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Various: Admin/TNP-470/Apoptosis/THE MARCH

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  • Janice and Ben Haines
    Greetings, There are four parts to this e-mail. 1) NHL-low administration 2) An abstract on TNP-470 and mention of leukemia 3) Interesting article on Apoptosis
    Message 1 of 1 , Sep 2, 1998
      There are four parts to this e-mail.
      1) NHL-low administration
      2) An abstract on TNP-470 and mention of leukemia
      3) Interesting article on Apoptosis sent to me by a member on here, no
      explanation if he wanted to post anonymously so here it is.
      4) THE MARCH latest newsletter (Janice and I are going of course!)

      First up, Administration, my Internet Service Provider (ISP) is called
      Wavefront and it is the domain name in the e-mail address of
      nhl-low@.... The problem is they are soon changing to VISI and
      that means a lot of work for me SO...I am going to dump their service and
      go with Findmail's service. It will be better all around, a lot more
      features, and cheaper for Janice and me. I will gladly pay the $4.95 a
      month to keep OUT all ADVERTISING in our e-mails. If we didn't we would get
      ads inside every e-mail, toughest for future research. Also, I am beefing
      up technically and going for a fairly expensive service offered from US
      West called DSL which will speed things up by a factor of eight so I can
      research more efficiently. Once they are off strike US West (US Stress or
      US Worst if you know people in the middle of the strike) will be our new
      ISP too. So, what does this mean for you? You might be getting messages
      from a NEW NHL-low (it might be called NHL-low2 and I will drop the 2 once
      I dump Wavefront.) Ignore all messages from NHL-low2 until I tell you the
      new list is up and running. YOU HAVE TO DO NOTHING, mail will come from
      Wavefront.com for a while yet. Do expect some glitches but I am fairly
      experienced so I don't forsee any major ones. The archives will stay in the
      same place and will be complete. It will take me time to setup and get
      everyone converted.
      Thanks in advance for your patience.

      Other things, I have been researching just like normal every day but there
      is very little new information on low grade lymphoma is all, thus the low
      volume of mail. I have been researching angiogenesis like crazy. All I can
      say is I am incredibly optimistic, those are the most promising therapies
      out there even though the first generation drugs (TNP-470 and Thalidomide)
      will not seem to show much hope. If they work even a little (especially in
      leukemia and lymphoma - in clinical trial the end of 1998) my optimism will
      soar for the future. Huge strides are being made in this field.

      Finally, hats off to Paul on here. Incredible, unselfish, funny, serious,
      and informative posts on his IDEC-Y2B8 treatment. We will 'expect to win'
      with guys like you on the team.

      Cancer Res 1998 Aug 15;58(16):3751-3756

      Suppression of hepatoma growth and angiogenesis by a fumagillin derivative
      TNP470: possible involvement of nitric oxide synthase.

      Yoshida T, Kaneko Y, Tsukamoto A, Han K, Ichinose M, Kimura S

      First Department of Medicine, Faculty of Medicine, The University of Tokyo,

      [Medline record in process]

      TNP470, a derivative of fumagillin, suppressed in vivo growth of human
      PLC/PRF/5 hepatoma and ameliorated cachexia of hepatoma-bearing mice. These
      in vivo effects were associated with reductions in microvessel and
      macrophage counts. In in vitro experiments, TNP470 inhibited the growth and
      migration of human hepatoma and bovine vascular endothelial (VE) cells.
      TNP470 did not inhibit the production of VE growth factor by the hepatoma,
      which suggests that this compound acts directly on VE cells in vivo. In
      contrast, TNP470 inhibited the production of leukemia inhibitory factor,
      which may be related to the amelioration of cancer cachexia. TNP470 induced
      apoptosis and enhanced the expression of beta-galactosidase, a biomarker of
      senescence, which was partly mimicked by a nitric oxide (NO) donor
      S-nitroso-N-acetyl penicillamin. TNP470 inhibited myristoylation and
      membrane translocation of NO synthase and increased the cellular content of
      NO synthase and production of NO. Therefore, it is suggested that the
      actions of TNP470 are mediated, at least in part, through the inhibition of
      membrane translocation of biologically active proteins.

      PMID: 9721889, UI: 98387344


      LA JOLLA, Calif., Aug. 31 /PRNewswire/ -- Idun Pharmaceuticals, Inc. today
      announced that the U.S. Patent and Trademark Office has issued patent
      number 5,786,173, titled "MCH4 and MCH5, Apoptotic Proteases, Nucleic Acids
      Encoding and Methods of Use." The apoptotic proteases MCH4 and MCH5 (which
      are also known as caspase 10 and caspase 8, respectively) were
      co-discovered by Idun scientists and scientists at Thomas Jefferson
      University in Philadelphia, Pennsylvania. Thomas Jefferson University
      granted Idun an exclusive license to the patent in November 1997. Idun also
      holds an exclusive license from Thomas Jefferson University to an issued
      patent covering caspase 6. Caspases are cysteine proteases that function in
      the effector phase of apoptosis, or programmed cell death. Caspases are
      normally expressed in living cells in an inactive state. In response to
      certain cell death-inducing stimuli, caspases become activated and cleave a
      number of protein substrates that are critical for cell viability,
      resulting in apoptosis. Caspases have become the target of pharmaceutical
      research to develop therapeutics for diseases characterized by excessive
      cell death.

