Wednesday, July 16, 2008
Another HER2 Test Receives FDA Approval
The FDA has given Invitrogen pre-market approval for company's new test for the HER2 gene, commonly expressed in breast cancer patients.
The kit is based on a technology called chromogenic in situ hybridization (CISH). The test uses a DNA probe for the HER2 gene, which is amplified in 18 to 30 percent of breast cancers and predicts whether a breast cancer patient is a candidate for trastuzumab treatment. Current medical practice requires that all patients who are considered for trastuzumab treatment be tested for HER2 amplification or overexpression. CISH test results are visualized under a standard bright-field microscope, as opposed to fluorescent in situ hybridization tests, in which the results must be visualized using a fluorescent microscope. This specialized microscope frequently requires that the analysis is done at a reference lab. In addition, HER2 CISH test results are quantifiable; removing the subjectivity inherent in tests based on immunohistochemistry (IHC) interpretation schemes."The current protocol for assessing HER2 gene status is for labs to initially screen tissue samples with immunohistochemistry to gauge whether there is an overabundance of the HER2 protein, as an indirect measure of gene amplification," said August Sick, vice president and general manager of Invitrogen's Cellular Analysis Business. "In the case of an inconclusive test, the samples are typically sent to an outside lab for confirmation. Because the SPOT-Light(R) HER2 CISH Kit doesn't need specialized equipment, any histology lab can now assess amplification of the HER2 gene while simultaneously examining tissue morphology."
Press release: FDA Grants Invitrogen Premarket Approval of Breast Cancer Test
Flashback: HERmark Breast Cancer Assay Is Now Available
Image courtesy Invitrogen Corp.: SPOT-Light HER2 Probe...
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Monday, July 14, 2008
Epocrates Rx Now on iPhone
Epocrates has announced that its free drug and formulary application, Epocrates Rx, is finally available for the iPhone through the iTunes store.
Some of the features from the product page:
Adult and pediatric dosing for FDA-approved and off-label indications Black box warnings, contraindications, and cautions Serious and common adverse reactions, and drug interactions organized by clinical category Pill pictures within the drug monograph showing you and your patients exactly what each drug looks like Safety and monitoring information, such as pregnancy risk categories, lactation safety ratings, monitoring parameters and therapeutic drug levels Manufacturer information, approximate retail pricing, and FDA/DEA status Pharmacology information, including metabolism, excretion (i.e., half-life), drug class, and mechanism of action Notes section for your personal notes
Press release: Epocrates Drug and Formulary Application on Apple App Store
Product page: Epocrates Rx for iPhone
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Thursday, July 10, 2008
HERmark Breast Cancer Assay Is Now Available
Monogram Biosciences, Inc. out of South San Francisco is announcing availability of their assay for the detection of a particularly aggressive type of breast cancer that exhibits presence of the HER2 protein.
From a press release by the company:
ERmark is a proprietary diagnostic that accurately quantifies HER2 total protein levels and HER2 homodimerization in patients with breast cancer. HERmark is a CLIA-validated assay that is performed exclusively in Monogram's CAP-certified clinical reference laboratory in South San Francisco. Robust, accurate, sensitive and reproducible measurements of HER2 status are reported to physicians with a turnaround time of 7 days.With the accurate measurements provided by HERmark, it is expected that as many as 15-20% of patients determined by conventional technologies to be HER2- negative would be reclassified by HERmark.
Key advantages of the HERmark Breast Cancer Assay include:
-- HERmark is highly sensitive and can detect HER2 at levels from 2,500 to over 1 million receptors per cell -- 7 to 10 times more sensitive than IHC.
-- HERmark provides a better measure of HER2 status by measuring the drug target -- the HER2 protein and HER2 homodimers -- rather than the HER2 gene.
-- The HERmark report is simple to interpret and provides a specific quantitative measure of HER2 expression, a HER2 status of "positive", "negative" or "equivocal" and indicates, relative to conventional measurements, how positive or how negative the patient is.
