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1.
Anticancer Res ; 40(1): 413-419, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892595

RESUMO

BACKGROUND/AIM: In patients with lung cancer, there has been no study that treated 'distant metastases' as 'metastatic patterns'. This study aimed to evaluate if specific 'metastatic patterns' exist in lung cancer patients. PATIENTS AND METHODS: Data were collected from lung cancer patients between 2009 and 2018. Metastatic patterns were analyzed using cluster analysis in patients with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, those with small cell lung cancer (SCLC), and those with squamous cell lung cancer (SqCLC). RESULTS: In 313 patients (127 patients with EGFR mutation, 87 patients with SCLC, and 99 patients with SqCLC), metastatic patterns existed in each of the three subset groups, and metastatic patterns of these groups were statistically different. CONCLUSION: The knowledge of the metastatic patterns might be useful for clinical practice in the foreseeable future, as it enables a more efficient detection of metastatic disease through imaging, and a more effective treatment at predicted metastatic sites.


Assuntos
Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/genética , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Metástase Neoplásica , Probabilidade
2.
Anticancer Res ; 40(1): 421-426, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892596

RESUMO

BACKGROUND/AIM: Distant organ metastases do not occur at random in lung cancer. A retrospective study was conducted in order to evaluate 1) what kinds of metastatic patterns exist in three different types of lung cancer, and 2) whether metastatic patterns affected prognosis in the different types of lung cancer. PATIENTS AND METHODS: Data were collected from all consecutive patients with diagnosed lung cancer between April 2009 and October 2018 in our hospitals. Cluster analysis was performed to classify patients. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model were used. RESULTS: Epidermal growth factor-mutated adenocarcinoma, small cell lung cancer, and squamous cell lung cancer had different 'metastatic patterns', survival, and unfavorable prognostic factors, respectively. CONCLUSION: There might be different metastatic patterns, survival, and unfavorable prognostic factors in each pathological and genetic type of lung cancer. It is worthwhile carrying out diagnostic imaging and treatment considering information on metastatic patterns.


Assuntos
Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação/genética , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
3.
Anticancer Res ; 40(1): 213-220, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892569

RESUMO

BACKGROUND/AIM: Kisspeptin produced from the KISS1 gene is secreted from the living cells, binds to endogenous receptor KISS1R (also called G protein-coupled receptor 54, GPR54), and has various functions in normal physiological conditions. Although an anti-metastatic role of kisspeptin in cancer is well known in several cancer types, its role in brain tumors is not yet understood. Herein, we investigated a the role of kisspeptin in glioblastoma cells. MATERIALS AND METHODS: Glioblastoma cells were treated with kisspeptin and subjected to proliferation, migration, and invasion assays. KISS1R dependency was tested by KISS1R silencing with KISS1R siRNAs. RESULTS: Kisspeptin inhibited migratory and invasive abilities of U87-MG, U-251-MG and U373-MG glioblastoma cells with no effect on cell viability. KISS1R gene silencing with KISS1R siRNAs blocked kisspeptin-induced glioblastoma cell invasiveness. Moreover, chemical inhibitors against Gq, PLC or PKC blocked kisspeptin-induced glioblastoma cell invasiveness. CONCLUSION: Kisspeptin induces glioblastoma cell invasiveness via the KISS1R-Gq-PLC-PKC signaling pathway.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Glioblastoma/metabolismo , Glioblastoma/patologia , Kisspeptinas/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais , Fosfolipases Tipo C/metabolismo , Linhagem Celular Tumoral , Ativação Enzimática , Humanos , Invasividade Neoplásica , Metástase Neoplásica
4.
J Urol ; 203(1): 62-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31112107

RESUMO

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Transcriptoma
5.
J Urol ; 203(1): 120-127, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430247