      "Caspases 8 and 10 are unique among the other caspase family members in
      that they are coupled to specific cell surface receptors that, when bound
      by their cytokine ligands, instruct cells to undergo apoptosis," said Emad
      Alnemri, Ph.D., Associate Professor of Microbiology and Immunology at
      Jefferson Medical College of Thomas Jefferson University. "Thus, caspases 8
      and 10 are positioned at the top of apoptotic signaling cascades initiated
      by members of a family of cytokine receptors, including the Fas and Tumor
      Necrosis Factor receptors." Dr. Alnemri, a member of the Kimmel Cancer
      Center and Deputy Director of the Center for Apoptosis Research, is a
      recognized expert in caspase research and a co-inventor on the patent.

      Studies from several laboratories, including Idun's, have demonstrated that
      inhibition of caspase 8 protects cells from apoptosis triggered by
      death-inducing cytokines. One set of studies focused on viruses, which
      carry a variety of genes that are known to inhibit apoptosis. "Viruses have
      designed two ways of preventing apoptosis that involve inhibition of
      caspase 8," noted Robert Armstrong, Ph.D., Section Head of Cell Biology at
      Idun and a co-inventor on the patent. "One type of viral gene product
      prevents caspase 8 from becoming activated, while another type functions as
      a potent inhibitor of the active caspase 8 protease. The fact that viruses
      invented two alternative approaches to inhibiting caspase 8 is indicative
      of the importance of caspase 8 in apoptotic signaling pathways."

      Idun is developing caspase inhibitors in several therapeutic areas. In
      collaboration with Novartis Pharma Ltd., Basel, Switzerland, Idun is
      pursing caspase inhibitors for treatment of neurodegenerative diseases and
      stroke. In addition, Idun is pursuing caspase inhibitors for treatment of
      cardiovascular diseases, inflammation and organ damage. "Recent studies
      have suggested a role for caspase-mediated apoptosis in diseases involving
      organ damage, for example in the liver and the myocardium, as well as in a
      number of inflammatory diseases," said Kevin Tomaselli, Ph.D., Idun's Vice
      President of Science and Technology and a co-inventor on the patent. "We
      are developing small molecule inhibitors of several caspases, including
      caspases 8 and 10. Idun is in pre-clinical development of caspase
      inhibitors for hepatic disease and is seeking corporate partners to pursue
      the cardiovascular and inflammation indications."

      Idun Pharmaceuticals creates innovative human therapeutics with a primary
      focus on controlling apoptosis, or programmed cell death. In addition to
      its focus on small molecule inhibitors of apoptosis for applications in
      central nervous system disorders, cardiovascular disease, inflammation, and
      organ damage, Idun's drug discovery programs focus on small molecule
      activators of apoptosis for applications in cancer.

      Source: Idun Pharmaceuticals, Inc. Contact: Kevin J. Tomaselli, Ph.D., Vice
      President, Science & Technology, of Idun Pharmaceuticals, 619-623-1330; or
      Barbara Lindheim (investor), 212-696-4455, ext. 237, or Amy Flood (media),
      of Noonan/Russo Communications, Inc., 415-677-4455, for Idun
      Pharmaceuticals, Inc. * 1997, PR Newswire Date:


      Wed, 2 Sep 1998 09:21:40 -0400 (EDT)
      From: THE MARCH <special@...>
      Subject: On THE MARCH Newsletter
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      September 2, 1998 Vol. 1 No. 7

      THE MARCH Coming Together to Conquer Cancer(SM) September 25 & 26, 1998


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      Look down on Interstate 95 or the Capital Beltway in the early morning
      hours of September 26, and you'll see something a little out of the
      ordinary: a caravan of buses - hundreds of them - all headed towards DC and
      THE MARCH!

