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05-10-2008, 08:02 PM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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first there was Tiptoe, now there is Dachsund!!
: Proc Natl Acad Sci U S A. 2008 May 8 [Epub ahead of print]
Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8.
Wu K, Katiyar S, Li A, Liu M, Ju X, Popov VM, Jiao X, Lisanti MP, Casola A, Pestell RG.
Departments of Cancer Biology and.
Oncogene-mediated signaling to the host environment induces a subset of cytokines and chemokines. The Drosophila Dac gene promotes migration of the morphogenetic furrow during eye development. Expression of the cell-fate determination factor Dachshund (DACH1) was lost in poor prognosis invasive breast cancer. Mouse embryo fibroblasts derived from Dach1(-/-) mice demonstrated endogenous Dach1 constitutively represses cellular migration. DACH1 inhibited cellular migration and invasion of oncogene (Ras, Myc, ErbB2, c-Raf)-transformed human breast epithelial cells. An unbiased proteomic analysis identified and immunoneutralizing antibody and reconstitution experiments demonstrated IL-8 is a critical target of DACH1 mediating breast cancer cellular migration and metastasis in vivo. DACH1 bound the endogenous IL-8 promoter in ChIP assays and repressed the IL-8 promoter through the AP-1 and NF-kappaB binding sites. Collectively, our data identify a pathway by which an endogenous cell-fate determination factor blocks oncogene-dependent tumor metastasis via a key heterotypic mediator.
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05-10-2008, 10:13 PM
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#2
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Senior Member
Join Date: Nov 2004
Location: Misty woods of WA State
Posts: 4,128
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HUH? I must have had too much wine tonight with the ribs.
But on second reading I am NOT seeing things.
Still don't quite understand ....
__________________
"When I hear music, I fear no danger. I am invulnerable. I see no foe. I am related to the earliest times, and to the latest." H.D. Thoreau
Live in the moment.
MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.
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05-10-2008, 10:51 PM
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#3
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Member
Join Date: Nov 2007
Location: Southern California
Posts: 15
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Interleukin 8 is one of many cyokines. apparently it is necessary or involved in the metastasis of breast cancer cells. apparently this Dasch gene protein inhibits metastasis by inhibiting the action of interleukin 8 when it is functioning properly.
It would be quite possible to develop a monoclonal antibody to inhibit interleukin 8 and help slow down metastasis. Avastin is a monoclonal antibody that inhibits Vascular Endothelial Growth Factor. Herceptin is a monoclonal antibody that in hibits the Her2Neu protein. Tocilizumab is a monoclonal antibody being developed against Interleukin 6 and is to be used to treat severe Rheumatoid Arthritis.Interleukin 6 is very involved in the cancer known as Multiple Myeloma so theoretically Tocilizumab might be valable in this disease too.
This new info about Dasch and Interlekin 8 opens p a new area to target. NF Kappa beta is also mentioned. Stimulation of NFKappa beta causes Interleukin 6 release and apparently the Dasch gene also inhibits this target also. In fact when NFKappa b is activated a large number of "pro-cancer" (for lack of a better word) chemicals are activated. I know as a pharmacist that NSAID drgs like Aspirin and Celebrex inhibit NFKappa b also and could be used in combination with this antibody against Interleukin 8, when it is developed.
Paul
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05-11-2008, 06:00 AM
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#4
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Senior Member
Join Date: Mar 2006
Posts: 1,843
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And excess Omega six promotes higher levels of IL6.
RB
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05-11-2008, 06:05 AM
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#5
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Senior Member
Join Date: Jul 2007
Location: Canada
Posts: 2,193
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I figured it out StephN. Lani is talking about making a monoclonal antibody out of the ovaries of weiner dogs.
