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BACKGROUND: As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. LncRNA MIR100HG promotes cell proliferation in TNBC. However, few studies have investigated the molecular mechanism of MIR100HG in TNBC. Thus, additional in-depth investigations are needed to unravel its associated regulatory mechanism. METHODS: MIR100HG and miR-5590-3p expression in TNBC tissue samples and cell lines was detected by RT-qPCR. Flow cytometry, transwell, wound-healing, CCK8 and colony formation assays were performed to analyse cell apoptosis, cell cycle, invasion, migration and proliferation. The protein expression of orthodenticle homeobox 1 (OTX1) and proteins in the ERK/MAPK signalling pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the interaction between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the interaction between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues. RESULTS: MIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth. CONCLUSIONS: MIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC.
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Enantio- and diastereoselective synthesis of multifunctional spiropyrazolone scaffolds has been achieved using secondary amine-catalyzed [4 + 2] annulations of α,ß,γ,δ-unsaturated pyrazolones with aldehydes. The pyrazolone substrates serve as C4 synthons to produce 6-membered, carbocycle-based, chiral spiropyrazolone derivatives. The synthesized chiral compounds showed potent toxicity against a panel of cancer cell lines. The most potent compound 3h-induced cell cycle arrest and macroautophagy in HCT116 colorectal cancer cells, triggering autophagy-dependent apoptotic cell death.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoproteínas/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Pirazolonas/síntesis química , Línea Celular Tumoral , Humanos , Estructura MolecularRESUMEN
To investigate the relationship between chemotherapy dose intensity and therapy efficacy of different molecular subtypes. Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. 315 patients were analyzed (251 showed clinical response, 38 acquired pCR). Patients with positive ER status, negative PR status, higher Ki67 level and higher RTDI had better therapy response. 13.5 and 84.5 % were identified the benchmark of Ki67 and RTDI, respectively. As the result of interior-subgroup comparison, luminal subgroups acquired better response rate when RTDI ≥ 84.5 %. In patients of luminal breast cancer, tumor size change arose from increasing of dose intensity and finally showed reached a plateau after RTDI ≥ 95 % (r (2) = 0.303, p < 0.001). As the result of intersubgroup comparison, TNBC patients were more likely to acquired better clinical and pathology response when RDTI < 84.5 %. Ki67 change arose sharply from increasing of dose intensity when RDTI < 84.5 % (r (2) = 0.656, p < 0.001), whereas the regression curve showed a terminal plateau in patients of RDTI ≥ 84.5 % (r (2) = 0.427, p < 0.001). Given lower RTDI, luminal patients are less likely to achieve response, and TNBC patients are associated with higher response rate. Dissimilar of therapy efficacy between luminal subtype and TNBC becomes inconspicuous as RTDI rises. Chemosensitivity may associate with dose intensity, especially in luminal subtypes, and tailored therapeutic strategies should be considered.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Adulto , Antineoplásicos/administración & dosificación , Biomarcadores de Tumor/genética , Neoplasias de la Mama/diagnóstico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Carga TumoralRESUMEN
OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PAâ+âBCL-10 µM, PAâ+âBCL-20 µM, and PAâ+âBCL-50 µM groups. The PA group was treated with PA (200 µM), while the PAâ+âBCL groups were co-treated with different concentrations of BCL (10 µM, 20 µM, 50 µM) for 24âhours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PAâ+âBCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PAâ+âBCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress.
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BACKGROUND: With the emergence of the gig economy as a new economic form, the influence of algorithmic technology control on gig workers' perceptions and engagement has become a topic of academic concern. This study explores the emotional impact of perceived algorithmic control on gig workers and how it affects their work engagement. METHODS: This study takes gig workers as the research object to build a structural equation model. Based on the background of gig economy and the Job Demands-Resources model, this paper constructs a mechanism model of the influence of perceived algorithmic control on the work engagement of gig workers. The research data in this paper are collected by questionnaire, and the research hypothesis is tested by the SEM structural model. RESULTS: The gig workers in this study believed that perceived algorithmic control positively affects employee work engagement. In addition, burnout was positively correlated with employee work engagement. Burnout played a partial mediating role in the relationship between perceived algorithmic control and employee work engagement. And flow experience played a moderating role through the indirect effect of burnout on employees' work engagement. CONCLUSION: Perceived algorithmic control causes burnout among gig workers, but strong algorithmic technology support provides them with rich work resources that can help them meet their work needs. That is, the gig workers may still demonstrate a high level of work engagement even if they experience burnout symptoms.
