Annals of Surgery
Annals of Surgery
5 years ago

The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice

The Allosteric Hemoglobin Effector ITPP Inhibits Metastatic Colon Cancer in Mice
Kron, Philipp, Graf, Rolf, Tschuor, Christoph, Humar, Bostjan, Lehn, Jean-Marie, Linecker, Michael, Limani, Perparim, Nicolau, Claude, Kachaylo, Ekaterina, Schneider, Marcel A., Clavien, Pierre-Alain, Ungethuem, Udo
Objective: To test the effects of enhanced intracellular oxygen contents on the metastatic potential of colon cancer. Background: Colorectal cancer is the commonest gastrointestinal carcinoma. Distant metastases occur in half of patients and are responsible for most cancer-related deaths. Tumor hypoxia is central to the pathogenesis of metastases. Myo-Inositoltrispyrophosphate (ITPP), a nontoxic, antihypoxic compound, has recently shown significant benefits in experimental cancer, particularly when combined with standard chemotherapy. Whether ITPP protects from distant metastases in primary colon cancer is unknown. Methods: ITPP alone or combined with FOLFOX was tested in a mouse model with cecal implantation of green fluorescent protein-labeled syngeneic colorectal cancer cells. Tumor development was monitored through longitudinal magnetic resonance imaging-based morphometric analysis and survival. Established serum markers of tumor spread were measured serially and circulating tumor cells were detected via fluorescence measurements. Results: ITPP significantly reduced the occurrence of metastases as well as other indicators of tumor aggressiveness. Less circulating tumor cells along with reduction in malignant serum markers (osteopontin, Cxcl12) were noted. The ITPP benefits also affected the primary cancer site. Importantly, animals treated with ITPP had a significant survival benefit compared with respective controls, while a combination of FOLFOX with ITPP conferred the maximum benefits, including dramatic improvements in survival (mean 86 vs 188 d). Conclusions: Restoring oxygen in metastatic colon cancer through ITPP inhibits tumor spread and markedly improves animal survival; an effect that is enhanced through the application of subsequent chemotherapy. These promising novel findings call for a clinical trial on ITPP in patients with colorectal cancer, which is under way.

Publisher URL: http://journals.lww.com/annalsofsurgery/Fulltext/2017/11000/The_Allosteric_Hemoglobin_Effector_ITPP_Inhibits.8.aspx

DOI: 10.1097/SLA.0000000000002431

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.