![](http://investorshub.advfn.com/images/default_ih_profile2_4848.jpg?cb=0)
Saturday, September 17, 2011 4:36:14 PM
From Wikipedia, the free encyclopedia
Circulating tumor cells (CTCs) are cells that have detached from a primary tumor and circulate in the bloodstream. CTCs may constitute seeds for subsequent growth of additional tumors (metastasis) in different tissues.
In 1869 Thomas Ashworth obeserved circulating tumor cells in the blood of a man with metastatic cancer. He postulated that “cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumours existing in the same person”. A thorough comparison of the morphology of the circulating cells to tumor cells from different lesions led Ashworth to conclude that “One thing is certain, that if they [CTC] came from an existing cancer structure, they must have passed through the greater part of the circulatory system to have arrived at the internal saphena vein of the sound leg”.[1] Cancer research has demonstrated the critical role circulating tumor cells play in the metastatic spread of carcinomas.[2] Technology with the requisite sensitivity and reproducibility to detect CTC in patients with metastatic disease was developed only recently.[3][4][5][6][7]
Contents
1 Frequency of CTC
2 Clinical utility
3 CellSearch Method
4 Morphological definition
5 Further characterisation of CTC
6 See also
7 References
Frequency of CTC
Figure 1: cell number of various blood cells in whole blood versus CTC
The detection of CTCs may have important prognostic and therapeutic implications but because their numbers can be very small, these cells are not easily detected.[8] Circulating tumor cells are found in frequencies in the order of 1-10 CTC per mL of whole blood in patients with metastatic disease. For comparison, a mL of blood contains a few million white blood cells and a billion red blood cells, see figure 1. This low frequency means that a key component of methods to detect CTC is the enrichment method.
First evidence indicates that CTC markers applied in human medicine are conserved in other species. Five of the more common markers including CK19 are also useful to detect CTC in the blood of dogs with malignant mammary tumors.[9]
[edit] Clinical utility
Figure 2: Kaplan Meier Analysis of overall survival before starting a new line of therapy for patients with metastatic breast, colorectal and prostate cancer. Patients were divided into those with Favorable and Unfavorable CTC (Unfavorable: >5 CTC/7.5mL for breast and prostate, >3 CTC/7.5mL for colon) [10]
To date, a variety of research methods have been developed to isolate and enumerate CTC.[11] The only U.S. Food and Drug Administration (FDA) cleared methodology for enumeration of CTC in whole blood is the CellSearch system.[12] Extensive clinical testing done using this method shows that presence of CTC is a strong prognostic factor for overall survival in patients with metastatic breast, colorectal or prostate cancer, see figure 2 [13][14][15][16][17][18][19]
CellSearch Method
Blood is sampled in an EDTA tube with an added preservative. Upon arrival in the lab, 7.5mL of blood is centrifuged and placed in a preparation system. This system first enriches the tumor cells immunomagnetically by means of ferrofluidic nanoparticles conjugated to epithelial cell adhesion molecule (EpCAM). Subsequently it stains the sample with a nuclear stain, and fluorescent antibody conjugates against CD45 and cytokeratin 8, 18 and 19 (CK). The sample is scanned on an analyzer, which takes images of the nuclear stain, the cytokeratin stain and the CD45 stain. A trained operator looks at the images of cells to identify those cells that are positive for the nuclear stain and the cytokeratin stain and negative for the CD45 stain. If the cell meets these criteria, the operator judges whether the morphology is suitable for a tumor cell. If the total number of tumor cells found is 5 or more, a sample is positive. In studies done on prostate, breast and colon cancer patients, median survival of metastatic patients with positive samples is about half the median survival of metastatic patients with negative samples.
Morphological definition
Morphological appearance is judged by human operators and is therefore subject to large inter operator variation.[20] Several CTC enumeration methods exist which use morphological appearance to identify CTC, which may also apply different morphological criteria. A recent study in prostate cancer showed that many different morphological definitions of circulating tumor cells have similar prognostic value, even though the absolute number of cells found in patients and normal donors varied by more than a decade between different morphological definitions.[21]
Further characterisation of CTC
Some drugs are particularly effective against cancers which fit certain requirements. For example Herceptin is very effective in patients who are Her2 positive, but much less effective in patients who are Her2 negative. Once the primary tumor is removed, biopsy of the current state of the cancer through traditional tissue typing is not possible anymore.[22] Often tissue sections of the primary tumor, removed years prior, are used to do the typing. Further characterisation of CTC may help determining the current tumor phenotype. FISH assays has been performed on CTC to as well as determination of IGF-1R, Her2, Bcl-2, [ERG (gene)|ERG], PTEN, AR status using immunofluorescence.
