A description of the findings appears in the online early May edition of theProceedings of the National Academy of Sciences. “Blocking one of these cell-recruiting signals in a mouse’s tumor made it much less likely to metastasize or spread.If a drug can be found that safely blocks the same signal in humans, it could be a very useful addition to current breast cancer treatment — particularly for patients with chemotherapy-resistant tumors.” said Gregg Semenza, M.D., Ph.D., a professor and director of the Vascular Biology Program in theJohns Hopkins University School of Medicine’s Institute for Cell Engineering. Semenza’s research group studies a chemical signal called hypoxia-inducible factor 1 (HIF-1), which cells release to help them cope with low-oxygen conditions. Earlier, the group determined that HIF-1 helps breast tumor cells survive the low-oxygen conditions in which they often live, and spread to other parts of the body such as the lungs. “In breast cancer, it’s not the original tumor that kills patients, but the metastases.” said Semenza. Also in a previous study, Semenza’s group found that HIF-1 induced adult stem cells called mesenchymal stem cells release a signal to nearby breast cancer cells, which made them more likely to spread. The researchers suspected this communication might run both ways and that the stem cells’ presence might also help the cancer to recruit the host animal’s white blood cells. Breast cancers need the support of several types of host cells in order to metastasize, including mesenchymal stem cells and one type of white blood cell, Semenza notes. Studying tumor cells grown in a dish, Semenza’s team used chemicals that blocked the functions of various proteins to map a web of signals flying among breast cancer cells, menenchymal stem cells and white blood cells. One positive feedback loop brought mesenchymal stem cells close in to the breast cancer cells. A separate loop of signals between the stem cells and cancer cells caused the cancer cells to release a chemical “beacon” that drew in white blood cells. The concentrations of all the signals in the web were increased by the presence of HIF-1 — and ultimately, by low-oxygen conditions. The team then used genetic engineering to reduce the levels of the cell-recruiting signals in breast cancer cells and implanted those cells into female mice. Compared with unaltered breast cancer cells, those with reduced recruiting power grew into similar-sized tumors, Semenza says, but were much less likely to spread. All of the breast cancer cells used in the study were so-called triple-negative, meaning they lack receptors for estrogen, progesterone and human epidermal growth factor receptor 2, so they do not respond to therapies that target those receptors. In people, triple-negative breast cancers also tend to be more deadly than other breast cancers because they contain more HIF-1, Semenza says. “This study adds to the evidence that a HIF-1 inhibitor drug could be an effective addition to chemotherapy regimens, especially for triple-negative breast cancers.” he said. Several potential drugs of this kind are now in the early stages of development, he notes. References
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Cliff Boodoosingh 12 March 2007 It is crucial to understand the differences among the types of hosting offered. As the Web hosting industry has matured, hosting offers have split into a few distinct categories, each with strengths and weaknesses. The host manages the server almost completely (though you maintain your site and your account). They can afford to charge you little since many clients are paying for use of the server. However, companies other than yours use the resources of that server. That means heavy traffic to one of the other sites on the server can hammer the performance of your site. Also, you typically are unable to install special software programs on these types of machines because the host will need to keep a stable environment for all of the clients using the server. Co-located hosting means that you buy a server from a hardware vendor, like Dell or HP, and you supply this server to the host. The Web host plugs your server into its network and its redundant power systems. The host is responsible for ensuring its network is available, and you are responsible for support and maintenance of your server. Good hosts offer management contracts to their co-location clients so that you can outsource much of the support to them and come to an arrangement similar to managed dedicated hosting. Most co-location hosts do not offer this service, however. You can find co-location providers we recommend at our Co-Location Hosting showcase. Unmanaged dedicated hosting is similar to co-location except that you lease a server from a host and do not own it yourself. Some very limited support (typically Web-based only) is included, but the level of support varies widely among unmanaged dedicated hosts. This type of server can be had for around $99/month. Support levels typically are provided only in general terms. Ask the host to go into specifics about what support it will provide will it apply security patches to your server? before signing up. This service is typically good for gaming servers (like Doom or Counterstrike servers) or hobbyist servers, but not for serious businesses that need responsive, expert-level service. Managed dedicated hosting means leasing a server from a host and having that company provide a robust level of support and maintenance on the server that is backed by quality guarantees. This maintenance typically includes services such as server uptime monitoring, a hardware warranty and security patch updates. Ensure that your managed dedicated host is specific about its managed services so that it does not disguise an unmanaged dedicated offering as a managed dedicated server. This has been known to happen, which is why it is important to do your homework and ask the right questions. You can find managed hosting providers we recommend, in our Managed Hosting showcase. This is excerpted from 9 Things to Know Before Selecting a Web Host by Chris Kivlehan, Marketing Manager at INetU Managed Hosting , Allentown, PA. He may be contacted at 610/266-7441 or at firstname.lastname@example.org .
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