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Winship, Duke journal, GBM's...... QUICK SEARCH: [advanced]Author:Keyword(s):Year: Vol: Page: Home | Help | Feedback | Subscriptions | Archive | Search | Table of ContentsNeuro-oncol 2005 7(2):134-153; DOI:10.1215/S1152851704001115 This ArticleFull Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map ServicesSimilar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Cited by other online articles Search for citing articles in: ISI Web of Science (2) Google ScholarArticles by Kaur, B. Articles by Van Meir, E. G. Articles citing this Article PubMedPubMed Citation Duke University Press Tumor BiologyHypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis Balveen Kaur, Fatima W. Khwaja, Eric A. Severson, Shannon L. Matheny, Daniel J. Brat and Erwin G. Van Meir2 Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery and Hematology/Oncology (F.W.K., E.A.S., S.L.M), and Pathology (D.J.B.), Winship Cancer Institute (B.K., E.G.V.M.), Emory University School of Medicine, Atlanta, GA 30322, USA 2 Address correspondence to Erwin G. Van Meir, Winship Cancer Institute, Emory University School of Medicine, 1365C Clifton Road, NE, Room C5078, Atlanta, GA 30322, USA (evanmei{at}emory.edu).AbstractGlioblastomas, like other solid tumors, have extensive areas of hypoxia and necrosis. The importance of hypoxia in driving tumor growth is receiving increased attention. Hypoxia-inducible factor 1 (HIF-1) is one of the master regulators that orchestrate the cellular responses to hypoxia. It is a heterodimeric transcription factor composed of and ß subunits. The subunit is stable in hypoxic conditions but is rapidly degraded in normoxia. The function of HIF-1 is also modulated by several molecular mechanisms that regulate its synthesis, degradation, and transcriptional activity. Upon stabilization or activation, HIF-1 translocates to the nucleus and induces transcription of its downstream target genes. Most important to gliomagenesis, HIF-1 is a potent activator of angiogenesis and invasion through its upregulation of target genes critical for these functions. Activation of the HIF-1 pathway is a common feature of gliomas and may explain the intense vascular hyperplasia often seen in glioblastoma multiforme. Activation of HIF results in the activation of vascular endothelial growth factors, vascular endothelial growth factor receptors, matrix metalloproteinases, plasminogen activator inhibitor, transforming growth factors and ß, angiopoietin and Tie receptors, endothelin-1, inducible nitric oxide synthase, adrenomedullin, and erythropoietin, which all affect glioma angiogenesis. In conclusion, HIF is a critical regulatory factor in the tumor microenvironment because of its central role in promoting proangiogenic and invasive properties. While HIF activation strongly promotes angiogenesis, the emerging vasculature is often abnormal, leading to a vicious cycle that causes further hypoxia and HIF upregulation. This article has been cited by other articles: (Search Google Scholar for Other Citing Articles) G. Garin, M. Mathews, and B. C. BerkTissue-Resident Bone Marrow-Derived Progenitor Cells: Key Players in Hypoxia-Induced AngiogenesisCirc. Res., November 11, 2005; 97(10): 955 - 957. [Full Text] [PDF] Home | Help | Feedback | Subscriptions | Archive | Search | Table of ContentsCopyright 2005 by Society for Neuro-Oncology
OT.....This is a printer friendly version of an article from the Daily RecordTo print this article open the file menu and choose Print.Back If you want to know For information on Sutent, visit www.pfizer.com or www.sutent.com. Estimated 2006 deaths for selected cancers: Type, United States, New JerseyAll: 564,830, 17,720Brain/nervous system: 12,820, 310Female breast, 40,970, 1,560Colon and rectum, 55,170, 1,800Leukemia, 22,280, 700Liver, 16,200, 470Lung, 162,460, 4,620Non-Hodgkin Lymphoma, 18,840, 600Ovary, 15,310, 510Pancreas, 32,300, 1,050Prostate, 27,350, 900Source: American Cancer Society Advertisement02/26/06 - Posted from the Daily Record newsroom Cancer drugs offer chance for normal lifeTargeted therapies from Pfizer, Bayer provide new hopeBY MICHAEL DAIGLE DAILY RECORD Hope for Julia Barchitta comes in the form of a daily pill that attacked the kidney cancer which had spread to her lungs and lymph nodes. She has been cancer-free for the past year.Barchitta, 62, a dean and head of the nursing department at Staten Island's Wagner College, was part of a study of the Pfizer cancer drug Sutent, which is now on the market after being approved by the Federal Drug Administration in late January.Sutent is one of an emerging group of drugs called targeted therapies that focus on the processes and materials that make cancer cells grow, and which offer researchers hope that cancers can be detected earlier, treatments can be less toxic, longer lasting, and that cancer mortality rates drop dramatically."This is a big effort,"said Pfizer's Dr. Charles Baum, the global clinical leader for Sutent research headquartered in La Jolla, Calif. Targeted therapies "attack the mechanisms of cancer. There is a long way to go, but the prognosis is better and better."Dr. Michael Kane, director or oncology at Mountainside Hospital, part of Atlantic Health System that includes Morristown Memorial Hospital, ran a trial using the drug Nexavar, a drug similar to Sutent but developed by Bayer Pharmaceuticals and Onxy Pharmaceuticals and approved by the FDA last December for treatment of kidney cancer.Tumors in approximately half the participants stopped growing and spreading, Kane said."That was the most important outcome," Kane said. While the drug did not reduce the size of tumors, the fact that they stabilized means that those patients have the chance to live longer and have better quality lives, he said.In time, he said, such treatments could change cancer into one of a number of illness like heart disease and diabetes that are considered chronic illnesses -- there is no cure, but the treatments keep the illness stable and patients live more normal lives.Kane said he is planning a trial using Sutent.Barchitta, who had already battled colon cancer and watched her husband die of the disease in 2003, said she was diagnosed with a spreading kidney cancer in July 2002. A year later, the cancer had spread to her lung and lymph nodes."Kidney