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Old 05-21-2009, 10:55 AM   #1
Lani
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new NSAID specifically targets her2+ breast cancer by decreasing her2 receptor trans-

cription

Mol Cancer Ther. 2009 May 12. [Epub ahead of print]

The nonsteroidal anti-inflammatory drug tolfenamic acid inhibits BT474 and SKBR3 breast cancer cell and tumor growth by repressing erbB2 expression.

Liu X, Abdelrahim M, Abudayyeh A, Lei P, Safe S.
Departments of 1Biochemistry and Biophysics and 2Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas; 3Cancer Research Institute, M. D. Anderson Cancer Center, Orlando Regional Health, Care, Orlando, Florida; and 4Department of Internal Medicine, Baylor College of Medicine, One Baylor Plaza and 5Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas.
Tolfenamic acid (TA) is a nonsteroidal anti-inflammatory drug that inhibits pancreatic cancer cell and tumor growth through decreasing expression of specificity protein (Sp) transcription factors. TA also inhibits growth of erbB2-overexpressing BT474 and SKBR3 breast cancer cells; however, in contrast to pancreatic cancer cells, TA induced down-regulation of erbB2 but not Sp proteins. TA-induced erbB2 down-regulation was accompanied by decreased erbB2-dependent kinase activities, induction of p27, and decreased expression of cyclin D1. TA also decreased erbB2 mRNA expression and promoter activity, and this was due to decreased mRNA stability in BT474 cells and, in both cell lines, TA decreased expression of the YY1 and AP-2 transcription factors required for basal erbB2 expression. In addition, TA also inhibited tumor growth in athymic nude mice in which BT474 cells were injected into the mammary fat pad. TA represents a novel and promising new anticancer drug that targets erbB2 by decreasing transcription of this oncogene. [Mol Cancer Ther 2009;8(5):1207-17].
PMID: 19435870
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Old 05-21-2009, 11:59 AM   #2
Ellie F
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Hi, my friend gets this on prescription and takes this for migraines.
Can't remember where I saw it but ibuprofen was also supposed to impact on her2 as it is a COX inhibitor. Wonder if this means that we will soon be prescibed low doses of these drugs as part of the battle to reduce spread?
Ellie
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Old 05-21-2009, 12:56 PM   #3
Rich66
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related:
1: Carcinogenesis. 2009 Apr 30. [Epub ahead of print] Links
Tolfenamic Acid Inhibits Esophageal Cancer Through Repression of Specificity Proteins and c-Met.

Papineni S, Chintharlapalli S, Abdelrahim M, Lee SO, Burghardt R, Abudayyeh A, Baker C, Herrera L, Safe S.
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466.
The nonsteroidal anti-inflammatory drug (NSAID) tolfenamic acid inhibits proliferation of SEG-1 and BIC-1 esophageal cancer cells with IC(50) values of 36 and 48 muM, respectively. TA also increased Annexin V staining in both cell lines, indicative of proapoptotic activity. Treatment of SEG-1 and BIC-1 cells with TA for up to 72 hr decreased expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and this was accompanied by decreased expression of the well characterized Sp-regulated genes cyclin D1, vascular endothelial growth factor (VEGF) and survivin. TA also decreased hepatocyte growth factor receptor, c-Met, a receptor tyrosine kinase that is overexpressed in esophageal cancer cells and tumors and is an important drug target. Knockdown of Sp1, Sp3 and Sp4 by RNA interference in SEG-1 and BIC-1 cells also decreased c-Met expression, demonstrating that c-Met is an Sp-regulated gene in esophageal cancer cells. Sp1 was overexpressed in esophageal cancer cells and tumors and increased Sp1 staining was observed in esophageal tumors from patients. TA (20 mg/kg/d) also decreased tumor growth and weight in athymic nude mice bearing SEG-1 cells as xenografts and this was accompanied by increased apoptosis and decreased Sp1 and c-Met staining in tumors from treated mice. Thus, TA-dependent downregulation of Sp transcription factors and c-Met defines a novel chemotherapeutic approach for treatment of esophageal cancer.
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Old 05-21-2009, 08:54 PM   #4
SoCalGal
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I have taken Advil for a million years. Maybe that's why I'm still here? Of course, for the last year it's been a no-no with the Avastin. Hmmmm.
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1996 cancer WTF?! 1.3 cm lumpectomy Er/Pr neg. Her2+ (20nodes NEGATIVE) did CMF + rads. NED.
2002 recurrence. Bilateral mastectomy w/TFL autologous recon. Then ACx2. Skin lymphatic rash. Taxotere w/Herceptin x4. Herceptin/Xeloda. Finally stops spreading.
2003 - Back to surgery, remove skin mets, and will have surgery one week later when pathology can confirm margins.
‘03 latisimus dorsi flap to remove skin mets. CLEAN MARGINS. Continue single agent Herceptin thru 4/04. NED.
‘04 '05 & 06 tiny recurrences - scar line. surgery to cut out. NED each time.
1/2006 Rads again, to scar line. NED.

