carcinoma tissues and laryngeal non­neoplastic tissues. Additionally, CLDN10 was expressed in laryngeal squamous carcinoma tissues and laryngeal non­neoplastic tissues; however, no significant difference was reported. Conversely, the expression levels of CLDN1 and CLDN7 mRNA and protein were downregulated in laryngeal squamous carcinoma tissues compared with in adjacent non­neoplastic tissues, whereas those of CLDN3 and CLDN8 were upregulated. A total of 80 samples of laryngeal squamous carcinoma and non­neoplastic tissues were analyzed for the expression of CLDN1, ­3, ­7 and ­8 via streptavidin­peroxidase immunohistochemical staining. It was revealed that the expression levels of CLDN1 and CLDN7 were downregulated in laryngeal squamous carcinoma tissues compared with in non­neoplastic mucosal tissues, whereas those of CLDN3 and CLDN8 were upregulated. Furthermore, the associations between CLDN expression and the clinicopathological factors of patients were analyzed. The expression levels of CLDN3 and CLDN7 were reported to be associated with distant metastasis and serve as potential predictors of poor prognosis. In conclusion, the findings of the present study demonstrated that the expression levels of CLDN1, ­3, ­7 and ­8 varied between laryngeal squamous carcinoma tissues and non­neoplastic tissues. The expression levels of these CLDNs may be useful molecular markers for the diagnosis of laryngeal carcinoma, and determining the metastasis and prognosis of this disease.


Assuntos
Claudina-1/genética , Claudina-3/genética , Claudinas/genética , Neoplasias Laríngeas/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma/genética , Carcinoma/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética , Proteínas de Junções Íntimas/genética
13.
Fam Cancer ; 18(3): 349-352, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31111311

RESUMO

Subtotal colectomy is usually the therapy of choice in Lynch syndrome patients diagnosed with colon cancer. In patients who develop cancer after the age of 50-60 years, segmental colectomy is considered a good alternative. Although the endoscopic treatment of early colorectal cancer in non-Lynch patients has increased in the last decades, almost all patients with a Lynch syndrome-associated colorectal malignancy undergo surgery, even if the tumour is diagnosed in a (very) early stage. One of the endoscopic treatment options for early colorectal cancer is an endoscopic full thickness resection (eFTR). This treatment modality allows optimal pathological examination of the resection specimen, as a transmural resection is performed with optimal T-staging of the tumour. We report a case of a 62 year old man, diagnosed with MSH2-Lynch syndrome, who underwent successful eFTR treatment of an early (pT1) colon cancer located in the ascending colon, with no signs of recurrence 12 months after treatment. We discuss the pros and cons of endoscopic resection of early colorectal carcinoma in Lynch syndrome patients.


Assuntos
Neoplasias do Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Carcinoma/genética , Carcinoma/cirurgia , Colo Ascendente/cirurgia , Neoplasias do Colo/patologia , Colonoscopia/instrumentação , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Detecção Precoce de Câncer , Humanos , Neoplasias Renais/genética , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/cirurgia
14.
Medicine (Baltimore) ; 98(18): e15519, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045845

RESUMO

BACKGROUND AND OBJECTIVE: Krüppel-like factor 8 (KLF8), a transcription factor, belongs to the KLF8 family. Currently, studies have shown that KLF8 is highly expressed in some tumors. However, the prognostic value and metastasis of KLF8 in cancers remain unclear. For the first time, we conducted meta-analysis to explore the relationship between KLF8 expression with prognosis and metastasis in various carcinomas patients. METHODS: Web of Science, PubMed, Embase, and Cochrane Library were systematically searched for eligible articles. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic value and metastasis of KLF8 expression in human cancer patients. RESULTS: The result revealed that highly expression level of KLF8 was significantly associated with poor overall survival (OS) (HR = 1.56, 95% CI: 1.26-1.87). Meanwhile, this significant correlation was also observed in subgroup analysis stratified by cancer types, source of HR, sample size, follow-up (months). In addition, highly expression of KLF8 was also closely associated with metastasis (HR = 1.37, 95% CI: 0.57-2.17) and tumor node metastasis stage (HR = 1.58, 95% CI: 0.90-2.25) in carcinomas. CONCLUSION: In summary, our meta-analysis indicates that overexpression of KLF8 may be associated with poor prognosis and higher incidence of metastasis in various carcinomas, and KLF8 may be used as a prognostic and metastatic indicator in human cancers.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Metástase Neoplásica/genética , Proteínas Repressoras/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Modelos de Riscos Proporcionais
15.
Int J Mol Sci ; 20(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052182

