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Old 03-11-2009, 07:04 AM   #1
Lani
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dumbell shaped twin nanoparticle homes in on her2 to give to give ultratargeted trtmt

Twin Nanoparticle Shown Effective at Targeting, Killing Breast Cancer Cells
[Brown University]
PROVIDENCE, R.I. [Brown University] — Breast cancer patients face many horrors, including those that arise when fighting the cancer itself. Medications given during chemotherapy can have wicked side effects, including vomiting, dizziness, anemia and hair loss. These side effects occur because medications released into the body target healthy cells as well as tumor cells.
The trick becomes how to deliver cancer-fighting drugs directly to the tumor cells. Brown University chemists think they have an answer: They have created a twin nanoparticle that specifically targets the Her-2-positive tumor cell, a type of malignant cell that affects up to 30 percent of breast cancer patients.
The combination nanoparticle binds to the Her-2 tumor cell and unloads the cancer-fighting drug cisplatin directly into the infected cell. The result: Greater success at killing the cancer while minimizing the anti-cancer drug's side effects.
"Like a missile, you don't want the anti-cancer drugs to explode everywhere," explained Shouheng Sun, a chemistry professor at Brown University and an author on the paper published online in The Journal of the American Chemical Society. "You want it to target the tumor cells and not the healthy ones."
The researchers created the twin nanoparticle by binding one gold (Au) nanoparticle with an iron-oxide (Fe3O4) nanoparticle. On one end, they attached a synthetic protein antibody to the iron-oxide nanoparticle. On the other end, they attached cisplatin to the gold nanoparticle. Visually, the whole contraption looks like an elongated dumbbell, but it may be better to think of it as a vehicle, equipped with a very good GPS system, that is ferrying a very important passenger.
In this case, the GPS comes from the iron-oxide nanoparticle, which homes in on a Her-2 breast-cancer cell like a guided missile. The attached antibody is critical, because it binds to the antigen, a protein located on the surface on the malignant cell. Put another way, the nanoparticle vehicle "docks" on the tumor cell when the antibody and the antigen become connected. Once docked, the vehicle unloads its "passenger," the cisplatin, into the malignant cell.
"It's like a magic bullet," said Chenjie Xu, a Brown graduate student and the lead author on the paper. Baodui Wang, a visiting scientist at Brown and now an associate professor at Lanzhou University in China, contributed to the paper.
In a neat twist, the Brown-led team used a pH-sensitive covalent bond to connect the gold nanoparticle with the cisplatin to ensure that the drug was not released into the body but remained attached to the nanoparticle until it was time for it to be released into the malignant cell.
In laboratory tests, the gold-iron oxide nanoparticle combination successfully targeted the cancer cells and released the anti-cancer drugs into the malignant cells, killing the cells in up to 80 percent of cases. "We made a Mercedes Benz now," Sun joked. "It's not a Honda Civic anymore."
The research builds on previous work in Sun's lab where researchers created peptide-coated iron-oxide nanoparticles that, in tests with mice, successfully located a brain tumor cell called U87MG.
The researchers will test the breast-cancer nanoparticle system in laboratory tests with animals. They also plan to create twin nanoparticles that can release the drug via remote-controlled magnetic heating.
The breast-cancer nanoparticle research was funded by the National Institutes of Health.
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Old 03-11-2009, 07:06 AM   #2
Lani
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the article