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Agotamiento Profesional , Compromiso Laboral , Humanos , Agotamiento Profesional/psicología , Encuestas y Cuestionarios , EmocionesRESUMEN
BACKGROUND: The dysregulation of exosomal microRNAs plays an important role in the progression of hepatocarcinogenesis. In this study, we investigated the therapeutic potential of synthetic exosomal miR-26a against HCC cells and explored the feasibility of tumor-derived exosomes as drug delivery vehicles. METHODS: Proliferation and migration assays were performed to examine the effects of miR-26a on HCC in vitro. The direct target gene of miR-26a was identified through miRecords analysis and target validation. The transferring efficiency and anti-HCC effect of exosomes with different origin were studied and the optimal miR-26a delivery method was established and verified in vitro and in vivo. In addition, the relationships between prognosis of HCC patients and miR-26a expression in HCC serum and exosomes were retrospectively analyzed. RESULTS: Here, we found that tumor cell-derived exosomes were taken in preferentially by HCC cells and promoted HCC progression through Wnt pathway by low-density lipoprotein receptor-related protein 6 (LRP6). HCC cells with vacuolar protein sorting-associated protein 35 knocked down were adopted to generate engineered LRP6-exosomes. The engineered HCC-derived exosomes loading miR-26a inhibited HCC progression in vitro and in vivo effectively. Overexpression of miR-26a impaired the growth and migration of HCC by targeting lymphoid enhancer factor 1 (LEF1). Moreover, low expression of exosomal miR-26a was an independent prognostic factor for recurrence and survival in HCC patients. CONCLUSIONS: Our findings suggested the exosomal miR-26a could serve as a non-invasive prognostic marker for HCC patients. Genetically modified tumor-derived exosomes showed preferable transfection efficiency but reduced Wnt activity, which provides a novel therapeutic strategy for HCC.
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Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Exosomas/genética , Exosomas/metabolismo , Exosomas/patología , Estudios Retrospectivos , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Proliferación CelularRESUMEN
Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study investigated the molecular mechanism and influences of MIR503HG, miR-224-5p, and homeobox A9 (HOXA9) on TNBC cell growth and migration. Dual-luciferase reporter gene and RNA immunoprecipitation were performed to examine the regulation of MIR503HG, miR-224-5p, and HOXA9. Cell proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays. Finally, nude mice were employed to investigate the influence of MIR503HG on TNBC tumor growth. HOXA9 protein levels were detected by immunohistochemical staining. MIR503HG and HOXA9 expression were reduced in TNBC, while miR-224-5p was increased. Overexpression of MIR503HG or HOXA9 reduced the cell migration ability and proliferation and promoted apoptosis, and knockdown of MIR503HG or overexpression of miR-224-5p exhibited the opposite effects. Furthermore, MIR503HG promoted HOXA9 expression by inhibiting miR-224-5p. Overexpression of miR-224-5p reversed the effects of MIR503HG overexpression on TNBC cells, while overexpression of HOXA9 reversed the effect of MIR503HG knockdown. Additionally, an in vivo study proved that MIR503HG inhibited TNBC tumor growth via the miR-224-5p/HOXA9 axis. MIR503HG inhibited cell proliferation and promoted the apoptosis of TNBC cells via the miR-224-5p/HOXA9 axis, which may function as a novel target for the treatment of TNBC.
