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04-10-2009, 09:34 AM
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#1
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Senior Member
Join Date: Mar 2006
Posts: 4,778
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WOW Gene therapy with reovitus reported to selectively kill breast cancer stem cells
Targeting stem cells
[Dalhousie University]
Dalhousie Medical School cancer researcher Dr. Patrick Lee has proven that a common virus can infect and kill breast cancer stem cells. This breakthrough finding is published in the current issue of Molecular Therapy, the prestigious journal of the American Society of Gene Therapy.
It is only within the past few years that the scientific community has understood the full significance of cancer stem cells and the urgent need to find a means of eliminating them.
"Cancer stem cells are essentially mother cells," explains Dr. Lee, Cameron Chair in Basic Cancer Research at Dalhousie Medical School. "They continuously produce new cancer cells, aggressively forming tumours even when there are only a few of them."
Cancer stem cells are difficult to kill as they respond poorly to chemotherapy and radiation. As Dr. Lee notes, "You can kill all the regular cancer cells in a tumour, but as long as there are cancer stem cells present, disease will recur."
Dr. Lee is optimistic that his team has found the key to destroying cancer stem cells. The researchers have recently shown that human reovirus, a common virus that does not cause disease, effectively targets and kills cancer stem cells in breast cancer tissue.
"We suspected that reovirus might be effective against cancer stem cells, because we have shown time and again how well it destroys regular cancer cells," remarks Dr. Lee, who was the first in the world to discover that a benign and naturally occurring virus could selectively infect and kill cancer cells without harming healthy cells. A Calgary-based company, Oncolytics Biotech Inc., is testing reovirus in clinical trials to prove the treatments are safe and effective.
Unlike most cancer studies, which use cancer cell lines developed for laboratory use, this study used fresh breast cancer tissue. This cancer tissue was removed from a patient of Dr. Carman Giacomantonio, a Capital Health surgical oncologist who is working with Dr. Lee on the reovirus research, along with post-doctoral fellow Dr. Paola Marcato and research assistant Cheryl Dean.
In addition to its ability to kill cancer cells and cancer stem cells, reovirus stimulates the anti-cancer immune system. Since virus therapy also invokes an anti-virus response, Dr. Lee and post-doctoral fellow Dr. Shashi Gujar are working on a way to harness the immune system so it attacks cancer cells while allowing the virus to freely infect and destroy cancerous cells. "Refining this two-pronged approach to killing cancer is our next step," says Dr. Lee. "We are taking advantage of the natural characteristics of reovirus and the immune system itself to create a powerful virus-based anti-cancer therapy."
Dr. Lee's discovery that reovirus effectively targets breast cancer stem cells has captured the attention of LeadDiscovery, a UK-based organization dedicated to promoting drug discovery and development. LeadDiscovery has identified the finding to be of particular interest to the drug development sector and will feature it in its next update to the global scientific community and pharmaceutical industry.
EARLY VIEW: ABSTRACT: Oncolytic Reovirus Effectively Targets Breast Cancer Stem Cells
[Nature: Molecular Therapy]
Recent evidence suggests that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are resistant to current anticancer therapies. Hence, novel cancer therapies will need to be tested for both tumor regression and CSC targeting. Herein we show that oncolytic reovirus that induces regression of human breast cancer primary tumor samples xenografted in immunocompromised mice also effectively targets and kills CSCs in these tumors. CSCs were identified based on CD24-CD44+ cell surface expression and overexpression of aldehyde dehydrogenase. Upon reovirus treatment, the CSC population was reduced at the same rate as non-CSCs within the tumor. Immunofluorescence of breast tumor tissue samples from the reovirus- and mock-treated mice confirmed that both CSCs and non-CSCs were infectible by reovirus, and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay showed that both populations died by apoptosis. Ras, which has been shown to mediate reovirus oncolysis, was found to be present at similar levels in all cell types, and this is consistent with their comparable sensitivity to reovirus. These experiments indicate that oncolytic reovirus has the potential to induce tumor regression in breast cancer patients. More important, the CSC population was equally reduced and was as susceptible to reovirus treatment as the non-CSC population
..sorry that is reovirus
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04-10-2009, 10:55 AM
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#2
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Senior Member
Join Date: Jun 2006
Location: San Antonio, TX
Posts: 2,357
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I love good news!!!!
__________________
MA in TX.
Grateful for each and every day....