RESUMO

PURPOSE: We tested the association of serum lipid levels prior to androgen deprivation therapy with the risk of castration resistant prostate cancer and metastasis. MATERIALS AND METHODS: We identified 302 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who received androgen deprivation therapy after radical prostatectomy for nonmetastatic disease, had never received statins before androgen deprivation therapy and had available serum lipid data within 2 years prior to androgen deprivation therapy. Cox proportional hazards models were used to test associations between total cholesterol (less than 200 vs 200 mg/dl or greater), low density lipoprotein (less than 130 vs 130 mg/dl or greater), high density lipoprotein (40 or greater vs less than 40 mg/dl) and triglycerides (less than 150 vs 150 mg/dl or greater) and the risk of castration resistant prostate cancer and metastasis after androgen deprivation therapy while adjusting for potential confounders. Subanalyses were restricted to men who remained statin nonusers after androgen deprivation therapy. RESULTS: Median followup after androgen deprivation therapy was 67 months. Castration resistant prostate cancer and metastasis developed in 42 and 44 men, respectively. Men with elevated cholesterol received androgen deprivation therapy in an earlier year and had longer followup and a higher rate of statin use after androgen deprivation therapy. On multivariable analysis total cholesterol and low density lipoprotein were unrelated to castration resistant prostate cancer. Low high density lipoprotein (less than 40 vs 40 mg/dl or greater) was suggestively linked to an increased risk of castration resistant prostate cancer (HR 1.86, 95% CI 0.99-3.48). The association was stronger in men who remained statin nonusers after androgen deprivation therapy (HR 3.64, 95% CI 1.45-9.17). Results for metastasis were similar to those for castration resistant prostate cancer. CONCLUSIONS: Among men with nonmetastatic prostate cancer who started androgen deprivation therapy serum cholesterol was unrelated to castration resistant prostate cancer or metastasis. Low high density lipoprotein was suggestively associated with risks of increased castration resistant prostate cancer and metastasis, particularly in statin never users. Further studies are needed to explore a potential role for lipids in prostate cancer progression after androgen deprivation therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Lipídeos/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prostatectomia , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Fatores de Risco
6.
Drugs Today (Barc) ; 55(11): 683-693, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31840683

RESUMO

BRAF V600E mutations are associated with 8-10% of metastatic colorectal cancers (mCRC) and carry a poor prognosis with limited therapeutic options. In contrast to metastatic melanoma, BRAF inhibition alone or in combination with mitogen-activated protein kinase kinase (MEK) inhibitors has shown little utility in the treatment of BRAF V600E-mutant mCRC. This is secondary to upstream activation of the epidermal growth factor receptor (EGFR) pathway and other escape mechanisms. Combining RAF and MEK inhibitors with inhibition of the EGFR pathway through an anti-EGFR receptor antibody (cetuximab) led to the BEACON clinical trial (binimetinib, encorafenib and cetuximab). Trial patients had undergone at least one prior line of chemotherapy. The trial met all its endpoints and is now included in NCCN (National Comprehensive Cancer Network) guidelines. Herein we provide updates in treatment options for patients with BRAF V600E-mutant mCRC, focusing on the practice-changing BEACON-triplet regimen, the first chemotherapy-free combination regimen for mCRC. This combination is being explored frontline in the ANCHOR clinical trial.


Assuntos
Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Sulfonamidas/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Humanos , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética
7.
Medicine (Baltimore) ; 98(50): e18227, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852082

RESUMO

OBJECTIVE: To identify the optimal treatment strategy after first-line induction chemotherapy for metastatic colorectal cancer (mCRC). METHODS: We conducted a meta-analysis of randomized controlled trials comparing bevacizumab-based maintenance therapy, observation, and continuous chemotherapy.We searched the PubMed, Embase, and Cochrane databases for relevant articles published through March 2018. All randomized phase-III trials evaluating bevacizumab-based maintenance treatment after bevacizumab-based induction treatment were eligible for inclusion. The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Hazard ratios (HRs) with 95% confidence intervals (CIs) or data for calculating HRs with 95% CIs were extracted. The RevMan v5.3 (Copenhagen, Denmark) software was used for data analysis. RESULTS: Nine trials (3121 patients) were included in this meta-analysis. Compared with observation alone, bevacizumab-based maintenance therapy significantly improved PFS (HR: 0.62, 95% CI: 0.47-0.82) and showed a trend toward prolonged OS (HR: 0.93, 95% CI: 0.83-1.05). The incidence of grade 3/4 toxicity, including hypertension and fatigue, was higher after maintenance therapy than after observation alone. PFS (HR: 0.91, 95% CI: 0.70-1.18) and OS (HR: 0.88, 95% CI: 0.74-1.04) did not differ between the maintenance treatment and continuous chemotherapy groups. Grade 3/4 toxicity, including diarrhea and sensory neuropathy, was less common after maintenance therapy than after continuous chemotherapy. CONCLUSION: Bevacizumab-based maintenance therapy significantly improved PFS, showed a trend toward prolonged OS, and reduced cumulative grade 3/4 toxicity relative to continuous chemotherapy with comparable efficacy. Although maintenance therapy was beneficial, the optimal strategy should be individualized.


