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Article ; Online: Targeting the DLL/Notch Signaling Pathway in Cancer: Challenges and Advances in Clinical Development.

You, Weon-Kyoo / Schuetz, Thomas J / Lee, Sang Hoon

2022 Volume 22, Issue 1, Page(s) 3–11

Abstract: The DLL/Notch signaling pathway plays an important role in cancer as a key driver in maintaining cancer stemness and inducing tumor angiogenesis. Many different types of DLL/Notch inhibitors have been developed and explored in clinical trials for cancer ... ...

Abstract	The DLL/Notch signaling pathway plays an important role in cancer as a key driver in maintaining cancer stemness and inducing tumor angiogenesis. Many different types of DLL/Notch inhibitors have been developed and explored in clinical trials for cancer treatment, including small-molecule compounds to inhibit gamma-secretase and antibodies targeting Notch ligands or receptors. Despite promising efficacy of these inhibitors in preclinical studies, the overall clinical outcomes have been insufficient to advance to the next stage of clinical development primarily due to safety concerns or modest efficacy. To overcome the narrow therapeutic window of DLL/Notch inhibitors, diverse strategies for improving the balance between the safety and efficacy are currently being explored. Here, we review the clinical perspective and potential of DLL/Notch inhibitors as anticancer agents based on recent results from multiple clinical studies. An antibody specifically targeting Notch ligands or receptors may offer a better approach to reduce concerns about toxicity derived from broad-spectrum DLL/Notch blockers. In addition, combination therapy with an angiogenesis inhibitor targeting VEGF could be a better option for increasing anticancer efficacy. Taken together, the results of clinical trials suggest a bispecific antibody blocking the DLL/Notch and VEGF/VEGFR signaling pathways as a promising approach for effective anticancer treatment.
MeSH term(s)	Humans ; Vascular Endothelial Growth Factor A ; Ligands ; Receptors, Notch/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Signal Transduction
Chemical Substances	Vascular Endothelial Growth Factor A ; Ligands ; Receptors, Notch
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-22-0243
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Zs.A 5750: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Genome-Wide CRISPR/Cas9 Screening Unveils a Novel Target ATF7IP-SETDB1 Complex for Enhancing Difficult-to-Express Protein Production.

Kim, Su Hyun / Park, Jong-Ho / Shin, Sungwook / Shin, Seunghyeon / Chun, Dahyun / Kim, Yeon-Gu / Yoo, Jiseon / You, Weon-Kyoo / Lee, Jae Seong / Lee, Gyun Min

ACS synthetic biology

2024 Volume 13, Issue 2, Page(s) 634–647

Abstract: With the emerging novel biotherapeutics that are typically difficult-to-express (DTE), improvement is required for high-yield production. To identify novel targets that can enhance DTE protein production, we performed genome-wide fluorescence-activated ... ...

Abstract	With the emerging novel biotherapeutics that are typically difficult-to-express (DTE), improvement is required for high-yield production. To identify novel targets that can enhance DTE protein production, we performed genome-wide fluorescence-activated cell sorting (FACS)-based clustered regularly interspaced short palindromic repeats (CRISPR) knockout screening in bispecific antibody (bsAb)-producing Chinese hamster ovary (CHO) cells. The screen identified the two highest-scoring genes,
MeSH term(s)	Cricetinae ; Animals ; Cricetulus ; CRISPR-Cas Systems/genetics ; CHO Cells ; Genome ; Protein Processing, Post-Translational ; Antibodies, Monoclonal/metabolism
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ISSN	2161-5063
ISSN (online)	2161-5063
DOI	10.1021/acssynbio.3c00646
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Article: Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis.

You, Weon-Kyoo / Stallcup, William B

Cancers

2017 Volume 9, Issue 8

Abstract: Our research has identified several examples in which reduced VEGF-A binding to deficient vascular extracellular matrix leads to deficits in tumor vascularization and tumor growth: (1) germline ablation of collagen VI in the stroma of intracranial B16F10 ...

