LIVIVO - Search results -

Search results

Result 1 - 10 of total 12

Search options

Article: Tumor Suppressor Candidate 2 (TUSC2): Discovery, Functions, and Cancer Therapy.

Arrigo, Austin / Regua, Angelina T / Najjar, Mariana K / Lo, Hui-Wen

2023 Volume 15, Issue 9

Abstract: Tumor Suppressor Candidate 2 (TUSC2) was first discovered as a potential tumor suppressor gene residing in the frequently deleted 3p21.3 chromosomal region. Since its discovery, TUSC2 has been found to play vital roles in normal immune function, and ... ...

Abstract	Tumor Suppressor Candidate 2 (TUSC2) was first discovered as a potential tumor suppressor gene residing in the frequently deleted 3p21.3 chromosomal region. Since its discovery, TUSC2 has been found to play vital roles in normal immune function, and TUSC2 loss is associated with the development of autoimmune diseases as well as impaired responses within the innate immune system. TUSC2 also plays a vital role in regulating normal cellular mitochondrial calcium movement and homeostasis. Moreover, TUSC2 serves as an important factor in premature aging. In addition to TUSC2's normal cellular functions, TUSC2 has been studied as a tumor suppressor gene that is frequently deleted or lost in a multitude of cancers, including glioma, sarcoma, and cancers of the lung, breast, ovaries, and thyroid. TUSC2 is frequently lost in cancer due to somatic deletion within the 3p21.3 region, transcriptional inactivation via TUSC2 promoter methylation, post-transcriptional regulation via microRNAs, and post-translational regulation via polyubiquitination and proteasomal degradation. Additionally, restoration of TUSC2 expression promotes tumor suppression, eventuating in decreased cell proliferation, stemness, and tumor growth, as well as increased apoptosis. Consequently, TUSC2 gene therapy has been tested in patients with non-small cell lung cancer. This review will focus on the current understanding of TUSC2 functions in both normal and cancerous tissues, mechanisms of TUSC2 loss, TUSC2 cancer therapeutics, open questions, and future directions.
Language	English
Publishing date	2023-04-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15092455
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article: RET signaling pathway and RET inhibitors in human cancer.

Regua, Angelina T / Najjar, Mariana / Lo, Hui-Wen

Frontiers in oncology

2022 Volume 12, Page(s) 932353

Abstract: Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer ... ...

Abstract	Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer types and are most prevalent in thyroid carcinomas and non-small cell lung cancer (NSCLC). In other tumor types such as breast cancer and salivary gland carcinomas, RET alterations can be found at lower frequencies. Aberrant RET activity is associated with poor prognosis of thyroid and lung carcinoma patients, and is strongly correlated with increased risk of distant metastases. RET aberrations encompass a variety of genomic or proteomic alterations, most of which confer constitutive activation of RET. Activating RET alterations, such as point mutations or gene fusions, enhance activity of signaling pathways downstream of RET, namely PI3K/AKT, RAS/RAF, MAPK, and PLCγ pathways, to promote cell proliferation, growth, and survival. Given the important role that mutant RET plays in metastatic cancers, significant efforts have been made in developing inhibitors against RET kinase activity. These efforts have led to FDA approval of Selpercatinib and Pralsetinib for NSCLC, as well as, additional selective RET inhibitors in preclinical and clinical testing. This review covers the current biological understanding of RET signaling, the impact of RET hyperactivity on tumor progression in multiple tumor types, and RET inhibitors with promising preclinical and clinical efficacy.
Language	English
Publishing date	2022-07-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.932353
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Antibody-Drug Conjugates for the Treatment of HER2-Positive Breast Cancer.

Najjar, Mariana K / Manore, Sara G / Regua, Angelina T / Lo, Hui-Wen

Genes

2022 Volume 13, Issue 11

Abstract: Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20-30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive ... ...

