scholarly journals S100A4 mRNA expression level is a predictor of radioresistance of pancreatic cancer cells

2013 ◽  
Vol 30 (4) ◽  
pp. 1601-1608 ◽  
Author(s):  
SHINGO KOZONO ◽  
KENOKI OHUCHIDA ◽  
TAKAO OHTSUKA ◽  
LIN CUI ◽  
DAIKI EGUCHI ◽  
...  
2020 ◽  
Vol 401 (10) ◽  
pp. 1153-1165 ◽  
Author(s):  
Antônio F. da Silva Filho ◽  
Lucas B. Tavares ◽  
Maira G. R. Pitta ◽  
Eduardo I. C. Beltrão ◽  
Moacyr J. B. M. Rêgo

AbstractPancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.


Oncotarget ◽  
2017 ◽  
Vol 8 (62) ◽  
pp. 104796-104805
Author(s):  
Ana-Barbara García-García ◽  
M. Carmen Gómez-Mateo ◽  
Rebeca Hilario ◽  
Pilar Rentero-Garrido ◽  
Alvaro Martínez-Domenech ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2136-2136
Author(s):  
Huong Chi Mai Tran ◽  
Rania Amrane ◽  
Elisabeth Mbemba ◽  
Michele Sabbah ◽  
Ismail Elalamy ◽  
...  

Abstract Background Cancer patients with venous thromboembolism (VTE) or at risk of VTE are treated with antithrombotic agents. Cancer cells express procoagulant properties and induce hypercoagulability in the microenvironment, that could impact the efficiency of the antithrombotic agents. Aims In the present study, we investigated the interaction between antithrombotic agents with pancreatic cancer cells, as well as with their microenvironment. The impact of apixaban, fondaparinux, enoxaparin and tinzaparin on the procoagulant properties of pancreatic cancer cells BXPC3 was examinated. Reciprocally, we also investigated the impact of BXPC3 on the potency of these antithrombotic agents. Methods BXPC3 cells (400 cells/μl) were exposed for 48 hours to apixaban (2 µg/ml), fondaparinux (2 µg/ml), enoxaparin, tinzaparin (2 anti-Xa IU/ml) or NaCL (control). Then, conditioned media (CM) and BXPC3 cells were harvested, separated and put in contact with normal platelet-poor plasma (PPP). Subsequently, thrombin generation (TG) was assessed using Thrombogram-Thrombinoscope® assay (Diagnostica Stago). Cells' viability was also assessed with the MTT assay. Gene expression for Tissue Factor (TF), Vascular Endothelial Growth Factor (VEGF), Thrombospondin 1 (THSB1) was assessed with RT-qPCR at the cells exposed or not to the antithrombotic agents. Expression of TF protein and activity of cancer cells was assessed using ELISA method. Residual anti-Xa activity in CM was measured using specific amidolytic assays for each antithrombotic agent. Results Apixaban, fondaparinux, enoxaparin, and tinzaparin significantly reduced cell viability by 25%, 12%, 14%, and 11% respectively. In the control experiment non treated BXPC3 cells enhanced TG. Pre-treatment of BXPC3 with the antithrombotic agents did not significantly modify their capacity to trigger and enhance TG. Among the studied agents only apixaban resulted in significant decrease of TF mRNA expression. However, protein expression of TF was not significantly modified by any of the antithrombotic agents. VEGF's mRNA expression was significantly decreased by fondaparinux and enoxaparin. THBS1's mRNA expression was significantly increased by apixaban. The concentrations of the anti-Xa activity of fondaparinux, enoxaparin and tinzaparin in the CM obtained at 48h after exposure of cells were reduced by 27%, 48% and 26% respectively as compared to those initially added in the culture medium. In contrast, the concentration of apixaban in the CM did not significantly change. The CM obtained by cells exposed to apixaban, fondaparinux, enoxaparin and tinzaparin inhibited TG by 70%, 30%, 40% and 90% respectively. Conclusion. Antithrombotic agents reduced the viability of BXPC3 cells. Among the studied agents, apixaban had the most pronounced effect on cells' viability. The antithrombotic agents had a potential downregulating effect on the proangiogenetic properties of BXPC3 via the decrease of VEGF gene expression (fondaparinux and enoxaparin) and enhancement of THBS1 gene expression (apixaban). Nevertheless, preincubation of BXPC3 with the antithrombotic agents did not alter the expression of TF protein and their effect on thrombin generation. Moreover, BXPCE exerted a "degradation" effect on LMWH and fondaparinux. Apixaban appeared to escape from this effect of the cancer cells. A significant inhibitory effect on thrombin generation was exerted by the residual concentrations of the antithrombotic agents in the microenvironment of cancer cells. The ensemble of these data highlight for the first time that the presence of antithrombotic agents in cancer cell microenvironment alters the biology of cancer cells and offer a constant antithrombotic effect in the microenvironment. Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Vol 64 (3) ◽  
pp. 31-37
Author(s):  
Anna Bogacz ◽  
Marlena Wolek ◽  
Bogna Juskowiak ◽  
Monika Karasiewicz ◽  
Adam Kamiński ◽  
...  