-- Clinical studies demonstrate that HERmark is an accurate method for stratifying patients with metastatic breast cancer who are more likely to respond to Herceptin-containing therapy.
Press release: Monogram Announces Commercial Availability of the HERmark(TM) Breast Cancer Assay...
Product page: HERmark...
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Monday, July 7, 2008
SenoRx Balloon Radiation Therapy Device for Breast CA Gets FDA Nod
SenoRx, Inc., an Aliso Viejo, California firm, is in the business of designing and developing so-called Multi-Lumen Radiation Balloon (MLB) catheters, devices for delivering radiation to the tissue surrounding the lumpectomy cavity following surgery for breast CA. The firm has just received a 510(k) clearance from the FDA for its second Contura™ MLB radiation balloon design.
Some patients who are potential candidates for balloon therapy are currently excluded because of the location of the lesion and their breast size. Contura’s advanced multi-lumen design may address this issue for certain patients. In addition, the Contura MLB uses vacuum to remove excess seroma and air to enhance conformance of often irregularly shaped lumpectomy cavity walls to the balloon surface in order to deliver precise radiation dosing through multiple radiation source lumens.“The novel proprietary design of our newest Contura Multi-Lumen Radiation Balloon (MLB) Catheter allows the clinician greater flexibility in appropriately fitting the lumpectomy cavity with a balloon catheter,” said Lloyd Malchow, SenoRx President and Chief Executive Officer. “The new-size Contura balloon may be appropriate for approximately 10 to15 percent of patients where a larger balloon is warranted and will allow us to compete for these cases. The product is currently being evaluated at several clinical sites and is expected to become generally available during the third quarter of 2008. The original Contura is 4 to 5 centimeters in diameter, while the new balloon can be used for larger lumpectomy cavities ranging from 5 to 6 centimeters in diameter.”
Press release: SenoRx Receives Additional 510(k) Clearance for Its Contura MLB...
Product page: Contura ...
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Thursday, July 3, 2008
Laser Opto-Acoustic Imaging Technology from Seno Medical
Here's what we know about the opto-acoustic imaging technology from Seno Medical Instruments, Inc., a San Antonio, Texas firm. A recent report on the wires says that there is a new research agreement between Seno Medical and two Canadian universities to study the company's first-ever commercially available opto-acoustic small animal imaging device. It turns out the technology, that utilizes the conversion of laser pulses into acoustic energy once the light hits tissue, can have profound consequences on development of future diagnostic imaging modalities for cancer and beyond.
The company explains its technology:
Laser opto-acoustic imaging technology combines optics and acoustics with a goal of improving the accuracy of the cancer diagnosis without the use of ionizing radiation (x-ray). The process starts by illuminating the breast with laser light of specific wavelengths. Tumors preferentially absorb the light over normal tissue and become slightly heated. A transient thermoelastic expansion causes a tumor to emit a pressure (acoustic) wave. This acoustic wave is then detected by an array of sensors positioned around the periphery of the breast held within the probe.Signals from the sensors are analyzed and assembled into high contrast, high-resolution images that present the lesion in striking color. Because image contrast is related to both blood volume and oxygenation status, lesions may be correlated with benign or malignant histopathology. This is because malignant tumors possess increased microvasculature, but deplete oxygen from the blood at a higher rate than benign growths. Deoxygenated blood results in brighter images in the presence of a shorter wavelength than it does in the presence of a longer wavelength.
This technology has the merit of both the high contrast and spectral specificity of optical imaging and the sensitivity and resolution of ultrasonic imaging. It is more than just a combination of the two methods. The goal is to incorporate laser illumination and ultrasonic detection to achieve very high detection sensitivity.
Laser opto-acoustic imaging may permit the identification of tumors as small as 2 mm and has demonstrated the ability to see submillimeter structures. Early detection is important because biologically advanced tumors are more capable of metastasis.
Technology page @ Seno Medical: Laser Opto-Acoustic Imaging...
