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Old 03-25-2010, 12:42 AM   #1
Lani
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use of weakened version of diarrhea-causing bacteria effective against her2+ breast

cancer in experimental model--there was a 74% reduction in tumors only 7 days after a mouse with her2+ bc was infected with the weakened Shigella bacteria

Shigella Mediated Depletion of Macrophages in a Murine Breast Cancer Model Is Associated with Tumor Regression

Katharina Galmbacher1#¤a, Martin Heisig1,2#, Christian Hotz1¤b, Joerg Wischhusen3, Antoine Galmiche1¤c, Birgit Bergmann1,2, Ivaylo Gentschev1¤d, Werner Goebel2¤e, Ulf R. Rapp1¤f, Joachim Fensterle1¤g*
1 Institut für Medizinische Strahlenkunde und Zellforschung, Universität Würzburg, Würzburg, Germany, 2 Institut für Mikrobiologie, Biozentrum, Universität Würzburg, Würzburg, Germany, 3 Universitätsfrauenklinik Würzburg, Würzburg, Germany
Abstract

A tumor promoting role of macrophages has been described for a transgenic murine breast cancer model. In this model tumor-associated macrophages (TAMs) represent a major component of the leukocytic infiltrate and are associated with tumor progression. Shigella flexneri is a bacterial pathogen known to specificly induce apotosis in macrophages. To evaluate whether Shigella-induced removal of macrophages may be sufficient for achieving tumor regression we have developed an attenuated strain of S. flexneri (M90TΔaroA) and infected tumor bearing mice. Two mouse models were employed, xenotransplantation of a murine breast cancer cell line and spontanous breast cancer development in MMTV-HER2 transgenic mice. Quantitative analysis of bacterial tumor targeting demonstrated that attenuated, invasive Shigella flexneri primarily infected TAMs after systemic administration. A single i.v. injection of invasive M90TΔaroA resulted in caspase-1 dependent apoptosis of TAMs followed by a 74% reduction in tumors of transgenic MMTV-HER-2 mice 7 days post infection. TAM depletion was sustained and associated with complete tumor regression.

These data support TAMs as useful targets for antitumor therapy and highlight attenuated bacterial pathogens as potential tools.

http://www.plosone.org/article/info%...l.pone.0009572
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Old 03-25-2010, 08:06 AM   #2
Shobha
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Re: use of weakened version of diarrhea-causing bacteria effective against her2+ brea

Good to know there is a possible solution to these traitor cells. I have always wondered by building my immunity am I actually promoting the mets somehow. I had read an earlier study about Macrophages.

Thanks Lani!
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DX: 06-30-2007 - left breast -stage IIIB, Her2/Neu 3+++, ER weakly positive, PR-
Taxol+herceptin weekly for 3 months
FEC+herceptin every 3 weeks for 3 months
BRCA 1 and 2 - Negative
Jan 2008 - Bilateral mastectomy, prophylactic Rt. side.
Radiation for 5 weeks
Completed my yr of herceptin on 07-14-2008
Brain MRI - 3/2/09 Clean
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Old 03-25-2010, 12:36 PM   #3
Rich66
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Re: use of weakened version of diarrhea-causing bacteria effective against her2+ brea

First capsaicin, then salmonella, now diarreah..
Looks like a swing through a Taco bell drive through will be just what the onco ordered. "Take two Chalupas and scan ya in the morning"
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Old 03-25-2010, 06:16 PM   #4
chrisy
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Re: use of weakened version of diarrhea-causing bacteria effective against her2+ brea

Rich that's good!
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June 2002 extensive hi grade DCIS (pre-cancer-stage 0, clean sentinal node) Mastectomy/implant - no chemo, rads. "cured?"
9/2004 Diag: Stage IV extensive liver mets (!) ER/PR- Her2+++
10/04-3/05 Weekly Taxol/Carboplatin/Herceptin , complete response!
04/05 - 4/07 Herception every 3 wks, Continue NED
04/07 - recurrence to liver - 2 spots, starting tykerb/avastin trial
06/07 8/07 10/07 Scans show stable, continue on Tykerb/Avastin
01/08 Progression in liver
02/08 Begin (TDM1) trial
08/08 NED! It's Working! Continue on TDM1
02/09 Continue NED
02/10 Continue NED. 5/10 9/10 Scans NED 10/10 Scans NED
12/10 Scans not clear....4/11 Scans suggest progression 6/11 progression confirmed in liver
07/11 - 11/11 Herceptin/Xeloda -not working:(
12/11 Begin MM302 Phase I trial - bust:(
03/12 3rd times the charm? AKT trial

5/12 Scan shows reduction! 7/12 More reduction!!!!
8/12 Whoops...progression...trying for Perjeta/Herceptin (plus some more nasty chemo!)
9/12 Start Perjeta/Herceptin, chemo on hold due to infection/wound in leg, added on cycle 2 &3
11/12 Poops! progression in liver, Stop Perjeta/Taxo/Herc
11/12 Navelbine/Herce[ptin - try for a 3 cycles, no go.
2/13 Gemzar/Carbo/Herceptin - no go.
3/13 TACE procedure
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Old 03-25-2010, 06:19 PM   #5
Laurel
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Re: use of weakened version of diarrhea-causing bacteria effective against her2+ brea

Rich, that was good! Thanks for the post, Lani. Here's to hoping this one makes the grade and kicks Her-2's butt.
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Dx'd w/multifocal DCIS/IDS 3/08
7mm invasive component
Partial mast. 5/08
Stage 1b, ER 80%, PR 90%, HER-2 6.9 on FISH
0/5 nodes
4 AC, 4 TH finished 9/08
Herceptin every 3 weeks. Finished 7/09
Tamoxifen 10/08. Switched to Femara 8/09
Bilat SPM w/reconstruction 10/08
Clinical Trial w/Clondronate 12/08
Stopped Clondronate--too hard on my gizzard!
Switched back to Tamoxifen due to tendon pain from Femara

15 Years NED
I think I just might hang around awhile....

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