cancer does not have a high success rate," she said, knowledge supported by the fact that her treatment --interferon, which is supposed to boost the body's immune system to help fight the spread of cancer -- was not effective."A year ago I thought I would not be here," she said.She said she felt the flu-like symptoms, fatigue and shortness of breath that are the side effects of interferon use. It became a challenge to perform her job and affected her ability to enjoy her three children and two grandchildren.Barchitta said she entered the Sutent trial in July 2004, pretty much as a last resort."I didn't have a choice," she said. "I had to hope a recovery was possible. I had to go on with hope. I prayed a lot."Tests done six weeks after she started taking Sutent, showed a "noticeable reduction" in the tumor, she said. Six weeks later it was smaller yet, and now there is no evidence of cancer."It has been a miracle for me," Barchitta said. "I will take it as long as I need to. It's working. I'm afraid to stop."Sutent, like all powerful medications, has side effects, including diarrhea, skin discoloration, mouth irritation, weakness and altered taste, the FDA said in its Jan. 26 approval of the drug.For Barchitta, the noticeable side effect is intense hand and foot pain -- "like walking on glass."In response, she said she stopped wearing high heels and skirts to work and started wearing sneakers."I gave up the high fashion,"she said. "Now it's sneakers. It's okay. If I have to wear sneakers for the rest of my life, I'll wear sneakers.""My life" is a phrase that a year ago meant something different to Barchitta."I can not say that the cancer won't recur, and I can't say this is a cure," she said. "But I'm very happy to be here. It is important for people with the disease to have hope, some hope."The first research steps toward today's targeted therapies began 30 to 35 years ago when Dr. Judah Folkman of Children's Hospital and the Harvard Medical School in Boston studied how tumors grow and spread, said Dr. Arnold Baskies, a medical advisor for the American Cancer Society who serves on the society's board of directors for New York and New Jersey.Folkman studied how tumors use a process called angiogenesis -- the creation of new blood vessels -- to see how cancer sustains itself and spreads throughout the body.That work led to the creation of drugs that inhibit angiogenesis, said BaskiesThe major research breakthrough was the discovery 10 years ago of the human genome -- human beings'genetic code, said Baskies, who is also a member of the New Jersey's Governor's Task Force for Cancer Prevention, Early Detection and Treatment."We learn what controls cancer and the triggering mechanism that begin cancer and spreads it, " Baskies said.That knowledge lead to the discoveries of the targeted therapies, he said."Targeted treatments can pinpoint the mechanism or enzyme that stops cancer," he said. "It is like using a BB instead of a shotgun pellet."Baum said that the general approach to cancer treatment such as chemotherapy kills cells that divide, but since all cells are always reproducing, the drugs would attack them as well as the cancer."Chemotherapy says, 'if it is dividing, it must be bad,'"Baum said.With Sutent, he said, "we know that cancer cells are genetically different. We target that difference. The drug attacks the blood supply to the tumor and the nutrients it needs to grow and spread."In its approval of Sutent, the FDA said in the cases of renal cell carcinoma, the drug showed an ability to shrink tumors -- 26 to 37 percent in patients with advance kidney cancer -- and the ability to slow the growth of gastrointestinal stromal tumors in patients who are unable to tolerate treatments by Gleevac, the current treatment.It was the first time the FDA had simultaneously approved a single drug for two separate treatment uses.Baum said Pfizer was able to get Sutent ready for FDA approval in five years, although work that resulted in the drug was started 10 years ago. The work was aided by the development of improved radiography imaging, which allowed scientists to know with more certainty if a treatment was working, he said.The reduction of side effect is also a key development, Baum said, as is the pill form of the medicine.Barchitta said that she once had to inject herself with interferon. She said taking a pill daily was much better.Baum said, "there is a big improvement in the quality of life. Patients don't have to take radiation, or plan a day to visit a clinic."Baskies called the pill form, "the nice part of it."Baum said that targeted therapies are treatments, not cures. "But these efforts are a new paradigm," he said.It is the future that these therapies represent that "make this an exciting time to be in cancer treatment," Kane said.There are successes, but also challenges, he said."There is evidence that cancers are smart and we can not underestimate how smart," he said. One goal is to match cancer's mechanisms of growth with the body's mechanisms of resistance.A breast cancer treatment, he said, targets the enzymes associated with the growth of those tumors, Kane said. "It targets proteins, the fuel of cancer cells," he said. "This could be the magic bullet. It kills the cancer cells without harming normal tissue."It is possible that combinations of chemotherapy and targeted therapies could be developed, he said.There is also work that is examining the potential connection of stem cells to cancer cells, he said. When a cancer dies, it leaves behind a small percentage of cells that could be the reason that the same cancer returns, he said. Researchers are trying to determine if there is a link between how stem cells can become any type of cell and how cancer cells grow.Baskies said there is the possibility that by examining cancers at the molecular level, breast cancer deaths could be reduced in a decade by 50 percent. That would mean that 35,000 fewer women would die of the disease , he said.The real promise of this approach, he said, is that it could become possible to examine a person's genome to determine the possibility that they would develop cancer and, if so, provide a preventative therapy that could alter that person's body chemistry so that the cancer would not form.Michael Daigle can be reached at (973) 267-7947 or at mdaigle@gannett.com.