__________________
PinkGirl
Dx Aug/05 at age 51
2cm. Stage 2A, Grade 3
ER+/PR-
Her2 +++
Sept 7/05 Mastectomy
4 FAC, 4 Taxol, no radiation
1 year of Herceptin
Tamoxifen for approx. 4 months,
Arimidex for 5 years
Prophylactic mastectomy June 22/09
" I yam what I yam." - Popeye
My Photo Album
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05-11-2008, 12:11 PM
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#6
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Senior Member
Join Date: Nov 2004
Location: Misty woods of WA State
Posts: 4,128
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Better NOT tell my daughter or my niece sinch they both have long-haired mini Dachs...
Close your long floppy ears Tootsie and Miloo.
Thanks for the lay-speak.
I heard about dozens of new targets being worked on when we were at San Diego, so this actually does not surprise me that much.
__________________
"When I hear music, I fear no danger. I am invulnerable. I see no foe. I am related to the earliest times, and to the latest." H.D. Thoreau
Live in the moment.
MY STORY SO FAR ~~~~
Found suspicious lump 9/2000
Lumpectomy, then node dissection and port placement
Stage IIB, 8 pos nodes of 18, Grade 3, ER & PR -
Adriamycin 12 weekly, taxotere 4 rounds
36 rads - very little burning
3 mos after rads liver full of tumors, Stage IV Jan 2002, one spot on sternum
Weekly Taxol, Navelbine, Herceptin for 27 rounds to NED!
2003 & 2004 no active disease - 3 weekly Herceptin + Zometa
Jan 2005 two mets to brain - Gamma Knife on Jan 18
All clear until treated cerebellum spot showing activity on Jan 2006 brain MRI & brain PET
Brain surgery on Feb 9, 2006 - no cancer, 100% radiation necrosis - tumor was still dying
Continue as NED while on Herceptin & quarterly Zometa
Fall-2006 - off Zometa - watching one small brain spot (scar?)
2007 - spot/scar in brain stable - finished anticoagulation therapy for clot along my port-a-catheter - 3 angioplasties to unblock vena cava
2008 - Brain and body still NED! Port removed and scans in Dec.
Dec 2008 - stop Herceptin - Vaccine Trial at U of W begun in Oct. of 2011
STILL NED everywhere in Feb 2014 - on wing & prayer
7/14 - Started twice yearly Zometa for my bones
Jan. 2015 checkup still shows NED
2015 Neuropathy in feet - otherwise all OK - still NED.
Same news for 2016 and all of 2017.
Nov of 2017 - had small skin cancer removed from my face. Will have Zometa end of Jan. 2018.
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05-11-2008, 06:24 PM
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#7
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Senior Member
Join Date: Sep 2005
Location: Grand Rapids, MI
Posts: 1,516
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Lucky for my 9 week old...
miniature short hair dashchund that HE is a boy...WHEW, lucky Oscar.
Rhonda
__________________
Rhonda
Dx 2/1/05, Stage 1, 0 nodes, Grade 3, ER/PR-, HER2+ (3.16 Fish)
2/7/05, Partial Mastectomy
5/18/05 Finished 6 rounds of dose dense TEC (Taxotere, Epirubicin and Cytoxan)
8/1/05 Finished 33 rads
8/18/05 Started Herceptin, every 3 weeks for a year (last one 8/10/06)
2/1/13...8 year Cancerversary and I am "perfect" (at least where cancer is concerned;)
" And in the end, it's not the years in your life that count. It's the life in your years."- Abraham Lincoln
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05-11-2008, 06:52 PM
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#8
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Senior Member
Join Date: Oct 2005
Posts: 3,519
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Wish I had known - as we had over 500 wiener-dogs competing at the world famous Buda, Texas Wiener Dog Races last weekend (2 blocks from my house)... I coulda done some "harvesting" LOL.
__________________
Brenda
NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)
Nov'03~ dX stage 2B
Dec'03~ Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~ Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~ micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~ micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg
Apr'07~ MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~ Started Tykerb/Xeloda, no WBR for now
June'07~ MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~ MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~ PET/CT & MRI show NED
Apr'08~ scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~ MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~ dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~ Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~ new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~ new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~ 25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.
"I would rather be anecdotally alive than statistically dead."
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