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Background: Current treatment options for intrahepatic cholangiocarcinoma (ICC) are limited by the lack of understanding of the disease pathogenesis. It has been known that mucin 1 (MUC1) is a cell surface mucin that highly expressed in various cancer tissues. However, its role in ICC has not been well studied. The purpose of this study was to investigate the clinical significance and biological function of MUC1 in ICC. Methods: qRT-PCR and western blot assays were performed to examine MUC1 expression. RNA-Seq (RNA Sequencing) s conducted to explore the RNA expression. A tissue microarray study including 214 ICC cases was also conducted to evaluate the clinical relevance and prognostic significance of MUC1. The role and underlying mechanisms of MUC1 in regulating cell growth and invasion were further explored both in vitro and in vivo models. Results: The mRNA and protein levels of MUC1 were significantly up-regulated in ICC compared to paired non-tumor tissues. Depletion of MUC1 in HCCC9810 cells significantly inhibited cell proliferation, migration and invasion in vitro and overexpression of MUC1 in RBE cells resulted in increased cell proliferation, migration and invasion. Both univariate and multivariate analysis revealed that the protein expression of MUC1 was associated with overall survival and relapse-free survival after tumor resection. Clinically, high MUC1 expression was more commonly observed in aggressive tumors. Further studies indicated that MUC1 exerted its function through activating Wnt/ ß-catenin pathway. Conclusions: Our data suggests that MUC1 promoted ICC progression via activating Wnt / ß-catenin pathway. This study not only deciphered the role of MUC in ICC pathogenesis, but also shed light upon identifying novel potential therapeutic targets.
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BACKGROUND: Hepatectomy for huge hepatocellular carcinoma (HCC) (diameter ≥10 cm) is characterized by high mortality. This study aimed to establish a preoperative model to evaluate the risk of postoperative 90-day mortality for huge HCC patients. METHODS: We retrospectively enrolled 1,127 consecutive patients and prospectively enrolled 93 patients with huge HCC who underwent hepatectomy (training cohort, n=798; validation cohort, n=329; prospective cohort, n=93) in our institute. Based on independent preoperative predictors of 90-day mortality, we established a logistic regression model and visualized the model by nomogram. RESULTS: The 90-day mortality rates were 9.6%, 9.2%, and 10.9% in the training, validation, and prospective cohort. The α-fetoprotein (AFP) level, the prealbumin levels, and the presence of portal vein tumor thrombosis (PVTT) were preoperative independent predictors of 90-day mortality. A logistic regression model, AFP-prealbumin-PVTT score (APP score), was subsequently established and showed good performance in predicting 90-day mortality (training cohort, AUC =0.87; validation cohort, AUC =0.91; prospective cohort, AUC =0.93). Using a cut-off of -1.96, the model could stratify patients into low risk (≤-1.96) and high risk (>-1.96) with different 90-day mortality rates (~30% vs. ~2%). Furthermore, the predictive performance for 90-day mortality and overall survival was significantly superior to the Child-Pugh score, the model of end-stage liver disease (MELD) score, and the albumin-bilirubin (ALBI) score. CONCLUSIONS: The APP score can precisely predict postoperative 90-day mortality as well as long-term survival for patients with huge HCC, assisting physician selection of suitable candidates for liver resection and improving the safety and efficacy of surgical treatment.
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The Ras-Related signaling pathway plays an important role in cell development and differentiation. A growing body of evidence collected in recent years has shown that the aberrant activation of Ras is associated with tumor-related processes. Several studies have indicated that indole and its derivatives can target regulatory factors and interfere with or even block the aberrant Ras-Related pathway to treat or improve malignant tumors. In this review, we summarize the roles of indole and its derivatives in the isoprenylcysteine carboxyl methyltransferase-participant Ras membrane localization signaling pathway and Ras-GTP/Raf/MAPK signaling pathway through their regulatory mechanisms. Moreover, we briefly discuss the current treatment strategies that target these pathways. Our review will help guide the further study of the application of Ras-Related signaling pathway inhibitors.
