scholarly journals Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoichi Katsube ◽  
Kazuhiro Noma ◽  
Toshiaki Ohara ◽  
Noriyuki Nishiwaki ◽  
Teruki Kobayashi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Near Infrared ◽  
Fibroblast Activation Protein ◽  
Therapeutic Resistance ◽  
Fibroblast Activation ◽  
Human Esophageal Cancer

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

scholarly journals Anticancer Effects of Dihydroartemisinin on Human Esophageal Cancer Cells In Vivo

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Cailing Jiang ◽  
Shumin Li ◽  
Yanjing Li ◽  
Yuxian Bai
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Esophageal Cancer Cell ◽  
Human Esophageal Cancer ◽  
Semisynthetic Derivative ◽  
Esophageal Cancer Cells ◽  
Dose Dependent

Despite recent advances in chemotherapy and surgical resection, the 5-year survival rate of esophageal cancer still remains at the low level. Therefore, it is very important to discover a new agent to improve the life expectancy of patients with esophageal cancer. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently exhibited promising anticancer activity against various cancer cells. But so far, the specific mechanism remains unclear. We have previously demonstrated that DHA reduced viability of esophageal cancer cells in a dose-dependent manner in vitro and induced cell cycle arrest and apoptosis. Here, we extended our study to further observe the efficacy of DHA on esophageal cancer cells in vivo. In the present study, for the first time, we found that DHA significantly inhibits cell proliferation in xenografted tumor compared with the control. The mechanism was that DHA induced cell apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vivo in a dose-dependent manner. The results suggested that DHA was a promising agent against esophageal cancer in the clinical treatment.

A novel fibroblast activation protein-targeted near-infrared fluorescent off–on probe for cancer cell detection, in vitro and in vivo imaging

2018 ◽  
Vol 6 (10) ◽  
pp. 1449-1451 ◽  
Author(s):  
Jie Xing ◽  
Qiuyu Gong ◽  
Ruifen Zou ◽  
Zihou Li ◽  
Yuanzhi Xia ◽  
...  
Keyword(s):  
Fluorescent Probe ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Fibroblast Activation Protein ◽  
Cell Detection ◽  
Fibroblast Activation ◽  
Design And Synthesis ◽  
Cancer Cell Detection

Design and synthesis of a novel fibroblast activation protein “off–on” near-infrared fluorescent probe for cell detection, in vitro and in vivo imaging.

Effect of Suramin on Human Esophageal Cancer Cells in Vitro and in Vivo

1997 ◽  
Vol 32 (8) ◽  
pp. 824-828 ◽  
Author(s):  
R. Shin ◽  
Y. Naomoto ◽  
Y. Kamikawa ◽  
N. Tanaka ◽  
K. Orita
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Human Esophageal Cancer ◽  
Esophageal Cancer Cells

scholarly journals Moscatilin Inhibits Growth of Human Esophageal Cancer Xenograft and Sensitizes Cancer Cells to Radiotherapy

2019 ◽  
Vol 8 (2) ◽  
pp. 187 ◽  
Author(s):  
Wun-Ke Chen ◽  
Chien-An Chen ◽  
Chih-Wen Chi ◽  
Li-Hui Li ◽  
Chin-Ping Lin ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
White Blood Cell Counts ◽  
Human Esophageal Cancer ◽  
Esophageal Cancer Cells ◽  
Plk1 Expression

Esophageal cancer prognosis remains poor in current clinical practice. We previously reported that moscatilin can induce apoptosis and mitotic catastrophe in esophageal cancer cells, accompanied by upregulation of polo-like kinase 1 (Plk1) expression. We aimed to validate in vitro activity and Plk1 expression in vivo following moscatilin treatment and to examine the treatment’s radiosensitizing effect. Human esophageal cancer cells were implanted in nude mice. Moscatilin was intraperitoneally (i.p.) injected into the mice. Tumor size, body weight, white blood cell counts, and liver and renal function were measured. Aberrant mitosis and Plk1 expression were assessed. Colony formation was used to measure survival fraction after radiation. Moscatilin significantly suppressed tumor growth in mice bearing human esophageal xenografts without affecting body weight, white blood cell counts, or liver and renal function. Moscatilin also induced aberrant mitosis and apoptosis. Plk1 expression was markedly upregulated in vivo. Moreover, moscatilin pretreatment enhanced CE81T/VGH and BE3 cell radioresponse in vitro. Moscatilin may inhibit growth of human esophageal tumors and sensitize esophageal cancer cells to radiation therapy.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals NR5A2 transcriptional activation by BRD4 promotes pancreatic cancer progression by upregulating GDF15

