F3-Targeted Cisplatin-Hydrogel Nanoparticles as an Effective Therapeutic That Targets Both Murine and Human Ovarian Tumor Endothelial Cells <i>In vivo</i>

Winer, Ira; Wang, Shouyan; Lee, Youg Eun Koo; Fan, Wenzhe; Gong, Yusong; Burgos-Ojeda, Daniela; Spahlinger, Greg; Kopelman, Raoul; Buckanovich, Ronald J.

doi:10.1158/0008-5472.can-10-1917

Cited by 85 publications

(80 citation statements)

References 29 publications

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“…p-Stat3 density was assessed as previously described (23). Briefly, 5 independent sections from TG101209 and DMSO treated tumors (n=4 each) were stained with anti-p-Stat3 (NEED AB 1:50) and signal detected with DAB as above.…”

Section: Methodsmentioning

confidence: 99%

CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis

Burgos-Ojeda

McLean

et al. 2015

Molecular Cancer Therapeutics

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Ovarian cancer is known to be composed of distinct populations of cancer cells, some of which demonstrate increased capacity for cancer initiation and/or metastasis. The study of human cancer cell populations is difficult due to long requirements for tumor growth, inter-patient variability and the need for tumor growth in immune-deficient mice. We therefore characterized the cancer initiation capacity of distinct cancer cell populations in a transgenic murine model of ovarian cancer. In this model, conditional deletion of Apc, Pten, and Trp53 in the ovarian surface epithelium (OSE) results in the generation of high grade metastatic ovarian carcinomas. Cell lines derived from these murine tumors express numerous putative stem cell markers including CD24, CD44, CD90, CD117, CD133 and ALDH. We show that CD24+ and CD133+ cells have increased tumor sphere forming capacity. CD133+ cells demonstrated a trend for increased tumor initiation while CD24+ cells vs CD24− cells, had significantly greater tumor initiation and tumor growth capacity. No preferential tumor initiating or growth capacity was observed for CD44+, CD90+, CD117+, or ALDH+ versus their negative counterparts. We have found that CD24+ cells, compared to CD24− cells, have increased phosphorylation of STAT3 and increased expression of STAT3 target Nanog and c-myc. JAK2 inhibition of STAT3 phosphorylation preferentially induced cytotoxicity in CD24+ cells. In vivo JAK2 inhibitor therapy dramatically reduced tumor metastases, and prolonged overall survival. These findings indicate that CD24+ cells play a role in tumor migration and metastasis and support JAK2 as a therapeutic target in ovarian cancer.

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Section: Methodsmentioning

confidence: 99%

CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis

Burgos-Ojeda

McLean

et al. 2015

Molecular Cancer Therapeutics

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“…Similarly, the F3 peptide binds to nucleolin, a protein that is overexpressed on the surface of tumor endothelial cells [537]. Winer et al [538] used non-toxic F3-conjugated polyacrylamide nanoparticles to deliver cisplatin to tumor vessels in murine and human ovarian cancer models. In vitro, the nanoparticles showed to be highly specificity for both, tumor and tumor endothelial cells, being cytotoxic only against the tumor endothelial cells.…”

Section: Peptidic Targetingmentioning

confidence: 99%

“…In vitro, the nanoparticles showed to be highly specificity for both, tumor and tumor endothelial cells, being cytotoxic only against the tumor endothelial cells. In vivo, the nanoparticles bind mainly to tumor vessels, generating a rapid tumor regression due to their antivascular effect [538]. …”

Section: Peptidic Targetingmentioning

confidence: 99%

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Pérez-Herrero

Fernández‐Medarde

2015

European Journal of Pharmaceutics and Biopharmaceutics

1,399

754

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Cancer is the second worldwide cause of death, exceeded only by cardiovascular diseases. It is characterized by uncontrolled cell proliferation and an absence of cell death that, except for hematological cancers, generates an abnormal cell mass or tumor. This primary tumor grows thanks to new vasculatization and, in time, adquires metastatic potential and spreads to other body sites, which causes metastasis and finally death. Cancer is caused by damage or mutations in the genetic material of the cells due to environmental or inherited factors. While surgery and radiotherapy are the primary treatment used for local and non-metastatic cancers, anti-cancer drugs (chemotherapy, hormone and biological therapies) are the choice currently used in metastasic cancers. Chemotherapy is based on the inhibition of the division of rapidly growing cells, which is a characteristic of the cancerous cells, but unfortunately, it also affects normal cells with fast proliferation rates, like the hair follicles, bone marrow and gastrointestinal tract cells, generating the characteristic side effects of chemotherapy. The indiscriminate destruction of normal cells, the toxicity of conventional chemotherapeutic Código de campo cambiado

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“…Compared to the free Coomassie Blue dye, the nanoparticles can be selectively targeted to specific tumors or tumor vasculature. They have the ability to act as a platform for delivering contrast agents and drugs into tumors in vivo [18, 19]. Previously, our lab has used CB-containing nanoparticles to delineate brain tumors visually [20].…”

Section: Introductionmentioning

confidence: 99%

Targeted blue nanoparticles as photoacoustic contrast agent for brain tumor delineation

et al. 2011

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Distinguishing a tumor from non-neoplastic tissue is a challenging task during cancer surgery. Several attempts have been made to use visible or fluorescent agents to aid in the visualization of a tumor during surgery. We describe a novel method to delineate brain tumors, using a highly sensitive photoacoustic imaging technique that is enhanced by tumor-targeting blue nanoparticles serving as a contrast agent. Experiments on phantoms and on rat brains, ex vivo, demonstrate the high sensitivity of photoacoustic imaging in delineating tumors containing contrast agent at a concentration much lower than needed for visualization by the naked eye. The limit of detection of the system for the nanoparticles is about 0.77 μg/mL in water (equivalent to 0.84 μmol/L Coomassie Blue dye). The present exploratory study suggests that photoacoustic imaging, when used with strongly optical absorbing contrast agents, could facilitate cancer surgery intraoperatively by revealing the distribution and extent of the tumor.

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F3-Targeted Cisplatin-Hydrogel Nanoparticles as an Effective Therapeutic That Targets Both Murine and Human Ovarian Tumor Endothelial Cells In vivo

Cited by 85 publications

References 29 publications

CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis

CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

Targeted blue nanoparticles as photoacoustic contrast agent for brain tumor delineation

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