Abstract	Our research has identified several examples in which reduced VEGF-A binding to deficient vascular extracellular matrix leads to deficits in tumor vascularization and tumor growth: (1) germline ablation of collagen VI in the stroma of intracranial B16F10 melanomas; (2) knockdown of the Tks5 scaffolding protein in MDA-MB-231 mammary tumor cells; (3) germline ablation of NG2 proteoglycan in the stroma of MMTV-PyMT mammary tumors; and (4) myeloid-specific ablation of NG2 in the stroma of intracranial B16F10 melanomas. Tumor hypoxia is increased in each of the four types of experimental mice, accompanied by increases in total VEGF-A. However, while VEGF-A is highly associated with tumor blood vessels in control mice, it is much more diffusely distributed in tumors in all four sets of experimental mice, likely due to reduced extent of the vascular extracellular matrix. In parallel to lost VEGF-A localization, tumor vessels in each case have smaller diameters and are leakier than tumor vessels in control mice. Tumor growth is decreased as a result of this poor vascular function. The fact that the observed vascular changes occur in the absence of alterations in vascular density suggests that examination of vessel structure and function is more useful than vascular density for understanding the importance of angiogenesis in tumor progression.
Language	English
Publishing date	2017-07-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers9080097
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Article ; Online: Enhanced cell growth, production, and mAb quality produced in Chinese hamster ovary-K1 cells by supplementing polyamine in the media.

Kang, Da Eun / An, Yeong Bin / Kim, Yeunju / Ahn, Seawon / Kim, Young Jin / Lim, Jung Soo / Ryu, Soo Hyun / Choi, Hyoju / Yoo, Jiseon / You, Weon-Kyoo / Lee, Dong-Yup / Park, Junsoo / Hong, Minsun / Lee, Gyun Min / Baik, Jong Youn / Hong, Jong Kwang

Applied microbiology and biotechnology

2023 Volume 107, Issue 9, Page(s) 2855–2870

Abstract: Polyamines such as putrescine (PUT), spermidine (SPD), and spermine (SPM) are amine group-containing biomolecules that regulate multiple intracellular functions such as proliferation, differentiation, and stress response in mammalian cells. Although ... ...

Abstract	Polyamines such as putrescine (PUT), spermidine (SPD), and spermine (SPM) are amine group-containing biomolecules that regulate multiple intracellular functions such as proliferation, differentiation, and stress response in mammalian cells. Although these biomolecules can be generated intracellularly, lack of polyamine-synthesizing activity has occasionally been reported in a few mammalian cell lines such as Chinese hamster ovary (CHO)-K1; thus, polyamine supplementation in serum-free media is required to support cell growth and production. In the present study, the effects of biogenic polyamines PUT, SPD, and SPM in media on cell growth, production, metabolism, and antibody quality were explored in cultures of antibody-producing CHO-K1 cells. Polyamine withdrawal from media significantly suppressed cell growth and production. On the other hand, enhanced culture performance was achieved in polyamine-containing media conditions in a dose-dependent manner regardless of polyamine type. In addition, in polyamine-deprived medium, distinguishing metabolic features, such as enriched glycolysis and suppressed amino acid consumption, were observed and accompanied by higher heterogeneity of antibody quality compared with the optimal concentration of polyamines. Furthermore, an excessive concentration of polyamines negatively affected culture performance as well as antibody quality. Hence, the results suggest that polyamine-related metabolism needs to be further investigated and polyamines in cell growth media should be optimized as a controllable parameter in CHO cell culture bioprocessing. KEY POINTS: • Polyamine supplementation enhanced cell growth and production in a dose-dependent manner • Polyamine type and concentration in the media affected mAb quality • Optimizing polyamines in the media is suggested in CHO cell bioprocessing.
MeSH term(s)	Cricetinae ; Animals ; Polyamines/pharmacology ; Polyamines/metabolism ; CHO Cells ; Cricetulus ; Spermidine/metabolism ; Putrescine/pharmacology ; Putrescine/metabolism ; Spermine/metabolism ; Spermine/pharmacology ; Cell Proliferation
Chemical Substances	Polyamines ; Spermidine (U87FK77H25) ; Putrescine (V10TVZ52E4) ; Spermine (2FZ7Y3VOQX)
Language	English
Publishing date	2023-03-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	392453-1
ISSN	1432-0614 ; 0171-1741 ; 0175-7598
ISSN (online)	1432-0614
ISSN	0171-1741 ; 0175-7598
DOI	10.1007/s00253-023-12459-7
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Zs.A 2229: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models

