scholarly journals MELODI - Mining Enriched Literature Objects to Derive Intermediates

2017 ◽  
Author(s):  
Benjamin Elsworth ◽  
Karen Dawe ◽  
Emma E Vincent ◽  
Ryan Langdon ◽  
Brigid M Lynch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pancreatic Cancer ◽  
Web Application ◽  
Scientific Literature ◽  
Literature Mining ◽  
Analytical Evaluation ◽  
Disease Mechanisms ◽  
The Relationship ◽  
Published Research

AbstractMotivationThe scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, prioritising mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritise mechanisms for more focused and detailed analysis.ResultsHere we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts. Two case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. Firstly, an analysis of ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Secondly, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studiedin vitro.AvailabilityMELODI has been implemented as a Python/Django web application, and is freely available to use [email protected]

scholarly journals E3 Ubiquitin Ligase TRIM29 Promotes Pancreatic Cancer Growth and Progression via Stabilizing Yes-associated Protein 1

2021 ◽  
Author(s):  
Xueqiang Deng ◽  
Xiaowei Fu ◽  
Hong Teng ◽  
Lu Fang ◽  
Bo Liang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Cycle Progression ◽  
Nude Mouse Model ◽  
Cycle Progression ◽  
Signal Cascade ◽  
The Relationship ◽  
Precise Role

Abstract Background: Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear.Methods: Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay.Results: TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation.Conclusion: Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.

DETECTION OF PANCREATIC CANCER CELLS (SUIT-2) USING AN FET-BASED BIOSENSOR WITH AN EXTENDED Au GATE

2012 ◽  
Vol 24 (02) ◽  
pp. 131-137
Author(s):  
Byunghyun Cho ◽  
Hee-Ho Lee ◽  
Jang-Kyoo Shin ◽  
Masaharu Murata ◽  
Kenoki Ohuchida ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Anticancer Drug ◽  
Medical Application ◽  
Human Pancreatic Cancer ◽  
Labview Software ◽  
Pancreatic Cancer Cells ◽  
Effect Transistor ◽  
The Relationship

In this paper, we assess the feasibility of detecting human pancreatic cancer cells using a field effect transistor (FET)-based biosensor with an extended Au gate for medical application. Pancreatic cancer is one of the most fatal cancers, and is very difficult to diagnose in its early stages. Gemcitabine is an anticancer drug, and when used in chemotherapy it induces cell death. During apoptosis, the surface potential of the pancreatic cancer cells is changed by gemcitabine. In the present study, this change was detected using an FET-based biosensor. This biosensor was fabricated with an extended Au gate, whose surface is a sensing area for cancer cells. A null-balancing circuit was used in the measurement system, and the LabVIEW software platform allowed the immune-reaction at the Au gate to be detected as an output voltage. The cancer cells were incubated for one day; during this time, the cancer cells adhered to the Au extended gate surface. As gemcitabine was introduced to the cancer cells in vitro, changes in the output of the biosensor were monitored. Pancreatic cancer cells with a resistance to gemcitabine were used to verify that the change in the output of the biosensor was due only to the interaction between the cancer cells and the gemcitabine. We also investigated the relationship between the starting time of the reaction and the concentration of the anticancer drug.

scholarly journals HAT1 Promotes Gemcitabine Resistance by Regulating the PVT1/EZH2 Complex in Pancreatic Cancer

2020 ◽  
Author(s):  
Yan Sun ◽  
Jian Shen ◽  
Dianyun Ren ◽  
Yingke Zhou ◽  
Jingyuan Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Statistical Significance ◽  
Gemcitabine Resistance ◽  
Development Of Resistance ◽  
Pancreatic Cancer Cells ◽  
Promising Therapeutic Target ◽  
The Relationship

Abstract Background: The poor prognosis of pancreatic cancer is primarily due to the development of resistance to therapies, including gemcitabine. PVT1 has been shown to interact with EZH2, promoting gemcitabine resistance in pancreatic cancer. Methods: In this study, we assessed the ability of PVT1/EZH2 targeting to reverse resistance to gemcitabine in pancreatic cancer cells. MTS assay, colony formation assay, and mouse xenotransplantation experiments were used to evaluate the anti-tumor effects of gemcitabine in HAT1 knockdown or overexpressing pancreatic cancer cells. The relationship between HAT1 and PVT1 in pancreatic cancer was determined by RNA sequencing, quantitative real-time PCR, and chromatin immunoprecipitation. Co-immunoprecipitation, pull-downs, western blotting, and immunohistochemistry were used to assess the relationship between HAT1 and EZH2 in pancreatic cancer. Chitosan (CS)-tripolyphosphate (TPP)-siHAT1 nanoparticles were developed to evaluate their effects on the anti-tumor potential of gemcitabine in pancreatic cancer. Student’s t-test, one-way analysis of variance (ANOVA), or two-way ANOVA was used to evaluate statistical significance. P-values <0.05 were considered statistically significant. All values were expressed as means ± SD. Results: Our results showed that the aberrant HAT1 expression promoted gemcitabine resistance in pancreatic cancer cells. We also found that HAT1 enhanced the binding of BRD4 to the PVT1 promoter, thereby promoting PVT1 transcription. Moreover, we found that HAT1 prevented EZH2 degradation by interfering with UBR4 binding to the N-terminal domain of EZH2, thus maintaining EZH2 protein stability. Finally, we showed that CS-TPP-siHAT1 nanoparticles augmented the anti-tumor effects of gemcitabine in pancreatic cancer cells in vitro and in vivo. Conclusions: Our findings suggest that by increasing the levels of the PVT1/EZH2 complex, HAT1 promotes gemcitabine resistance in pancreatic cancer. Therefore, HAT1 is a promising therapeutic target for pancreatic cancer.