Abstract	Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20-30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted monoclonal antibodies with the potent cytotoxic effects of various small molecules, such as tubulin inhibitors and topoisomerase inhibitors. To date, two HER2-targeting ADCs have been approved by the FDA for the treatment of HER2-positive breast cancer: Ado-trastuzumab emtansine (T-DM1; Kadcyla
MeSH term(s)	Humans ; Female ; Ado-Trastuzumab Emtansine/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Maytansine/therapeutic use ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Immunoconjugates/therapeutic use ; Immunoconjugates/pharmacology ; Antineoplastic Agents/therapeutic use ; Antibodies, Monoclonal
Chemical Substances	Ado-Trastuzumab Emtansine (SE2KH7T06F) ; Maytansine (14083FR882) ; Antibodies, Monoclonal, Humanized ; Immunoconjugates ; Antineoplastic Agents ; Antibodies, Monoclonal
Language	English
Publishing date	2022-11-08
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13112065
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Trk receptor tyrosine kinases in metastasis and cancer therapy.

Regua, Angelina T / Doheny, Daniel / Arrigo, Austin / Lo, Hui-Wen

Discovery medicine

2020 Volume 28, Issue 154, Page(s) 195–203

Abstract: Tropomyosin receptor kinases (TRKs) were first identified in 1986 when NTRK1 was discovered as part of an oncogenic fusion gene in colorectal cancer and the discovery of NTRK2 and NTRK3 followed shortly after. In the decades since their discovery, TRKs ... ...

Abstract	Tropomyosin receptor kinases (TRKs) were first identified in 1986 when NTRK1 was discovered as part of an oncogenic fusion gene in colorectal cancer and the discovery of NTRK2 and NTRK3 followed shortly after. In the decades since their discovery, TRKs have been implicated in a number of cancer types due to their canonical roles in promoting cell proliferation and survival. Studies have shown that increased expression and/or activity of TRKs can be indicative of metastatic potential, suggesting that TRKs can be therapeutic targets in aggressive cancers. While predominantly known for forming oncogenic gene fusions, aberrant alternative splicing does not appear to be a prerequisite for TRK-mediated metastasis. However, expression and activity of each TRK can confer either a pro-apoptotic or pro-survival effect in different tissue types, predicting a complex treatment paradigm for patients exhibiting abnormalities in TRK expression or activity. While preclinical studies on TRK kinases continue, clinical advances in TRK inhibition were achieved upon Larotrectinib (Vitrakvi) becoming the first FDA-approved pan-TRK inhibitor. This review summarizes findings regarding TRK expression and activity in different tissue types, the biological impact of aberrant TRK signaling, and the potential for additional inhibitor design.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Clinical Trials as Topic ; Humans ; Neoplasm Metastasis ; Neoplasms/enzymology ; Neoplasms/pathology ; Neoplasms/therapy ; Receptor Protein-Tyrosine Kinases/metabolism ; Signal Transduction
Chemical Substances	Biomarkers, Tumor ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2020-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	1944-7930
ISSN (online)	1944-7930
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Transgenic mouse models of breast cancer.

Regua, Angelina T / Arrigo, Austin / Doheny, Daniel / Wong, Grace L / Lo, Hui-Wen

Cancer letters

2021 Volume 516, Page(s) 73–83

Abstract: Transgenic breast cancer mouse models are critical tools for preclinical studies of human breast cancer. Genetic editing of the murine mammary gland allows for modeling of abnormal genetic events frequently found in human breast cancers. Genetically ... ...

Abstract	Transgenic breast cancer mouse models are critical tools for preclinical studies of human breast cancer. Genetic editing of the murine mammary gland allows for modeling of abnormal genetic events frequently found in human breast cancers. Genetically engineered mouse models (GEMMs) of breast cancer employ tissue-specific genetic manipulation for tumorigenic induction within the mammary tissue. Under the transcriptional control of mammary-specific promoters, transgenic mouse models can simulate spontaneous mammary tumorigenesis by expressing one or more putative oncogenes, such as MYC, HRAS, and PIK3CA. Alternatively, the Cre-Lox system allows for tissue-specific deletion of tumor suppressors, such as p53, Rb1, and Brca1, or specific knock-in of putative oncogenes. Thus, GEMMs can be designed to implement one or more genetic events to induce mammary tumorigenesis. Features of GEMMs, such as age of transgene expression, breeding quality, tumor latency, histopathological characteristics, and propensity for local and distant metastasis, are variable and strain-dependent. This review aims to summarize currently available transgenic breast cancer mouse models that undergo spontaneous mammary tumorigenesis upon genetic manipulation, their varying characteristics, and their individual genetic manipulations that model aberrant signaling events observed in human breast cancers.
MeSH term(s)	Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Disease Models, Animal ; Female ; Humans ; Mammary Glands, Animal/pathology ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Mice, Transgenic/genetics
Language	English
Publishing date	2021-06-06
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2021.05.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1177: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Correction: Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis.