Recent AEMD News
- Aethlon Medical Announces Financial Results for the Fiscal Year Ended March 31, 2024 and Provides Corporate Update • PR Newswire (US) • 06/27/2024 08:15:00 PM
- Aethlon Medical to Release Fiscal Year End Financial Results and Host Conference Call on June 27, 2024 • PR Newswire (US) • 06/21/2024 12:01:00 PM
- Aethlon Medical Receives Ethics Committee Approval for Hemopurifier® Cancer Trial • PR Newswire (US) • 06/18/2024 12:01:00 PM
- Aethlon Medical Prepares for Potentially Transformative Phase 1 Cancer Treatment Studies • PR Newswire (US) • 06/03/2024 12:01:00 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/24/2024 05:24:31 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/17/2024 08:05:28 PM
- Form EFFECT - Notice of Effectiveness • Edgar (US Regulatory) • 05/17/2024 04:15:21 AM
- Form 424B4 - Prospectus [Rule 424(b)(4)] • Edgar (US Regulatory) • 05/16/2024 08:05:23 PM
- Form POS AM - Post-Effective amendments for registration statement • Edgar (US Regulatory) • 05/15/2024 01:27:15 PM
- Aethlon Medical Announces Pricing of $4.7 Million Public Offering • PR Newswire (US) • 05/15/2024 01:15:00 PM
- Form S-1/A - General form for registration of securities under the Securities Act of 1933: [Amend] • Edgar (US Regulatory) • 05/13/2024 09:30:18 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/10/2024 12:01:40 PM
- Aethlon Medical Reports Positive Results From an In Vitro Binding Study of Its Hemopurifier® in Removing Extracellular Vesicles From Cancer Patient Plasma • PR Newswire (US) • 05/10/2024 12:01:00 PM
- Aethlon Medical Enters Into Materials Transfer Agreement for Santersus AG's NucleoCapture and HemoNucleoCapture Devices • PR Newswire (US) • 02/21/2024 01:01:00 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 02/14/2024 10:15:40 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 02/14/2024 09:15:41 PM
- Aethlon Medical Announces Fiscal Third Quarter Financial Results and Provides Corporate Update • PR Newswire (US) • 02/14/2024 09:15:00 PM
- Aethlon Medical to Release Fiscal Third Quarter Financial Results and Host Conference Call on February 14, 2024 • PR Newswire (US) • 02/07/2024 01:00:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/02/2024 11:06:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/02/2024 11:04:32 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 01/02/2024 11:02:52 PM
- Form 8-K/A - Current report: [Amend] • Edgar (US Regulatory) • 12/22/2023 09:01:12 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 11/27/2023 12:49:31 PM
Glidelogic Corp. Becomes TikTok Shop Partner, Opening a New Chapter in E-commerce Services • GDLG • Jul 5, 2024 7:09 AM
Freedom Holdings Corporate Update; Announces Management Has Signed Letter of Intent • FHLD • Jul 3, 2024 9:00 AM
EWRC's 21 Moves Gaming Studios Moves to SONY Pictures Studios and Green Lights Development of a Third Upcoming Game • EWRC • Jul 2, 2024 8:00 AM
BNCM and DELEX Healthcare Group Announce Strategic Merger to Drive Expansion and Growth • BNCM • Jul 2, 2024 7:19 AM
NUBURU Announces Upcoming TV Interview Featuring CEO Brian Knaley on Fox Business, Bloomberg TV, and Newsmax TV as Sponsored Programming • BURU • Jul 1, 2024 1:57 PM
Mass Megawatts Announces $220,500 Debt Cancellation Agreement to Improve Financing and Sales of a New Product to be Announced on July 11 • MMMW • Jun 28, 2024 7:30 AM