Assuntos
Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/secundário , Humanos , Metástase Neoplásica , Resultado do Tratamento
8.
Medicine (Baltimore) ; 98(50): e18306, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852112

RESUMO

This retrospective analysis of patients aims to show the blood levels of preoperative inflammatory markers in patients with glioblastoma and brain metastasis and to provide the diagnostic accuracy of the neutrophil-lymphocyte (NLR), lymphocyte-monocyte (LMR), and platelet-lymphocyte (PLR) ratios between the 2 groups of patients.The retrospective reviews of the neutrophil, lymphocyte, monocyte, and platelet counts were analyzed in 80 patients with newly diagnosed glioblastoma and 70 patients with brain metastasis. The NLR, LMR, and PLR were calculated in each group. The differences in all the parameters were compared between the 2 groups.Although the neutrophil, monocyte, and platelet counts were higher and the lymphocyte count was lower in patients with metastasis, the difference was not significant. A significantly higher PLR (P = .004) and a lower LMR (P = .01) were found in patients with brain metastasis. Although both PLR and LMR had diagnostic accuracy in differentiating glioblastoma from brain metastasis, LMR showed the highest diagnostic accuracy. NLR showed no diagnostic accuracy.Systemic inflammation is more severe in glioblastoma than in brain metastasis, and LMR is more sensitive and/or specific than PLR in differentiating glioblastoma from brain metastasis. Therefore, LMR (less likely PLR) can be used as an index for differentiating between glioblastoma and brain metastasis before surgery.


Assuntos
Plaquetas/patologia , Neoplasias Encefálicas/secundário , Glioblastoma/diagnóstico , Linfócitos/patologia , Monócitos/patologia , Procedimentos Neurocirúrgicos , Neutrófilos/patologia , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/diagnóstico , Diagnóstico Diferencial , Feminino , Seguimentos , Glioblastoma/cirurgia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Contagem de Plaquetas , Período Pré-Operatório , Estudos Retrospectivos
9.
Medicine (Baltimore) ; 98(51): e18472, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861027

RESUMO

Previous researches have shown that anesthesia can affect the outcomes of many kinds of cancer after surgery. Here, we investigated the association between anesthesia and patient outcomes after elective open intrahepatic cholangiocarcinoma surgery.This was a retrospective cohort study of patients who received elective open intrahepatic cholangiocarcinoma surgery between January 2005 and December 2014. Patients were grouped according to the anesthesia received, that is, propofol or desflurane anesthesia. Kaplan-Meier analysis was performed and survival curves were constructed from the date of surgery to death. After propensity matching, univariable and multivariable Cox regression models were used to compare hazard ratios for death. Subgroup analyses were performed for tumor node metastasis staging and postoperative metastasis and recurrence.A total of 34 patients (21 deaths, 62.0%) with propofol anesthesia and 36 (31 deaths, 86.0%) with desflurane anesthesia were eligible for analysis. After propensity matching, 58 patients remained in each group. In the matched analysis, the propofol anesthesia had a better survival with hazard ratio of 0.51 (95% confidence interval, 0.28-0.94, P = .032) compared with desflurane anesthesia. In addition, subgroup analyses showed that patients under propofol anesthesia had less postoperative metastases (hazard ratio, 0.36; 95% confidence interval, 0.15-0.88; P = .025), but not fewer postoperative recurrence formation (hazard ratio, 1.17; 95% confidence interval 0.46-2.93; P = .746), than those under desflurane anesthesia in the matched groups.In a limited sample size, propofol anesthesia was associated with better survival in open intrahepatic cholangiocarcinoma surgery. Prospective and large sample size researches are necessary to evaluate the effects of propofol anesthesia on the surgical outcomes of intrahepatic cholangiocarcinoma surgery.