Dong-Hoon Yeom / Yo-Seob Lee / Ilhwan Ryu / Sunju Lee / Byungje Sung / Han-Byul Lee / Dongin Kim / Jin-Hyung Ahn / Eunsin Ha / Yong-Soo Choi / Sang Hoon Lee / Weon-Kyoo You

International Journal of Molecular Sciences, Vol 22, Iss 241, p

2021 Volume 241

Abstract: Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in ... ...

Abstract	Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in xenograft models. A bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone and is currently being evaluated in a phase 1 clinical study of heavy chemotherapy or targeted therapy pre-treated cancer patients (ClinicalTrials.gov Identifier: NCT03292783). However, the effects of a combination of ABL001 and chemotherapy on tumor vessels and tumors are not known. Hence, the effects of ABL001, with or without paclitaxel and irinotecan were evaluated in human gastric or colon cancer xenograft models. The combination treatment synergistically inhibited tumor progression compared to each monotherapy. More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.
Keywords	anti-angiogenesis ; delta-like ligand ; irinotecan ; paclitaxel ; therapeutic antibody ; VEGF ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616 ; 610
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: N-terminal selective conjugation method widens the therapeutic window of antibody-drug conjugates by improving tolerability and stability.

Ko, Min Ji / Song, Daehae / Kim, Juhee / Kim, Jae Yong / Eom, Jaehyun / Sung, Byungje / Son, Yong-Gyu / Kim, Young Min / Lee, Sang Hoon / You, Weon-Kyoo / Jung, Jinwon

mAbs

2021 Volume 13, Issue 1, Page(s) 1914885

Abstract: Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and ...

Abstract	Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and narrow therapeutic windows. To overcome these limitations, we have applied reductive alkylation to develop a new type of ADC that has cytotoxic drugs conjugated to the N-terminal of an antibody through amine bonds introduced via reductive alkylation reactions (NTERM). To test whether the NTERM-conjugated ADCs can widen therapeutic windows, we synthesized three different ADCs by conjugating trastuzumab and monomethyl auristatin-F using three different methods, and compared their stability, efficacy, and toxicity. The NTERM-conjugated ADC was more stable
MeSH term(s)	Alkylation ; Animals ; Antineoplastic Agents, Immunological/chemistry ; Antineoplastic Agents, Immunological/pharmacokinetics ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/toxicity ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Drug Compounding ; Drug Stability ; Female ; Immunoconjugates/chemistry ; Immunoconjugates/pharmacokinetics ; Immunoconjugates/pharmacology ; Immunoconjugates/toxicity ; Oligopeptides/chemistry ; Oligopeptides/pharmacokinetics ; Oligopeptides/pharmacology ; Oligopeptides/toxicity ; Protein Stability ; Rats, Nude ; Rats, Sprague-Dawley ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Trastuzumab/chemistry ; Trastuzumab/pharmacokinetics ; Trastuzumab/pharmacology ; Trastuzumab/toxicity ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; Rats
Chemical Substances	Antineoplastic Agents, Immunological ; Immunoconjugates ; Oligopeptides ; monomethylauristatin F ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2021-04-27
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2537838-7
ISSN	1942-0870 ; 1942-0870
ISSN (online)	1942-0870
ISSN	1942-0870
DOI	10.1080/19420862.2021.1914885
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: High delta-like ligand 4 expression correlates with a poor clinical outcome in gastric cancer.