ounce "o" silver = 4 shares "o" ENMD.....did sum trading today.....trying to catch dat ENMD bottom.......shoulda got on that Ipod ramp, AAPL ten bagger......arrrrrgh!
could be a tsunami in ENMD pps soon.....been waiting to post tsunami link to mark the bottom....I think I nailed it ( the bottom )
any leaky vessel mocus?......that's the way I like it, uh uh, that's the way I like it, uh uh.....#msg-7852902
OT...new nano news.......Back to Story - Help
Nanotechnology May Help Treat Cancer
By EMMA ROSS, AP Medical WriterTue Nov 1, 5:18 PM ET
Experiments on mice have shown promise for the future of nanotechnology in treating cancer — research that could bring doctors a step closer to using the technology to release cancer-killing drugs inside tumors while leaving the rest of the body unscathed.
After seeing how some mice were cured of human prostate cancer with the technology, cancer specialists at the European Cancer Conference in Paris said Tuesday they had high hopes for its future application.
"There are a lot of candidates for intelligent carriers and these nanoparticles are among them," said Dr. Gordon McVie, a professor at the European Institute of Oncology in Milan, Italy, who was not involved with the research.
"This is a new system, and the more systems we have, the better, because we'll probably be lucky if we get one system to work out of 10," he said. "It looks as if it could be quite good."
Dr. David Kerr, a professor of clinical pharmacology and cancer therapeutics at Oxford University in England who also was not connected with the research, said the approach may have the edge on others. Previous designs of nanoparticles have used antibodies to zone in on cancer cells.
"The body's immunodefense system can create antibodies to the therapeutic antibodies, deactivate them and prevent the antibody binding to the right cancer cells. This looks like a step forward," Kerr said.
Nanotechnology is the science of manipulating matter smaller than 100 nanometers and taking advantage of properties that are present only at that level, such as conductivity. A nanometer is one-billionth of a meter, or about one-millionth the size of a pin head. The prefix comes from "nanos," the Greek word for dwarf.
Nanotech has been around for several decades, but only now is its potential starting to be realized. Medicine is expected to be one of the fields to benefit most from the technology. In cancer, it is hoped the technology will allow for more precisely targeted drugs and surgery and less toxic chemotherapy.
The study, done by scientists at Harvard Medical School and the Massachusetts Institute of Technology, involved engineering nanoparticles embedded with the cancer drug Taxotere. The particles were then injected into human tumors created from prostate cancer cell lines and implanted into the flanks of mice. The mice were watched for 100 days.
The technology being tested involves a nanoparticle made of a hydrogen and carbon polymer with bits of drug bound up in its fabric and attached to a substance that homes in on cancer cells. The polymer gradually dissolves, exposing the nuggets of drug little by little.
The mice were divided into five groups, including one that had their tumors injected with ineffective saltwater. A second group died after injections of a nanoparticle containing no drugs.
Another group was given one shot of the drug, experienced an initial decrease in tumor size and then suffered a strong rebound. They also died.
Other mice were injected with a nanoparticle-encased drug, but one that was not designed to specifically target cancer cells.
"What happens here is the lymphatic system of the tumor can take it up and wash it away, because the nanoparticle is not targeted to the cancer cells," said the study's presenter, Dr. Omid Farokhzad of Harvard Medical School. The tumor initially shrank to half its original size, but then rebounded.
In a final group of mice, scientists injected the targeted nanoparticles containing the drug.
"The tumor completely disappeared," Farokhzad said.
Injecting targeted nanoparticles into the bloodstream and having them seek out tumors and get inside on their own is the ultimate goal, but direct injection is also promising for cancers where the tumor is accessible and hasn't spread, such as early prostate cancer, Farokhzad said. He said his group hopes to test the approach in prostate cancer patients within two years.
Kerr said he doubted that direct injection of tumors would turn out to be a useful treatment in itself. "Cancer tends, almost from the outset, to be a systemic disease," he said. "This is only one design step toward what ultimately must be a systemic treatment."