      Organizations and communities close to the Washington area, and some not so
      close, are filling buses with survivors, supporters and caregivers who are
      joining the National Rally to conquer cancer. These are just a few of the
      groups you'll see on The Mall in September:

      Ebenezer Missionary Baptist Church, Rocky Mount, NC: 15 buses! The Cancer
      Institute of New Jersey, New Brunswick, NJ: 10 buses! American Cancer
      Society, Baltimore, MD American Cancer Society, Glen Allen, VA American
      Cancer Society, Newcastle, DE Asheville, OH Cleveland Coalition for Cancer
      Survivorship, OH Comp. Cancer Center of Wake Forest Univ., Winston-Salem,
      NC Duke Comprehensive Cancer Center, Durham, NC Fox-Chase Cancer Center,
      Philadelphia, PA Get Away Travel & Tours, Erie, PA Hershey, PA Huntsville,
      AL Jefferson Cancer Network, Philadelphia, PA Keep The Faith-Cancer Web
      Organization, Pikeville, KY Mary Babb Randolph Cancer Center, Morgantown,
      WV Massey Cancer Center, Richmond, VA Northeast Regional Cancer Institute,
      Scranton, PA Pinegrove, PA Ruby Memorial Hospital, Morgantown, WV Sidney
      Kimmel Cancer Center, Philadelphia St. Luke's Hospital, New York, NY Susan
      G. Komen Breast Cancer Foundation, Summit, NJ UNC Lineberger Comprehensive
      Cancer Center, Chapel Hill, NC University of Penn Cancer Center,
      Philadelphia University of Virginia Cancer Center, Charlottesville VA
      Cancer Treatment Centers, Richmond, VA

      Thanks to all of our Bus Captains - keep up the great work!

      Want to get on a bus? Visit http://www.themarch.org/dc/buses.html.



      University of Missouri, Columbia, Aug. 25 - It's a dozen radio, television
      and print interviews later and Dani Grady's still on a roll. Simply put:
      Today's reception at the Ellis Fischel Cancer Center here was a smashing
      success for Grady and her co-riders.

      "I can't tell you how great this is," Grady says, her voice pulsating with
      emotion. "The people are so supportive of our ride and what THE MARCH is
      doing. It's unbelievable. And we really, really appreciate everything
      everyone is doing for us. Last Friday's reception in Kansas City was
      spectacular and we want people to know that. These receptions really pump
      us up!"

      It was Day 37 of Grady's 10-week, 4,000-mile Conquer Cancer Coast-To-Coast
      National Bike Tour. The entourage crossed the halfway point in Kansas and
      are headed across the Midwest.

      For Peter Maretz, the ride through Missouri was particularly poignant. Four
      years ago the San Diego attorney and veteran triathlete battled melanoma.
      "Being here with Dani is so special, I can't really describe it," Maretz
      said. "Lots of people know abo ut us, and the ride is getting great coverage.

      "Believe it or not, people are asking for our autographs! We were in a
      country restaurant scarfing back more carbohydrates than I've ever seen
      before and this kid saw our signs and asked for our autographs. And around
      Arrow Rock we met this woman with the Optimists Club who's organizing for
      THE MARCH. We met a professor from the University of Missouri who was
      cycling, and he asked for our autographs, too. It's just incredible."

      Check out Dani's web site at www.thrivers.org for updates! Still ahead:

      Sept. 8, Noon, Detroit: Following a morning media blitz, Grady will join
      MARCH President Ellen Stovall for a large reception at the Karmanos Cancer
      Institute. Sept. 9, 9 a.m., Cleveland: The University Hospitals Ireland
      Cancer Center at Case Western Reserve University is hosting a public
      reception for the bicyclists. A group of riders will join the tour as it
      heads to Pittsburgh. Sept. 10, 4 p.m., Pittsburgh: Dr. John Kirkwood,
      director of the University of Pittsburgh Cancer Institute, will participate
      in a reception and is recruiting a group of patients and survivors to ride
      out of town with the bicyclists. Sept. 15, Philadelphia: 10 a.m., Sidney
      Kimmel Cancer Center, Jefferson Medical College, reception and ride; 4
      p.m., University of Pennsylvania Cancer Center reception Sept. 16,
      Philadelphia: 9 a.m., Fox Chase Cancer Center is hosting a reception.



      MARCH events are popping up all over the country! Check the web site,
      http://www.themarch.org/community/events, for an updated listing of
      community events in your area. Please contact Jennifer Granston at
      1.877.THE.MARCH, ext. 207 or jgransto@... with any additions,
      updates or changes. Here's the latest news:

