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1.
Front Oncol ; 14: 1448695, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39474113

RESUMO

Protein tyrosine kinase 7 (PTK7) is an evolutionarily conserved transmembrane receptor and a specialized tyrosine kinase protein lacking kinase activity. PTK7 has been found to be strongly associated with a variety of diseases, including cancer. In this review, we will provide a comprehensive overview of the involvement of PTK7 in human cancer, focusing on the changing research landscape of PTK7 in cancer research, the molecular mechanisms of PTK7 involved in cancer progression, the targetability of PTK7 in cancer therapy, and the potential application of PTK7 in cancer management, thus demonstrating that PTK7 may be an underestimated contributor to human cancer.

2.
Front Genet ; 15: 1441189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39323867

RESUMO

Background: High heterogeneity is an essential feature of malignant tumors. This study aims to reveal the drivers of hepatocellular carcinoma heterogeneity for prognostic stratification and to guide individualized treatment. Methods: Omics data and clinical data for two HCC cohorts were derived from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Atlas (ICGC), respectively. CNV data and methylation data were downloaded from the GSCA database. GSVA was used to estimate the transcriptional activity of KEGG pathways, and consensus clustering was used to categorize the HCC samples. The pRRophetic package was used to predict the sensitivity of samples to anticancer drugs. TIMER, MCPcounter, quanTIseq, and TIDE algorithms were used to assess the components of TME. LASSO and COX analyses were used to establish a prognostic gene signature. The biological role played by genes in HCC cells was confirmed by in vitro experiments. Results: We classified HCC tissues into two categories based on the activity of prognostic pathways. Among them, the transcriptional profile of cluster A HCC is similar to that of normal tissue, dominated by cancer-suppressive metabolic pathways, and has a better prognosis. In contrast, cluster B HCC is dominated by high proliferative activity and has significant genetic heterogeneity. Meanwhile, cluster B HCC is often poorly differentiated, has a high rate of serum AFP positivity, is prone to microvascular invasion, and has shorter overall survival. In addition, we found that mutations, copy number variations, and aberrant methylation were also crucial drivers of the differences in heterogeneity between the two HCC subtypes. Meanwhile, the TME of the two HCC subtypes is also significantly different, which offers the possibility of precision immunotherapy for HCC patients. Finally, based on the prognostic value of molecular subtypes, we developed a gene signature that could accurately predict patients' OS. The riskscore quantified by the signature could evaluate the heterogeneity of HCC and guide clinical treatment. Finally, we confirmed through in vitro experiments that RFPL4B could promote the progression of Huh7 cells. Conclusion: The molecular subtypes we identified effectively exposed the heterogeneity of HCC, which is important for discovering new effective therapeutic targets.

3.
Dig Dis Sci ; 69(4): 1263-1273, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38451429

RESUMO

BACKGROUND: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. AIMS: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. METHODS: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. RESULTS: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. CONCLUSIONS: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Estudos Retrospectivos , Estudos de Coortes , Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Pancreáticas/patologia
4.
Ann Med ; 56(1): 2306194, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38279689

RESUMO

BACKGROUND: Although ERAS Program had some advantages in laparoscopic distal gastrectomy (LDG), its efficacy and safety remained unclear. We conducted a systematic review and meta-analysis to assess the efficacy and safety of the ERAS group and the traditional care (TC) group in LDG. METHODS: Multiple databases were retrieved from 1 January 2000 to 30 April 2023. The risk ratio (RR), standardized mean difference (SMD) and their 95% confidence interval (CI) were used to estimate the results. RESULTS: Our meta-analysis contained 17 randomized controlled trials (RCTs) studies, which comprised 1468 patients. Regarding efficacy, the ERAS group had significantly shorter postoperative time to first flatus (SMD = -1.29 [95% CI: -1.68, -0.90]), shorter time to first defecation (SMD = -1.26 [95% CI: -1.90, -0.61]), shorter hospital stays (SMD = -0.99 [95% CI: -1.34, -0.63]), and lower hospitalization costs (SMD = -1.17 [95% CI: -1.86, -0.48]) compared to the TC group. Furthermore, in the ERAS group, C-reactive protein levels were lower on postoperative days 1, 3 or 4, and 7; albumin levels were higher on postoperative days 3 or 4 and 7; and interleukin-6 levels were lower on postoperative days 1 and 3. Regarding safety, the overall postoperative complication rate was lower in the ERAS group (RR: 0.76 [95% CI: 0.60, 0.97]), but there was no significant difference in the individual postoperative complication rate. Other indicators were also not statistically significant. CONCLUSION: The combination of ERAS Program with laparoscopy surgery was safe and effective for the perioperative management of patients with distal gastric cancer.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Laparoscopia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gastrectomia/efeitos adversos , Resultado do Tratamento
5.
Ann Hepatol ; 28(6): 101136, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37479060

