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  • More Promising Susan Keay Research

    IC Nerd Alert! Here's another interesting study by Susan Keay, the reearcher who discovered the APF factor in the urine of IC patients. She and her colleagues have determined that they can inhibit the effect of apf by using an apf antagonist. Interesting stuff. Doncha just love science! - Jill

    Normalization of proliferation and tight junction formation in bladder epithelial cells from patients with interstitial cystitis/painful bladder syndrome by D-proline and D-pipecolic acid derivatives of antiproliferative factor - Abstract

    Tuesday, 08 March 2011

    Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. Veterans Administration Maryland Health Care System, Baltimore, Maryland; Structural Biophysics Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland; Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland; Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.

    Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that IC/PBS bladder epithelial cells make a glycopeptide antiproliferative factor or "APF" (Neu5Acα2-3Galβ1-3GalNAcα-O-TVPAAVVVA) that induces abnormalities in normal cells similar to those in IC/PBS cells in vitro, including decreased proliferation, decreased tight junction formation, and increased paracellular permeability. We screened inactive APF derivatives for their ability to block antiproliferative activity of asialylated-APF ("as-APF") in normal bladder cells, and determined the ability of as-APF-blocking derivatives to normalize tight junction protein expression, paracellular permeability, and/or proliferation of IC/PBS cells. Only two of these derivatives [Galβ1-3GalNAcα-O-TV-(D-pipecolic acid)-AAVVVA and Galβ1-3GalNAcα-O-TV-(D-proline)-AAVVVA] blocked as-APF antiproliferative activity in normal cells (p< .001 for both). Both of these antagonists also 1) significantly increased mRNA expression of ZO-1, occludin, and claudins 1, 4, 8, and 12 in IC/PBS cells by qRT-PCR; 2) normalized IC/PBS epithelial cell tight junction protein expression and tight junction formation by confocal immunofluorescence microscopy; and 3) decreased paracellular permeability of (14) C-mannitol and (3) H-inulin between confluent IC/PBS epithelial cells on Transwell plates, suggesting that these potent APF antagonists may be useful for development as IC/PBS therapies.

    Written by:
    Keay S, Kaczmarek P, Zhang CO, Koch K, Szekely Z, Barchi JJ Jr, Michejda C.
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  • #2
    Wow, very confusing, but still great news! Glad to hear something new from Dr. Keay!
    ~Ashley

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    • #3
      will this method reverse the damage to the bladder?
      <center>
      <a href="http://s1086.photobucket.com/albums/j441/linda5552/?action=view&amp;current=Picture005.jpg" target="_blank"><img src="http://i1086.photobucket.com/albums/j441/linda5552/th_Picture005.jpg" border="0" alt="Photobucket" ></a>
      </center>

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      • #4
        Yeah.. she's been pretty quiet in the last two years probably to work on any patents that might be related to apf. Linda, I have no idea.
        Would you like to talk with someone about your IC struggles? The ICN now offers personal coaching sessions that include myself, Julie Beyer RD on the diet and Dr. Heather Howard on Sexuality. http://www.icnsales.com/icn-personal-coaching/

        Looking for books, magazines & reports on IC? Please visit the ICN Shop at: http://www.icnsales.com: Your ICN subscription & purchases in our shop support these message boards, chats and special events. BECOME AN ICN ANGEL TODAY!

        Please remember that the information on the ICN is provided with the understanding that ICN, its founder, staff, volunteers, and participants are not engaged in rendering medical or professional medical services. We cannot and do not give medical advice. Only your personal physician can do this for you.






