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Article: Iron-induced kidney cell damage: insights into molecular mechanisms and potential diagnostic significance of urinary FTL.

Punchai, Soraya / Chaiyagot, Nachayada / Artkaew, Nadthanicha / Jusakul, Apinya / Cha'on, Ubon / Thanan, Raynoo / Vaeteewoottacharn, Kulthida / Lert-Itthiporn, Worachart

Frontiers in molecular biosciences

2024 Volume 11, Page(s) 1352032

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2024-02-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2024.1352032
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Article: The Hallmarks of Liver Fluke Related Cholangiocarcinoma: Insight into Drug Target Possibility.

Loilome, Watcharin / Namwat, Nisana / Jusakul, Apinya / Techasen, Anchalee / Klanrit, Poramate / Phetcharaburanin, Jutarop / Wangwiwatsin, Arporn

Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer

2023 Volume 219, Page(s) 53–90

Abstract: Cholangiocarcinoma (CCA) is a malignant tumor of the biliary tree that is classified into three groups based on its anatomic location: intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA). Perihilar CCA is the most common type and accounts for 50-60% ...

Abstract	Cholangiocarcinoma (CCA) is a malignant tumor of the biliary tree that is classified into three groups based on its anatomic location: intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA). Perihilar CCA is the most common type and accounts for 50-60% of CCA cases. It is followed by distal CCA and then intrahepatic CCA that account for 20-30% and 10-20% of cases, respectively. This chapter discusses the hallmarks of liver fluke related CCA and explores insights into drug target possibilities.
MeSH term(s)	Animals ; Humans ; Fasciola hepatica ; Cholangiocarcinoma/drug therapy ; Dyskinesias ; Bile Duct Neoplasms/drug therapy ; Bile Ducts, Intrahepatic
Language	English
Publishing date	2023-09-02
Publishing country	Germany
Document type	Journal Article
ISSN	0080-0015
ISSN	0080-0015
DOI	10.1007/978-3-031-35166-2_4
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Article ; Online: FGF10/FGFR2 Signaling: Therapeutically Targetable Vulnerability in Ligand-responsive Cholangiocarcinoma Cells.

Oeurn, Kimyeun / Jusakul, Apinya / Jaidee, Rattanaporn / Kukongviriyapan, Veerapol / Senggunprai, Laddawan / Prawan, Auemduan / Kongpetch, Sarinya

In vivo (Athens, Greece)

2023 Volume 37, Issue 4, Page(s) 1628–1637

Abstract: Background/aim: Increasing evidence has revealed FGFR2 as an attractive therapeutic target for cancer including cholangiocarcinoma (CCA). The present study investigated the oncogenic mechanisms by which FGF10 ligand activates FGFR2 in CCA cells and ... ...

Abstract	Background/aim: Increasing evidence has revealed FGFR2 as an attractive therapeutic target for cancer including cholangiocarcinoma (CCA). The present study investigated the oncogenic mechanisms by which FGF10 ligand activates FGFR2 in CCA cells and determined whether FGFR inhibitors could suppress FGF10-mediated migration of CCA cells. Materials and methods: Effects of FGF10 on the proliferation, migration, and invasion of KKU-M213A cells were assessed using clonogenic and transwell assays. Protein expression levels of FGFR2 and pro-angiogenic factors were determined via immunoblotting and antibody array analysis. FGFR2 knockdown using a small interfering RNA was used to validate the role of FGF10 in promoting cell migration via FGFR2. The effects of infigratinib (FGFR inhibitor) on cell viability, were determined in KKU-100, KKU-M213A, KKU-452 cells. Moreover, the efficacy of the FGFR inhibitor in suppressing migration via FGF10/FGFR2 stimulation was assessed in KKU-M213A cells. Results: FGF10 significantly increased the expression of phospho-FGFR/FGFR2 and promoted the proliferation, migration, and invasion of KKU-M213A cells. FGF10 increased the expression levels of p-Akt, p-mTOR, VEGF, Slug, and pro-angiogenic proteins related to metastasis. Cell migration mediated by FGF10 was markedly decreased in FGFR2-knockdown cells. Moreover, FGF10/FGFR2 promoted the migration of cells, which was suppressed by the FGFR inhibitor. Conclusion: FGF10/FGFR2 activates the Akt/mTOR and VEGF/Slug pathways, which are associated with the stimulation of migration and invasion in CCA. Moreover, the FGF10/FGFR2 signaling was inhibited by an FGFR inhibitor resulting suppression of cell migration, which warrants further studies on their clinical utility for CCA treatment.
MeSH term(s)	Humans ; Proto-Oncogene Proteins c-akt/metabolism ; Ligands ; Vascular Endothelial Growth Factor A ; Cell Line, Tumor ; Cholangiocarcinoma/drug therapy ; Cholangiocarcinoma/genetics ; TOR Serine-Threonine Kinases ; Protein Kinase Inhibitors/therapeutic use ; Bile Ducts, Intrahepatic/metabolism ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/genetics ; Cell Proliferation ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/therapeutic use ; Fibroblast Growth Factor 10/pharmacology ; Fibroblast Growth Factor 10/therapeutic use
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Ligands ; Vascular Endothelial Growth Factor A ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Protein Kinase Inhibitors ; FGFR2 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1) ; FGF10 protein, human ; Fibroblast Growth Factor 10
Language	English
Publishing date	2023-06-27
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13248
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Article ; Online: Anticancer properties and metabolomic profiling of Shorea roxburghii extracts toward gastrointestinal cancer cell lines.