RESUMO

Class I histone deacetylases (HDACs) generally promote cell proliferation and tumorigenesis, whereas class IIA HDACs like HDAC4 and HDAC5 may promote or impede cancer development in a tissue-dependent manner. In urothelial carcinoma (UC), HDAC5 is often downregulated. Accordingly, HDAC5 was weakly expressed in UC cell lines suggesting a possible tumor-suppressive function. We therefore characterized the effects of stable HDAC5 expression in four UC cell lines (RT112, VM-Cub-1, SW1710 and UM-UC-3) with different phenotypes reflecting the heterogeneity of UC, by assessing proliferation, clonogenicity and migration ability. Further, we detailed changes in the proteome and transcriptome by immunoblotting, mass spectrometry and RNA sequencing analysis. We observed that HDAC5 overexpression in general decreased cell proliferation, but in one cell line (VM-Cub-1) induced a dramatic change from an epitheloid to a mesenchymal phenotype, i.e., epithelial-mesenchymal transition (EMT). These phenotypical changes were confirmed by comprehensive proteomics and transcriptomics analyses. In contrast to HDAC5, overexpression of HDAC4 exerted only weak effects on cell proliferation and phenotypes. We conclude that overexpression of HDAC5 may generally decrease proliferation in UC, but, intriguingly, may induce EMT on its own in certain circumstances.


Assuntos
Carcinoma/metabolismo , Proliferação de Células , Transição Epitelial-Mesenquimal , Histona Desacetilases/genética , Neoplasias da Bexiga Urinária/metabolismo , Urotélio/patologia , Carcinoma/genética , Linhagem Celular Tumoral , Células HEK293 , Histona Desacetilases/metabolismo , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Bexiga Urinária/genética , Urotélio/metabolismo
16.
J Vet Med Sci ; 81(7): 1034-1039, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31142682

RESUMO

Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0-3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored ≥2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.


Assuntos
Neoplasias das Glândulas Anais/metabolismo , Carcinoma/veterinária , Doenças do Cão/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias das Glândulas Anais/genética , Sacos Anais/metabolismo , Animais , Glândulas Apócrinas/metabolismo , Carcinoma/genética , Carcinoma/metabolismo , Doenças do Cão/genética , Cães , Citometria de Fluxo/veterinária , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , RNA Mensageiro , Receptor ErbB-2/genética , Trastuzumab/farmacologia
17.
Am Soc Clin Oncol Educ Book ; 39: 79-86, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099688

RESUMO

Beyond breast and ovarian cancers, mutations in the BRCA1 and BRCA2 genes increase risks for pancreatic and prostate cancers and contribute to the prevalence of these cancers. Mutations in a number of other genes have also been shown to increase the risk for these cancers as well. Genetic testing is playing an increasingly important role in the treatment of patients with pancreatic and prostate cancer and is now recommended for all patients with pancreatic or metastatic prostate cancer, as well as patients with high Gleason grade prostate cancer and a remarkable family history. Identification of an inherited mutation can direct evaluation of the patient for other cancer risks as well as identification and management of disease in at-risk relatives. Growing evidence suggests improved responses to PARP inhibitors and other therapies in patients with mutations in the BRCA and other DNA repair genes. Although more work must be done to clarify the prevalence and penetrance of mutations in genes other than BRCA1 and BRCA2 in patients with pancreatic and prostate cancer, in most cases, testing is now being done with a panel of multiple genes. Because of the complexities in panel testing and the increased likelihood of finding variants of uncertain significance, pre- and post-test genetic counseling are essential.


Assuntos
Carcinoma/genética , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Mutação , Neoplasias Pancreáticas/genética , Neoplasias da Próstata/genética , Biomarcadores Tumorais , Carcinoma/diagnóstico , Carcinoma/epidemiologia , Carcinoma/terapia , Feminino , Testes Genéticos , Humanos , Masculino , Programas de Rastreamento , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia
18.
J BUON ; 24(2): 853-858, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128046

RESUMO

PURPOSE: Plant metabolites have gained considerable attention as the anticancer agents over the last few decades. Previous studies have indicated the potential of taxifolin as an anticancer agent. However, the information on the anticancer activity of taxifolin against skin scar cell carcinoma as well as several other types of cancers is scantly. Against this background, the present study was designed to investigate the anticancer activity of taxifolin against a panel of skin scar cell carcinoma cell lines. MATERIALS AND METHODS: Proliferation rate of the cells was monitored by MTT assay. DAPI and annexin V/PI assay was used to investigate the induction of apoptosis. Flow cytometery was employed to carry out the cell cycle analysis. Transwell assay was used to check the invasion of the cancerous cells. RESULTS: The results indicated that taxifolin inhibits the growth of the skin scar cell carcinoma cell lines. However the anticancer effects were more profound on the SSCC cancer cells (IC50, 20 µM). In contrast the anticancer effects of taxifolin on the non-cancerous skin cells were minimal. Further investigation revealed that the anticancer effects of taxifolin on the SSCC cells is due to the induction of apoptosis and cell cycle arrest. Moreover, taxifolin could also inhibit the invasion of SSCC cells which was associated with downregulation of the MMP-2 and MMP-9 expression indicative of the potential of taxifolin in the treatment of scar cell carcinoma Conclusion: It is was found that taxifolin inhibited the growth of skin scar cell carcinoma growth by triggering apoptosis and cell cycle arrest and also inhibited cell invasion capacity and therefore this study warrants further investigation on the anticancerous potential of taxifolin.


Assuntos
Carcinoma/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Quercetina/análogos & derivados , Neoplasias Cutâneas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cicatriz/patologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Serina-Treonina Quinases TOR/genética
19.
Dis Markers ; 2019: 8040361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019584

RESUMO

Backgrounds: The objective of the present research was to systematically revise the international literature about the genetic biomarkers related to oral cancer (OC) evaluating the recent findings in clinical studies. Methods: A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. The authors conducted the search of articles in the English language published from 2008 to 2018. The present systematic review included only papers with significant results about correlation between wound healing, genetic alteration, and OC. Prognostic capacity of genetic markers was not evaluated in vivo. Results: The first analysis with filters recorded about 1884 published papers. Beyond reading and consideration of suitability, only 20 and then 8 papers, with case report exclusion, were recorded for the revision. Conclusion: All the researches recorded the proteomic and genetic alterations in OC human biopsy cells. The gene modification level in the different studies, compared with samples of healthy tissues, has always been statistically significant, but it is not possible to associate publications with each other because each job is based on the measurement of different biomarkers and gene targets. Further investigations should be required in order to state scientific evidence about a clear advantage of using these biomarkers for diagnostic purpose.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Estudos de Avaliação como Assunto , Neoplasias Bucais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/patologia , Ensaios Clínicos como Assunto , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia
20.
Dis Markers ; 2019: 4586405, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984306

RESUMO

Purpose: To compare the expression level of apelin in muscle-invasive bladder cancer and matched paracarcinoma tissues and investigate the relationship between apelin and clinical prognosis in the patients. Methods: To assess apelin expression by using immunohistochemical method compared with bladder tumors and matched paracarcinoma tissues. Subsequently, the correlation of apelin expression with the clinicopathological features of bladder cancer patients was analyzed. Kaplan-Meier survival curves method was used to analyze apelin prognostic significance for muscle-invasive bladder cancer patients (including 404 muscle-invasive bladder cancer patients and 28 normal bladder tissues, in TCGA dataset). Results: Apelin protein level was overexpressed in bladder tumor tissues compared with paracarcinoma tissues. Furthermore, high apelin expression was associated with high tumor stage (P < 0.05), distant metastasis (P < 0.05), and vascular invasion (P < 0.05). Kaplan-Meier curve analyses showed that the overexpression of apelin was a potential predictor of overall survival and disease-free survival. Conclusion: Apelin was upregulated in bladder tumor tissues compared with matched adjacent noncancer tissues, especially in the high tumor stage, distant metastasis, and vascular invasion. What is more, high expression of apelin in muscle-invasive bladder cancer indicates the poor prognosis. These data suggested that apelin might be a therapeutic potential biomarker in muscle-invasive bladder cancer patients.


Assuntos
Apelina/genética , Biomarcadores Tumorais/genética , Carcinoma/metabolismo , Neoplasias Musculares/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Apelina/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma/genética , Carcinoma/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/genética , Neoplasias Musculares/secundário , Prognóstico , Regulação para Cima , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
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