He said there may be a use for the direct injection of nanoparticles to deliver vaccines to tumors. The idea is that the cancer can be vaccinated against itself, meaning the immune system would then destroy the cancer in other parts of the body.
Copyright © 2005 The Associated Press. All rights reserved. The information contained in the AP News report may not be published, broadcast, rewritten or redistributed without the prior written authority of The Associated Press.
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Melillo is getting around.....http://www.thresholdpharm.com/sec/pr_1115678151 ...... #msg-7781431
Merriman sez Jupiter moves into Scorpio on October 25, 2005 for a year....He thinks there will be "cures" for cancer during this period, but he doesn't say which companies have the mojo, I hope it's ENMD......http://www.mmacycles.com/fc2005.htm
Nie, Langer labs get more funding.....
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Contact the NCI Media Relations Branch
Posted: 10/03/2005
National Cancer Institute Awards $26.3 Million to Establish Seven Centers of Cancer Nanotechnology Excellence
The National Cancer Institute (NCI), part of the National Institutes of Health (NIH), today announced the implementation of a major component of its $144.3 million five-year initiative for nanotechnology in cancer research. First year awards totaling $26.3 million will help establish seven Centers of Cancer Nanotechnology Excellence (CCNEs).
"We believe that nanotechnology will have a transformative effect on cancer diagnosis and treatment. In fact, its impact is already visible in the research being conducted through many of the centers we are announcing today," said Andrew von Eschenbach, M.D., director of the National Cancer Institute. "Through the applications of nanotechnology, we will increase the rate of progress towards eliminating the suffering and death due to cancer."
Nanotechnology, the development and engineering of devices so small that they are measured on a molecular scale, has demonstrated promising results in cancer research and treatment. NCI launched the plan to create the NCI Alliance for Nanotechnology in Cancer in September 2004, as a comprehensive, integrated initiative to develop and translate cancer-related nanotechnology research into clinical practice.
NCI's Alliance for Nanotechnology in Cancer encompasses four major program components, including the CCNEs. CCNEs are multi-institutional hubs that will focus on integrating nanotechnology into basic and applied cancer research and provide new solutions for the diagnosis and treatment of cancer.
Each of the CCNE awardees is associated with one or more NCI-designated Cancer Centers, affiliated with schools of engineering and physical sciences, and partnered with not-for-profit organizations and/or private sector firms, with the specific intent of advancing the technologies being developed.
Today's CCNE awardees (in alphabetical order) are:
Carolina Center of Cancer Nanotechnology Excellence, University of North Carolina, Chapel Hill, N.C. This center will focus on the fabrication of "smart" or targeted nanoparticles and other nanodevices for cancer therapy and imaging. Principal investigator: Rudolph Juliano, Ph.D. (University of North Carolina).
Center of Nanotechnology for Treatment, Understanding, and Monitoring of Cancer, University of California, San Diego, Calif. This center will focus on a smart, multifunctional, all-in-one platform capable of targeting tumors and delivering payloads of therapeutics. Principal investigator: Sadik Esener, Ph.D. (UCSD).
Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology, Atlanta, Ga. This center will aim to innovate and accelerate the development of nanoparticles attached to biological molecules for cancer molecular imaging, molecular profiling and personalized therapy. Principal investigators: Shuming Nie, Ph.D., and Jonathan Simons, M.D. (Emory University and Georgia Institute of Technology).
MIT-Harvard Center of Cancer Nanotechnology Excellence, Cambridge, Mass. This center will focus on diversified nanoplatforms for targeted therapy, diagnostics, noninvasive imaging, and molecular sensing. Principal investigators: Robert Langer, Ph.D. (MIT), and Ralph Weissleder, M.D., Ph.D. (Harvard University, Massachusetts General Hospital).
Nanomaterials for Cancer Diagnostics and Therapeutics, Northwestern University, Evanston, Ill. This center plans to design and test nanomaterials and nanodevices to improve cancer prevention, detection, diagnosis and treatment. Principal investigator: Chad Mirkin, Ph.D. (Northwestern University).
Nanosystems Biology Cancer Center, California Institute of Technology, Pasadena, Calif. This center will focus on the development and validation of tools for early detection and stratification of cancer through rapid and quantitative measurement of panels of serum and tissue-based biomarkers. Principal investigator: James Heath, Ph.D. (California Institute of Technology).
The Siteman Center of Cancer Nanotechnology Excellence at Washington University, St. Louis, Mo. This center has a comprehensive set of projects for the development of nanoparticles for in vivo imaging and drug delivery, with special emphasis on translational medicine. Principal investigator: Samuel Wickline, M.D. (Washington University).
"NCI has supported the application of nanotechnology to cancer through a variety of programs and interactions with the scientific community for more than seven years, and we're very gratified that our activities are helping to advance a pipeline of new product opportunities," noted NCI Deputy Director Anna Barker, Ph.D. "In what we believe will be a paradigm shift for cancer research, unprecedented numbers of multidisciplinary teams of basic and clinical researchers at world-class institutions are networking their research together to focus on the key cancer nanotech opportunities. The depth and diversity of the Centers of Nanotechnology Excellence award submissions were extraordinary. With the advent of the CCNEs, we are particularly looking forward to new nanotech-based therapeutic delivery systems that could enhance the efficacy and tolerability of cancer treatments - an advance that would greatly benefit cancer patients."