RESUMO

INTRODUCTION AND OBJECTIVES: In hepatocellular carcinoma (HCC), the prognosis of patients with microvascular invasion (MVI) is poor. Therefore, in this study, we established and evaluated the performance of a novel nomogram to predict MVI in patients with HCC. MATERIALS AND METHODS: We retrospectively obtained clinical data of 497 patients with HCC who underwent hepatectomy at Liaoning Cancer Hospital from November 1, 2018, to November 4, 2021. The patients (n = 497) were randomized in a 7:3 ratio into the training cohort (TC, n = 349) and the validation cohort (VC, n = 148). We performed Least Absolute Shrinkage and Selection Operator (LASSO) and univariate as well as multivariate logistic regression analyses (ULRA, MRLA) on patients in the TC to identify factors independently predicting MVI. RESULTS: Preoperative FIB-4, AFU, AFP levels, liver cirrhosis, and non-smooth tumor margin were independent risk factors for preoperative MVI prediction. The C-index of the TC, VC, and the entire cohort was 0.846, 0.786, and 0.829, respectively. The calibration curves demonstrated the outstanding agreement between predicted MVI incidences by our model and the actual MVI risk. Decision curve analysis (DCA) confirmed the significance of our predictive model in clinical settings. The Kaplan-Meier (KM) survival curve showed that the recurrence-free survival (RFS) and overall survival (OS) of patients in the high-MVI risk group were poor compared to those in the low-MVI risk group. CONCLUSIONS: We constructed and evaluated the performance of the novel nomogram for predicting MVI risk. Our predictive model could adequately predict MVI risk and aid clinicians in selecting appropriate therapeutic strategies for patients.

6.
Front Public Health ; 10: 908955, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148350

RESUMO

Background: There is a lack of in-depth analysis regarding the disease burden of childhood cancer in China. Indeed, this is the first time the topic has been addressed in detail. Drawing on population-based data for the past 30 years, this study systematically analyzes the composition and long-term trend of this disease burden in China. Methods: GBD 2019 contained population-based data from 1990 to 2019 and was prepared using Microsoft Excel 2016. We used AAPC and ARIMA models for trend analysis and prediction formulation. Results: In 2019, there were 45,601 new cases, 9,156 cancer deaths, and 782,530 DALYs in China. From 1990 to 2019, leukemia, together with brain and CNS cancer, invariably ranked highest in terms of new cases, cancer deaths, and DALYs. Leukemia accounted for more than 50%, but decreased over time. By contrast, the proportions for brain and CNS cancer increased. There were significant decreases in the overall incidence, mortality, and DALY rates in China, but these were still higher than the corresponding global average levels. Considering all types of childhood cancer, the incidence rate of testicular cancer showed the biggest increase, and the mortality and DALY rates of leukemia showed the largest decrease. In terms of different age groups, the overall incidence rate of childhood cancers increased in 0 to 4 age group, but it decreased in 5 to 14 age groups. The overall mortality and DALY rates of childhood cancers decreased in all four age groups. Over the next 10 years, the overall incidence rate of childhood cancer will increase, but the overall mortality and DALY rates will decrease. The increase in malignant skin melanoma will comprise the largest rise in the incidence, while the decrease for leukemia will be the largest fall in the incidence, cancer deaths, and DALYs. Conclusion: The disease burden of all childhood cancers in China remains highly serious, especially for certain types of cancer and certain age groups. China should focus more emphatically on the incidence of childhood cancer in future, and it must consistently strengthen investment in the relevant research and medical resources to reduce the disease burden in this field.


