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1.
J Cell Mol Med ; 24(1): 760-771, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31762191

RESUMO

High rates of de novo lipid synthesis have been discovered in certain kinds of tumours, including gallbladder cancer (GBC). Unlike several other tumours, GBC is highly insensitive to standard adjuvant therapy, which makes its treatment even more challenging. Although several potential targets and signalling pathways underlying GBC chemoresistance have been revealed, the precise mechanisms are still elusive. In this study, we found that α-Mangostin, as a dietary xanthone, repressed the proliferation and clone formation ability, induced cell cycle arrest and the apoptosis, and suppressed de novo lipogenesis of gallbladder cancer cells. The underlying mechanisms might involve the activation of AMPK and, therefore, the suppression of SREBP1 nuclear translocation to blunt de novo lipogenesis. Furthermore, SREBP1 silencing by siRNA or α-mangostin enhanced the sensitivity of gemcitabine in gallbladder cancer cells. In vivo studies also displayed that MA or gemcitabine administration to nude mice harbouring NOZ tumours can reduce tumour growth, and moreover, MA administration can significantly potentiate gemcitabine-induced inhibition of tumour growth. Corroborating in vitro findings, tumours from mice treated with MA or gemcitabine alone showed decreased levels of proliferation with reduced Ki-67 expression and elevated apoptosis confirmed by TUNEL staining, furthermore, the proliferation inhibition and apoptosis up-regulation were obviously observed in MA combined with gemcitabine treatment group. Therefore, inhibiting de novo lipogenesis via targeting the AMPK/SREBP1 signalling by MA might provide insights into a potential strategy for sensitizing GBC cells to chemotherapy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31674061

RESUMO

BACKGROUND: Mitochondrial shape is dynamically changed by fusion and fission processes in cells, and dysfunction of this process has become one of the emerging hallmarks of cancer. However, the expression patterns and biological effects of mitochondrial fission and fusion proteins in pancreatic cancer (PC) are still unclear. METHODS: The expressions of mitochondrial fission and fusion proteins were first evaluated by quantitative reverse transcription polymerase chain reaction and western blot analysis in both PC cell lines and tissue samples. In addition, the biologic functions of the differentially expressed proteins in PC cell growth and metastasis both in vitro and in vivo and their potential underlying mechanisms were systematically explored. RESULTS: We first found that DRP1 was substantially upregulated in PC cell lines and tissue samples mainly due to the downregulation of miR-29a, which contributed to the poor survival of PC patients. DRP1 promoted the growth and metastasis of PC cells both in vitro and in vivo by inducing G1-S cell cycle transition and matrix metalloproteinase 2 secretion. Mechanistic investigations revealed that increased DRP1 upregulation-mediated mitochondrial fission and subsequently enhanced aerobic glycolysis were involved in the promotion of growth and metastasis by DRP1 in PC cells. CONCLUSIONS: Our findings demonstrate that mitochondrial fusion protein DRP1 plays a critical oncogenic role in PC cells by enhancing aerobic glycolysis, which could serve as a novel therapeutic target for PC treatment.