Doheny, Daniel / Sirkisoon, Sherona / Carpenter, Richard L / Aguayo, Noah Reeve / Regua, Angelina T / Anguelov, Marlyn / Manore, Sara G / Arrigo, Austin / Jalboush, Sara Abu / Wong, Grace L / Yu, Yang / Wagner, Calvin J / Chan, Michael / Ruiz, Jimmy / Thomas, Alexandra / Strowd, Roy / Lin, Jiayuh / Lo, Hui-Wen

Oncogene

2024

Language	English
Publishing date	2024-04-27
Publishing country	England
Document type	Published Erratum
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-024-03046-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2218: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Breast cancer extracellular vesicles-derived miR-1290 activates astrocytes in the brain metastatic microenvironment via the FOXA2→CNTF axis to promote progression of brain metastases.

Sirkisoon, Sherona R / Wong, Grace L / Aguayo, Noah R / Doheny, Daniel L / Zhu, Dongqin / Regua, Angelina T / Arrigo, Austin / Manore, Sara G / Wagner, Calvin / Thomas, Alexandra / Singh, Ravi / Xing, Fei / Jin, Guangxu / Watabe, Kounosuke / Lo, Hui-Wen

Cancer letters

2022 Volume 540, Page(s) 215726

Abstract: Mechanisms underlying breast cancer brain metastasis (BCBM) are still unclear. In this study, we observed that extracellular vesicles (EVs) secreted from breast cancer cells with increased expression of tGLI1, a BCBM-promoting transcription factor, ... ...

Abstract	Mechanisms underlying breast cancer brain metastasis (BCBM) are still unclear. In this study, we observed that extracellular vesicles (EVs) secreted from breast cancer cells with increased expression of tGLI1, a BCBM-promoting transcription factor, strongly activated astrocytes. EV-derived microRNA/miRNA microarray revealed tGLI1-positive breast cancer cells highly secreted miR-1290 and miR-1246 encapsulated in EVs. Genetic knockin/knockout studies established a direct link between tGLI1 and both miRNAs. Datamining and analysis of patient samples revealed that BCBM patients had more circulating EV-miRs-1290/1246 than those without metastasis. Ectopic expression of miR-1290 or miR-1246 strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-1290- or miR-1246-overexpressing astrocytes promoted mammospheres. Furthermore, miRs-1290/1246 suppressed expression of FOXA2 transcription repressor, leading to CNTF cytokine secretion and subsequent activation of astrocytes. Finally, we conducted a mouse study to demonstrate that astrocytes overexpressing miR-1290, but not miR-1246, enhanced intracranial colonization and growth of breast cancer cells. Collectively, our findings demonstrate, for the first time, that breast cancer EV-derived miR-1290 and miR-1246 activate astrocytes in the brain metastatic microenvironment and that EV-derived miR-1290 promotes progression of brain metastases through the novel EV-miR-1290→FOXA2→CNTF signaling axis.
MeSH term(s)	Animals ; Astrocytes/metabolism ; Brain/pathology ; Brain Neoplasms/secondary ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Ciliary Neurotrophic Factor/metabolism ; Extracellular Vesicles/metabolism ; Female ; Hepatocyte Nuclear Factor 3-beta/genetics ; Hepatocyte Nuclear Factor 3-beta/metabolism ; Humans ; Mice ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Transcription Factors/metabolism ; Tumor Microenvironment
Chemical Substances	Ciliary Neurotrophic Factor ; FOXA2 protein, human ; MIRN1290 microRNA, human ; MicroRNAs ; Transcription Factors ; Hepatocyte Nuclear Factor 3-beta (135845-92-0)
Language	English
Publishing date	2022-05-16
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2022.215726
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1177: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: NEDD4 degrades TUSC2 to promote glioblastoma progression.