Other components of the NCI Alliance for Nanotechnology in Cancer include the following:
Cancer Nanotechnology Platform Partnerships are tightly focused programs designed to develop the technologies to underpin new products in six key programmatic areas: molecular imaging and early detection, in vivo imaging, reporters of efficacy (e.g., real-time assessment of treatment), multifunctional therapeutics, prevention and control, and research enablers (opening new pathways for research). These 12, five-year awards, with first-year funding totaling $7 million dollars, will be announced this month.
The Nanotechnology Characterization Laboratory (NCL), established at NCI's Frederick, Md., facility earlier this year, performs analytical tests to guide the research community, support regulatory decisions, and help identify and monitor environmental, health and safety ramifications of nanotech applications. The NCL recently completed its first year of operation and is actively characterizing nanoparticles for academic and commercial researchers through a rigorous set of analytical protocols. The NCL works in concert with the National Institute of Standards and Technology (NIST) and the U.S. Food and Drug Administration (FDA). For more information, please visit http://ncl.cancer.gov.
Multidisciplinary research training and team development: The application of nanotechnology to cancer requires cross-disciplinary training in biological and physical sciences. The Alliance will support training and career development initiatives to establish integrated teams of cancer researchers, through mechanisms such as the NIH National Research Service Awards for Senior Fellows and the NIH National Research Service Awards for Postdoctoral Fellows. Applications are now being accepted for training awards (http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-06-010.html). In addition, through NCI's collaboration with the National Science Foundation, $12.8 million in grants were awarded last month to four institutions over the next five years for U.S. science and engineering doctoral students to focus on interdisciplinary nanoscience and technology research with applications to cancer (http://www.cancer.gov/newscenter/pressreleases/NCINSFIGERT).
For more information about the NCI Alliance on Nanotechnology in Cancer, please visit http://nano.cancer.gov.
For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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OT....what's cooking?....http://pharmalicensing.com/licensing/displicopp/3243
sept 3...#msg-7613122 ....5 days before tsunami hit #msg-4884403 (click link in post).....got ENMD?... ggg
Dallas is jumping...pretty good link....http://www.nbc5i.com/index.html
Looks like the NCI is following Duke in choosing panzem over YC-1....note "nitric oxide" under publications......... Giovanni Melillo, M.D. SAIC FrederickNational Cancer Institute-FrederickAddress: Building 432, Rm 218Frederick, MD 21702-1201Phone:301-846-5050Fax:301-846-6081Email:melillo@dtpax2.ncifcrf.govNovel therapeutic strategies related to Hypoxia inducible factor-1 (HIF-1).Current interests of the DTP-Tumor Hypoxia Laboratory include the development of pharmacological and molecular strategies targeting hypoxia-inducible factor-1 (HIF-1) activity. In vitro and in vivo studies support a role for the HIF-1 in angiogenesis and tumor progression. Therefore, HIF-1 is a novel molecular target for development of cancer therapeutics and anti-angiogenic drugs. To identify novel HIF-1 inhibitors we are developing a screening system based on a luciferase reporter assay. A second interest of the laboratory is to identify and characterize novel hypoxia and HIF-1-inducible genes and to study the molecular mechanisms by which hypoxia promotes gene expression in the tumor microenvironment. To fully elucidate the gene expression profile under hypoxic conditions we are using the microarray technique. We are interested in studying hypoxic induction of novel genes in normal cells infiltrating the tumor (i.e. human monocytes) as well as in cancer cell lines. Interactive possibilities and available reagents include: hypoxia-inducible reporter gene vectors. CredentialsDr. Giovanni Melillo obtained his medical doctor degree from the University of Naples, Italy in 1981. He had his residency and fellowship in Medical Oncology at the National Tumor Institute in Naples. In 1991 he was awarded a CNR-NATO international fellowship and he joined the Laboratory of Molecular Immunoregulation at the NCI-FCRDC as a visiting scientist. He then joined the Laboratory of Experimental Immunology at the NCI-FCRDC where he characterized the role of a hypoxia-responsive element in the promoter of the inducible nitric oxide synthase gene. In July 1996 he became a Clinical associate at the Clinical Oncology Program of the NCI in Bethesda where he became interested in the role of hypoxia-induced angiogenesis in tumor progression. In July 1999 he became a Senior Investigator with the DTP-Tumor Hypoxia Laboratory at the NCI-Frederick. His current interests are to develop novel therapeutic strategies to target hypoxia inducible factor-1 (HIF-1) activity and to identify and characterize novel hypoxia and HIF-1-inducible genes. Recent PublicationsNCBI PubMed listing of publications by Giovanni Melillo. 