Kim, Youjin / Byeon, Sun-Ju / Hur, Joonyoung / Lee, Kangkook / Kim, Dongin / Ahn, Jin-Hyung / Lee, Sang Hoon / You, Weon-Kyoo / Kim, Seung Tae / Park, Se Hoon / Kang, Won Ki / Kim, Kyoung-Mee / Lee, Jeeyun

Journal of Cancer

2019 Volume 10, Issue 14, Page(s) 3172–3178

Abstract: ... ...

Abstract	Background
Language	English
Publishing date	2019-06-02
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.30257
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Article ; Online: Grabody B, an IGF1 receptor-based shuttle, mediates efficient delivery of biologics across the blood-brain barrier.

Shin, Jung-Won / An, Sungwon / Kim, Dongin / Kim, Hyunjoo / Ahn, Jinhyung / Eom, Jaehyun / You, Weon-Kyoo / Yun, Hyesu / Lee, Bora / Sung, Byungje / Jung, Jinwon / Kim, Sehyun / Son, Yonggyu / Sung, Eunsil / Lee, Hanbyul / Lee, Suyeon / Song, Daehae / Pak, Youngdon / Sandhu, Jagdeep K /

Haqqani, Arsalan S / Stanimirovic, Danica B / Yoo, Jiseon / Kim, Donghwan / Maeng, Sungho / Lee, Jeonghun / Lee, Sang Hoon

Cell reports methods

2022 Volume 2, Issue 11, Page(s) 100338

Abstract: Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular ... ...

Abstract	Effective delivery of therapeutics to the brain is challenging. Molecular shuttles use receptors expressed on brain endothelial cells to deliver therapeutics. Antibodies targeting transferrin receptor (TfR) have been widely developed as molecular shuttles. However, the TfR-based approach raises concerns about safety and developmental burden. Here, we report insulin-like growth factor 1 receptor (IGF1R) as an ideal target for the molecular shuttle. We also describe Grabody B, an antibody against IGF1R, as a molecular shuttle. Grabody B has broad cross-species reactivity and does not interfere with IGF1R-mediated signaling. We demonstrate that administration of Grabody B-fused anti-alpha-synuclein (α-Syn) antibody induces better improvement in neuropathology and behavior in a Parkinson's disease animal model than the therapeutic antibody alone due to its superior serum pharmacokinetics and enhanced brain exposure. The results indicate that IGF1R is an ideal shuttle target and Grabody B is a safe and efficient molecular shuttle.
MeSH term(s)	Animals ; Blood-Brain Barrier/metabolism ; Biological Products/metabolism ; Endothelial Cells/metabolism ; Brain/metabolism ; Biological Transport ; Antibodies/metabolism
Chemical Substances	Biological Products ; Antibodies
Language	English
Publishing date	2022-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2667-2375
ISSN (online)	2667-2375
DOI	10.1016/j.crmeth.2022.100338
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Article ; Online: NG2 Proteoglycan-Dependent Contributions of Pericytes and Macrophages to Brain Tumor Vascularization and Progression.

Stallcup, William B / You, Weon-Kyoo / Kucharova, Karolina / Cejudo-Martin, Pilar / Yotsumoto, Fusanori

Microcirculation (New York, N.Y. : 1994)

2016 Volume 23, Issue 2, Page(s) 122–133

Abstract: The NG2 proteoglycan promotes tumor growth as a component of both tumor and stromal cells. Using intracranial, NG2-negative B16F10 melanomas, we have investigated the importance of PC and Mac NG2 in brain tumor progression. Reduced melanoma growth in Mac- ...