Assuntos
Anestesia Intravenosa/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Desflurano , Propofol , Idoso , Anestésicos Intravenosos , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias , Estudos Retrospectivos , Taiwan/epidemiologia
10.
Autops. Case Rep ; 9(4): e2019120, Oct.-Dec. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024278

RESUMO

Chordoma is a rare tumor. It has unique clinical, pathological and immunohistochemical characteristics. Accurate diagnosis is essential as the tumor shows an aggressive clinical course and requires a multimodal therapeutic approach. A case with wide spread distant metastatic disease that was initially thought to represent metastatic thyroid carcinoma is presented. Appropriate clincopathologic correlation and the histologic findings raised the possibility of poorly differentiated chordoma. The diagnosis was confirmed by immunohistochemistry for INI-1 and Brachyury. The approach to the diagnosis emphasizing the clinical and pathologic findings of this case is discussed and reviewed in the context of the published literature.


Assuntos
Humanos , Masculino , Adulto , Cordoma/diagnóstico , Cordoma/patologia , Extremidade Superior , Proteína SMARCB1/uso terapêutico , Metástase Neoplásica , Notocorda/lesões
11.
Zhonghua Er Ke Za Zhi ; 57(11): 863-869, 2019 Nov 02.
Artigo em Chinês | MEDLINE | ID: mdl-31665841

RESUMO

Objective: To analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods: The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children's Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results: The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ(2)=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ(2)=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ(2)=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ(2)=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05). Conclusions: The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.


Assuntos
Neoplasias da Medula Óssea/patologia , Neuroblastoma/patologia , Neoplasias da Medula Óssea/mortalidade , Neoplasias da Medula Óssea/radioterapia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Metástase Neoplásica , Neuroblastoma/mortalidade , Neuroblastoma/radioterapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
Medicine (Baltimore) ; 98(44): e17769, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689840

RESUMO

RATIONALE: The treatment of metastatic melanoma has been revolutionized in the past decade because of the development of immunotherapies and targeted therapies. Despite these developments, there is still an unmet clinical need for more advanced combination therapies for the subset of patients who remain resistant to immunotherapy or targeted therapy alone. To our knowledge, no reports have been published on combinations of PD-1 blockades and c-KIT inhibitors in melanoma patients. Furthermore, data are limited regarding the safety and efficacy of this combination in patients harboring KIT mutations. PATIENT CONCERNS AND DIAGNOSIS: We report a case of an 82-year-old female with metastatic melanoma who was found to have double KIT mutations at V559 and N822I. INTERVENTIONS: She was treated with a combination of c-KIT inhibitor and PD-1 blockade after being resistant to anti-PD-1 monotherapy. OUTCOMES: Patient developed two episodes of grade 2 liver toxicity requiring treatment breaks followed by a dose reduction. Her transaminitis eventually resolved and patient remained on combination treatment for almost two years with good control of her disease prior to progression. LESSONS: Treatment options for patients who progress after PD-1 inhibitors are very limited; therefore, there is a high unmet clinical need for this patient population. Combining Imatinib with checkpoint inhibitors may be efficacious in patients with metastatic melanoma and KIT mutations. This novel combination can cause additional toxicities which seem to be overall manageable.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mesilato de Imatinib/administração & dosagem , Melanoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Cutâneas/tratamento farmacológico , Idoso de 80 Anos ou mais , Feminino , Humanos , Melanoma/genética , Melanoma/patologia , Mutação , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Resultado do Tratamento
13.
Zhonghua Gan Zang Bing Za Zhi ; 27(10): 766-771, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31734990

RESUMO

Objective: To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis. Methods: The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test. Results: The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%; 59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased. Conclusion: POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico
14.
Anticancer Res ; 39(11): 5879-5890, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704812