3.
Ann Clin Lab Sci ; 49(4): 448-456, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31471333

RESUMO

PURPOSE: This study examined the tumor expression of programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) in patients with GEP-NEN. This study aims to reveal the relationship of their expression with clinicopathological characteristics and prognosis. METHODS: PD1 and PD-L1 expression in tumors from 120 GEP-MEN patients was evaluated using immunohistochemistry. The correlations of the expression of PDL1/PD1 and clinicopathological features were assessed. RESULTS: Immunohistochemical staining indicated that PD-L1 was expressed in the tumor cells of 52.5% patients with GEP-NENs, and PD-L1 expression was positively correlated with the World Health Organization (WHO) classification, American Joint Committee on Cancer (AJCC) stage, lymphatic metastasis and prognosis. Meanwhile, PD-1 was expressed in tumor infiltrating lymphocytes within 55.8% tumor samples, and PD-1 expression was positively correlated with AJCC stage and GEP-NENs prognosis. Moreover, survival analysis indicated that the overall median survival of patients with PD-L1/PD-1-positive tumors significantly differed from that of patients with PD-L1/PD-1-negative tumors. Multivariate analysis confirmed that AJCC stage and Chromogranin A expression in tumor tissues were independent prognostic factors for overall survival. In conclusion, PDL1 was an independent prognostic factor for patients with GEP-NENs. Our results suggested that patients with GEP-NENs might be appropriate for PD1/PDL1-targeted therapy. CONCLUSIONS: Our findings show that the expression of PD-L1 and PD-1 correlates with patient prognosis, and may thus serve as potential pathological prognostic markers of GEP-NENs. Immunotherapy using PD-1/PD-L1 inhibitors may be a promising strategy for GEP-NENs patients with PD-L1/PD-1 positively expressed.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Intestinais/metabolismo , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Gástricas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Neoplasias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Neoplasias Gástricas/patologia , Análise de Sobrevida , Adulto Jovem
4.
Lung Cancer ; 130: 18-24, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30885342

RESUMO

OBJECTIVES: Sequential combination of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and chemotherapy has shown greater benefits than either treatment alone in non-small-cell lung cancer (NSCLC). In this follow-up of the ENSURE study, we evaluated progression-free survival (PFS) with first-line erlotinib followed by chemotherapy at progression versus the inverse treatment sequence in 175 Chinese patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: Forty-five of the 175 patients included in the follow-up analysis experienced progressive disease (PD). Those with PD on first-line erlotinib (n = 24) received gemcitabine/cisplatin while those who failed first-line chemotherapy (n = 21) received erlotinib until second-line PD. The primary endpoint was PFS in the crossover subpopulation. Post-hoc analysis of survival outcomes was also measured for the overall population of 175 Chinese patients. RESULTS: Among patients who crossed over at progression, PFS was comparable between those who received second-line erlotinib and those who received second-line chemotherapy (median, 26.3 months and 23.4 months, respectively; P = 0.529). Regardless of the sequence in which the therapies were administered, patients in the crossover treatment subgroup benefited from either second-line therapy after progression with a median overall survival of 51.6 months versus 23.0 months achieved among patients in the non-crossover treatment subgroup. Post-hoc biomarker analyses of Kaplan-Meier survival curves and Cox regression showed that survival benefits with either treatment sequence were similar between patients with circulating free DNA EGFR mutations in exons 19 and 21; however, those with undetectable mutations achieved significantly greater survival benefits. CONCLUSION: In advanced EGFR mutation-positive NSCLC, first-line erlotinib followed by chemotherapy at progression demonstrated comparable PFS benefit with the inverse treatment sequence, irrespective of mutation subtype. Utilizing both EGFR-TKIs and chemotherapy, irrespective of the sequence, maximizes survival benefits for patients.

5.
Chem Biol Interact ; 304: 1-9, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30831090

RESUMO

Ribosomal protein S15A (RPS15A) has emerged as a novel oncogene of various human cancers. However, whether RPS15A is involved in pancreatic cancer remains unclear. In this study, we aimed to investigate the potential relevance of RPS15A in pancreatic cancer and elucidate the underlying regulatory mechanism. We found that RPS15A expression was significantly up-regulated in pancreatic cancer cell lines. RPS15A knockdown resulted in a decrease of cell proliferation and colony formation, and induced cell cycle arrest in G0/G1 phases of pancreatic cancer cells in vitro. In addition, RPS15A knockdown down-regulated ß-catenin expression and blocked the activation of Wnt signaling. Notably, RPS15A was identified as a target gene of microRNA-519d-3p (miR-519d-3p), a tumor suppressive miRNA. Further data showed that miR-519d-3p negatively regulated RPS15A expression in pancreatic cancer cells. Moreover, miR-591d-3p expression was significantly decreased in pancreatic cancer cell lines and tissues and was inversely correlated with RPS15A expression. The overexpression of miR-519d-3p significantly inhibited the proliferation and Wnt/ß-catenin signaling in pancreatic cancer cells, mimicking the similar effect of RPS15A knockdown. However, restoration of RPS15A expression partially reversed the antitumor effect of miR-519d-3p. Taken together, our results demonstrate that RPS15A knockdown or RPS15A inhibition by miR-519d-3p suppresses the growth of pancreatic cancer cells associated with the inhibition of Wnt/ß-catenin signaling. Our study suggests that the miR-519d-3p/RPS15A/Wnt/ß-catenin regulation axis plays an important role in the progression of pancreatic cancer and may serve as potential targets for treatment of pancreatic cancer.