Diag. 12/05 at age 60
Stage II, Grade 3, 4.5 cm primary tumor
ER/PR- Her2 +3 strongly positive
Her2 by FISH 7.7 amplified
vascular invasion
Ki67 20% borderline
Jan - March '06 Taxotere/Adriamycin X 3 to try to shrink tumor - it grew
April '06 Rt Modified Radical Mas, 7 of 9 nodes positive
April - Aug. '06 Herceptin/Taxol/Carboplatin X 8 (dose dense)
Sept - Dec. '06 Navelbine/Herceptin x 8 (dose dense)
Radiation & Herceptin Jan. 22 - March 1, 2007
Finished Herceptin Dec. 10 '08! One extra year.
Port removed August, 2012.
8 1/2 years since diagnosis! 5 1/2 Years NED!
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04-10-2009, 11:26 AM
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#3
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Senior Member
Join Date: Feb 2008
Location: Bayarea,CA
Posts: 679
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Where can I go to get infected with this reovirus?!!!
Wow. This does seem promising - perhaps a new vaccine will be developed ...
Thanks Lani! You keep our hope alive with these posts - I really look forward to them every day.
__________________
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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04-10-2009, 12:30 PM
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#4
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Senior Member
Join Date: Feb 2009
Posts: 1,526
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I'll second that Shobna! Lani don't know how you do it but your posts make me believe that we will beat this thing. This Easter I am praying ++ that God helps us find the cure real soon. Ellie
Last edited by Ellie F; 04-10-2009 at 12:30 PM..
Reason: correct spelling
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04-10-2009, 01:04 PM
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#5
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Senior Member
Join Date: Sep 2005
Location: Central Coast, CA
Posts: 3,207
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Lani, that is exciting - the stem cell issue may be the key.
As for being infected, I'll gladly trade that virus for the cold I have right now
__________________
Chris in Scotts Valley
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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04-10-2009, 01:12 PM
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#6
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Senior Member
Join Date: Oct 2005
Posts: 3,519
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"A Calgary-based company, Oncolytics Biotech Inc., is testing reovirus in clinical trials to prove the treatments are safe and effective. Unlike most cancer studies, which use cancer cell lines developed for laboratory use, this study used fresh breast cancer tissue. This cancer tissue was removed from a patient of Dr. Carman Giacomantonio, a Capital Health surgical oncologist who is working with Dr. Lee on the reovirus research, along with post-doctoral fellow Dr. Paola Marcato and research assistant Cheryl Dean."
I wonder if those of us who have tissue samples could have ours used in this clinical trial?
__________________
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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04-10-2009, 02:05 PM
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#7
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Senior Member
Join Date: Jun 2006
Location: san luis obispo, ca
Posts: 1,150
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Lani, Thanks again for your posts...they do keep hope alive and remind us how fast things are moving along these days ( compared to 5 years ago). I look forward to reading your new-found info and trials everyday.
Thank You and Love,
Vickie
__________________
Love and Hugs, Vickie
Life's not about waiting for the storm to pass,
It's about learning to dance in the rain.
Feb 04 IBC IIIC/IV er-/pr- her2+++
3/04 TCH X4
7/ 04 MRM 9/04 Taxol/herceptin wkly 1 yr 33X rads
11/04 skin mets 33x rads,10/05 Avast/Herc. 11 mos.
8/ 06 PET mets lymphs, neck
9/ 06 Navelbine/herceptin
11/ 06 PET NED
2/ 07 skin mets, 4/07 Xeloda, 5/07 add Tykerb
2/ 08 Tykerb failed. Doxil /Herceptin 6 months
8/08 PET skin mets, 8/08 Abraxane/Avastin
11/ 08 PET prog., skin mets
1/09 PET/CT progress, 1/09 Ixempra, 2/09 add Xeloda and low dose Naltrexone
2/09 off Ixempra/Xeloda
3/09 navelbine/herc/cytoxin 4/09 PET shows regress.7/09 start Topotecan. Failed.
8/09 extensive mets rgt brst, back and torso. starting Pazopanib clinical trial.
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04-10-2009, 02:15 PM
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#8
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Senior Member
Join Date: Jul 2007
Location: Canada
Posts: 2,193
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__________________
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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04-15-2009, 02:35 PM
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#9
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Senior Member
Join Date: Feb 2008
Location: South East Wisconsin
Posts: 3,431
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"Unlike most cancer studies, which use cancer cell lines developed for laboratory use, this study used fresh breast cancer tissue. This cancer tissue was removed from a patient of Dr. Carman Giacomantonio"
I wonder if this could accelerate the acceptability of the research since there isn't the whole "we aint mice" caveat.
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