Assuntos
Leucemia , Neoplasias Testiculares , Criança , Efeitos Psicossociais da Doença , Humanos , Incidência , Leucemia/epidemiologia , Masculino , Anos de Vida Ajustados por Qualidade de Vida
7.
J Gastrointest Oncol ; 12(5): 2172-2191, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34790383

RESUMO

BACKGROUND: Gastrointestinal malignant cancers affect many sites in the intestinal tract, including the colon. In this study, we purposed to improve prognostic predictions for colon cancer (CC) patients by establishing a novel biosignature of immune-related genes (IRGs) based on the tumor microenvironment (TME). METHODS: Using the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) algorithm, we calculated the stromal and immune scores of every CC patient extracted from The Cancer Genome Atlas (TCGA). We then identified 4 immune-related messenger RNA (mRNA) biosignatures through a Cox and least absolute shrinkage and selection operator (LASSO) univariate analysis, and a Cox multivariate analysis. Relationships between tumor immune infiltration and the risk score were evaluated through the CIBERSORT algorithm and Tumor Immune Estimation Resource (TIMER) database. RESULTS: Our studies showed that individuals who had a high immune score (P=0.017) and low stromal score (P=0.041) had a favorable overall survival (OS) rate. By comparing high/low scores cohort, 220 differentially expressed genes (DEGs) were determined. Then an immune-related four-mRNA biosignature, including PDIA2, NAFTC1, VEGFC, and CD1B was identified. Kaplan-Meier, calibration, and receiver operating characteristic (ROC) curves verified the model's performance. By using univariate and multivariate Cox analyses, we found each biosignature was an independent risk factor for assessing a CC patient's survival. Three external GEO cohorts validated its good efficiency in estimating OS among individuals with CC. Moreover, the signature was also related to infiltration of several cells of the immune system in the tumor microenvironment. CONCLUSIONS: The resultant model in our study included 4 IRGs associated with the TME. These IRGs can be utilized as an auxiliary variable to estimate and help improve the prognosis of individuals with CC.

8.
Cancer Control ; 28: 10732748211051536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34713730

RESUMO

BACKGROUND: Pancreatic cancer is an aggressive cancer and is predicted to become the second leading cause of cancer-related deaths in China. To understand the epidemic trend of pancreatic cancer and formulate targeted preventive measures, it is important to analyze the incidence and mortality of pancreatic cancer. METHODS: The incidence and mortality data of pancreatic cancer in China were obtained from Global Burden of Disease (GBD) data. We used joinpoint regression analysis to calculate the magnitude and direction of trends, and the age-period-cohort method to analyze the effects of chronological age, time period, and birth cohort. RESULTS: The age-standardized rates (ASRs) for both incidence and mortality of pancreatic cancer increased from 1990 to 2019, and were higher in males than females. The incidence and mortality rates have increased year by year in the age group above 25 years. The most common age group was 55-79 years, accounting for approximately 50% of all incident cases. In terms of incidence and mortality rates, the overall net drifts were above 0. The local drifts in all age groups were above 0 in both sexes and males, while the local drifts in the 15-39 age groups were below 0 in females. The longitudinal age curves increased with age, with higher incidence and mortality rates, mainly in older age groups. The period rate ratios increased by year. The cohort rate ratios showed an upward trend before 1970 and fluctuated after 1975. CONCLUSIONS: The burden of pancreatic cancer is still very high in China, and attention should be paid to the key population that is, males and older people. The results of our study can be used by policy makers to allocate resources efficiently to improve early diagnosis and treatment, improving the awareness of self-protection, and advocating a healthy lifestyle to prevent pancreatic cancer.


Assuntos
Neoplasias Pancreáticas/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Distribuição por Sexo , Adulto Jovem
9.
Med Sci Monit ; 27: e934229, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34355706

RESUMO

Retracted on authors' request due to detected data flaws. Reference: Rui Zhang, Jibin Li, Xiaofei Yan, Keer Jin, Wenya Li, Xin Liu, Jianfeng Zhao, Wen Shang, Yefu Liu. Long Noncoding RNA Plasmacytoma Variant Translocation 1 (PVT1) Promotes Colon Cancer Progression via Endogenous Sponging miR-26b. Med Sci Monit. 2018; 24: LBR8685-8692. 10.12659/MSM.910955.