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Triplenegative breast cancer (TNBC) is a subtype of breast cancer with a high degree of malignancy. TNBC is prone to distant metastasis and has a poor prognosis. A number of TNBCrelated microRNAs (miRNAs) have been studied and identified. However, the detailed roles of miR5745p in TNBC remain poorly understood. miR5745p, SRY (sex determining region Y)box 2 (SOX2), Bcell lymphoma/leukaemia 11A (BCL11A), SKI like protooncogene (SKIL) and epithelialmesenchymal transition (EMT)related miRNAs and proteins were measured by reverse transcriptionquantitative PCR and western blotting analysis, respectively. A luciferase reporter assay was employed to validate the direct targeting of SOX2 and BCL11A by miR5745p. MTT, colony formation and Transwell assays were performed to analyse the biological functions of miR5745p in TNBC cells. A nude mouse xenograft model was used to verify the effects of miR5745p on the tumorigenesis of TNBC in vivo. The results demonstrated that miR5745p levels were decreased in breast cancer tissues and cells. miR5745p repressed proliferation, migration and EMT in TNBC cells. Further experiments confirmed that miR5745p reduced tumour size and metastasis in vivo. miR5745p targeted BCL11A and SOX2 to inhibit the SKIL/transcriptional coactivator with PDZbinding motif/connective tissue growth factor axis, and the inhibitory effect of miR5745p in TNBC cells was at least partly dependent on SOX2 and BCL11A. In addition, the regulation of downstream oncogenes by SOX2 was dependent on BCL11A. To the best of our knowledge, this is the first study to report the association between the miR5745p/BCL11A/SOX2 axis and the tumorigenesis of TNBC, which provides a new mechanism for understanding the progression of TNBC.
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Regulación hacia Abajo , MicroARNs/genética , Proteínas Represoras/genética , Factores de Transcripción SOXB1/genética , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Persona de Mediana Edad , Trasplante de Neoplasias , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción SOXB1/metabolismo , Transactivadores/metabolismo , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Carga TumoralRESUMEN
Intrahepatic cholangiocarcinoma (ICC) is a cancer type with high malignancy and a current lack of biomarkers to predict recurrence. In the present study, to identify potential biomarkers, five ICC datasets from the Gene Expression Omnibus database were analyzed to construct initial datasets by using a robust rank aggregation approach. A total of 19 upregulated genes were identified in the initial datasets. The genes identified were then further analysed using data from The Cancer Genome Atlas. Only mucin 1 (MUC1) exhibited significance regarding differential expression and survival prediction. Finally, the expression levels of MUC1 were assessed using reverse transcription-quantitative PCR in 61 pairs of ICC tumor and matched non-cancerous samples. The expression of MUC1 was significantly elevated in ICC tissues compared with that in matched non-cancerous counterparts (P=0.001). Patients with high MUC1 expression levels had significantly shorter overall survival (OS, P=0.009) and recurrence-free survival (RFS, P=0.012). MUC1 was identified as an independent prognostic factor for OS [hazard ratio (HR)=2.364, 95%CI: 1.214-4.485; P=0.023] and RFS (HR=2.552 95%CI: 1.294-5.032; P=0.007) in the multivariate analysis. Using receiver operating characteristic analysis, a co-index including MUC1 had a high accuracy for predicting survival [MUC1 combined with serum levels of CEA and cancer antigen 19-9, and lymph node metastasis, area under curve (AUC)=0.746, 95%CI: 0.620-0.872] and recurrence (MUC1 combined with bile duct invasion and lymph node metastasis, AUC=0.729, 95%CI: 0.605-854). In conclusion, MUC1 is highly expressed in ICC tissue and is a potential prognostic biomarker and therapeutic target for ICC.