Assuntos
MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Ribossômicas/genética , Via de Sinalização Wnt/genética , Proliferação de Células/efeitos dos fármacos , Células HEK293 , Humanos , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Ribossômicas/metabolismo , Células Tumorais Cultivadas
6.
J Hematol Oncol ; 12(1): 16, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764882

RESUMO

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

7.
Cancer Biol Ther ; 20(5): 617-632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30462562

RESUMO

Triple-negative breast cancer (TNBC) has a poor prognosis mainly due to insensitivity or resistance to standard anthracycline- and taxane-based chemotherapy, urgently calling for new adjuvants to reverse drug resistance. Dual-target murine double minute 2 (MDM2) and murine double minute X (MDMX) inhibitor has been proved to play a critical part against cancer, particularly focusing on the tremendous potential to enhance the efficacy of doxorubicin (DOX), however little was reported in TNBC. In the present study, we investigated the synergistic antitumor effect of the MDM2/MDMX inhibitor with DOX using three TNBC cell lines, two in situ transplantation tumor models and 214 clinical samples. We observed that the MDM2/MDMX inhibitor combined with DOX could not only inhibit cell vitality and migration and invasion abilities, but also highly inhibit tumor growth in TNBC nude mice. Besides, co-treatment of MDM2/MDMX inhibitor and DOX suppressed epithelial to mesenchymal transition (EMT) through increasing the TAK1-binding protein 1 (TAB1), transforming growth factor ß-activated kinase 1 (TAK1) and p38 mitogen-activated protein kinase (MAPK) expression. Small interfering RNA-mediated TAB1 knockdown induced the EMT, desensitized cells to DOX and enhanced the migration and invasion abilities. High MDM2/MDMX expression was positively associated with weak TAB1 expression in 214 TNBC tumor tissues confirmed by immumohistochemical staining and MDM2/MDMX/TAB1 expression was significantly related to TNBC patient survival. These findings indicate that dual-target MDM2/MDMX inhibitor could increase the sensitization of doxorubicin and inhibit migration and invasion abilities in TNBC cells through p38 MAPK pathway activation caused EMT suppression and hence could be useful in TNBC treatments in future.