Rimkus, Tadas K / Arrigo, Austin B / Zhu, Dongqin / Carpenter, Richard L / Sirkisoon, Sherona / Doheny, Daniel / Regua, Angelina T / Wong, Grace L / Manore, Sara / Wagner, Calvin / Lin, Hui-Kuan / Jin, Guangxu / Ruiz, Jimmy / Chan, Michael / Debinski, Waldemar / Lo, Hui-Wen

Cancer letters

2022 Volume 531, Page(s) 124–135

Abstract: Whether tumor suppressor candidate 2 (TUSC2) plays an important role in glioblastoma (GBM) progression is largely unknown. Whether TUSC2 undergoes polyubiquitination is unknown. Herein, we report that TUSC2 protein expression is reduced/lost in GBM ... ...

Abstract	Whether tumor suppressor candidate 2 (TUSC2) plays an important role in glioblastoma (GBM) progression is largely unknown. Whether TUSC2 undergoes polyubiquitination is unknown. Herein, we report that TUSC2 protein expression is reduced/lost in GBM compared to normal brain due to protein destabilization; TUSC2 mRNA is equally expressed in both tissues. NEDD4 E3 ubiquitin ligase polyubiquitinates TUSC2 at residue K71, and the TUSC2-K71R mutant is resistant to NEDD4-mediated proteasomal degradation. Analysis of GBM specimens showed NEDD4 protein is highly expressed in GBM and the level is inversely correlated with TUSC2 protein levels. Furthermore, TUSC2 restoration induces apoptosis and inhibits patient-derived glioma stem cells (PD-GSCs) in vitro and in vivo. Conversely, TUSC2-knockout promotes PD-GSCs in vitro and in vivo. RNA-Seq analysis and subsequent validations showed GBM cells with TUSC2-knockout expressed increased Bcl-xL and were more resistant to apoptosis induced by a Bcl-xL-specific BH3 mimetic. A TUSC2-knockout gene signature created from the RNA-seq data predicts poor patient survival. Together, these findings establish that NEDD4-mediated polyubiquitination is a novel mechanism for TUSC2 degradation in GBM and that TUSC2 loss promotes GBM progression in part through Bcl-xL upregulation.
MeSH term(s)	Brain Neoplasms/pathology ; Cell Line, Tumor ; Genes, Tumor Suppressor ; Glioblastoma/pathology ; Glioma/genetics ; Humans ; Tumor Suppressor Proteins/genetics ; Ubiquitination
Chemical Substances	TUSC2 protein, human ; Tumor Suppressor Proteins
Language	English
Publishing date	2022-02-12
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2022.01.029
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1177: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: TrkA Interacts with and Phosphorylates STAT3 to Enhance Gene Transcription and Promote Breast Cancer Stem Cells in Triple-Negative and HER2-Enriched Breast Cancers.

Regua, Angelina T / Aguayo, Noah R / Jalboush, Sara Abu / Doheny, Daniel L / Manore, Sara G / Zhu, Dongqin / Wong, Grace L / Arrigo, Austin / Wagner, Calvin J / Yu, Yang / Thomas, Alexandra / Chan, Michael D / Ruiz, Jimmy / Jin, Guangxu / Strowd, Roy / Sun, Peiqing / Lin, Jiayuh / Lo, Hui-Wen

Cancers

2021 Volume 13, Issue 10

Abstract: JAK2-STAT3 and TrkA signaling pathways have been separately implicated in aggressive breast cancers; however, whether they are co-activated or undergo functional interaction has not been thoroughly investigated. Herein we report, for the first time that ... ...