Press release: Seno Medical Instruments Launches First-Ever Commercially Available Opto-Acoustic Small Animal Imaging Research System...
Flashbacks: Optoacoustic Technology for Early Cancer Detection
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Tuesday, May 27, 2008
Advaxis Hopes to Make it Big with Listerial Cancer Vaccines
A press release from Advaxis, Inc., a North Brunswick, New Jersey company, says that the firm has filed an investigational new drug application with the FDA "to assess the safety, efficacy, and immunogenicity of vaccination with Listeria monocytogenes expressing human papilloma virus Type 16 E7 (Lovaxin C) for the treatment cervical intraepithelial carcinoma stage 2/3."
So, let us get it straight. Now we have a company that tries to utilize a bacterium responsible for a common food poisoning to fight a common cancer? Indeed, and the reason is the strong T cell mediated immune response that the human body mounds against Listeria, hence the organism could potentially be used as a vaccine vehicle. According to Advaxis, the firm holds the rights to a portfolio of patents based on the work of Dr. Yvonne Paterson from the University of Pennsylvania, protecting its use of Listeria and listerial products in hopes of developing vaccines against a variety of diseases.
Advaxis, on its technology page, explains how it plans to exploit the pathogen:
Listeria has a unique life cycle. It infects Antigen Presenting Cells (APC), which are the cells that activate immune cells and tell them what to attack. Because of this, Listeria becomes perfectly positioned to have the maximum effect on the immune system in terms of directing it against specific targets. Even more unusual is Listeria's ability to stimulate both helper T cells (CD4+) and killer T cells (CD8+), since both are necessary for an antitumor response and it is unusual for a single pathogen to stimulate both in the way Listeria does.Antigen Processing Cells normally engulf foreign elements to remove them from the body and present them to the immune system.
Following their ingestion, they are encapsulated and digested in a phagolysosome. Fragments of the digested invader are used to stimulate the immune system through the exogenous pathway (exogenous; since the invader came from outside the cell).
This pathway is associated with the formation of MHC class II complexes and the activation of specific CD4+ helper T cells directed against the invader. This is the most common response to a foreign invader.
A certain percentage of Listeria, however, are able to break out of the phagolysosomes and enter into the cytoplasm of the cell, where they are safe from lysosomal destruction. After escaping from the phagolysosome, the bacteria multiply in the cell. Additionally, Listeria is able to migrate into neighboring cells and spread without entering the extracellular space.
Once in the cytoplasm, Listeria is capable of stimulating the immune system via the endogenous pathway (endogenous; because Listeria is now living within the cell). The endogenous pathway is associated with MHC class I complex formation and resultant CD8+ killer T cells.
Listeria also has other effects; such as the maturation of dendritic cells, which is most powerful APC and is essential for a strong antitumor response.
Thus, Listeria has the ability to stimulate multiple limbs of the immune response simultaneously and in an integrated way that serves to bring a number of immune mechanisms together to attack cancer...
The details of Listeria intracellular activity are important for understanding Advaxis technology. Inside the phagolysosome, Listeria produces and secretes the virulence factor listeriolysin O ("LLO"), a protein that generates a hole in the membrane of the phagolysosome and allows the bacteria to escape into the relatively safe cytoplasm. Once in the cytoplasm, however, LLO still retains some activity and is also capable of creating a hole in the cell membrane. This would destroy the host cell, and spill the bacteria back out into the intercellular space where it would be exposed to more immune cell attacks and destruction. To prevent this, a sequence of approximately 30 amino acids is present in the LLO protein, called the PEST sequence (for the predominant amino acids it contains). This PEST sequence is recognized by the host cells and targets the LLO protein for rapid digestion, thus giving LLO a very short life span. The benefit for the Listeria is that the LLO is neutralized and the bacteria can continue to prosper inside the cell, which also remains alive.