10.
Cell Death Dis ; 12(9): 803, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34420039

RESUMO

Hepatocellular carcinoma (HCC) is the most common visceral neoplasms with its heterogeneity and high rate of recurrence. HCC is characterized to be delayed diagnosis and the development of resistant disease. However, the molecular mechanism for HCC pathogenesis and progression remains largely unknown. Here, we demonstrated that ubiquitin-specific protease14 (USP14) is highly expressed in HCC samples, and the higher expression of USP14 is positively correlated with poor prognosis. Interestingly, USP14 is involved in the maintenance of HIF1-α stability to activate HIF1-α-induced transactivation via its deubiquitinase activity. USP14 depletion or its specific inhibitor IU1 treatment decreased cell proliferation, invasion, migration, and Vascular Mimicry (VM) formation even under hypoxia conditions in HCC cell lines. Moreover, we provided the evidence to show that knockdown of USP14 or USP14 inhibitor (IU1) treatment inhibited tumor growth in tumor-bearing nude mice. Our findings suggest that USP14 maintains HIF1-α stability through its deubiquitination activity, providing a potential biomarker for the early diagnosis and therapy of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Invasividade Neoplásica , Prognóstico , Estabilidade Proteica , Ativação Transcricional/genética , Resultado do Tratamento , Ubiquitina Tiolesterase/genética
11.
Mol Med Rep ; 20(3): 2519-2532, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322223

RESUMO

Changes in the methylation levels of tumor suppressor genes or proto­oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection­induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression profile (GSE19665 and GSE62232) and methylation profile (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein­protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identified. These genes were enriched in the Gene Ontology biological processes terms of 'inflammatory response' [Fos proto­oncogene, AP­1 transcription factor subunit (FOS)] and 'cell cycle process' [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV­positive HCC.


Assuntos
Aurora Quinase A/genética , Carcinoma Hepatocelular/genética , Metilação de DNA , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/virologia , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Hepacivirus/isolamento & purificação , Hepatite C/complicações , Hepatite C/genética , Humanos , Neoplasias Hepáticas/virologia
12.
World J Gastrointest Oncol ; 11(6): 489-498, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31236199

RESUMO

BACKGROUND: Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM: To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma. METHODS: A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients' wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or three-dimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups; the related factors affecting overall survival time were analyzed. RESULTS: The median survival time of the control group was 10.5 mo; the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo; P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION: Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

13.
Med Sci Monit ; 24: 8685-8692, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30504754

RESUMO

BACKGROUND Recently, long noncoding RNAs (lncRNAs) have received wide attention in the area of tumor progression. Dysregulation of lncRNAs has been shown to participated in colon cancer, a known malignant tumor. This study aimed to identify the way lncRNA PVT1 affects the progression of colon cancer. MATERIAL AND METHODS Both human colon cancer tissues and 30 paired adjacent normal tissue samples, as well as the colon cancer cells, were collected. Then quantitative real-time (qRT-PCR) was performed to detect the expression of lncRNA PVT1 and miR-26b. Furthermore, the role of PVT1 was determined by function assays such as cell proliferation assay, invasion assay, and wound healing assay. The mechanism was studied using western blot assay and luciferase assay. RESULTS We demonstrate that the expression of PVT1 was significantly higher in tumor tissue compared with the adjacent normal tissue with a lower expression of miR-26b. Moreover, PVT1 promoted tumor growth, migration, and invasion in vitro. In addition, further experiments revealed that miR-26b was a direct target of PVT1 and could inhibit cell migration, invasion, and proliferation in colon cancer. CONCLUSIONS Our results suggest that PVT1 could promote metastasis and proliferation of colon cancer via endogenous sponging and inhibiting the expression of miR-26b, which may highlight the significance of lncRNA PVT1 in colon cancer tumorigenesis.