1. Melillo, G., Musso, T., Sica, A., Taylor, L.S., Cox, G.W., and Varesio, L.: A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J. Exp. Med. 182:1683-1693, 1995. 2. Melillo, G., Brooks, A., Musso, T., Taylor, L.S., Cox, G.W., and Varesio, L.: Functional requirement of the hypoxia-responsive element in the activation of the inducible nitric oxide synthase (iNOS) promoter by the iron chelator desferrioxamine. J. Biol. Chem. 272: 12236-12243, 1997.3. Melillo, G., Sausville, E. A., Cloud, K., Lahusen, T., Varesio, L., and Senderowicz, A.M.: Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of VEGF expression in human monocytes. Cancer Res. 59: 5433-5437, 1999.4. Carta, L., Pastorino, S., Melillo, G., Bosco, M.C., Massazza, S., and Varesio, L.: Engineering of Macrophages to Produce IFN-g in Response to Hypoxia. J. Immunol. 166:5374-5380, 2001.5. Shoemaker, R.H., Scudiero, D.A., Melillo, G., Currens, M.J., Monks, A.P., Rabow, A.A., Covell, D.G., and Sausville, E.A.: Application of high-throughput, molecular-tageted screening to anticancer drug discovery. Current Topics in Medicinal Chemistry 2:229-246, 2002.6. Rapisarda A., Uranchimeg B., Scudiero D.A., Selby M., Sausville E.A., Shoemaker R.H., and Melillo G: Identification of Small Molecule Inhibitors of Hypoxia Inducible Factor 1 (HIF-1) Transcriptional Activation Pathway. Cancer Res. 62: 4316-4324, 2002.7. Tan, A.R., Messmann, R.A., Sausville, E.A., Headlee, D., Arbuck, S.G., Murgo, A.J., Melillo, G., Zhai S., Figg W.D., Swain S.M., and Senderowicz A.M.: Phase I Clinical and Pharmacokinetic Study of Flavopiridol Administered as a Daily 1-Hour Infusion in Patients with Advanced Neoplasms. J. Clin. Oncol. 20(19): 4074-4082, 2002.8. Rybak SM, Sanovich E, Hollingshead MG, Borgel SD, Newton DL, Melillo G, Kong D, Kaur G, and Sausville EA: "Vasocrine" formation of tumor cell-lined vascular spaces: Implications for rationale design of antiangiogenic therapies. Cancer Res. 63: 2812-2819, 2003.[ DTP Home ] [DTP Pathways ] [DTP Discovery ] [DTP Development ] [DTP Site Search ] [DTP Data Search ]
That was funny during a Bush speech the other day. Bush read a list of government programs "social security, medicaid, medicare, housing, WIC, food stamps" on and on.....The list was so long he had to stop and catch his breath.
The real hero during this mess is the taxpayer, the working stiff that's paying the freight.
remember Angel Heart?....freaky New Orleans movie.....http://www.imdb.com/title/tt0092563
police shoot 8....Return to the referring page.
Las Vegas SUN
Today: September 04, 2005 at 14:13:5 PDT
Police Shoot 8 on New Orleans Bridge
ASSOCIATED PRESS
NEW ORLEANS (AP) -
0904dv-hurricaneupdate Police shot eight people carrying guns on a New Orleans bridge Sunday, killing five or six of them, a deputy chief said.
Deputy Police Chief W.J. Riley said the shootings took place on the Danziger Bridge, which connects Lake Pontchartrain and the Mississippi River.
He said he had no other details.
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Folks should (and should have heeded) heed this warning from NOAA.....http://www.cpc.ncep.noaa.gov/products/outlooks/hurricane.html
I got choked up earlier, local radio did Elvis...http://www.lyricsfreak.com/e/elvis-presley/47869.html
Nooray and Art Bell host Coast to Coast, pretty cool stuff.....an ion article....http://www.indiadaily.com/editorial/2070.asp
Boondocks as in Green acres, gardens, goats, we don't make a party outta of loving....gg
Probably BS, but George Nooray on Coast to Coast has had on expert guest's this week suggesting that the weather is being manipulated by a foreign enemy. They say the enemy ionizes a tropical storm, and can guide the storm to a general location.
The 2005 hurricane season may mirror the 2004 season. If I lived on the Texas coast I'd be making exit plans. Maria is forming now, and the gulf surface temperture is 88 degress. The goal is to flee the masses as much as the hurricane. There's lots of friendly small towns in West Texas and Panhandle areas. I'm talking your Claudes, Big Springs, Borgers....boonie mocus
yahoo most emailed photos, mostly Katrina related....http://news.yahoo.com/news?tmpl=index2&cid=1756
"Sea surface temperatures are the highest ever recorded in the Atlantic".....http://www.wunderground.com/hurricane/active2005.asp
C_Peptide...I'll do the OT thing from now on. Gendicine is similar to Advexin, I find it interesting that INGN was granted Chinese patents...old post..#msg-3882258
combo success...http://biz.yahoo.com/prnews/050808/dam024.html?.v=18
spruced up web page....http://www.nano.gatech.edu/faculty-staff/profile.php?id=66
recent RA abstract...http://www.icms.com.au/inflammation2005/abstract/218.htm
"A beautiful mind" was on last night....I guess I may be a tad delusional....I have a thing about #74....however...#msg-7259151
lime green mystery....Medgenn web site had a soothing lime green background, can't find the site now...The new ENMD site had a cool lime green background ,but they took it dowm.....Does Maaco do lime green?
