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04-22-2010, 07:21 PM
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#1
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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Her2 anemia treatment may be different
Anemia different in Her2 patients?
Cancer Res. 2009 Dec 15;69(24):9163-8.
Upregulation of neutrophil gelatinase-associated lipocalin by ErbB2 through nuclear factor-kappaB activation.
Li SH, Hawthorne VS, Neal CL, Sanghera S, Xu J, Yang J, Guo H, Steeg PS, Yu D.
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
PURCHASE TEXT
Abstract
ErbB2 (HER2, neu) is a receptor tyrosine kinase overexpressed in about 25% of invasive breast carcinomas. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted glycoprotein expressed in a variety of cancers, including breast carcinomas. NGAL can inhibit erythroid cell production, leading to anemia. Anemia usually occurs in cancer patients and negatively affects quality of life. However, current treatment for cancer-related anemia has potential complications. ErbB2, NGAL, and anemia have all been associated with increased metastasis and poor prognosis in breast cancer patients, although the relationship between ErbB2 and NGAL expression is not clear. Here, using breast cancer cell lines in vitro and transgenic mice carrying the activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV-neu) in vivo, we show that ErbB2 overexpression leads to NGAL upregulation, which is dependent on nuclear factor-kappaB (NF-kappaB) activity. MMTV-neu transgenic mice developed anemia after tumor onset, and anemia progression could be partially arrested by a NF-kappaB inhibitor and ErbB2-targeted therapy. Taken together, upregulation of NGAL by ErbB2 through NF-kappaB activation is involved in cancer-related anemia, and the ErbB2, NF-kappaB, and NGAL pathways may serve as potential therapeutic targets for cancer-related anemia.
PMID: 19951994 [PubMed - indexed for MEDLINE]PMCID: PMC2794902 [Available on 2010/12/15]
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04-23-2010, 06:28 AM
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#2
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Re: Her2 anemia treatment may be different
The researchers were comparing the cellular pathways of bc in humans, to those of the mouse models that are used to test human drugs. At page 21, they state:
"The MMTV-Neu strain, however, does not accurately recapitulate HER2-overexpressing cancers arising in women, since MMTV-Neu tumors do not show significant gene overlap with the HER2- positive subtype but are more similar to human ‘luminal’ tumors."
I don't know what the implications are for research on Her2+ bc treatments using MMTV-Neu bc strains in mice, but thought I would bring it up.
Hopeful
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04-23-2010, 10:12 AM
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#3
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Senior Member
Join Date: Mar 2010
Location: Missouri
Posts: 28
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Re: Her2 anemia treatment may be different
Rich and Hopeful,
Thanks much for sharing the research information. I've been battling anemia symptoms since my 3rd chemo treatment. Two weeks ago I had a blood transfusion + delayed my chemo one week to help bring my counts up a notch, but they are still low. I'll ask my oncologist to help decifer the information you shared in case any of it can help with treating my anemia so I can avoid another blood transfusion or further delay of my chemo treatment (I just have one more to go!).
__________________
Yvonne
Nov 09 - Grade 3 IDC + Grade 3 DCIS, ER/PR-, HER2+++, KI-67 91%; BRAC 1 and 2 negative
Dec 09 - Mastectomy LB, 2.4 cm, 1/27 nodes, Stage IIB
Jan 10 - Taxotere/Carboplatin/Herceptin (TCH) for 18 weeks (1X every 3 weeks); Herceptin every week for 18 weeks then every 3 weeks 'til week 51
Apr 10 - Blood transfusion to increase red blood cells
Apr 10 - Change regimen to Taxotere/Cisplatin/Herceptin
May 10 - Chemo done!
Jul 10 - Brain MRI normal
Dec 10 - PET scan NED
Dec 30 10 - Last Herceptin
Feb 11 - Port removed
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04-23-2010, 11:47 AM
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#4
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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Re: Her2 anemia treatment may be different
Hopeful, in addition mmtvNEU tumors in mice are ER-.
Since her2 bc in humans comes in more than two flavors (ER+,ER-) it would seem obvious that other pathways are activated, they come from different Cancer stem cells/cancer progenitor cells, etc.
Inhibiting nfKappa beta and inflammation seems to be good idea in any case nevertheless, but I wouldn't overread too much into this, as almost all her2_ bc patients get chemo in addition to their herceptin and it is possible for this to change their blood-forming potential both long and shortterm.
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04-23-2010, 01:42 PM
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#5
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Senior Member
Join Date: Aug 2006
Posts: 3,380
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Re: Her2 anemia treatment may be different
Thanks, Lani, I was hoping you would see this and jump in.
Hopeful
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