3/07 Heartbreaking news - mets! lungs.sternum. Try Tykerb/Xeloda. Tykerb/Carbo/Gemzar. Switch Oncs.
12/07 Herceptin.Tykerb. Markers go stable.
2/8/08 gamma knife 13mm stupid brain met.
3/08 Herceptin/tykerb/avastin/zometa.
3/09 brain NED. Lungs STABLE.
4/09 attack sternum (10 daysPHOTONS.5 days ELECTRONS)
9/09 MARKERS normal!
3/10 PET/CT=manubrium intensely metabolically active but stable. NEDhead.
Wash out 5/10 for tdm1 but 6/10 CT STABLE, PET improving. Markers normal. Brain NED. Resume just Herceptin plus ZOMETA
Dec 2010 Brain NED, lungs/sternum stable. markers normal.
MAR 2011 stop Herceptin/allergy! Go back on Tykerb and switch to Xgeva.
May-Aug 2011 Tykerb Herceptin Xgeva.
Sept 2011 Tykerb, Herceptin, Zometa, Avastin.
April 2012 sketchy drug trial in NYC. 6 weeks later I’m NED!
OCT 2012 PET/CT shows a bunch of freakin’ progression. Back to LA and Herceptin.avastin.zometa.
12/20/12 add in PERJETA!
March 2013 – 5 YEARS POST continue HAPZ
APRIL 2013 - 6 yrs stage 4. "FAILED" PETscan on 4/2/13
May 2013: rePetted - improvement in lungs, left adrenal stable, right 6th rib inactive, (must be PERJETA avastin) sternum and L1 fruckin'worsen. Drop zometa. ADD Xgeva. Doc says get rads consultant for L1 and possible biopsy of L1. I say, no thanks, doc. Lets see what xgeva brings to the table first. It's summer.
June-August 2013HAPX Herceptin Avastin Perjeta xgeva.
Sept - now - on chemo hold for calming tummy we hope. Markers stable for 2 months.
Nov 2013 - Herceptin-Perjeta-Avastin-Xgeva (collageneous colitis, which explains tummy probs, added Entocort)
December '13 BRAIN MRI ned in da head.
Jan 2014: CONTINUING on HAPX…
FEB 2014 PetCT clinical “impression”: 1. newbie nodule - SUV 1.5 right apical nodule, mildly hypermetabolic “suggestive” of worsening neoplastic lesion. 2. moderate worsening of the sternum – SUV 5.6 from 3.8
3. increasing sclerosis & decreasing activity of L1 met “suggests” mild healing. (SUV 9.4 v 12.1 in May ‘13)
4. scattered lung nodules, up to 5mm in size = stable, no increased activity
5. other small scattered sclerotic lesions, one in right iliac and one in thoracic vertebral body similar in appearance to L1 without PET activity and not clearly pathologic
APRIL 2014 - 6 YRS POST GAMMA ZAP, 7 YRS MBC & 18 YEARS FROM ORIGINAL DX!
October 2014: hold avastin, continue HPX
Feb 2015 Cancer you lost. NEDHEAD 7 years post gamma zap miracle, 8 years ST4, +19 yrs original diagnosis.
Continue HPX. Adding back Avastin
Nov 2015 pet/ct is mixed result. L1 SUV is worse. Continue Herceptin/avastin/xgeva. Might revisit Perjeta for L1. Meantime going for rads consult for L1
December 2015 - brain stable. Continue Herceptin, Perjeta, Avastin and xgeva.
Jan 2016: 5 days, 20 grays, Rads to L1 and continue on HAPX. I’m trying to "save" TDM1 for next line. Hope the rads work to quiet L1. Sciatic pain extraordinaire :((
Markers drop post rads.
2/24/16 HAP plus X - markers are down
SCIATIC PAIN DEAL BREAKER.
3/23/16 Laminectomy w/coflex implant L4/5. NO MORE SCIATIC PAIN!!! Healing.
APRIL 2016 - 9 YRS MBC
July 2016 - continue HAP plus Xgeva.
DEC 2016 - PETCT: mets to sternum, lungs, L1 still about the same in size and PET activity. Markers not bad. Not making changes if I don't need to. Herceptin/Perjeta/Avastin/Xgeva
APRIL 2017 10 YEARS MBC
December 2017 - Progression - gonna switch it up
FEB 2018 - Kadcyla 3 cycles ---->progression :(
MAY30th - bronchoscopy, w/foundation1 - her2 enriched
Aug 27, 2018 - start clinical trial ZW25
JAN 2019 - ZW25 seems to be keeping me stable
APRIL 2019 - ONE DOZEN YEARS LIVING METASTATIC
MAY 2019 - progression back on herceptin add xeloda
JUNE 2019 - "6 mos average survival" LMD & CNS new single brain met - one zap during 5 days true beam SBRT to cord met
10/30/19 - stable brain and cord. progression lungs and bones. washing out. applying for ds8201a w nivolumab. hope they take me.
12/27/19 - begin ds8401a w nivolumab. after 2nd cycle nodes melt away. after 3rd cycle chest scan shows Improvement, brain MRI shows improvement, resolved areas & nothing new. switch to plain ENHERTU. after 4th cycle, PETscan shows mostly resolved or improved results. Markers near normal. I'm stunned but grateful.
10/26/20 - June 2021 Tucatinib/xeloda/herceptin - stable ish.
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Old 05-21-2009, 10:46 PM   #5
Rich66
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A million years? I'll have what she's having
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Old 05-22-2009, 02:32 PM   #6
Brenda_D
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I've been on the NSAID Volteran (diclofenac) for at least 5 five years for inflammation. During that period I got her2 positive BC.
I'll have to ask my new onc about this new drug.
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12/12/06- IDC Stage III, 4x A/C, 35 rads, Herceptin 1 year
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Old 12-07-2009, 07:27 PM   #7
Rich66
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Re: new NSAID specifically targets her2+ breast cancer by decreasing her2 receptor tr