      * Morgantown, WV: During the sold-out September 5th football game between
      West Virginia University and Ohio State, gameboards in Mountaineer stadium
      will be flashing information about THE MARCH throughout the entire
      halftime! Speak with the athletic depar tment at your local schools about
      doing the same. * Tampa, FL: The governor of Florida has declared September
      26th "MARCH DAY". Their event will take place at the Ice Palace and will
      feature a 6-block "symbolic" march. Organizers have been very busy
      promoting THE TAMPA MARCH - they have been featured in 4 newspaper articles
      and on a Sunday morning show for the local CBS affiliate. And you can't
      drive through Tampa without learning about THE MARCH - 20 billboards
      currently display all the details! * San Antonio, TX: The first MARCH Town
      Hall Meeting was held here in City Council Chambers on August 25. Prior to
      the 25th, the event was featured in the San Antonio News Express and on a
      morning show of the local NBC affiliate. Their CBS affiliate will accompany
      the San Antonio delegation to THE MARCH in Washington. * Chicago, IL: A
      city-wide candlelight vigil will be held Friday, September 25 in Grant
      Park. * Hampton, Newport News & Norfolk, VA: Mayors of these cities are
      proclaiming September 26 "THE MARCH DAY, Coming Together To Conquer
      Cancer". Local Farm Fresh grocery stores are distributing MARCH brochures,
      and Gear Up Printing of Hampton sponsored the production of MARCH posters
      which are being distributed to local merchants and medical care facilities.
      * Staunton, VA: Bosom Buddies staffed MARCH volunteer tables at the Augusta
      and Rockingham County Fairs. They distributed over 2000 brochures and
      collected hundreds of names for the Honor Roll that will be displayed at
      the National Candlelight Vigil on Se ptember 25.



      Getting the word out is VITAL! If you have received materials from THE
      MARCH, it is important that those items are distributed to a wide variety
      of places throughout your community. Think of places you and your family
      members go to regularly such as work, church, school, the senior's center,
      local restaurants, grocery stores, dry cleaners, video store, gym, group
      meeting halls, etc. If you have not received a package of MARCH promotional
      items or would like to get more, please call the field organizing de
      partment at 1.877.THE.MARCH. Please visit the Internet promotion section of
      our website at http://www.themarch.org/help/ipromo.html to find out how you
      can promote THE MARCH on the Internet.


      HONOR ROLL: Names due Friday, September 11

      Reminder: THE MARCH is collecting names and photographs of individuals who
      lost their lives to cancer for presentation September 25 and 26. Names must
      be submitted exactly as you wish to see them displayed, must include a
      city/state designation, and can b e sent via e-mail to
      honorroll@... or by fax to THE MARCH, Operations and Logistics at
      202.861.3326. Names and photographs should be mailed to: THE MARCH, Attn:
      Honor Roll -- Operations & Logistics, 1730 K Street NW, 4th Floor,
      Washington, DC 2 0006.

      PLEASE NOTE: * We cannot guarantee that all names and photographs will be
      included. * Photographs should be no larger than 3" x 5" and mailed in
      packaging that prevents damage. * All photographs become the property of
      THE MARCH and will not be returned. * NAMES WILL NOT BE TAKEN OVER THE PHONE.

      If you have any questions, please feel free to call the Operations &
      Logistics staff toll-free at 1.877.843.6272 ext. 227.



      The official MARCH T-shirt is a Fruit of the Loom 50/50 blend in Navy with
      THE MARCH logo on the front and artwork on the back. One shirt sells for
      $8.00 in advance, plus shipping and handling, and $10.00 at the event on
      September 26. They are available in adult sizes L, XL and XXL, and
      "one-size-fits-all" for children.

      The poster measures 13 ¾" wide by 24 ½" long and costs $5.00 plus shipping
      and handling.

      Order yours today! We accept VISA and MasterCard. Call 1.877.654.0415.



      The Sidney Kimmel Foundation for Cancer Research, our Presenting Sponsor,
      was established by Sidney Kimmel, founder and chairman of Jones Apparel
      Group. Since its formation in 1993, the Foundation has supported the
      programs of accomplished young investiga tors which emphasize basic cancer
      research, the rapid translation of science concepts into potential
      therapeutic applications and clinical research with innovative treatment
      strategies. The Kimmel Foundation has also funded The Philadelphia Heart
      Institut e; The Sidney Kimmel Cancer Center, San Diego; and the Kimmel
      Cancer Center of Jefferson Medical College, Philadelphia.

      Convening Organizations: National Coalition for Cancer Survivorship;
      Friends of Cancer Research; Intercultural Cancer Council

      Presenting Underwriters: Bristol-Myers Squibb Oncology; GlaxoWellcome;
      CaPCURE/Milken Family Foundation; Pharmacia & Upjohn


      NATIONAL HEADQUARTERS 1730 K Street, NW Washington, D.C. 20006

      e-mail: info@... web site: www.themarch.org fax:
      1.202.861.4794 phone: 1.877.THE.MARCH (1.877.843.6272)


      Friday, September 25, 1998

      Sunset Candlelight Vigil & Interfaith Service Lincoln Memorial

      Saturday, September 26, 1998

      9:00am Cancer Education Activities and Displays The National Mall

      Noon THE MARCH Rally & Entertainment The National Mall Capitol End

      For the latest transportation and housing information, please call us
      toll-free at 1.877.THE.MARCH (1.877.843.6272)

      To volunteer at our National Headquarters or at the events on The National
      Mall, please call the Volunteer Coordinator at 1.877. 843.6272, ext. 241
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