ot...merge time...http://biz.yahoo.com/prnews/050821/nysu019.html?.v=18
You're welcome potsy, I'm all in...I like this too... EntreMedSite Search: CONTACT US / SITE MAP CORPORATE SUMMARY PIPELINE THERAPEUTIC PATHWAYS INVESTOR RELATIONS MEDIA CENTER ELECTRONIC MEDIA KIT PRESS RELEASES PRESS RELEASE ARCHIVES CLINICAL TRIALS • NEWS • RECENT PRESENTATIONS • SEC FILINGSPRESS RELEASE ARCHIVESReport Demonstrates Activity of 2ME2 With Paclitaxel in Head and Neck CarcinomaPreclinical Results Support Potential Clinical StudyJanuary 19, 2005ROCKVILLE, MD, Jan. 19 -- EntreMed, Inc. (Nasdaq: ENMD), a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammation, today announced a published preclinical report supporting the use of 2-methoxyestradiol (2ME2) in combination with paclitaxel in the treatment of recurrent or advanced head and neck squamous cell carcinoma (HNSCC). Paclitaxel is a first-line treatment for recurrent head and neck squamous cell carcinoma. These findings, published in the December issue of Clinical Cancer Research (Vol. 10, No. 24: 8665- 8673), demonstrated that 2ME2 exhibited both antitumor and antiangiogenic activity in an animal model of head and neck squamous cell carcinoma. EntreMed is currently conducting clinical studies with 2ME2 (Panzem®) in patients with advanced cancer.Specifically, the study demonstrated that 2ME2, alone or in combination with paclitaxel, significantly inhibited tumor growth in a preclinical xenograft model. The study also showed that 2ME2 inhibits tumor cell proliferation and promotes apoptosis (cell death) in vitro, as well as providing an additive or synergistic effect with paclitaxel.The study further demonstrated that 2ME2 inhibits HIF-1alpha (hypoxia- inducible factor) nuclear activity in a dose-dependent manner and that 2ME2 affects the expression of HIF-1alpha regulated genes, specifically up- regulating bid, a pro-apoptotic bcl-2 family member, and inhibits the expression of VEGF (vascular endothelial growth factor), an angiogenic growth factor.EntreMed Vice President and Chief Medical Officer, Carolyn F. Sidor, M.D., commented on the publication, "The findings from this study further support the antitumor and antiangiogenic activities of 2ME2. Inhibiting HIF-1alpha is important, since its overexpression correlates with metastasis, decreased responses to chemotherapy and radiation and mortality in HNSCC. This study suggests a new possible therapeutic indication where anti-HIF-1alpha agents like 2ME2 could be useful in treating advanced cancers. The use of 2ME2 in combination with paclitaxel, which also induces apoptosis, provides important input for further development of Panzem® NCD alone and in combination with chemotherapy."Head and neck squamous cell carcinoma affects over 300,000 Americans, with nearly 30,000 new cases annually. These tumors are generally already advanced when diagnosed, the five-year mortality rate is about 50%, and tumor recurrence is common. The complete article, "2-Methoxyestradiol Inhibits Hypoxia-Inducible Factor 1alpha, Tumor Growth, and Angiogenesis and Augments Paclitaxel Efficacy in Head and Neck Squamous Cell Carcinoma," co-authored by scientists at the National Institutes of Health and EntreMed, Inc., is available in Clinical Cancer Research (Vol. 10, No. 24, pg. 8665).About EntreMedEntreMed, Inc. (Nasdaq: ENMD) is a clinical-stage pharmaceutical company developing therapeutic candidates primarily for the treatment of cancer and inflammation. Panzem® (2-Methoxyestradiol or 2ME2), the Company's lead drug candidate, is currently in clinical trials for advanced cancer, as well as in preclinical development for indications outside of oncology. EntreMed's goal is to develop and commercialize new compounds based on the Company's expertise in angiogenesis, cell cycle regulation and inflammation -- processes vital to the treatment of cancer and other diseases. The Company's expertise has also led to the discovery of new molecules, including analogs of 2ME2, peptides of tissue factor pathway inhibitor (TFPI), and inhibitors of fibroblast growth factor-2 (FGF-2) and proteinase activated receptor-2 (PAR-2). EntreMed is developing these potential drug candidates for either in-house advancement or external partnering. Additional information about EntreMed is available on the Company's website at http://www.entremed.com and in various filings with the Securities and Exchange Commission. Panzem® NCD is in clinical trials and has not been approved by the Food and Drug Administration.Forward Looking StatementsThis release contains, and other statements that EntreMed may make may contain, forward-looking statements within the meaning of the Private Securities Litigation Reform Act with respect to the outlook for expectations for future financial or business performance, strategies, expectations and goals. Forward-looking statements are typically identified by words or phrases such as "believe," "feel," "expect," "anticipate," "intend," "outlook," "estimate," "target," "assume," "goal," "objective," "plan," "remain," "seek," "trend," and variations of such words and similar expressions, or future or conditional verbs such as "will," "would," "should," "could," "might," "can," "may," or similar expressions. Forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over time. Forward-looking statements speak only as of the date they