Brenda D,
An alert on Diclofenac
http://www.medscape.com/viewarticle/713451
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Mom's treatment history (link)
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Old 12-07-2009, 07:54 PM   #8
Adriana Mangus
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Re: new NSAID specifically targets her2+ breast cancer by decreasing her2 receptor tr

Dear Lani;

I do believe the report.

My lovely mother, she will be 87 in June is healthy as a horse. She's been taking anti-inflamatory meds for at least the last 50 years. She constantly complains of aches and pains.

I suspect she suffers from fibromyalgia-- I do,-- but she refuses to believe that, and living in Mexico all of her life there was not a tool or a doctor that would/could have help.

She was dx however with a small tiny tumor in the cervix , it was removed and she continued with her OTC meds.

I'm the youngest and the only one with BC, it's important to mention that am also the only one in the family who does not like to take any type of pain killers, even for fibromyalgia. I do practice yoga when the pain is too much to take.

I will open a bottle right now and start taking Ibuprofen, it won't hurt me and perhaps it will keep the mets at bay. I hope.

Love,

Adriana
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1994 - rt brst, .lump, underarm node dissection,chemo+rad 1.2 cms, Grade 3.
28 nodes neg
Er,Pr, Positive HER2 status unknown
2003- Recur to rt lung.July 16 ( B-Day!)
Her2+++ Er,Pr, Negative
2003 - Aug04--Navelbine + Herceptin
2004- 2007--
NED - Herceptin, only
2007 Feb-April Xeloda added to hereceptin
2007-May Back on Navelbine+Herceptin
2008-Feb-Mar 15 Ses Rad to Rt. Lung
2008- Oc 17 Add Tykerb to Herceptin
2009- June-- Discont Tykerb
2009 July 7--Current Taxol + Herceptin
2009 Dec--Discontinued treatment due to progression. Looking into cyberknife.
2010-Aug Accepted to TDM1, no SE, except liver count went up.
2010-2011 September got kicked out of the trial, due to a small spot found on lung.
2011- 2012 September thru early 2013 on Herceptin
2013- March Bone density shows small spot on 5th rib.
2013 - April 4th appt with onc. will post after discussing course of treatment.
2013-March-April Cyber knife to brain and radiation to rib. Chest --base line before chemo-CT-Scan stable for lung issue. CA2729 Normal.
2013 April Herceptin- TDMI
2013 Sept Herceptin + Perjeta . CA2729 within normal range. Brain and Pet scans October 31st. will post results.
2013 October Brain MRI- mixed response. Will see Onc/rad on Halloween.
2013 October/November Brain-MRI nothing new. Repeat MRI next year in May.

2013 December Continue Herceptin and Perjeta. Stable at the moment.
2014 February Brain MRI -clear!
2014 January Added Taxotere to Perjeta+Herceptin.
2014 March Stopped chemo-chest ct-scan next.

2014- March Scans shows tumor's larger, CA2729 higher. Discontinue Herceptin.
2014 April Perjeta+ Halaven
2014 April CA2729 went down 60 points after one cycle. Cough does not want to go away.
2014 June Continue on Perjeta + Halaven-- no more cough. Stable
2014 June Back on Herceptin + abraxane
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Old 12-08-2009, 04:13 AM   #9
Ellie F
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Re: new NSAID specifically targets her2+ breast cancer by decreasing her2 receptor tr

may be the way forward with these nsai drugs is the metronomic approach, taking maybe one tablet each day. Seems like that may keep the beast down but not do too much damage.Just a thought1
Ellie
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