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OBJECTIVE: To investigate the effects and safety of catgut embedding on alleviating insomnia. METHODS: Totally 510 patients with insomnia were divided into 5 Chinese medicine (CM) syndrome types: Xin (Heart) and Pi (Spleen) deficiency, yin deficiency with excess fire, Xin and gut qi deficiency, Wei (Stomach) disorder, and qi and blood deficiency, respectively. These 5 types of patients were randomly assigned to a catgut embedding group, an acupuncture group or a medication group (30 cases in Xin and Pi deficiency type, Wei disorder type, Xin and gut qi deficiency type, respectively; 40 cases in yin deficiency with excess fire type and qi and blood deficiency type, respectively). In the catgut embedding group, patients were treated by implanting catgut into acupoints once every 10 days for a total of 30 days. In the acupuncture group, patients were treated with acupuncture once per day over 30 days (excluding weekends); and patients in the medication group took 1 mg Eurodin Tablet orally every night for 30 days. Pittsburgh Sleep Quality Index (PSQI) was evaluated before treatment, on 30 and 60 days after the first treatment, respectively. The International Unified Sleep Efficiency Value (IUSEV) was measured at 30 and 60 days. The safety was evaluated after treatment and adverse events were analyzed. RESULTS: The objective PSQI scores including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, daytime dysfunction, and total scores at 30 days were significantly improved compared with pre-treatment in the catgut embedding and acupuncture groups (P<0.01 or P<0.05). At 30 days, the PSQI scores in catgut embedding group were superior to the medication group in the patients with each type of insomnia, with the exception of sleep duration (P<0.01 or P<0.05). At 60 days, significant differences were found between the catgut embedding group and the medication group (P<0.01 for all indices). The IUSEV scores in the catgut embedding group were significantly higher than the acupuncture group at 60 days, and the scores in acupuncture group were higher than the medication group at 30 days (P<0.05 for all types). No severe adverse events were found in this study. CONCLUSIONS: Acupoint catgut embedding and acupuncture were more effective than medication in alleviating insomnia syndrome in different Chinese medicine syndrome type. However, the sustained effects of acupoint catgut embedding were superior to acupuncture.
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Puntos de Acupuntura , Catgut , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Humanos , Qi , SíndromeRESUMEN
Protecting group-controlled annulations of tetra-substituted oxindole olefins and sulfur ylides have been achieved for the synthesis of multifunctional cyclopropane- and dihydrofuran-fused spirooxindoles. Under precise annulation regulation, a variety of cyclopropane- and dihydrofuran-fused spirooxindoles containing vicinal quaternary carbon centers were produced in up to 90% yield with up to 20 : 1 dr. This reaction demonstrates high regio-, chemo- and diastereoselectivity, broad functional group tolerance and gram-scale capacity.
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BACKGROUND: The role of osteopontin (OPN) in intrahepatic cholangiocarcinoma (ICC) remains controversial. This study aimed to explore the prognostic value of OPN in patients with ICC undergoing curative resection. METHODS: Patients undergoing curative resection from 2005 to 2016 were identified for inclusion in this retrospective study. The expression level of OPN in tumors was measured in each of the 228 patients by immunohistochemistry. Circulating OPN in serum was tested in 124 patients by ELISA. Tumor volume was calculated according to preoperative imaging or operation record. Proliferation assay, wound healing assay, and invasion assay were performed to investigate the biological function. RESULTS: Low expression of OPN in tissue was associated with lymph node metastasis (P=0.009) and shorter overall survival (OS) (P=0.001). A low level of circulating OPN/volume was associated with multiple tumors (P<0.001), vascular invasion (P=0.027), visceral peritoneal perforation (P=0.001), and lymph node metastasis (P=0.002). It was also able to predict the invasive behavior, lymph node metastasis, and early recurrence with the area under the receiver operating curve (AUC) of being 0.719, 0.708 and 0.622 respectively. Patients with a low level of circulating OPN/volume had shorter OS (P=0.028) and disease-free survival (DFS) (P=0.004) and could benefit from adjuvant chemotherapy (P=0.011). Compared with negative controlled cells, ICC cell lines, which expressed more OPN, showed a decelerated proliferation rate, the weaker ability of migration and invasion, while the opposite was true for the cells expressed less OPN. MMP1, MMP10, and CXCR4 were negatively regulated by OPN. CONCLUSIONS: A low level of circulating OPN/volume could indicate aggressive characteristics, along with poor prognosis and efficacy of adjuvant chemotherapy in ICC patients. Over expression of OPN may inhibit phenotypes facilitating ICC metastasis by negatively regulating MMP1, MMP10, and CXCR4.