Janthamala, Sutthiwan / Promraksa, Bundit / Thanee, Malinee / Duenngai, Kunyarat / Jusakul, Apinya / Kongpetch, Sarinya / Kraiklang, Ratthaphol / Thanee, Kidsada / Pinlaor, Porntip / Namwat, Nisana / Saya, Hideyuki / Techasen, Anchalee

BMC complementary medicine and therapies

2024 Volume 24, Issue 1, Page(s) 178

Abstract: Background: Gastrointestinal cancer (GIC) ranks as the highest cause of cancer-related deaths globally. GIC patients are often diagnosed at advanced stages, limiting effective treatment options. Chemotherapy, the common GIC recommendation, has ... ...

Abstract	Background: Gastrointestinal cancer (GIC) ranks as the highest cause of cancer-related deaths globally. GIC patients are often diagnosed at advanced stages, limiting effective treatment options. Chemotherapy, the common GIC recommendation, has significant disadvantages such as toxicity and adverse effects. Natural products contain substances with diverse pharmacological characteristics that promise for use in cancer therapeutics. In this study, the flower of renowned Asian medicinal plant, Shorea roxburghii was collected and extracted to investigate its phytochemical contents, antioxidant, and anticancer properties on GIC cells. Methods: The phytochemical contents of Shorea roxburghii extract were assessed using suitable methods. Phenolic content was determined through the Folin-Ciocalteu method, while flavonoids were quantified using the aluminum chloride (AlCl Results: Among the four different solvent extracts, ethyl acetate extract had the highest phenolic and flavonoid contents. Water extract exhibited the strongest reducing power and DPPH scavenging activity following by ethyl acetate. Interestingly, ethyl acetate extract demonstrated the highest inhibitory activity against three GIC cell lines (KKU-213B, HepG2, AGS) with IC Conclusions: This study highlights the potential of natural compounds in Shorea roxburghii in the development of more effective and safer anticancer agents as options for GIC as well as shedding light on new avenues for cancer treatment.
MeSH term(s)	Humans ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Cell Line, Tumor ; Gastrointestinal Neoplasms/drug therapy ; Apoptosis/drug effects ; Antioxidants/pharmacology ; Antineoplastic Agents, Phytogenic/pharmacology ; Cell Survival/drug effects ; Metabolomics ; Phytochemicals/pharmacology ; Flavonoids/pharmacology ; Flavonoids/analysis
Chemical Substances	Plant Extracts ; Antioxidants ; Antineoplastic Agents, Phytogenic ; Phytochemicals ; Flavonoids
Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Journal Article
ISSN	2662-7671
ISSN (online)	2662-7671
DOI	10.1186/s12906-024-04479-1
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Article ; Online: Alteration of STK11 Expression Associated With Cholangiocarcinoma Progression.

Sirithawat, Papitchaya / Jusakul, Apinya / Kongpetch, Sarinya / Thanee, Malinee / Srichanchara, Peerada / Panjaroensak, Suparada / Kimawaha, Phongsaran / Janthamala, Sutthiwan / Aphivatanasiri, Chaiwat / Techasen, Anchalee

In vivo (Athens, Greece)

2023 Volume 37, Issue 4, Page(s) 1638–1648

Abstract: Background/aim: Serine/threonine kinase 11 (STK11), a tumor suppressor, controls 5' AMP-activated protein kinase (AMPK) signaling in a variety of cellular functions. Mutated STK11 has been identified as a novel driver gene that promotes cancer ... ...