Since the activation of the immune system is also dependent upon the digestion of antigens and the creation of small fragments that can be used as recognition sites for an immune attack, Advaxis reasoned that we might use this mechanism that rapidly breaks down LLO to also break down antigens, which are released in both the phagolysosome and in the cytoplasm of the APC. To do so, we created a proprietary method in which we engineer Listeria to secrete a "fusion protein" which is comprised of a specific antigen that we wish to use as the focus for an immune attack fused to a segment of LLO. In this way, we can accelerate the breakdown of antigens into immuno-active fragments because the PEST sequence of the fusion protein is recognized and the secreted antigen fusion protein is routed for rapid degradation, thus accelerating both the rate at which antigen fragments are created and the speed with which they are delivered to the immune system for use in the creation of recognition molecules that activate T cells. Furthermore, the fusion of the antigen to LLO is essential to promote the secretion of the antigen, because the signal sequence needed for LLO secretion is kept intact in the fusion protein.
To read more, head on to Advaxis technology page...
Press release: Advaxis Files Investigational New Drug Application with U.S. Food and Drug Administration...
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Wednesday, May 21, 2008
The Third Install in the US of Aquilion ONE CT from Toshiba
Toshiba's gargantuan dynamic volume system called AquilionONE, the device that features a coverage area of 320 detectors rows in addition to a respectable 650 lb table capacity, has now been installed at Beth Israel Deaconess Medical Center in Boston, according to a press release obtained by Medgadget. This is the third install of this device in the US. We first covered AquilionONE CT back in November 2007, when it was first unveiled at the RSNA 2007 conference. So when two days ago we were all excited about high demand for 256-slice CT scanners, we should have have kept a more proper perspective: the 320-slice system is also here to stay, albeit initially in smaller numbers. A representative for the company, tells Medgadget: "The Aquilion ONE has a coverage area of 320 detector rows, can capture actual organ movement (like blow flowing through the heart) and can image an entire organ in one gantry rotation. Additionally, the Aquilion ONE can capture the heart in one heart beat."
From the press release:
As a testament to the growing demand to improve patient care while reducing healthcare costs, Toshiba America Medical Systems, Inc. has installed the Aquilion ONE™ dynamic volume CT system at Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School in Boston."In one of the country's leading medical teaching hospitals, we hope the Aquilion ONE's ability to image an entire organ and show function for the first time will mean faster, more accurate diagnosis, better patient outcomes and ultimately lower healthcare costs for our patients," explained Dr. Vassilios D. Raptopoulos, interim radiologist-in-chief, Department of Radiology and director, CT services, Beth Israel Deaconess Medical Center. "We are grateful to be one of the first teaching hospitals in the United States using this advanced technology."
Toshiba's Aquilion ONE dynamic volume CT system utilizes 320 ultra-high resolution detector rows (0.5 mm in width) to image an entire organ in a single gantry rotation. The result is unparalleled in diagnostic imaging today and produces a 4D clinical video showing up to 16 cm of anatomical coverage, enough to capture the entire brain or heart, and show its movement such as blood flow.
"The Aquilion ONE has the potential to provide a single, comprehensive exam that can replace a variety of duplicative and invasive procedures," added Dr. Raptopoulos. "Its versatility and ability to diagnose disease fast will be used within our radiology department to detect and treat life-threatening conditions, including cancer, heart disease, stroke and other neurovascular conditions."
To get impressed, head on to the Aquilion ONE Clinical Movie Theatre at Toshiba, and check out some of the studies presented there...
Product page: Aquilion ONE...
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Monday, May 19, 2008
Demand Is High for Brilliance iCT, a 256-Slice CT from Philips
It seems just like it was yesterday when we were covering 64 slice CT scanners as the best and the latest thing in cardiac diagnostics. But technology is moving forward, and the demand for monstrous 256-slice CT scanners is quite high. Readers might recall our coverage of Toshiba's Aquilion beta 256, the world's first 256-slice CT scanner. Philips Electronics is now reporting that their 256 scanner, Brilliance iCT, unveiled last November, is now installed in 5 medical centers across the world (MetroHealth Medical Center in Cleveland, Methodist Hospital in Indianapolis, Carmel Medical Center in Haifa, Israel, in Washington Hospital Center in Washington, D.C., and in Lenox Hill Hospital in NYC), with 50 (!) more systems to be installed by the end of 2008.