RESUMO

BACKGROUND/AIM: The aim of the study was to investigate the prognostic role of androgen receptor (AR), mineralocorticoid receptor (MR) and glucocorticoid receptor ß (GRß) expression in HER-2 negative breast cancer patients. MATERIALS AND METHODS: The study population (n=152) was enriched with triple-negative breast cancers (TNBC) (n=96; 63.2%). The median follow-up time was 100 months. AR, MR and GRß immunocytochemical staining was compared with that of epithelial-mesenchymal transition (EMT) markers (vimentin, SIP1, ZEB1). RESULTS: High expression of cytoplasmic MR was associated with dismal local relapse-free survival (RR=13.923; 95%CI=1.071-181.045; p=0.044) in tumours with non-TNBC phenotype. AR and GRß were more frequently expressed in ER+/PR+/HER2- tumours, while cytoplasmic MR was more often expressed in TNBC tumours (for all, p<0.0005). GRß and AR were associated with decreased vimentin expression (p<0.005), indicating their association with attenuated EMT. CONCLUSION: Cytoplasmic MR expression is a strong predictor of local recurrence in non-metastatic breast cancer patients with non-TNBC tumour phenotype.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/classificação , Neoplasias da Mama/mortalidade , Citoplasma/metabolismo , Recidiva Local de Neoplasia/mortalidade , Receptores de Mineralocorticoides/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Androgênicos/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
15.
Anticancer Res ; 39(11): 5943-5951, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704819

RESUMO

BACKGROUND/AIM: To investigate the function of preferentially expressed antigen of melanoma (PRAME) in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: mRNA expression levels of PRAME were analyzed in resected esophageal tissues of 150 ESCC patients and correlated with clinicopathological parameters. We also investigated the potential function of PRAME by analyzing coordinately expressed genes in 13 ESCC cell lines. RESULTS: RT-qPCR analysis of clinical samples revealed aberrantly high PRAME expression in tumors compared with normal esophageal tissues. High PRAME expression was significantly associated with shorter disease-specific survival and hematogenous recurrence, but not with overall recurrence. The cumulative incidence of hematogenous recurrence was significantly greater for patients with high compared to those with low PRAME expression. In vitro, PCR array analysis revealed that PRAME was coordinately expressed with EGFR, ITGB, and TCF3. CONCLUSION: PRAME is overexpressed in ESCC tissues and may serve as a novel biomarker for predicting hematogenous recurrence.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Recidiva Local de Neoplasia/patologia , RNA Mensageiro/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Prognóstico , RNA Mensageiro/genética , Taxa de Sobrevida
16.
Anticancer Res ; 39(11): 6015-6023, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704827

RESUMO

BACKGROUND/AIM: We previously reported that expression of melanoma-associated antigen (MAGE)-D4 mRNA was a prognostic factor for esophageal squamous cell carcinoma (ESCC). The aim of this study was to validate the expression of MAGE-D4 in two additional patient cohorts, and to investigate its biological functions. MATERIALS AND METHODS: The role of MAGE-D4 in cell proliferation, adhesion, and migration was determined by gene knockdown experiments in the KYSE590 cell line. MAGE-D4 protein expression was analyzed in ESCC tissues by immunohistochemistry. A second validation cohort consisted of an ESCC mRNA dataset from The Cancer Genome Atlas. RESULTS: Knockdown of MAGE-D4 significantly decreased cell proliferation and migration. Expression of MAGE-D4 protein was significantly associated with disease-free survival. In the second validation cohort, high MAGE-D4 mRNA expression was associated with significantly shorter overall survival and disease-free survival. CONCLUSION: MAGE-D4 plays an important role in the malignant behavior of ESCC. MAGE-D4 was validated as a prognostic indicator in two independent ESCC patient cohorts.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/secundário , Proteínas de Neoplasias/metabolismo , Idoso , Antígenos de Neoplasias/genética , Apoptose , Biomarcadores Tumorais/genética , Adesão Celular , Proliferação de Células , Estudos de Coortes , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/cirurgia , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Prognóstico , RNA Interferente Pequeno/genética , Taxa de Sobrevida , Células Tumorais Cultivadas
17.
J Environ Pathol Toxicol Oncol ; 38(3): 195-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679307