Summary Introduction: Breast cancer is the most common malignant cancer among women. Both drug resistance and metastasis are major problems in the treatment of breast cancer. Therefore, adjuvant therapy may improve patients’ survival and affect their quality of life. It is suggested that epigallocatechin gallate (EGCG) which is well known for its chemopreventive activity and acts on numerous molecular targets may inhibit the growth and metastasis of some cancers. Hence, discovering the metastatic molecular mechanisms for breast cancer may be useful for therapy. Objective: The aim of the study was to determine the effect of EGGC on the mRNA expression level of genes such as ZEB1, ABCB1, MDM2, TWIST1 and PTEN in MCF-7 breast cancer cells. Methods: MCF7/DOX were cultured in the presence of 0.2 μM DOX and EGCG (20-50 μM). The mRNA expression level was determined by real-time quantitative PCR using RealTime ready Custom Panel 96 kit. Results: Our results showed an important increase (about 2-fold for 20 μM EGCG + 0.2 μM DOX and 2.5-fold for 50 μM EGCG + 0.2 μM DOX, p<0.05) in ZEB1 expression levels. In case of ABCB1 gene lack of influence on the mRNA level was observed (p>0.05). We also observed significant decrease of ZEB1 expression in MCF7 cells with 20 μM and 50 μM EGCG (p<0.05). In addition, EGCG (20 μM) caused an increase of MDM2 and PTEN mRNA levels in almost 100% (p<0.05) and 40% (p>0.05), respectively. Lack of the influence of EGCG was noted for the TWIST1 gene expression. In case of MCF7/DOX we showed an increase of mRNA level of PTEN gene about 50% (p<0.05). Conclusions: These results suggest that EGCG may be potentially used in adjuvant therapy in the breast cancer treatment.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16773-e16773
Author(s):  
Juan Du ◽  
Linxi Zhu ◽  
Huizi Sha ◽  
Zhengyun Zou ◽  
Lixia Yu ◽  
...  

e16773 Background: Pancreatic cancer is a kind of digestive tumor with low incidence but high degree of malignancy. It is characterized by difficult in early detection and invasive metastasis. Together with high recurrence and metastasis rate after resection, the prognosis of pancreatic cancer is extremely poor. To explore the role of BRCA1 mRNA expression in the chemotherapy of unresectable pancreatic cancer and the synergistic effect of chemotherapy and immunotherapy, our center has carried out a clinical trial which focuses on individualized chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression in the first-line treatment of unresectable pancreatic cancer. Methods: The expression of BRCA1 mRNA in tumor tissues of patients with pancreatic cancer was detected. According to the expression level, gemcitabine combined with nab-paclitaxel-based or gemcitabine combined with oxaliplatin-based biweekly chemotherapy combined with sequential GM-CSF and IL-2 immunotherapy was applied. Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: A total of 25 patients were enrolled in the study. All of them were observed for toxic side effects and 24 of them were evaluated for efficacy. The median overall survival and median progression-free survival were 11.9 months and 6.3 months. The disease control rate was 91.7%, of which 37.5% (9/24) patients achieved partial remission (PR), 54.2% (13/24) patients achieved stable disease (SD) and 8.3% (2/24) patients were assessed as progressive disease(PD). Of the 15 patients with medium or high expression in BRCA1 mRNA, 7 achieved PR and 8 achieved SD. Of the 9 patients with low BRCA1 mRNA expression, 2 achieved PR, 5 achieved SD and 2 had PD. The proportion of eosinophils in the blood of some patients with good therapeutic effects was significantly higher than that before treatment. Hematological and non-hematological toxicity during the treatment were mostly grade 1~2. The two most common grade 3~4 adverse events were fever and thrombocytopenia. Conclusions: Our results suggest that individualized selection of chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression level in the treatment of unresectable pancreatic cancer have curative effect and controllable adverse reactions. The improvement of treatment efficiency may be related to the activation of non-specific immune response.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 33-33 ◽  
Author(s):  
Kazuhiko Tamura ◽  
Takafumi Watanabe ◽  
Masanobu Enomoto ◽  
Hideo Sudou ◽  
Jiro Ogata ◽  
...  