Abstract	JAK2-STAT3 and TrkA signaling pathways have been separately implicated in aggressive breast cancers; however, whether they are co-activated or undergo functional interaction has not been thoroughly investigated. Herein we report, for the first time that STAT3 and TrkA are significantly co-overexpressed and co-activated in triple-negative breast cancer (TNBC) and HER2-enriched breast cancer, as shown by immunohistochemical staining and data mining. Through immunofluorescence staining-confocal microscopy and immunoprecipitation-Western blotting, we found that TrkA and STAT3 co-localize and physically interact in the cytoplasm, and the interaction is dependent on STAT3-Y705 phosphorylation. TrkA-STAT3 interaction leads to STAT3 phosphorylation at Y705 by TrkA in breast cancer cells and cell-free kinase assays, indicating that STAT3 is a novel substrate of TrkA. β-NGF-mediated TrkA activation induces TrkA-STAT3 interaction, STAT3 nuclear transport and transcriptional activity, and the expression of STAT3 target genes,
Language	English
Publishing date	2021-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13102340
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Combined inhibition of JAK2-STAT3 and SMO-GLI1/tGLI1 pathways suppresses breast cancer stem cells, tumor growth, and metastasis.

Oncogene

2020 Volume 39, Issue 42, Page(s) 6589–6605

Abstract: Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are particularly aggressive and associated with unfavorable prognosis. TNBC lacks effective treatments. HER2-positive tumors have treatment options but often acquire resistance to HER2- ... ...

Abstract	Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are particularly aggressive and associated with unfavorable prognosis. TNBC lacks effective treatments. HER2-positive tumors have treatment options but often acquire resistance to HER2-targeted therapy after initial response. To address these challenges, we determined whether novel combinations of JAK2-STAT3 and SMO-GLI1/tGLI1 inhibitors synergistically target TNBC and HER2 breast cancer since these two pathways are concurrently activated in both tumor types and enriched in metastatic tumors. Herein, we show that novel combinations of JAK2 inhibitors (ruxolitinib and pacritinib) with SMO inhibitors (vismodegib and sonidegib) synergistically inhibited in vitro growth of TNBC and HER2-positive trastuzumab-resistant BT474-TtzmR cells. Synergy was also observed against breast cancer stem cells. To determine if the combination is efficacious in inhibiting metastasis, we treated mice with intracardially inoculated TNBC cells and found the combination to inhibit lung and liver metastases, and prolong host survival without toxicity. The combination inhibited orthotopic growth, VEGF-A expression, and tumor vasculature of both TNBC and HER2-positive trastuzumab-refractory breast cancer. Lung metastasis of orthotopic BT474-TtzmR xenografts was suppressed by the combination. Together, our results indicated that dual targeting of JAK2 and SMO resulted in synergistic suppression of breast cancer growth and metastasis, thereby supporting future clinical testing.
MeSH term(s)	Alternative Splicing ; Anilides/pharmacology ; Anilides/therapeutic use ; Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biphenyl Compounds/pharmacology ; Biphenyl Compounds/therapeutic use ; Bridged-Ring Compounds/pharmacology ; Bridged-Ring Compounds/therapeutic use ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Drug Synergism ; Female ; Humans ; Janus Kinase 2/antagonists & inhibitors ; Janus Kinase 2/metabolism ; Mice ; Neoplasm Metastasis/drug therapy ; Neoplasm Metastasis/pathology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/pathology ; Nitriles ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Pyridines/pharmacology ; Pyridines/therapeutic use ; Pyrimidines/pharmacology ; Pyrimidines/therapeutic use ; Receptor, ErbB-2/metabolism ; STAT3 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Smoothened Receptor/antagonists & inhibitors ; Smoothened Receptor/metabolism ; Trastuzumab/pharmacology ; Trastuzumab/therapeutic use ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology ; Xenograft Model Antitumor Assays ; Zinc Finger Protein GLI1/genetics ; Zinc Finger Protein GLI1/metabolism
Chemical Substances	11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene ; Anilides ; Biphenyl Compounds ; Bridged-Ring Compounds ; GLI1 protein, human ; HhAntag691 ; Nitriles ; Protein Kinase Inhibitors ; Pyrazoles ; Pyridines ; Pyrimidines ; SMO protein, human ; STAT3 Transcription Factor ; STAT3 protein, human ; Smoothened Receptor ; Zinc Finger Protein GLI1 ; sonidegib (0RLU3VTK5M) ; ruxolitinib (82S8X8XX8H) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2020-09-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-020-01454-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2218: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito