scholarly journals New Heparanase-Inhibiting Triazolo-Thiadiazoles Attenuate Primary Tumor Growth and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2959
Author(s):  
Uri Barash ◽  
Shobith Rangappa ◽  
Chakrabhavi Dhananjaya Mohan ◽  
Divakar Vishwanath ◽  
Ilanit Boyango ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Enzymatic Activity ◽  
Heparan Sulfate ◽  
Cancer Progression ◽  
Primary Tumor ◽  
Neutralizing Antibodies ◽  
Tumor Development ◽  
Primary Tumor Growth ◽  
Tumor Growth And Metastasis ◽  
Preclinical And Clinical Studies

Compelling evidence ties heparanase, an endoglycosidase that cleaves heparan sulfate side (HS) chains of proteoglycans, with all steps of tumor development, including tumor initiation, angiogenesis, growth, metastasis, and chemoresistance. Moreover, heparanase levels correlate with shorter postoperative survival of cancer patients, encouraging the development of heparanase inhibitors as anti-cancer drugs. Heparanase-inhibiting heparin/heparan sulfate-mimicking compounds and neutralizing antibodies are highly effective in animal models of cancer progression, yet none of the compounds reached the stage of approval for clinical use. The present study focused on newly synthesized triazolo–thiadiazoles, of which compound 4-iodo-2-(3-(p-tolyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)phenol (4-MMI) was identified as a potent inhibitor of heparanase enzymatic activity, cell invasion, experimental metastasis, and tumor growth in mouse models. To the best of our knowledge, this is the first report showing a marked decrease in primary tumor growth in mice treated with small molecules that inhibit heparanase enzymatic activity. This result encourages the optimization of 4-MMI for preclinical and clinical studies primarily in cancer but also other indications (i.e., colitis, pancreatitis, diabetic nephropathy, tissue fibrosis) involving heparanase, including viral infection and COVID-19.

scholarly journals CD24 Is an Effector of HIF-1–Driven Primary Tumor Growth and Metastasis

2012 ◽  
Vol 72 (21) ◽  
pp. 5600-5612 ◽  
Author(s):  
Shibu Thomas ◽  
Michael A. Harding ◽  
Steven C. Smith ◽  
Jonathan B. Overdevest ◽  
Matthew D. Nitz ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Primary Tumor ◽  
Primary Tumor Growth ◽  
Tumor Growth And Metastasis

Inhibition of Urokinase Activity Reduces Primary Tumor Growth and Metastasis Formation in a Murine Lung Carcinoma Model

2010 ◽  
Vol 181 (6) ◽  
pp. 611-619 ◽  
Author(s):  
Ingrid Henneke ◽  
Susanne Greschus ◽  
Rajkumar Savai ◽  
Martina Korfei ◽  
Philipp Markart ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Carcinoma ◽  
Primary Tumor ◽  
Metastasis Formation ◽  
Primary Tumor Growth ◽  
Murine Lung ◽  
Tumor Growth And Metastasis

scholarly journals VEGF-B promotes cancer metastasis through a VEGF-A–independent mechanism and serves as a marker of poor prognosis for cancer patients

2015 ◽  
Vol 112 (22) ◽  
pp. E2900-E2909 ◽  
Author(s):  
Xiaojuan Yang ◽  
Yin Zhang ◽  
Kayoko Hosaka ◽  
Patrik Andersson ◽  
Jian Wang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Lung Squamous Cell Carcinoma ◽  
Primary Tumor Growth ◽  
Perivascular Cell ◽  
Tumor Microvasculature ◽  
Cell Coverage ◽  
Independent Mechanism

The biological functions of VEGF-B in cancer progression remain poorly understood. Here, we report that VEGF-B promotes cancer metastasis through the remodeling of tumor microvasculature. Knockdown of VEGF-B in tumors resulted in increased perivascular cell coverage and impaired pulmonary metastasis of human melanomas. In contrast, the gain of VEGF-B function in tumors led to pseudonormalized tumor vasculatures that were highly leaky and poorly perfused. Tumors expressing high levels of VEGF-B were more metastatic, although primary tumor growth was largely impaired. Similarly, VEGF-B in a VEGF-A–null tumor resulted in attenuated primary tumor growth but substantial pulmonary metastases. VEGF-B also led to highly metastatic phenotypes in Vegfr1 tk−/− mice and mice treated with anti–VEGF-A. These data indicate that VEGF-B promotes cancer metastasis through a VEGF-A–independent mechanism. High expression levels of VEGF-B in two large-cohort studies of human patients with lung squamous cell carcinoma and melanoma correlated with poor survival. Taken together, our findings demonstrate that VEGF-B is a vascular remodeling factor promoting cancer metastasis and that targeting VEGF-B may be an important therapeutic approach for cancer metastasis.