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Feng Guo ◽  
Yingke Zhou ◽  
Hui Guo ◽  
Dianyun Ren ◽  
Xin Jin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transcriptional Activation ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Cancer Cells ◽  
Gene Sets ◽  
And Migration

AbstractNR5A2 is a transcription factor regulating the expression of various oncogenes. However, the role of NR5A2 and the specific regulatory mechanism of NR5A2 in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly studied. In our study, Western blotting, real-time PCR, and immunohistochemistry were conducted to assess the expression levels of different molecules. Wound-healing, MTS, colony formation, and transwell assays were employed to evaluate the malignant potential of pancreatic cancer cells. We demonstrated that NR5A2 acted as a negative prognostic biomarker in PDAC. NR5A2 silencing inhibited the proliferation and migration abilities of pancreatic cancer cells in vitro and in vivo. While NR5A2 overexpression markedly promoted both events in vitro. We further identified that NR5A2 was transcriptionally upregulated by BRD4 in pancreatic cancer cells and this was confirmed by Chromatin immunoprecipitation (ChIP) and ChIP-qPCR. Besides, transcriptome RNA sequencing (RNA-Seq) was performed to explore the cancer-promoting effects of NR5A2, we found that GDF15 is a component of multiple down-regulated tumor-promoting gene sets after NR5A2 was silenced. Next, we showed that NR5A2 enhanced the malignancy of pancreatic cancer cells by inducing the transcription of GDF15. Collectively, our findings suggest that NR5A2 expression is induced by BRD4. In turn, NR5A2 activates the transcription of GDF15, promoting pancreatic cancer progression. Therefore, NR5A2 and GDF15 could be promising therapeutic targets in pancreatic cancer.

scholarly journals Molecular imaging and deep learning analysis of uMUC1 expression in response to chemotherapy in an orthotopic model of ovarian cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hongwei Zhao ◽  
Hasaan Hayat ◽  
Xiaohong Ma ◽  
Daguang Fan ◽  
Ping Wang ◽  
...  
Keyword(s):  
Neural Networks ◽  
Ovarian Cancer ◽  
Deep Learning ◽  
Cancer Progression ◽  
In Vivo Imaging ◽  
Near Infrared ◽  
Response To Therapy ◽  
Response To Chemotherapy

Abstract Artificial Intelligence (AI) algorithms including deep learning have recently demonstrated remarkable progress in image-recognition tasks. Here, we utilized AI for monitoring the expression of underglycosylated mucin 1 (uMUC1) tumor antigen, a biomarker for ovarian cancer progression and response to therapy, using contrast-enhanced in vivo imaging. This was done using a dual-modal (magnetic resonance and near infrared optical imaging) uMUC1-specific probe (termed MN-EPPT) consisted of iron-oxide magnetic nanoparticles (MN) conjugated to a uMUC1-specific peptide (EPPT) and labeled with a near-infrared fluorescent dye, Cy5.5. In vitro studies performed in uMUC1-expressing human ovarian cancer cell line SKOV3/Luc and control uMUC1low ES-2 cells showed preferential uptake on the probe by the high expressor (n = 3, p < .05). A decrease in MN-EPPT uptake by SKOV3/Luc cells in vitro due to uMUC1 downregulation after docetaxel therapy was paralleled by in vivo imaging studies that showed a reduction in probe accumulation in the docetaxel treated group (n = 5, p < .05). The imaging data were analyzed using deep learning-enabled segmentation and quantification of the tumor region of interest (ROI) from raw input MRI sequences by applying AI algorithms including a blend of Convolutional Neural Networks (CNN) and Fully Connected Neural Networks. We believe that the algorithms used in this study have the potential to improve studying and monitoring cancer progression, amongst other diseases.

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