        Comment


        • #5
          Originally posted by Linda May View Post
          will this method reverse the damage to the bladder?
          when can they start using this treatment?
          <center>
          <a href="http://s1086.photobucket.com/albums/j441/linda5552/?action=view&amp;current=Picture005.jpg" target="_blank"><img src="http://i1086.photobucket.com/albums/j441/linda5552/th_Picture005.jpg" border="0" alt="Photobucket" ></a>
          </center>

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          • #6
            Jill, is there anything we can do to support this research? Like raising money?
            ~Ashley

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            • #7
              Originally posted by Linda May View Post
              will this method reverse the damage to the bladder?
              how do they determine if you apf?
              <center>
              <a href="http://s1086.photobucket.com/albums/j441/linda5552/?action=view&amp;current=Picture005.jpg" target="_blank"><img src="http://i1086.photobucket.com/albums/j441/linda5552/th_Picture005.jpg" border="0" alt="Photobucket" ></a>
              </center>

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              • #8
                Linda, there's a lot of info about APF in this thread: http://www.ic-network.com/forum/showthread.php?t=58781
                ~Ashley

                Comment


                • #9
                  Hmmm

                  I swear every time I read about APF, it makes me wonder if my compounds I am making as drug therapeutics would be appropriate for this. My compounds have been found to inhibit cancer cell proliferation. I make compounds that come from an ancient chinese medicinal mushroom. We have had very promising results with the actual compounds with the mushroom along with other analogues.

                  I enjoy reading these science papers. I think it is interesting to look at derivatives of amino acids along with the different coding to go on.

                  Interesting.

                  Erin
                  24 year old Ph.D student in Organic Chemistry

                  Loves to listen to music, play with my animals (cat, fish, 2 hamsters), and live life to the fullest each and every day.

                  My blog (just started):

                  http://imaginenoworries.blogspot.com/

                  Medications:
                  Elavil 25mg (helped with nighttime urination-used to be 7 or more times a night, now just once)
                  Cymbalta 60mg
                  Gabapentin (Neurontin) (3200mg/day)
                  Zyrtec 10mg
                  Xanax 0.5mg up to 3 times a day(spasms, anxiety)
                  Uribel
                  Macrobid 100mg (only on days when doing an instill)
                  Albuterol
                  Yaz Birth Control (3 months on birth control, then period)
                  Pelvic floor therapy
                  Valium 5 mg (inserted vaginally)
                  MScontin 30 mg (3 times a day)
                  Percocet 10/325mg (every 6 hours)
                  TENS Therapy, CVS machine, 30 minutes once or twice a day
                  Sanctura XR 60 mg (to help control severe bladder spasms that are causing urinary retention episodes and enable normal bladder sensations)

                  *** 1/4 of a teaspoon of baking soda in an 8 ounce glass of water up to 4 times a day*****

                  Instill:

                  Currently doing hyaluronic acid instillations (cystistat-6 instillations, once a week, already had 4...not sure if helping)

                  Used to do these:

                  Solu-Cortef (act-o-vial) 100 mg: 2 mL
                  Marcaine (bupivicaine) 0.5 % 25 mL
                  20,000 units Heparin
                  3 mL sodium bicarbonate

                  Diagnoses: Moderate IC, scoliosis, asthma, ovarian cysts, PFD, IBS, Fibromyalgia, vulvodynia, Fowler's syndrome (mild) 'Central Sensitivity Syndrome.'

                  Comment


                  • #10
                    Wow, Erin, that's really interesting.
                    ~Ashley

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                    • #11
                      In plane English, what does it mean?

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                      • #12
                        Landish,
                        I think it means that they are looking at substances that block APF. If APF is blocked the thought is damage supposedly caused by APF will blocked.

                        Suzanne

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                        • #13
                          It sounds like Dr. Keay may be on the right track. Maybe this one will lead to our "magic pill."


                          Donna
                          Stay safe


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                          • #14
                            Ooh Jill, very exciting indeed! I was just wondering what Dr. Keay was up too with that grant she got to work with that pharmaceutical company. Thank you so much for that piece of info. Yes Donna, lets keep our fingers crossed. I think the APF finding is so promising for us!!!

                            Jill
                            "Where there is hope there can be faith. Where there is faith, miracles can occur."

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                            • #15
                              To answer a previous question on how APF is determined, from what we have read it seems they have to do a biopsy, and correct me if I'm wrong. It would be wonderful if they could do this with a UA, but soewhere over the rainbow...SIGH Jill, wife of Bob

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