ABSTRACT: Dumbbell-like Au-Fe3O4 Nanoparticles for Target-Specific Platin Delivery
[Journal of the American Chemical Society; Subscribe]
Dumbbell-like Au-Fe3O4 nanoparticles (NPs) were made and coupled with Herceptin and a platin complex. The platin-Au-Fe3O4-Herceptin NPs act as a target-specific nanocarriers for delivery of platin into Her2-positive breast cancer cells (Sk-Br3) with strong therapeutic effects. The conjugate has a half-maximal inhibitory concentration (IC50) toward Sk-Br3 cells of 1.76 μg of Pt/mL, which is lower than that needed for cisplatin (3.5 μg/mL). The work demonstrates that the dumbbell-like Au-Fe3O4 NPs are promising nanocarriers for highly sensitive diagnostic and therapeutic applications.
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Old 03-11-2009, 10:28 AM   #3
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Thanks Lani for the post. This is one reason why I continue to pray for scientists who spend hours in the laboratory doing their research. My daughter and niece are two of them. More often than not they see more failures than successess. I thank God for the talent he gave them and for their ability to use it.
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9/15/08 (age 52) - Mammo: calcifications
9/22/08 - Biopsy: DCIS, grade 3. ER,PR status: Pos. in 75-90% of tumor cells.
10/01/08 - Ob/Gyn appt.: found complex, mostly cystic mass on right ovary - 11cmx12cmx 8cm
10/15/08 - Hysterectomy & Oophorectomy, Lumpectomy: Cyst on uterus, not ovary - all was benign. Breast - 5 of 6 bad margins. 2 Sentinel Lymph nodes removed, both negative. Stage 0, Tis, N0
12/11/08 - Mastectomy & DIEP reconstruction: Surprise! 2 cm Invasive DC, grade 2 found. One benign internal mammary lymph node. Stage 1, T1c, N0, all clean margins. ER+ (Proportion Score = 2/5, Intensity Score = 2/3) and PR+(Proportion Score = 3/5, Intensity Score = 2/3)
HER2 score = 3+
1/09/09 - Oncotype DX: Recurrence S/core of 60 !?!?! ER status is NEG!! PR staus is NEG! HER2 score = 12.2 (still positive, greater than 11.5 is positive).
1/20/09 - Started chemo: TCH
5/26/09 - FINISHED CHEMO!
1/05/10 - FINISHED HERCEPTIN!
1/22/10 - Port-a-catheter removed!
3/07/18 - Still NED
9/10/23 - Still NED
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Old 03-11-2009, 10:32 AM   #4
Believe51
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Location: RHODE ISLAND (Ed getting me a latte on 2nd Cancerversary Cruise 2008) 'BELIEVE': To accept as true or real, To have faith in, To presume ALWAYS BELIEVE
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One more great stride for Rhode Island research. Another leap for us.>>Believe51
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9/7/06Husband 50yrs=StageIV IBC/HER2+,BoneMets10/06TaxotereX10,'H'1X wk,Zometa,Tamoxifen4/12/07Last Tax5/18/07Pet=Rapid Cell Activity,No Organ Mets,Lytic Lesions,Degeneration,Some Bone Repair5/07ChemoFail6/01/07Pleural Thoracentisis=Effusions,NoMalignantCells6/19/07+7/2/07DFCI
6/25/07BrainMRI=BrainMets,Many<9mm7/10/07WBR/PelvisRad37.5Gx15&Nutritionist8/19/07T/X9/20/07BrainMRI=2<2mm10/6/07Pet=BoneProgression
10/24/07ChemoFail11/9/07A/Cx10,EndTam12/7/07Faslodex12/10/07Muga7512/13/07BlasticLesions1/7/08BrainMRI=Clear4/1/08Pet=BoneImprovement,
NoProgression,Stable4/7/08BrainPerfect5/16/08Last A/C8/26/08BrainMets=10(<9mm)9/10/08Gamma10/30/08Met=5mm12/19/08Gamma5mets5
12/22/08SpinalMets1/14/09SpinalRads2/17/09BrainMRI=NoNewMets4/20/09BoneScan5/14/09Ixempra6/1/09BrainMRI=NumerousMets6/24/09DFCIw/DrBurstein6/26/09Continue
Ixempra/Faslodex/Zometa~TM now lower7/17/09Stop Ixempra By Choice9/21/09HOSPICE10/16/09Earned His Deserved Wings And Halo=37 Month Fight w/Stage 4 IBC, Her2+++,My Hero!!
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Old 03-11-2009, 11:38 AM   #5
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hurry, please!
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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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Old 03-11-2009, 08:29 PM   #6
caya
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Amazing news Lani - I'm with Brenda - HURRY!!!

all the best
caya
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ER90%+/PR 50%+/HER 2+
1.7 cm and 1.0 cm.
Stage 1, grade 2, Node Negative (16 nodes tested)
MRM Dec.18/06
3 x FEC, 3 x Taxotere
Herceptin - every 3 weeks for a year, finished May 8/08

Tamoxifen - 2 1/2 years
Femara - Jan. 1, 2010 - July 18, 2012
BRCA1/BRCA2 Negative
Dignosed 10/16/06, age 48 , premenopausal
Mild lymphedema diagnosed June 2009 - breast surgeon and lymph. therapist think it's completely reversible - hope so.
Reclast infusion January 2012
Oopherectomy October 2013
15 Years NED!!
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Old 03-11-2009, 10:08 PM   #7
karen z
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absolutely amazing research.
kz
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