Yin Yang 1 plays an essential role in breast cancer and negatively regulates p27.

Yin Yang 1 (YY1) is highly expressed in various types of cancers and regulates tumorigenesis through multiple pathways. In the present study, we evaluated YY1 expression levels in breast cancer cell lines, a breast cancer TMA, and two gene arrays. We observed that, compared with normal samples, YY1 is generally overexpressed in breast cancer cells and tissues. In functional studies, depletion of YY1 inhibited the clonogenicity, migration, invasion, and tumor formation of breast cancer cells, but did not affect the clonogenicity of nontumorigenic cells. Conversely, ectopically expressed YY1 enhanced the migration and invasion of nontumorigenic MCF-10A breast cells. In both a monolayer culture condition and a three-dimensional Matrigel system, silenced YY1 expression changed the architecture of breast cancer MCF-7 cells to that resembling MCF-10A cells, whereas ectopically expressed YY1 in MCF-10A cells had the opposite effect. Furthermore, we detected an inverse correlation between YY1 and p27 expression in both breast cancer cells and xenograft tumors with manipulated YY1 expression. Counteracting the changes in p27 expression attenuated the effects of YY1 alterations on these cells. In addition, YY1 promoted p27 ubiquitination and physically interacted with p27. In conclusion, our data suggest that YY1 is an oncogene and identify p27 as a new target of YY1.

Development of iron-containing multiwalled carbon nanotubes for MR-guided laser-induced thermotherapy.

AIMS: To test iron-containing multiwalled carbon nanotubes (MWCNTs) as bifunctional nanomaterials for imaging and thermal ablation of tumors. MATERIALS & METHODS: MWCNTs entrapping iron were synthesized by chemical vapor deposition. The T2-weighted contrast enhancement properties of MWCNTs containing increasing amounts of iron were determined in vitro. Suspensions of these particles were injected into tumor-bearing mice and tracked longitudinally over 7 days by MRI. Heat-generating abilities of these nanomaterials following exposure to near infrared (NIR) laser irradiation was determined in vitro and in vivo. RESULTS: The magnetic resonance contrast properties of carbon nanotubes were directly related to their iron content. Iron-containing nanotubes were functional T2-weighted contrast agents in vitro and could be imaged in vivo long-term following injection. Iron content of nanotubes did not affect their ability to generate thermoablative temperatures following exposure to NIR and significant tumor regression was observed in mice treated with MWCNTs and NIR laser irradiation. CONCLUSION: These data demonstrate that iron-containing MWCNTs are functional T2-weighted contrast agents and efficient mediators of tumor-specific thermal ablation in vivo.

Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation.

Multiwalled carbon nanotubes (MWCNTs) exhibit physical properties that render them ideal candidates for application as noninvasive mediators of photothermal cancer ablation. Here, we demonstrate that use of MWCNTs to generate heat in response to near-infrared radiation (NIR) results in thermal destruction of kidney cancer in vitro and in vivo. We document the thermal effects of the therapy through magnetic resonance temperature-mapping and heat shock protein-reactive immunohistochemistry. Our results demonstrate that use of MWCNTs enables ablation of tumors with low laser powers (3 W/cm(2)) and very short treatment times (a single 30-sec treatment) with minimal local toxicity and no evident systemic toxicity. These treatment parameters resulted in complete ablation of tumors and a >3.5-month durable remission in 80% of mice treated with 100 microg of MWCNT. Use of MWCNTs with NIR may be effective in anticancer therapy.

Synthetic and natural iron chelators: therapeutic potential and clinical use.

Iron-chelation therapy has its origins in the treatment of iron-overload syndromes. For many years, the standard for this purpose has been deferoxamine. Recently, considerable progress has been made in identifying synthetic chelators with improved pharmacologic properties relative to deferoxamine. Most notable are deferasirox (Exjade(®)) and deferiprone (Ferriprox(®)), which are now available clinically. In addition to treatment of iron overload, there is an emerging role for iron chelators in the treatment of diseases characterized by oxidative stress, including cardiovascular disease, atherosclerosis, neurodegenerative diseases and cancer. While iron is not regarded as the underlying cause of these diseases, it does play an important role in disease progression, either through promotion of cellular growth and proliferation or through participation in redox reactions that catalyze the formation of reactive oxygen species and increase oxidative stress. Thus, iron chelators may be of therapeutic benefit in many of these conditions. Phytochemicals, many of which bind iron, may also owe some of their beneficial properties to iron chelation. This review will focus on the advances in iron-chelation therapy for the treatment of iron-overload disease and cancer, as well as neurodegenerative and chronic inflammatory diseases. Established and novel iron chelators will be discussed, as well as the emerging role of dietary plant polyphenols that effectively modulate iron biochemistry.