RESUMO

UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/ß-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-ß/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/ß-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/ß-catenin signal pathway and migration by TGF-ß/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Curcumina/farmacologia , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Organismos Livres de Patógenos Específicos
18.
Enzymes ; 46: 59-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727277

RESUMO

Renal cell carcinoma is the seventh most common cancer in the United States, and its metastatic form has a very poor prognosis due to a lack of effective treatment and thorough understanding on metastatic mechanism. This chapter will demonstrate a novel concept that intratumoral heterogeneity is essential for metastasis in renal cell carcinoma. We will first introduce the in vitro system and the mouse model that led to the finding of the cooperative mechanism for metastasis. Then, the results from the CAM model illustrate the cooperative interactions that lead to metastasis also occur in this model. We believe that the CAM model, as a unique and sustainable system, can open up new opportunities to study the metastatic disease.


Assuntos
Carcinoma de Células Renais/patologia , Membrana Corioalantoide/patologia , Neoplasias Renais/patologia , Transplante de Neoplasias , Animais , Embrião de Galinha , Modelos Animais de Doenças , Humanos , Camundongos , Metástase Neoplásica , Prognóstico
19.
Cancer Immunol Immunother ; 68(10): 1721-1724, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31606778

RESUMO

Natural killer (NK) cells are innate immune lymphocytes which express an array of activating and inhibitory receptors. These receptors bind a large spectrum of ligands, which are expressed on stressed, malignantly transformed or virally infected cells, as well as on bacterial, fungal, and parasitic pathogens. The decision on whether or not to kill the target is based on the integration of activating and inhibitory signals sent downstream from NK cell receptors. One of the most prominent NK cell activating receptor families is the family of natural cytotoxicity receptors (NCRs) which includes NKp30, NKp44, and NKp46. NKp46 is the only NCR to have a fully functional mouse orthologue denoted Ncr1. Despite a large body of evidence highlighting its importance in the clearance of both solid and liquid tumors, the membrane-bound tumor ligand for NKp46 and its mouse orthologue Ncr1 is still unknown. Here we review the discovery of a novel role for NKp46/Ncr1, not only in tumor clearance but also in prevention of metastasis by structural editing of primary tumors.


Assuntos
Células Matadoras Naturais/imunologia , Neoplasias/prevenção & controle , Receptores de Células Matadoras Naturais/metabolismo , Animais , Humanos , Camundongos , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/metabolismo
20.
Neoplasma ; 66(6): 946-953, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31607131

RESUMO

The aim of this study was to determine the expression levels of TTK in clear cell renal cell carcinoma (ccRCC) tissues and its possible link with the clinical pathologic characteristics and the prognosis of patients suffering this disease, and to further explore the potential role of TTK in the progression of ccRCC. Immunohistochemical (IHC) assays were performed to detect the expression levels of TTK in 112 samples of ccRCC tissues and corresponding non-tumor tissues. According to the results of IHC assays, patients were divided into TTK high expression and low expression group. Clinical analysis related to the clinical features (age, gender, T stage), and the potential link between TTK expression levels and clinical features were analyzed. In addition, the effects of TTK on the proliferation and invasion of ccRCC cells were detected through colony formation assay and transwell assays, respectively. The possible effects of TTK on tumor growth and metastasis were measured in mice. We found a high expression level of TTK in human ccRCC tissues from patients who received surgical treatment. We also found its expression level was obviously associated with clinical characteristics, such as T stage (p=0.008) and lymphatic metastasis (p=0.023). We further confirmed that knockdown of TTK suppressed cell proliferation and invasion in 2 types of ccRCC cells, HTB-47 and CRL-1932 cells. Furthermore, TTK contributes to tumor growth and metastasis of ccRCC in mice. We found that TTK affected the progression of ccRCC and further mechanically confirmed it could be a novel therapeutic target for ccRCC treatment.


Assuntos
Carcinoma de Células Renais/patologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias Renais/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Animais , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Camundongos , Metástase Neoplásica , Prognóstico
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