PG545, A Heparanase Inhibitor, Inhibits Pancreatic Cancer Tumor Cell Proliferation in Vitro and in Vivo

2012 ◽  
Vol 172 (2) ◽  
pp. 341
Author(s):  
K.T. Ostapoff ◽  
N. Awasthi ◽  
R.E. Schwarz ◽  
R.A. Brekken
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Cancer Tumor ◽  
Proliferation In Vitro

ErbB3 Inhibitory Surrobodies Inhibit Tumor Cell Proliferation In Vitro and In Vivo

2012 ◽  
Vol 11 (7) ◽  
pp. 1411-1420 ◽  
Author(s):  
Pamela K. Foreman ◽  
Medini Gore ◽  
Philip A. Kobel ◽  
Li Xu ◽  
Helena Yee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Proliferation In Vitro ◽  
Inhibit Tumor Cell Proliferation

scholarly journals Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo

2006 ◽  
Vol 5 (1) ◽  
pp. 160-169 ◽  
Author(s):  
Holly K. Koblish ◽  
Shuyuan Zhao ◽  
Carol F. Franks ◽  
Robert R. Donatelli ◽  
Rose M. Tominovich ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Human Tumor ◽  
Tumor Cell Proliferation ◽  
Human Tumor Cell ◽  
Proliferation In Vitro

Use of PG545, a heparanase inhibitor, to inhibit pancreatic cancer tumor cell proliferation and migration in vitro and in vivo.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 234-234
Author(s):  
Katherine Ostapoff ◽  
Niranjan Awasthi ◽  
Roderich Schwarz ◽  
Rolf A. Brekken
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

234 Background: Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy, as result there is an ongoing search to find novel effective strategies. Resistance is due in part to the high proportion of stromal tissue within the primary tumor. This intricate ECM (extracellular matrix) includes heparan-sulfate glycosaminoglycans which participate in tumor progression, angiogenesis and metastasis. PG545 is a heparanase inhibitor developed to target these pathways. Methods: In vitro cell viability assays were performed using WST-1 reagent and migration was evaluated using T- scratch assay. Animal survival experiments were performed by intraperitoneal injection of AsPC-1 (0.75 x 10^6) cells. In vivo tumor growth experiments were performed by orthotopic injection of PanO2-HY (5x10^5) cells. Results: PG545 significantly inhibited proliferation of tumor cells (AsPC-1 and PanO2) and fibroblasts (WI-38). PG545 caused only a modest inhibition in endothelial cell (HUVECs) proliferation. Migration was significantly inhibited by 1 µM PG545 in AsPC-1 and PanO2 after 12 hours. In a metastatic model of pancreatic cancer, treatment with PG545 (10 mg/kg 1st week, 5 mg/kg 2nd week) improved survival (35 days) compared to saline (22 days) and gemcitabine (28 days). In an immunocompetent orthotopic model, mice treated with PG545 (5 mg/kg twice weekly) had significantly decreased tumor weights after 3 weeks of therapy (p=0.002). Total metastatic events were also reduced in PG545 compared to gemcitabine and control treatment in the PanO2 model. Conclusions: PG545 inhibits tumor cell proliferation and migration in vitro and prolongs survival and inhibits tumor growth in vivo. Additionally it inhibits metastasis in vivo. Further studies are underway to elucidate the mechanism of inhibition and changes to pancreatic tumor microenvironment.

scholarly journals The human vault RNA enhances tumorigenesis and chemoresistance through the lysosome

2020 ◽  
Author(s):  
Iolanda Ferro ◽  
Jacopo Gavini ◽  
Lisamaria Bracher ◽  
Marc Landolfo ◽  
Daniel Candinas ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Chemotherapy Resistance ◽  
Autophagic Flux ◽  
Tumor Cell Proliferation ◽  
Apoptosis Resistance ◽  
Knock Out ◽  
Vault Rna

AbstractThe small non-coding vault RNA (vtRNA) 1-1 has been shown to confer apoptosis resistance in several malignant cell lines and also to modulate the autophagic flux in hepatocytes, thus highlighting its pro-survival role. Here we describe a new function of vtRNA1-1 in regulating in vitro and in vivo tumor cell proliferation, tumorigenesis and chemoresistance. By activating extracellular signal-regulated kinases (ERK 1/2), vtRNA1-1 knock-out (KO) inhibits transcription factor EB (TFEB), leading to a downregulation of the coordinated lysosomal expression and regulation (CLEAR) network genes and lysosomal compartment dysfunction. Pro-tumorigenic pathways dysregulation and decreased lysosome functionality potentiate the anticancer effect of conventional targeted cancer drugs in the absence of vtRNA1-1. Finally, vtRNA1-1 KO-reduced lysosomotropism, together with a higher intracellular compound availability, significantly reduced tumor cell proliferation in vitro and in vivo. These findings reveal the role of vtRNA1-1 in ensuring intracellular catabolic compartment stability and functionality, suggesting its importance in lysosome-mediated chemotherapy resistance.

scholarly journals Assessment of Tracer 99mTc(V)-DMSA Uptake as a Measure of Tumor Cell Proliferation In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e54361 ◽  
Author(s):  
Fatma J. Al-Saeedi ◽  
Princy M. Mathew ◽  
Yunus A. Luqmani
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Proliferation In Vitro

scholarly journals NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Atsushi Takatori ◽  
Shamim Hossain ◽  
Atsushi Ogura ◽  
Jesmin Akter ◽  
Yohko Nakamura ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Inhibitory Effect ◽  
Tumor Cell Proliferation ◽  
Growth Inhibitory Effect ◽  
Extracellular Domains ◽  
Growth Inhibitory ◽  
Fniii Domain

Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.

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