Assuntos
Neoplasias do Colo/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose/genética , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Progressão da Doença , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica
14.
Future Oncol ; 14(26): 2701-2712, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30265158

RESUMO

AIM: In this study, we aim to use bioinformatics approach to identify paclitaxel-targeted modulators potentially involved in the process of reversing the trastuzumab resistance. Materials & methods: We extracted data from GSE77346 to identify potential trastuzumab resistance-related genes, used bioinformatics analysis and functional/activity network approach to find genes involved in trastuzumab resistance reversal. RESULTS: We identified hub differentially expressed genes related to trastuzumab resistance, trastuzumab targeting and paclitaxel targeting, respectively. We then found C-Jun may be critical in trastuzumab resistance reversal.  This process may involve transcriptional activation of DUSP1 by JUN, which lead to regulation of DUSP1-related signaling pathways. CONCLUSION: The present study revealed paclitaxel may reverse the trastuzumab resistance by JUN, which possibly in turn regulated DUSP1 and DUSP1-related signaling pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Paclitaxel/farmacologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Fosfatase 1 de Especificidade Dupla/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Paclitaxel/uso terapêutico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico
15.
Cell Biochem Biophys ; 71(1): 397-400, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25146335

RESUMO

Little is known about the relationship about Helicobacter pylori (H. pylori) infection and pancreatic, and this study was set to investigate how H. pylori infection is correlated with pancreatic cancer and provide references for the clinical prevention and treatment of pancreatic cancer. 56 cases of pancreatic cancer patients admitted to the hospital from August 2012 to August 2013 were collected as the observation group. The anti-Hp IgG (H. pylori-specific antibodies), Hp IgM (H. pylori antibodies), and CagA-Hp-IgG (H. pylori serotoxin-associated protein a antibody) in the serum were measured and compared with the related indicators of control group (60 cases of healthy subjects). The H. pylori infection rate was 64.29% in the observation group, and that in the control group was 46.67%. Our results showed that the H. pylori infection rate in the observation group was significantly higher than that in the control group, which was statistically different (P < 0.01). The positive rate of CagA-Hp in the observation group was 38.88, and 21.53% in the control group, for which the observation group was significantly higher than the control group (P < 0.05). The occurrence of H. pylori infection in patients with pancreatic cancer was also positively correlated with the smoking history and the history of chronic pancreatitis (P < 0.05). Helicobacter pylori infection is one of the risk factors for pancreatic cancer, and the patients with positive CagA-Hp have the higher risk, so the prevention and treatment of H. pylori infection would be beneficial for the prevention and treatment of pancreatic cancer.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Neoplasias Pancreáticas/microbiologia , Adulto , Idoso , Anticorpos Antibacterianos/metabolismo , Feminino , Helicobacter pylori/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Fatores de Risco
16.
Tumour Biol ; 36(4): 2403-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25481511

RESUMO

Long non-coding RNAs (lncRNAs) have been proved to serve as a critical role in cancer development and progression. However, little is known about the pathological role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer patients. The aims of this study are to measure the expression of lncRNA MALAT1 in pancreatic cancer patients and to explore the clinical significance of the lncRNA MALAT1. Using qRT-PCR, the expression of lncRNA MALAT1 was measured in 126 pancreatic cancer tissues and 15 adjacent non-cancerous tissues. In the present study, our results indicated that lncRNA MALAT1 was highly expressed in pancreatic cancer compared with adjacent non-cancerous tissues (P < 0.001), and positively correlated with clinical stage (early stages vs. advanced stages, P < 0.001), tumor size (<2 vs. ≥2 cm, P = 0.004), lymph node metastasis (negative vs. positive, P < 0.001), and distant metastasis (absent vs. present, P = 0.001) in pancreatic cancer patients. Furthermore, we also found that lncRNA MALAT1 overexpression was an unfavorable prognostic factor in pancreatic cancer patients (P < 0.001), regardless of clinical stage, tumor size, lymph node metastasis, and distant metastasis. Finally, increased lncRNA MALAT1 expression was an independent poor prognostic factor for pancreatic patients through multivariate analysis (P = 0.018). In conclusion, overexpression of lncRNA MALAT1 serves as an unfavorable prognostic biomarker in pancreatic cancer patients.


Assuntos
Neoplasias Pancreáticas/genética , Prognóstico , RNA Longo não Codificante/biossíntese , Idoso , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , RNA Longo não Codificante/genética
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