Abstract	Background/aim: Serine/threonine kinase 11 (STK11), a tumor suppressor, controls 5' AMP-activated protein kinase (AMPK) signaling in a variety of cellular functions. Mutated STK11 has been identified as a novel driver gene that promotes cancer progression. The purpose of this study was to investigate the alteration of STK11 and its correlation with clinicopathological data in cholangiocarcinoma (CCA). Materials and methods: Gene mutation and expression analyses were performed using cBioportal and Gene Expression Profiling Interactive Analysis version 2 (GEPIA2). qRT-PCR was performed to measure STK11 mRNA levels and immunohistochemistry was performed to investigate STK11 protein expression in CCA tissues. Results: The results from publicly available cancer datasets showed that 2.7% of CCA cases had STK11 mutations. Most of STK11 gene mutations are of the truncating type and result in low STK11 mRNA and protein expression. We detected a correlation between STK11 mutation status and the tendency for shorter patient survival. The results of qRT-PCR revealed that STK11 mRNA levels were statistically significantly lower in CCA patients with mutated STK11 compared to those with wild-type STK11 (p-value=0.013). Immunohistochemical staining showed high STK11 expression in 43.8% and low expression in 56.2% of CCA tissues examined. Low STK11 protein expression resulted in poor prognosis compared with high STK11 expression, especially in CCA papillary carcinoma. Univariate and multivariate analysis revealed that high STK11 expression was associated with a decreased hazard ratio of patient survival rates (HR=0.696, p-value=0.06 and HR=0.666, p-value=0.04, respectively). Conclusion: Alteration of STK11 mutational or mRNA/protein status might be used as a potential predictive biomarker for the prognosis of the clinical outcomes in CCA patients.
MeSH term(s)	Humans ; Cholangiocarcinoma/genetics ; Cholangiocarcinoma/pathology ; Prognosis ; Bile Ducts, Intrahepatic/metabolism ; Bile Duct Neoplasms/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; AMP-Activated Protein Kinase Kinases
Chemical Substances	RNA, Messenger ; STK11 protein, human (EC 2.7.11.1) ; AMP-Activated Protein Kinase Kinases (EC 2.7.11.3)
Language	English
Publishing date	2023-06-25
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13249
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Article ; Online: Inhibition of FGFR2 enhances chemosensitivity to gemcitabine in cholangiocarcinoma through the AKT/mTOR and EMT signaling pathways.

Jaidee, Rattanaporn / Kukongviriyapan, Veerapol / Senggunprai, Laddawan / Prawan, Auemduan / Jusakul, Apinya / Laphanuwat, Phatthamon / Kongpetch, Sarinya

Life sciences

2022 Volume 296, Page(s) 120427

Abstract: Aim: To investigate the oncogenic role of FGFR2 in carcinogenesis in cholangiocarcinoma (CCA) cells. In addition, the feasibility of using FGFR inhibitors in combination with standard chemotherapy was also explored for the chemosensitizing effect in CCA ...

Abstract	Aim: To investigate the oncogenic role of FGFR2 in carcinogenesis in cholangiocarcinoma (CCA) cells. In addition, the feasibility of using FGFR inhibitors in combination with standard chemotherapy was also explored for the chemosensitizing effect in CCA cells. Main methods: Five CCA cell lines were used to screen FGFR2 expression by Western immunoblotting. Two CCA cell lines, KKU-100 and KKU-213A, were knocked down of the FGFR2 gene using siRNA. Cell viability was assessed by the MTS cell proliferation assay. Reproductive cell death was assessed by clonogenic assay. The effects on cell migration and invasion were analyzed by the Transwell chamber method. Cell cycle analysis was performed by flow cytometry. Cell angiogenesis was assessed by HUVEC tube formation and human angiogenesis antibody array analysis. Proteins associated with proliferative and metastatic properties were evaluated by Western blotting. Key findings: Knockdown of FGFR2 suppressed cell growth and colony formation in CCA cells in association with G2/M cell cycle arrest and downregulation of STAT3, cyclin A and cyclin B1. Silencing FGFR2 enhanced the suppressive effect of gemcitabine (Gem) on cell migration and invasion. The combination of infigratinib, an FGFR inhibitor, and Gem, interrupted cell growth, migration, and invasion via downregulation of FGFR/AKT/mTOR pathways and the EMT-associated proteins vimentin and slug. Moreover, the combination also suppressed tube formation together with decreased expression of the proangiogenic factor VEGF. Significance: Inhibition of FGFRs by infigratinib enhanced the antitumor effect of Gem in CCA cells through downregulation of the FGFR/AKT/mTOR, FGFR/STAT3 and EMT signaling pathways.
MeSH term(s)	Antimetabolites, Antineoplastic/pharmacology ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/metabolism ; Bile Duct Neoplasms/pathology ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Cholangiocarcinoma/drug therapy ; Cholangiocarcinoma/metabolism ; Cholangiocarcinoma/pathology ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Drug Resistance, Neoplasm/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/physiology ; Humans ; Neovascularization, Pathologic/drug therapy ; Neovascularization, Pathologic/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/antagonists & inhibitors ; Receptor, Fibroblast Growth Factor, Type 2/genetics ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Antimetabolites, Antineoplastic ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R) ; MTOR protein, human (EC 2.7.1.1) ; FGFR2 protein, human (EC 2.7.10.1) ; Receptor, Fibroblast Growth Factor, Type 2 (EC 2.7.10.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-02-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120427
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Article: Therapeutic targeting of ARID1A and PI3K/AKT pathway alterations in cholangiocarcinoma.