Abstract	The NG2 proteoglycan promotes tumor growth as a component of both tumor and stromal cells. Using intracranial, NG2-negative B16F10 melanomas, we have investigated the importance of PC and Mac NG2 in brain tumor progression. Reduced melanoma growth in Mac-NG2ko and PC-NG2ko mice demonstrates the importance of NG2 in both stromal compartments. In each genotype, the loss of PC-endothelial cell interaction diminishes the formation of endothelial junctions and assembly of the basal lamina. Tumor vessels in Mac-NG2ko mice have smaller diameters, reduced patency, and increased leakiness compared to PC-NG2ko mice, thus decreasing tumor blood supply and increasing hypoxia. While the reduced PC interaction with endothelial cells in PC-NG2ko mice results from the loss of PC activation of β1 integrin signaling in endothelial cells, reduced PC-endothelial cell interaction in Mac-NG2ko mice results from 90% reduced Mac recruitment. The absence of Mac-derived signals in Mac-NG2ko mice causes the loss of PC association with endothelial cells. Reduced Mac recruitment may be due to diminished activation of integrins in the absence of NG2, causing decreased Mac interaction with endothelial adhesion molecules that are needed for extravasation. These results reflect the complex interplay that occurs between Mac, PC, and endothelial cells during tumor vascularization.
MeSH term(s)	Animals ; Antigens/genetics ; Antigens/metabolism ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Macrophages/metabolism ; Macrophages/pathology ; Mice ; Mice, Knockout ; Neoplasm Proteins/genetics ; Neoplasm Proteins/metabolism ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/pathology ; Pericytes/metabolism ; Pericytes/pathology ; Proteoglycans/genetics ; Proteoglycans/metabolism
Chemical Substances	Antigens ; Neoplasm Proteins ; Proteoglycans ; chondroitin sulfate proteoglycan 4
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1217758-1
ISSN	1549-8719 ; 1073-9688
ISSN (online)	1549-8719
ISSN	1073-9688
DOI	10.1111/micc.12251
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Zs.A 4187: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models.

Yeom, Dong-Hoon / Lee, Yo-Seob / Ryu, Ilhwan / Lee, Sunju / Sung, Byungje / Lee, Han-Byul / Kim, Dongin / Ahn, Jin-Hyung / Ha, Eunsin / Choi, Yong-Soo / Lee, Sang Hoon / You, Weon-Kyoo

International journal of molecular sciences

2020 Volume 22, Issue 1

Abstract	Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in xenograft models. A bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone and is currently being evaluated in a phase 1 clinical study of heavy chemotherapy or targeted therapy pre-treated cancer patients (ClinicalTrials.gov Identifier: NCT03292783). However, the effects of a combination of ABL001 and chemotherapy on tumor vessels and tumors are not known. Hence, the effects of ABL001, with or without paclitaxel and irinotecan were evaluated in human gastric or colon cancer xenograft models. The combination treatment synergistically inhibited tumor progression compared to each monotherapy. More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.
MeSH term(s)	Adaptor Proteins, Signal Transducing/antagonists & inhibitors ; Animals ; Antibodies, Bispecific/pharmacology ; Antibodies, Bispecific/therapeutic use ; Apoptosis/drug effects ; Calcium-Binding Proteins/antagonists & inhibitors ; Cell Line, Tumor ; Disease Models, Animal ; Disease Progression ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Mice ; Neovascularization, Pathologic/drug therapy ; Niacinamide/analogs & derivatives ; Niacinamide/pharmacology ; Niacinamide/therapeutic use ; Pyrazoles/pharmacology ; Pyrazoles/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Xenograft Model Antitumor Assays
Chemical Substances	Adaptor Proteins, Signal Transducing ; Antibodies, Bispecific ; Calcium-Binding Proteins ; DLL4 protein, human ; Pyrazoles ; Vascular Endothelial Growth Factor A ; asciminib ; Niacinamide (25X51I8RD4)
Language	English
Publishing date	2020-12-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22010241
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