8.
Cancer Med ; 7(9): 4361-4370, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30062861

RESUMO

BACKGROUND: Gastroesophageal Junction neuroendocrine neoplasms (GEJ-NENs) are rare and heterogeneous tumors. We aim to analyze the clinicopathlogical features and prognostic factors of GEJ-NENs and to compare the outcome of GEJ-NENs with other gastric NENs. METHODS: A total of 297 GEJ-NENs patients were enrolled from 10 Chinese hospitals and 3152 gastric NENs patients, including 274 GEJ-NENs, were retrieved from Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: The clinical characteristics of GEJ-NENs among different races were different. All Chinese patients had GEJ-NENs of grade 3, with 67.7% of poorly differentiated NEC and 32.3% of MANEC. In SEER database, 70.8% of white, 62.5% of black, and 87.5% of AP patients had poorly differentiated/undifferentiated tumors. In Cox multivariate analysis, NEC/MANEC (HR 2.09, 95%CI 1.24-3.56; P = 0.006), lymph node metastasis (HR 3.52, 95%CI 1.68-7.34; P = 0.001), and distant metastases (HR 3.90, 95%CI 2.50-6.08; P < 0.001) are independent predictors of overall survival. Surgical resection showed a median OS improvement of 13.1-73.3 months (HR 0.21, 95% CI 0.14-0.33, P < 0.001). Adjuvant therapy did not improve survival for postoperative GEJ-NEN patients (P = 0.141). GEJ-NENs were larger, higher grade, more distant metastasis, and worse prognosis than other gastric NENs. CONCLUSION: GEJ-NENs were mostly poorly differentiated carcinomas, and all of Chinese patients were NEC/MANEC. The outcome of MANEC was preferable to NECs. Both lymph nodes metastasis and distant disease were independent predictors of prognosis. Surgical resection can improve survival, but postoperative adjuvant therapy had no additional benefit. GEJ-NENs have worse survival than other gastric NENs.


Assuntos
Junção Esofagogástrica/patologia , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Tumores Neuroendócrinos/epidemiologia , Prognóstico , Estudos Retrospectivos , Programa de SEER
9.
Breast Cancer Res ; 20(1): 74, 2018 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-29996906

RESUMO

BACKGROUND: Estrogen promotes breast cancer development and progression mainly through estrogen receptor (ER). However, blockage of estrogen production or action prevents development of and suppresses progression of ER-negative breast cancers. How estrogen promotes ER-negative breast cancer development and progression is poorly understood. We previously discovered that deletion of cell cycle inhibitors p16Ink4a (p16) or p18Ink4c (p18) is required for development of Brca1-deficient basal-like mammary tumors, and that mice lacking p18 develop luminal-type mammary tumors. METHODS: A genetic model system with three mouse strains, one that develops ER-positive mammary tumors (p18 single deletion) and the others that develop ER-negative tumors (p16;Brca1 and p18;Brca1 compound deletion), human BRCA1 mutant breast cancer patient-derived xenografts, and human BRCA1-deficient and BRCA1-proficient breast cancer cells were used to determine the role of estrogen in activating epithelial-mesenchymal transition (EMT), stimulating cell proliferation, and promoting ER-negative mammary tumor initiation and metastasis. RESULTS: Estrogen stimulated the proliferation and tumor-initiating potential of both ER-positive Brca1-proficient and ER-negative Brca1-deficient tumor cells. Estrogen activated EMT in a subset of Brca1-deficient mammary tumor cells that maintained epithelial features, and enhanced the number of cancer stem cells, promoting tumor progression and metastasis. Estrogen activated EMT independent of ER in Brca1-deficient, but not Brca1-proficient, tumor cells. Estrogen activated the AKT pathway in BRCA1-deficient tumor cells independent of ER, and pharmaceutical inhibition of AKT activity suppressed EMT and cell proliferation preventing BRCA1 deficient tumor progression. CONCLUSIONS: This study reveals for the first time that estrogen promotes BRCA1-deficient tumor initiation and progression by stimulation of cell proliferation and activation of EMT, which are dependent on AKT activation and independent of ER.


Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Neoplasias Mamárias Animais/genética , Receptores Estrogênicos/genética , Animais , Proteína BRCA1/deficiência , Mama/patologia , Neoplasias da Mama/patologia , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor de Quinase Dependente de Ciclina p18/genética , Transição Epitelial-Mesenquimal/genética , Estrogênios/genética , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Mamárias Animais/patologia , Camundongos , Células-Tronco Neoplásicas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
BMC Cancer ; 17(1): 783, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29166866

RESUMO

BACKGROUND: Among colorectal cancer (CRC) survivors, how the prior tumor location affects the risk of subsequent primary colorectal cancer (SPCRC) and the outcome of those suffering from SPCRC remain unknown. METHODS: CRC cases diagnosed from 1973 to 2012 were screened for SPCRC development using the Surveillance, Epidemiology, and End Results database. The relative risk of SPCRC was estimated using the standardized incidence ratio. Survivals were analyzed using the Kaplan-Meier and Cox regression model. RESULTS: The overall risk of SPCRC increased by 27% in CRC survivors compared to that of the general population. The risk increased in patients with both prior right colon cancer (RCC) and left colon cancer (LCC), and was concentrated in the first 5 years after the prior diagnosis, and among young patients. Among the 6701 SPCRC patients identified, patients with prior RCC were more likely to be elderly, female, and with more low or undifferentiated disease than those with prior LCC or rectal cancer (ReC). The overall survivals differed by both prior tumor location (P < 0.0001) and age (P < 0.0001), and the difference by tumor location remained significant when adjusted or stratified by any other potential prognostic factor except age. The cancer specific survivals differed by age (P < 0.0001) rather than by prior tumor location (P = 0.455). CONCLUSIONS: The overall risk of SPCRC increased among patients with both prior RCC and LCC, but not among those with ReC. The different survival outcomes in CRC survivors suffering from SPCRC were largely explained by the patient age but not by the prior tumor location.


Assuntos
Neoplasias Colorretais/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/história , Neoplasias Colorretais/mortalidade , Feminino , História do Século XX , História do Século XXI , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Programa de SEER
12.
Onco Targets Ther ; 10: 4765-4772, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29026322

RESUMO

A novel molecular classification of gastric cancer by the Asian Cancer Research Group (ACRG) is a potential advance in diagnosis and treatment, and it helps to determine prognosis. The use of immunohistochemistry (IHC) rather than gene expression analysis to determine tumor subtypes was evaluated with the aim of determining the feasibility of using the ACRG molecular classification. A total of 69 esophagogastric junction (EGJ) carcinomas were classified as microsatellite instable (MSI, 17.40%, 12 of 69), microsatellite stable with markers of epithelial-to-mesenchymal transition (MSS/EMT, 18.84%, 13 of 69), microsatellite stable with active tumor protein 53 (MSS/TP53+, 27.53%, 19 of 69), and microsatellite stable with inactive TP53 (MSS/TP53-, 36.23%, 25 of 69). The molecular classification did not significantly correlate with anyone of the clinicopathological characteristics of the EGJ carcinoma patients, including age, gender, depth of tumor invasion, the presence of lymph node metastasis, histologic grade, and p-TNM stage of the American Joint Committee on Cancer (P>0.05). Kaplan-Meier survival analysis and log rank tests showed that molecular classification, histologic grade, p-TNM stage, and postoperative adjuvant chemotherapy were significantly associated with overall survival (OS; P<0.05). MSI tumors had the best overall prognosis followed by MSS/TP53- and MSS/TP53+. MSS/EMT tumors had the worst overall prognosis. Multivariate analysis revealed that histologic grade (hazard ratio [HR] =2.216, 95% CI =1.202-4.086), p-TNM stage (HR =2.216, 95% CI =1.202-4.086), and molecular subtype (HR =2.216, 95% CI =1.202-4.086) were independently associated with OS. The preliminary results suggested that the ACRG molecular classification may be a valuable independent prognostic marker for EGJ carcinoma patients and could be performed by IHC analysis.