Tessiri, Supharada / Techasen, Anchalee / Kongpetch, Sarinya / Namjan, Achira / Loilome, Watcharin / Chan-On, Waraporn / Thanan, Raynoo / Jusakul, Apinya

PeerJ

2022 Volume 10, Page(s) e12750

Abstract: Background: Genetic alterations in : Methods: Alterations of : Results: The analysis of a total of 795 CCA samples revealed that : Conclusion: These findings suggest a dependency of ARID1A-deficient CCA tumors with the activation of the PI3K/ ... ...

Abstract	Background: Genetic alterations in Methods: Alterations of Results: The analysis of a total of 795 CCA samples revealed that Conclusion: These findings suggest a dependency of ARID1A-deficient CCA tumors with the activation of the PI3K/AKT-pathway, and that they may be more vulnerable to selective AKT pathway inhibitors which can be used therapeutically.
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.12750
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Article ; Online: Serum Angiopoietin-Like Protein 4: A Potential Prognostic Biomarker for Prediction of Vascular Invasion and Lymph Node Metastasis in Cholangiocarcinoma Patients.

Aung, Tin May / Ciin, Mang Ngaih / Silsirivanit, Atit / Jusakul, Apinya / Lert-Itthiporn, Worachart / Proungvitaya, Tanakorn / Roytrakul, Sittiruk / Proungvitaya, Siriporn

Frontiers in public health

2022 Volume 10, Page(s) 836985

Abstract: Cholangiocarcinoma (CCA) is a tumor arising from cholangiocytes lining the bile ducts. Vascular invasion and lymph node metastasis are important prognostic factors for disease staging as well as clinical therapeutic decisions for CCA patients. In the ... ...

Abstract	Cholangiocarcinoma (CCA) is a tumor arising from cholangiocytes lining the bile ducts. Vascular invasion and lymph node metastasis are important prognostic factors for disease staging as well as clinical therapeutic decisions for CCA patients. In the present study, we applied CCA sera proteomic analysis to identify a potential biomarker for prognosis of CCA patients. Then, using bioinformatics tools, we identified angiopoietin-like protein 4 (ANGPTL4) which expressed highest signal intensity among candidate proteins in proteomic analysis of CCA sera. Expression of ANGPTL4 in CCA tissues was determined using immunohistochemistry. The results showed that ANGPTL4 was stained at higher level in CCA cells when compared with normal cholangiocytes. The high expression of ANGPTL4 was associated with lymph node metastasis and advanced tumor stage (
MeSH term(s)	Angiopoietin-Like Protein 4/blood ; Bile Duct Neoplasms/pathology ; Bile Ducts, Intrahepatic/pathology ; Biomarkers, Tumor ; Cholangiocarcinoma/pathology ; Humans ; Lymphatic Metastasis/diagnosis ; Prognosis ; Proteomics
Chemical Substances	ANGPTL4 protein, human ; Angiopoietin-Like Protein 4 ; Biomarkers, Tumor
Language	English
Publishing date	2022-03-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2022.836985
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Article: Establishment of a Potential Serum Biomarker Panel for the Diagnosis and Prognosis of Cholangiocarcinoma Using Decision Tree Algorithms.

Kimawaha, Phongsaran / Jusakul, Apinya / Junsawang, Prem / Thanan, Raynoo / Titapun, Attapol / Khuntikeo, Narong / Techasen, Anchalee

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 4

Abstract: Potential biomarkers which include S100 calcium binding protein A9 (S100A9), mucin 5AC (MUC5AC), transforming growth factor β1 (TGF-β1), and angiopoietin-2 have previously been shown to be effective for cholangiocarcinoma (CCA) diagnosis. This study ... ...