33 Background: In this study, we measured the mRNA expression level of cancer-critical genes from the gastric/colorectal cancer tissues obtained through endoscopic biopsy before treatments and compared its consistency with the sample tissues surgically resected from identical cases. Methods: The study was made on 13 gastric and 19 colorectal cancer cases with patients’ consent. We picked identical cases and measured mRNA expression levels from the tissues endoscopically taken before treatment and the surgically resected ones. For the measurement, DNP (DanenbergTumorProfile) method was used. Examination items are as follows: TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, Topo-I, EGFR, and VEGF. Results: Upon comparing the consistency between endoscopically sampled biopsy tissues and surgically taken tissues from identical cases, it was found that eight out of ten items showed strong correlations in colorectal cancer cases. The results are as follows: FPGS(r=0.91, p<0.001); GGH(r=0.87, p<0.001); EGFR(r=0.86, p<0.001); Topo I (r=0.81, p<0.001); TS(r=0.79, p<0.001); DHFR(r=0.70, p<0.01); VEGF(r=0.67, p<0.01); and TP(r=0.62, p<0.05). In case of gastric cancers, strong correlations were found in three out of ten items with the following results: EGFR (r=0.98, p<0.001); TS (r=0.91, p<0.001; and DPD (r=0.74, p<0.05). Conclusions: Today’s progresses of preoperative chemotherapy and radiotherapy and developments of endoscopic and surgical treatments allow diverse options for treatments. In such circumstances, the significance of knowing the expression of cancer-critical genes between individuals before treatment in conducting custom-made treatment is profound. There are two issues in applying the expression of cancer-critical genes found through endoscopic biopsy: one is whether enough cancer cells can be obtained through biopsy, and the other is whether the sampled cancer cells reflect the characteristics of primary focus. While there remain issues to be addressed, certain results were achieved in this study. Currently, we are working on accumulating cases to compare them and find out whether the results can be applied to custom-made treatments.


2021 ◽  
Author(s):  
Weiyi Huang ◽  
Lili Chen ◽  
Pengming Sun

Abstract Purpose: Ovarian cancer is one of the common gynecological malignancies, which is prone to metastasize and thus causes a high fatality rate. Estrogen-related receptor alpha (ERRα) is highly expressed in various malignant tumors. Our objective was to explore the impact of ERRα expression on the progression of ovarian cancer. Methods: The correlation between ERRα expression level and clinical pathological parameters in ovarian cancer tissues were analysed via cancer public database CPTAC. The expression level of ERRα in ovarian cancer cells were confirmed by RT-qPCR and Western Blot methods. The cellular ERRα expression was up-regulated via lentivirus transfection and down-regulated via specific antagonist. The invasion and metastasis capabilities of ovarian cancer cells were observed by wound healing assay and trans-well chamber assay. Results: The CPTAC database showed that the ERRα expression levels were higher in the late-stage and high-grade ovarian cancer tissues compared with those in early-stage and low-grade tissues. Ovarian cancer cells with higher expression level of ERRα had stronger invasion and metastasis capabilities in vitro. After up-regulating the ERRα expression level, the invasion and metastasis capabilities of ovarian cancer cells were enhanced, while down-regulation weakened. Moreover, there was a positive correlation between the percentages of wound closure and cellular ERRα mRNA expression level (r=0.921, P<0.01), and the cell invasiveness was also positively correlated with the cellular ERRα mRNA expression level (r=0.926, P<0.01). Conclusions: Our results suggest that ERRα may play a positive role in the progression of ovarian cancer, and may serve as a promising predictive biomarker.


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