13.
Oncol Lett ; 14(1): 250-256, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693161

RESUMO

The present study aimed to investigate the clinicopathological significance of programmed cell death ligand-1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in extrahepatic cholangiocarcinoma (ECC). PD-L1 and PD-1 expression was detected by immunohistochemical methods in 70 ECC formalin-fixed, paraffin-embedded tissue specimens and 50 para-carcinoma tissue specimens. The associations of PD-L1 and PD-1 expression with clinicopathological characteristics and prognosis of ECC patients were explored. Positive rates of PD-L1 and PD-1 expression were increased in ECC tissues compared with those in the corresponding para-carcinoma tissues. Besides, the expression of PD-L1 was correlated with the expression of PD-1 (P<0.05). Statistical analysis revealed that the expression of PD-L1 and PD-1 in ECC tissues exhibited no correlation with patient age, sex or histological grade, but was significantly correlated with tumor-node-metastasis (TNM) stage and lymphatic metastasis. Univariate analysis demonstrated that PD-L1 expression, PD-1 expression, TNM stage and lymphatic metastasis were significantly associated with the survival time of patients. Further multivariate analysis revealed the PD-L1 expression was an independent prognostic factor of patients with ECC. These preliminary results suggested that PD-L1 or PD-1 immunodetection may be a valuable prognostic marker for ECC patients, and that PD-L1 immunodetection may be used as an independent factor to evaluate the prognosis of ECC patients.

14.
PLoS One ; 12(6): e0179910, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28644878

RESUMO

Current studies do not accurately evaluate the influence of tumor location on survival of colorectal cancer patients. This study aimed to explore whether tumor location could be identified as another high-risk factor in stage II colorectal cancer by using data identified from the Surveillance, Epidemiology, and End Results database. All colorectal cancer patients between 2004 and 2008 were grouped into three according to tumor location. Of 33,789 patients diagnosed with stage II colorectal cancer, 46.8% were right colon cancer, 37.5% were left colon cancer and 15.7% were rectal cancer. The 5-year cancer specific survivals were examined. Right colon cancer was associated with the female sex, older age (> 50), and having over 12 lymph nodes resected. Conversely, rectal cancer was associated with the male sex, patients younger than 50 years of age and insufficient lymph node resection. The characteristics of left colon cancer were between them and associated with Asian or Pacific Islander populations, T4 stage, and Grade II patients. The prognostic differences between three groups were significant and retained after stratification by T stage, histological grade, number of regional nodes dissected, age at diagnose, race and sex. Furthermore, the significant difference of location was retained as an independent high-risk parameter. Thus, stage II colorectal cancers of different locations have different clinic-pathological features and cancer-specific survivals, and tumor location should be recognized as another high-risk parameter in stage II colorectal cancer.


Assuntos
Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/diagnóstico , Fatores de Risco , Programa de SEER , Fatores Sexuais , Análise de Sobrevida , Adulto Jovem
15.
Oncotarget ; 8(29): 47037-47051, 2017 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-28410201

RESUMO

OBJECTIVES: This study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences. RESULT: A total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups. MATERIALS AND METHOD: From the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared. CONCLUSION: Histological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect.


Assuntos
Neoplasias Esofágicas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Programa de SEER , Estados Unidos/epidemiologia , Estados Unidos/etnologia
16.
Oncotarget ; 8(24): 38825-38840, 2017 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-28418915

RESUMO

The present study assessed the role of metastasis-associated protein 1 (MTA1) in epithelial to mesenchymal transition (EMT) and metastasis in non-small-cell lung cancer (NSCLC) cells using a normal lung epithelium cell line, three NSCLC cell lines, a mouse NSCLC model, and 56 clinical NSCLC samples. We observed that MTA1 overexpression decreased cellular adhesion, promoted migration and invasion, and changed cytoskeletal polarity. MTA1 knockdown had the opposite effects. MTA1 overexpression decreased E-cadherin, Claudin-1, and ZO-1 levels and increased Vimentin expression in vitro and in vivo, through activation of AKT/GSK3ß/ß-catenin signaling. However, treatment with the AKT inhibitor MK2206 did not completely rescue effects associated with MTA1 expression changes, indicating that pathways other than the AKT/GSK3ß/ß-catenin pathway could be involved in MTA1-induced EMT. Compared with normal lung tissues, MTA1 expression was elevated in NSCLC patient tissues and was correlated with American Joint Committee on Cancer stage, T stage, lymphatic metastasis, and patient overall survival. Additionally, MTA1 expression was positively associated with p-AKT and cytoplasmic ß-catenin levels. These findings indicate MTA1 promotes NSCLC cell EMT and metastasis via AKT/GSK3ß/ß-catenin signaling, which suggests MTA1 may be an effective anti-NSCLC therapeutic target.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Repressoras/metabolismo , Adulto , Idoso , Animais , Antígenos CD , Apoptose , Biomarcadores Tumorais/genética , Caderinas/genética , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Adesão Celular , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Histona Desacetilases/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Repressoras/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Vimentina/genética , Vimentina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/genética , beta Catenina/metabolismo
19.
Oncol Lett ; 13(1): 129-136, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28123532