Abstract	Potential biomarkers which include S100 calcium binding protein A9 (S100A9), mucin 5AC (MUC5AC), transforming growth factor β1 (TGF-β1), and angiopoietin-2 have previously been shown to be effective for cholangiocarcinoma (CCA) diagnosis. This study attempted to measure the sera levels of these biomarkers compared with carbohydrate antigen 19-9 (CA19-9). A total of 40 serum cases of CCA, gastrointestinal cancers (non-CCA), and healthy subjects were examined by using an enzyme-linked immunosorbent assay. The panel of biomarkers was evaluated for their accuracy in diagnosing CCA and subsequently used as inputs to construct the decision tree (DT) model as a basis for binary classification. The findings showed that serum levels of S100A9, MUC5AC, and TGF-β1 were dramatically enhanced in CCA patients. In addition, 95% sensitivity and 90% specificity for CCA differentiation from healthy cases, and 70% sensitivity and 83% specificity for CCA versus non-CCA cases was obtained by a panel incorporating all five candidate biomarkers. In CCA patients with low CA19-9 levels, S100A9 might well be a complementary marker for improved diagnostic accuracy. The high levels of TGF-β1 and angiopoietin-2 were both associated with severe tumor stages and metastasis, indicating that they could be used as a reliable prognostic biomarkers panel for CCA patients. Furthermore, the outcome of the CCA burden from the Classification and Regression Tree (CART) algorithm using serial CA19-9 and S100A9 showed high diagnostic efficiency. In conclusion, results have shown the efficacy of CCA diagnosis and prognosis of the novel CCA-biomarkers panel examined herein, which may prove be useful in clinical settings.
Language	English
Publishing date	2021-03-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11040589
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Article: Inhibition of FGFR2 enhances chemosensitivity to gemcitabine in cholangiocarcinoma through the AKT/mTOR and EMT signaling pathways

Jaidee, Rattanaporn / Kukongviriyapan, Veerapol / Senggunprai, Laddawan / Prawan, Auemduan / Jusakul, Apinya / Laphanuwat, Phatthamon / Kongpetch, Sarinya

Life sciences. 2022 May 01, v. 296

2022

Abstract: To investigate the oncogenic role of FGFR2 in carcinogenesis in cholangiocarcinoma (CCA) cells. In addition, the feasibility of using FGFR inhibitors in combination with standard chemotherapy was also explored for the chemosensitizing effect in CCA cells. ...

Abstract	To investigate the oncogenic role of FGFR2 in carcinogenesis in cholangiocarcinoma (CCA) cells. In addition, the feasibility of using FGFR inhibitors in combination with standard chemotherapy was also explored for the chemosensitizing effect in CCA cells. Five CCA cell lines were used to screen FGFR2 expression by Western immunoblotting. Two CCA cell lines, KKU-100 and KKU-213A, were knocked down of the FGFR2 gene using siRNA. Cell viability was assessed by the MTS cell proliferation assay. Reproductive cell death was assessed by clonogenic assay. The effects on cell migration and invasion were analyzed by the Transwell chamber method. Cell cycle analysis was performed by flow cytometry. Cell angiogenesis was assessed by HUVEC tube formation and human angiogenesis antibody array analysis. Proteins associated with proliferative and metastatic properties were evaluated by Western blotting. Knockdown of FGFR2 suppressed cell growth and colony formation in CCA cells in association with G2/M cell cycle arrest and downregulation of STAT3, cyclin A and cyclin B1. Silencing FGFR2 enhanced the suppressive effect of gemcitabine (Gem) on cell migration and invasion. The combination of infigratinib, an FGFR inhibitor, and Gem, interrupted cell growth, migration, and invasion via downregulation of FGFR/AKT/mTOR pathways and the EMT-associated proteins vimentin and slug. Moreover, the combination also suppressed tube formation together with decreased expression of the proangiogenic factor VEGF. Inhibition of FGFRs by infigratinib enhanced the antitumor effect of Gem in CCA cells through downregulation of the FGFR/AKT/mTOR, FGFR/STAT3 and EMT signaling pathways.
Keywords	angiogenesis ; antibodies ; antineoplastic activity ; carcinogenesis ; cell cycle checkpoints ; cell death ; cell growth ; cell movement ; cell proliferation ; cell viability ; chemosensitization ; cyclins ; drug therapy ; fibroblast growth factor receptor 2 ; flow cytometry ; genes ; humans ; metastasis ; slugs ; vimentin
Language	English
Dates of publication	2022-0501
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2022.120427
Database	NAL-Catalogue (AGRICOLA)

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