Here's what Philips says about its Brilliance iCT with Essence technology:
... customers tout the system’s ability to provide greater dimension and depth across a range of clinical areas such as whole brain perfusion, cardiac CT with Step & Shoot technology that images the heart in two beats while reducing dose, head and neck angiography, full field of view lung studies, virtual colonoscopy and abdominal and pelvic imaging. Brilliance iCT with Essence technology offers an impressive combination of speed, power and coverage to improve image quality while incorporating the latest dose reduction technology. Overall patient experience is improved through shorter scan times.In addition to the 256 slice intelligent Brilliance iCT, the Brilliance 64-channel configuration is also designed with Essence technology. Unique and proprietary to Philips, Essence technology brings advances to the X-ray tube, detector system, and reconstruction engine while offering a scalable platform to enhance image quality and dose efficiencies.
“With Brilliance iCT, the superb image quality aids our clinicians in the diagnosis of complicated health conditions,” said Dr. Nathan Peled, head department of radiology of Carmel Medical Center in Haifa, Israel. “The system has delivered increased rotation speeds and improved image quality and clinical performance for diagnostic confidence in routine and advanced radiological imaging.”
Below you can find the technical backgrounder paper distributed by the company:
Product page: Brilliance iCT...
Press release: Philips accelerates plans to install Brilliance iCT around the world...
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Monday, April 28, 2008
Online Lung Cancer Mutation Database to Help Oncologists in Decision Making
The European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC) in Geneva, Switzerland have launched an online database designed to improve clinical outcomes for patients with non-small-cell lung cancer:
The online database brings together data on all the known somatic mutations (tumor derived - tumor specific) in a molecule called epithelial growth factor receptor (EGFR). Somatic mutations in this cell-surface molecule are known to affect treatment with the newer tyrosine kinase inhibitor class of drugs."We have known for some time that some EGFR mutations correlate with response to tyrosine kinase inhibitors for lung cancer patients," says Dr. Samuel Murray from Department of Molecular Pathology and Translational Oncology, Metropolitan Hospital, Athens, Greece. "But there have been so many articles published on this topic that we felt that it would be virtually impossible for any given center or individual to interpret the clinical relevance of a given mutation."
"So we worked on the assumption that a comprehensive list of all somatic EGFR mutations coupled with data on the response of non-small-cell lung cancers treated with tyrosine kinase inhibitors (TKIs) would help clinicians determine whether a specific mutation was likely to correlate with clinical benefit."
The database includes cumulative data from thousands of patients. In addition, independent patient data (IPD) for patients who have been treated with tyrosine kinase inhibitors and some who have not, is being added. A total of 12,244 patients are included, of whom 3,381 had somatic mutations in EGFR. The researchers catalogued 254 different mutations.
Ultimately, the database offers a chance to improve treatment for people receiving tyrosine kinase inhibitors. "We believe that for the more common mutations the database allows clinicians to make more robust decisions concerning their treatment options for NSCLC," says Dr. Murray.
Press release: Mutation database helps personalized treatment of lung cancer
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Tuesday, April 8, 2008
Injectable Dosimeter May Help During Radiation Therapy
Researchers at Purdue University have successfully embedded a wireless radiation dosimeter into a capsule small enough to be injectable by needle. Using the device may become standard practice during radiation treatment of tumors.
The prototype is enclosed in a glass capillary small enough to inject into a tumor with a syringe, said Ziaie, who has a dual appointment in Purdue's Weldon School of Biomedical Engineering.Research findings are detailed in a paper appearing in the June issue of IEEE Transactions On Biomedical Engineering. The paper was written by doctoral student Chulwoo Son and Ziaie.
Whereas conventional imaging systems can provide a three-dimensional fix on a tumor's shifting position during therapy, these methods are difficult to use during radiation therapy, are costly and sometimes require X-rays, which can damage tissue when used repeatedly, Ziaie said.