OC-05 Inhibition of tissue factor by Ixolaris reduces primary tumor growth and metastasis in a murine model of melanoma

2010 ◽  
Vol 125 ◽  
pp. S162
Author(s):  
A. Da Silva de Oliveira ◽  
L.G. Lima ◽  
D.E. Machado ◽  
L.E. Nasciutti ◽  
L.C. Petersen ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tissue Factor ◽  
Murine Model ◽  
Primary Tumor ◽  
Primary Tumor Growth ◽  
Tumor Growth And Metastasis

A CXCR4 Antagonist CTCE-9908 Inhibits Primary Tumor Growth and Metastasis of Breast Cancer

2009 ◽  
Vol 155 (2) ◽  
pp. 231-236 ◽  
Author(s):  
Eugene H. Huang ◽  
Balraj Singh ◽  
Massimo Cristofanilli ◽  
Juri Gelovani ◽  
Caimiao Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Primary Tumor ◽  
Primary Tumor Growth ◽  
Cxcr4 Antagonist ◽  
Tumor Growth And Metastasis

scholarly journals PPARγ ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis

2002 ◽  
Vol 110 (7) ◽  
pp. 923-932 ◽  
Author(s):  
Dipak Panigrahy ◽  
Samuel Singer ◽  
Lucy Q. Shen ◽  
Catherine E. Butterfield ◽  
Deborah A. Freedman ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Primary Tumor ◽  
Primary Tumor Growth ◽  
Tumor Growth And Metastasis

scholarly journals Maresin 1: a Novel Macrophage Derived Endogenous Proresolving Inhibitor of Primary Tumor Growth and Metastasis

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Kristen Lehner ◽  
Megan Sulciner ◽  
Sesquile Ramon ◽  
Dayna Mudge ◽  
Sui Huang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Primary Tumor ◽  
Primary Tumor Growth ◽  
Maresin 1 ◽  
Tumor Growth And Metastasis

scholarly journals Overexpression of the μ-Opioid Receptor in Human Non-Small Cell Lung Cancer Promotes Akt and mTOR Activation, Tumor Growth, and Metastasis

2012 ◽  
Vol 116 (4) ◽  
pp. 857-867 ◽  
Author(s):  
Frances E. Lennon ◽  
Tamara Mirzapoiazova ◽  
Bolot Mambetsariev ◽  
Ravi Salgia ◽  
Jonathan Moss ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Progression ◽  
Primary Tumor ◽  
Small Cell ◽  
Carcinoma Cells ◽  
Bronchioloalveolar Carcinoma ◽  
Primary Tumor Growth ◽  
Small Cell Lung ◽  
Μ Opioid Receptor

Background Recent epidemiologic studies suggesting that there were differences in cancer recurrence contingent on anesthetic regimens have raised the possibility that μ-opioid agonists can influence cancer progression. Based on our previous studies indicating the μ-opioid receptor (MOR) is up-regulated in several types of non-small cell lung cancer, this study examined the functional significance of MOR overexpression to elucidate a possible mechanism for the epidemiologic findings. Methods Stable vector control and MOR1 overexpressing human bronchioloalveolar carcinoma cells were evaluated using immunoblot analysis, proliferation and transendothelial extravasation assays with or without Akt inhibitor, mTOR inhibitor (temsirolimus), or the peripheral MOR antagonist, methylnaltrexone. In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in lungs of the nude mouse model. Results The authors provide evidence that MOR is an important regulator of lung cancer progression. MOR overexpression increased Akt and mTOR activation, proliferation, and extravasation in human bronchioloalveolar carcinoma cells. In vivo, overexpression of MOR in human bronchoalveolar carcinoma cells increased primary tumor growth rates in nude mice by approximately 2.5-fold and lung metastasis by approximately 20-fold compared with vector control cells (n = 4 per condition). Conclusions The overexpression data suggest a possible direct effect of MOR on Akt and mTOR activation and lung cancer progression. Such an effect provides a plausible explanation for the epidemiologic findings. The authors' observations further suggest that exploration of MOR in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option.

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