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OBJECTIVE: To investigate the early diagnosis of breast cancer with nonpalpable tumor. METHODS: Forty-six cases of clinical nonpalpable tumor were examined by mammography and sonography.The cases of nipple discharge were also examined by fiberoptic ductoscopy. RESULTS: Breast cancer in 46 cases was diagnosed by pathological examination. Of them, 34 diagnosed with breast cancer were found with nodus, calcification or confused structure, and so on, 5 were considered benign tumor, and 7 were not found lesion by mammography. Thirty-one cases were diagnosed with breast cancer, 6 with benign tumor, and 9 were not found occupying lesion by sonography. Occupying lesions were found in 6 cases of nipple discharge by fiberoptic ductoscopy and were finally diagnosed by biopsy. CONCLUSION: Mammography and sonography are important methods in early discovering breast cancer. Early diagnosis rate of breast cancer can be elevated by signs of early breast cancer and combined examination of mammograply and sonography.
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Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Ultrasonografía MamariaRESUMEN
OBJECTIVE: The aim of the study was to estimate breast cancer risk conferred by individual single-nucleotide polymorphisms of breast cancer susceptibility genes. METHODS: We analyzed the 48 tagging single-nucleotide polymorphisms of 8 breast cancer susceptibility genes involved in the monoubiquitinated FANCD2-DNA damage repair pathway in 734 Chinese women with breast cancer and 672 age-matched healthy controls. RESULTS: Forty-five tagging single-nucleotide polymorphisms were successfully genotyped by SNPscan, and the call rates for each tagging single-nucleotide polymorphisms were above 98.9%. We found that 13 tagging single-nucleotide polymorphisms of 5 genes ( Parter and localizer of Breast cancer gene2 ( PALB2), Tumour protein 53 ( TP53), Nijmegen breakage syndrome 1, Phosphatase and tensin homolog deleted from chromosome 10 ( PTEN), and Breast cancer gene 1 ( BRCA1-interacting protein 1)) were significantly associated with breast cancer risk. A total of 5 tagging single-nucleotide polymorphisms (rs2299941 of PTEN, rs2735385, rs6999227, rs1805812, and rs1061302 of Nijmegen breakage syndrome 1) were tightly associated with breast cancer risk in sporadic cases, and 5 other tagging single-nucleotide polymorphisms (rs1042522 of TP53, rs2735343 of PTEN, rs7220719, rs16945628, and rs11871753 of BRCA1-interacting protein 1) were tightly associated with breast cancer risk in familial and early-onset cases. CONCLUSIONS: Some of the tagging single-nucleotide polymorphisms of 5 genes ( PALB2, TP53, Nijmegen breakage syndrome 1, PTEN, and BRCA1-interacting protein 1) involved in the monoubiquitinated FANCD2-DNA damage repair pathway were significantly associated with breast cancer risk.
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Pueblo Asiatico/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Daño del ADN , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Alelos , Biomarcadores de Tumor , Estudios de Casos y Controles , China/epidemiología , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/metabolismo , Femenino , Genotipo , Humanos , Oportunidad Relativa , Medición de Riesgo , Transducción de SeñalRESUMEN
BACKGROUND: To investigate the necessity of routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC) patients without indications of lymph node metastasis (LNM) preoperatively. METHODS: 422 consecutive ICC patients who undergone curative resection from January 2009 to December 2014 were enrolled and categorized as two groups (hepatectomy only or hepatectomy plus LND). Clinicopathologic data was compared between the groups by χ2 or Fisher's exact test. Overall survival (OS) and recurrence-free survival (RFS) were calculated by the Kaplan-Meier method and differences were analyzed using the log-rank test. Cox regression model was adopted for multivariable analysis. RESULTS: The median OS time of all 422 patients was 41.4 months. One-, 3-, and 5-year OS was 67%, 47%, and 35%, respectively. A total of 73 patients had undergone curative resection combined with LND, of whom 20.5% (15/73) were confirmed lymph node positive pathologically. The clinicopathologic characteristics between LND and control groups showed no significant differences. Of the 422 patients, 271 patients had recurrence. The recurrence rates were 65.8% for the LND group and 63.9% for the non-LND group. Survival analysis revealed that, neither the OS (LND vs. non-LND: 32.2 months vs. 46.2 months; p = 0.16) nor the RFS (LND vs. non-LND: 23.1 months vs. 17.0 months; p = 0.09) had significant difference. Multivariate analysis revealed that tumor size, tumor number, carbohydrate antigen19-9, carcinoembryonic antigen, and gamma-glutamyl transpeptidase were independent predictive factors for OS and RFS. CONCLUSION: Routine LND may not improve survival in resectable ICC patients with negative LNM diagnosis before operation.