are made, and EntreMed assumes no duty to update forward-looking statements. Actual results could differ materially from those currently anticipated due to a number of factors, including those set forth in EntreMed's Securities and Exchange Commission filings under "Risk Factors," including risks relating to EntreMed's need for additional capital and the uncertainty of additional funding; the early-stage products under development; uncertainties relating to clinical trials; our success in the further clinical development of Panzem® NCD, dependence on third parties; future capital needs; and risks relating to the commercialization, if any, of the Company's proposed products (such as marketing, safety, regulatory, patent, product liability, supply, competition and other risks).For more information, contact:Ginny DunnAssociate Director, Corporate Communications & Investor Relations(240) 864-2643 9:59am: ENMD 2.57 (-0.09) 10:14am: ^NBI 753.62 (+0.56) 10:15am: ^IXIC 2135.88 (-9.27) 10:15am: ^BTK 605.05 (-0.63) N/A: ^DJ 0.00 (N/A) EntreMed, Inc. • 9640 Medical Center Drive, Rockville, MD 20850 • (240) 864-2600 • (240) 864-2601 (fax) Copyright © 2000 - 2005, EntreMed, Inc.By using this site, or any of our services, you agree to our terms and conditions.Web Application Development & Online Presence Management by Brightline Media Inc.
You're welcome docaaron...The cancercell piece refers to radiation and was funded in part by Aeolus, so I don't know how panzem fits in their equation...The Duke panzem trial is a chemo combo so I guess Dewhirst is referring to panzem ( bottom of article) The Duke trial should start later 05........ Back to Story - HelpProtein May Hold Key to Cancer Radiation Treatments By Randy DotingaHealthDay ReporterWed Aug 17,11:47 PM ET WEDNESDAY, Aug. 17 (HealthDay News) -- Like other cancer treatments, radiation isn't always a cure. Tumors can come back within months or years to wreak more havoc.But now, researchers say they're gaining a better understanding of how to tinker with the body's biochemistry to make radiation more effective.Manipulation of a protein known as HIF-1 seems to provide added protection against the return of cancer after radiation treatment, according to a new study involving mice.The "trick," said study author Dr. Mark W. Dewhirst, is to avoid turning the protein into a villain that actually makes it harder to control the cancer.The research won't provide immediate benefits to cancer patients. But scientists are currently researching several drugs that may be able to control the protein, said Dewhirst, a professor of radiation oncology at Duke University. Along with chemotherapy, radiation is a routine treatment for cancer. Contrary to popular belief, radiation doesn't burn tumors. Instead, the energy produced by radiotherapy damages the DNA inside cells, making them die, Dewhirst said.But radiation doesn't always work. Both radiation and chemotherapy can boost the levels of the HIF-1 protein, a "master switch" that controls more than 70 other proteins that govern cellular tasks, Dewhirst said. In the process, HIF-1 can keep cancer cells alive by protecting blood vessels that feed tumors.But the HIF-1 protein can also help by making the cancer cells more vulnerable to radiation, Dewhirst said.In the new study, Dewhirst and a colleague tried to unravel the workings of the protein by conducting experiments on mice. They report their findings in the August issue of Cancer Cell.The researchers reported that blocking HIF-1 immediately after radiation treatment helped boost the amount of time before the tumors returned.Scientists plan to see if their theories about HIF-1 hold true during chemotherapy treatment, and tests of drugs that target the protein should begin in humans later this year, Dewhirst said.But years of research will be needed to understand the HIF-1 protein, Dewhirst said. "We are far from knowing everything there is to know about it."More informationLearn more about radiation therapy from the National Cancer Institute.Copyright © 2005 HealthDay. All rights reserved.The information contained above is intended for general reference purposes only. It is not a substitute for professional medical advice or a medical exam. Always seek the advice of your physician or other qualified health professional before starting any new treatment. Medical information changes rapidly and while Yahoo and its content providers make efforts to update the content on the site, some information may be out of date. No health information on Yahoo, including information about herbal therapies and other dietary supplements, is regulated or evaluated by the Food and Drug Administration and therefore the information should not be used to diagnose, treat, cure or prevent any disease without the supervision of a medical doctor. Copyright © 2005 Yahoo! Inc. All rights reserved.Questions or CommentsPrivacy Policy -Terms of Service - Copyright/IP Policy - Ad Feedback
HIF-1 made the cover....http://www.cancercell.org
Duke hif-1 news...out today....http://www.eurekalert.org/pub_releases/2005-08/cp-rml080805.php
rubik's cube.....#msg-5519377
pssst...#msg-5389473
I like to make predictions....posted this 5 days before the tsunami hit...#msg-4884403 the next shoe to drop, leaky vessel....#msg-5072135
NCD....winner....smokin..http://www.elan.com/EDT/Announcements/06-Jul-2005.asp