scholarly journals Transcription Factor HBP1 Enhances Radiosensitivity by Inducing Apoptosis in Prostate Cancer Cell Lines

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yicheng Chen ◽  
Yueping Wang ◽  
Yanlan Yu ◽  
Liwei Xu ◽  
Youyun Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Expression Level ◽  
Prostate Cancer Cells ◽  
Expression Levels ◽  
The Relationship

Radiotherapy for prostate cancer has been gradually carried out in recent years; however, acquired radioresistance often occurred in some patients after radiotherapy. HBP1 (HMG-box transcription factor 1) is a transcriptional inhibitor which could inhibit the expression of dozens of oncogenes. In our previous study, we showed that the expression level of HBP1 was closely related to prostate cancer metastasis and prognosis, but the relationship between HBP1 and radioresistance for prostate cancer is largely unknown. In this study, the clinical data of patients with prostate cancer was compared, and the positive correlation was revealed between prostate cancer brachytherapy efficacy and the expression level of HBP1 gene. Through research on prostate cancer cells in vitro, we found that HBP1 expression levels were negatively correlated with oncogene expression levels. Furthermore, HBP1 overexpression could sensitize prostate cancer cells to radiation and increase apoptosis in prostate cancer cells. In addition, animal model was employed to analyze the relationship between HBP1 gene and prostate cancer radiosensitivity in vivo; the result showed that knockdown of HBP1 gene could decrease the sensitivity to radiation of xenograft. These studies identified a specific molecular mechanism underlying prostate cancer radiosensitivity, which suggested HBP1 as a novel target in prostate cancer radiotherapy.

scholarly journals Investigation of Anti-Tumor Effects of an MLK1 Inhibitor in Prostate and Pancreatic Cancers

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 742
Author(s):  
Yu-Ching Fan ◽  
Kai-Chen Hsu ◽  
Tony-Eight Lin ◽  
Dietmar Zechner ◽  
Sung-Po Hsu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pancreatic Cancer ◽  
Kinase Assay ◽  
Inhibitory Effects ◽  
Orthotopic Mouse Model ◽  
Growth Environment ◽  
Pancreatic Cancers ◽  
In Vitro Kinase Assay ◽  
Prevention Of Cancer

It was shown that mixed lineage kinase 1 (MLK1) regulates pancreatic cancer growth; however, its role in prostate cancer remains unclear. We showed that MLK1 is a tumor marker in prostate cancer by analyzing clinical gene expression data and identified a novel MLK1 inhibitor (NSC14465) from the compound library of the National Cancer Institute (NCI) using a MLK1 protein structure. The inhibitory effects of MLK1 were validated by an in vitro kinase assay and by monitoring phosphorylation signaling, and the anti-proliferation function was shown in several prostate and pancreatic cancer cell lines. We also demonstrated anti-tumor ability and prevention of cancer-related weight loss in a syngeneic orthotopic mouse model of pancreatic cancer that mimicked the tumor growth environment in the pancreas. Our results demonstrate that the MLK1 inhibitor is an anti-tumor agent for malignant prostate and pancreatic cancers.

scholarly journals E3 ubiquitin ligase TRIM29 promotes pancreatic cancer growth and progression via stabilizing Yes-associated protein 1

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xueqiang Deng ◽  
Xiaowei Fu ◽  
Hong Teng ◽  
Lu Fang ◽  
Bo Liang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Cycle Progression ◽  
Nude Mouse Model ◽  
Cycle Progression ◽  
Signal Cascade ◽  
The Relationship ◽  
Precise Role

Abstract Background Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear. Methods Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay. Results TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation. Conclusion Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

Plasminogen Depletion during Streptokinase Treatment or Two-Chain Urokinase Incubation Correlates with Decreased Clot Lysability Ex Vivo and In Vitro

1993 ◽  
Vol 70 (06) ◽  
pp. 0998-1004 ◽  
Author(s):  
Páll T Önundarson ◽  
H Magnús Haraldsson ◽  
Lena Bergmann ◽  
Charles W Francis ◽  
Victor J Marder
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Time Dependent ◽  
State Variables ◽  
Thrombolytic Treatment ◽  
Direct Proportion ◽  
Plasmin Activity ◽  
Plasma Exposure ◽  
The Relationship

SummaryThe relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

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