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BACKGROUND: Several studies have shown a positive association between body mass index (BMI) and the development of hormone receptor-positive breast cancer in postmenopausal women; however, the associations between BMI groups and molecular subtypes have yet to be well defined in premenopausal breast cancer patients. METHODS: A total of 2465 female breast cancer patients diagnosed at our institution were recruited for this study. Clinicopathologic information (including age, body height and weight, as well as tumor subtypes and stages) was collected; analyses of these characteristics and the associations between them were performed. RESULTS: A total of 1951 cases were included in the study. The mean age was 47.3 years, the majority of patients were of normal weight, premenopausal, had stage 2 cancer, and did not present with positive nodes. The prevalence of the luminal A, luminal B, human epidermal growth factor receptor 2+, and triple-negative subtypes were 57.8%, 11.6%, 6.1%, and 24.5%, respectively. There were significant differences in the clinicopathologic features among BMI groups in premenopausal patients. The case-only odds ratio (OR) analysis revealed that normal weight patients tended to have luminal B cancer (OR = 1.4, P = 0.206), and overweight and obese patients tended to have triple-negative cancer in premenopausal patients (OR = 2.8, OR = 3.7, respectively; P < 0.001). CONCLUSION: IN CHINESE WOMEN, BREAST CANCER CAME WITH THESE CHARACTERISTICS: young mean age (premenopause), luminal A subtype, and the majority of them were within a normal weight range. In premenopausal patients, underweight patients tended to have luminal A, lower human epidermal growth factor receptor 2+ expression, stage 1 and no positive node cancer. However, overweight and obese patients tended to have a triple-negative, stage 3, and lymph node metastatic cancer.
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BACKGROUND: Ten genes are associated with increased susceptibility to inherited breast cancer have also been associated with population breast cancer risk, and all are involved directly or indirectly in the monoubiquitinated FANCD2-DNA damage repair pathway. We analyzed 13 haplotype blocks in eight of these genes to estimate the breast cancer risk conferred by individual haplotypes. METHODS: Haplotype blocks were constructed with 48 tag single-nucleotide polymorphisms (tSNPs) identified in eight breast cancer susceptibility genes, TP53, PTEN, CHEK2, ATM, NBS1, RAD50, BRIP1, and PALB2. Genotyping was performed by SNPscan on 734 female patients and 672 female age-matched controls. RESULTS: Forty-five tSNPs were successfully genotyped by SNPscan, and call rates for each tSNP were above 98.9%. Thirteen haplotype blocks of eight genes were constructed with 41 successfully genotyped tSNPs. We found that seven haplotypes from four haplotype blocks located within three genes (NBS1, PTEN, and BRIP1) were significantly associated with breast cancer risk. Among these, four haplotypes (ATC in block 1 of NBS1, GCCCC and GCCCT in block 2 of NBS1, and GCT in block 2 of BRIP1) were correlated with breast cancer risk in sporadic cases (OR (95% CI) 1.350(1.124-1.623), 0.752(0.584-0.969), 0.803(0.649-0.993), and 0.776(0.604-0.997), respectively), and only one haplotype (GGCCT in block 2 of NBS1) was significantly associated with breast cancer risk in familial and early-onset cases (OR(95% CI) 1.902(1.134-3.191)). CONCLUSIONS: Four haplotypes within two genes (NBS1 and BRIP1) involved in the monoubiquitinated FANCD2-DNA damage-repair pathway are significantly associated with increased sporadic breast cancer risk, while one haplotype within NBS1 is correlated with an increased risk of familial or early-onset breast cancer, indicating that specific haplotypes may be distinct predictors of breast cancer.