RESUMO

Molecular tumor markers hold considerable promise for accurately predicting the recurrence and progression of colorectal cancer (CRC) in patients. However, in the majority of cases, single marker analysis has been found to have low accuracy, and is of little practical use in clinical practice. The present study investigated the prognostic value of the combined detection of the protein expression of metastasis suppressor 23-H1 (Nm23-H1) and p53 using immunohistochemical analysis, and the mRNA expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction in 110 cases of stage II and III CRC. The results revealed that the expression levels of Nm23-H1 in CRC tissues were lower, compared with those in normal tissues (χ2=18.249; P<0.001), and the protein expression levels of p53 were higher in the CRC tissues (χ2=23.940; P<0.001); although the mRNA expression levels of Nm23-H1 and p53 presented with the same trend. The protein expression of Nm23-H1 was correlated with lymph node metastases (χ2=11.847; P=0.001) and pathological patterns (χ2=6.911; P=0.032). However, it did not correlate with patient gender or age, or with tumor World Health Organization classification or invasive depth (P>0.05). No significant correlation was observed between the expression of p53 and clinicopathological features (P>0.05). Patients with CRC with Nm23-H1(+)/p53(-) tumors had increased survival rates, with a five-year overall survival rate of 83.8% and a five-year disease-free survival rate of 70.2%. The five-year overall survival rates in other study cohorts were lower, compared with the Nm23-H1(+)/p53(-) group (P<0.0125), and this was the same for the five-year disease-free survival rate (P<0.0125). In conclusion, the present study demonstrated that the combined detection of the protein expression of Nm23-H1 and p53 was associated with the long term survival rates of patients with stage II and III CRC; and this may offer potential for use as a predictor of survival rates in patients with CRC.

20.
Oncotarget ; 8(63): 106913-106925, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29290999

RESUMO

Objectives: The purposes of this study were to determine whether neoadjuvant or adjuvant radiotherapy affected disease-specific survival (DSS) in patients with rectal cancer and whether stratification by tumor stage affected the results. Results: 55.5% patients had neoadjuvant-radiotherapy (NRT), and 18.3% patients had adjuvant- radiotherapy (ART). Multivariable models showed that treatment type was independently associated with DSS. Patients with stages III/IV tumors who received ART plus chemotherapy had significantly worse DSS than did those who received NRT plus chemotherapy (NCRT) (P = 0.03). Among patients with stage II tumors, those who received ART plus chemotherapy and those who received NCRT had similar DSS. Further stratification by risk group revealed that patients with stage IIIA tumors who received ART plus chemotherapy had significantly better DSS than did those who received NCRT (P = 0.04). The ART plus chemotherapy and NCRT groups had similar DSS in patients with stage IIA tumors. Among high-risk patients (T3N+/T4), the NCRT group had significantly better DSS than did the ART plus chemotherapy group. Patients who underwent surgery only had the worst DSS of all the treatment groups. Materials and Methods: From the Surveillance, Epidemiology, and End Results database, patients diagnosed with stages II-IV rectal cancer from 2004-2014 were identified. Clinicopathologic features, treatments, and DSS in different treatment groups were compared. Conclusions: NCRT or ART plus chemotherapy can reduce deaths from rectal cancer. Patients with stage IIIA tumors will benefit most from ART plus chemotherapy, whereas NCRT should be recommended to patients with stages II, IIIB, or higher tumors.

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