The new device uses radio frequency identification, or RFID, technology, which does not emit damaging X-rays.
The device, which has no batteries and will be activated with electrical coils placed next to the patient, contains a miniature version of dosimeters worn by workers in occupations involving radioactivity. The tiny dosimeter could provide up-to-date information about the cumulative dose a tumor is receiving over time.
Press release: Needle-size device created to track tumors, radiation dose...
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Thursday, April 3, 2008
Scientists Develop Anti-Angiogenesis Nanoparticles
Investigators from the Washington University School of Medicine in St. Louis have developed nanoparticles laden with fumagillin, an angiogenesis inhibitor, known to be extremely neurotoxic in systemic dose. When given to tumor-bearing rabbits, the nanoconstructs were shown to be very effective in suppressing the neovasculature and inhibiting adenocarcinoma development, in concentrations way below a toxic dose:
"Many chemotherapeutic drugs have unwanted side effects, and we've shown that our nanoparticle technology has the potential to increase drug effectiveness and decrease drug dose to alleviate harmful side effects," says lead author Patrick M. Winter, Ph.D., research assistant professor of medicine and biomedical engineering.The nanoparticles are extremely tiny beads of an inert, oily compound that can be coated with a wide variety of active substances. In an article published online in The FASEB Journal, the researchers describe a significant reduction of tumor growth in rabbits that were treated with nanoparticles coated with a fungal toxin called fumagillin. Human clinical trials have shown that fumagillin can be an effective cancer treatment in combination with other anticancer drugs.
In addition to fumagillin, the nanoparticles' surfaces held molecules designed to stick to proteins found primarily on the cells of growing blood vessels. So the nanoparticles latched on to sites of blood vessel proliferation and released their fumagillin load into blood vessel cells. Fumagillin blocks multiplication of blood vessel cells, so it inhibited tumors from expanding their blood supply and slowed their growth.
Human trials have also shown that fumagillin can have neurotoxic side effects at the high doses required when given by standard methods. But the fumagillin nanoparticles were effective in very low doses because they concentrate where tumors create new blood vessels. The rabbits that received fumagillin nanoparticles showed no adverse side effects.
Senior author Gregory M. Lanza, M.D., Ph.D., associate professor of medicine and of biomedical engineering, and Samuel A. Wickline, M.D., professor of medicine, of physics and of biomedical engineering, are co-inventors of the nanoparticle technology. The nanoparticles measure only about 200 nanometers across, or 500 times smaller than the width of a human hair. Their cores are composed mostly of perfluorocarbon, a safe compound used in artificial blood.
The nanoparticles can be adapted to many different medical applications. In addition to carrying drugs to targeted locations, they can be manufactured to highlight specific targets in magnetic resonance imaging (MRI), nuclear imaging, CT scanning and ultrasound imaging.
Washington University School of Medicine in St. Louis: Nano-sized technology has super-sized effect on tumors...
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Monday, March 31, 2008
SIRTeX to Trial Radiation Spheres for Liver Cancer
Australian company SIRTeX has received FDA approval to begin trials of their injectable, beta radiating microspheres thought to directly target intrahepatic tumor sites.
From the product brochure:
SIR-Spheres microspheres consist of biocompatible microspheres containing yttrium-90 with a size between 20 and 60 microns in diameter. Yttrium-90 is a high-energy pure betaemitting isotope with no primary gamma emission. The maximum energy of the beta particles is 2.27MeV with a mean of 0.93MeV. The maximum range of emissions in tissue is 11mm with a mean of 2.5mm. The half-life is 64.1 hours. In therapeutic use, requiring the isotope to decay to infinity, 94% of the radiation is delivered in 11 days. The average number of particles implanted is 30 – 60 x 106. SIR-Spheres microspheres are a permanent implant.SIR-Spheres microspheres are implanted into a hepatic tumor by injection into either the common hepatic artery or the right or left hepatic artery via the chemotherapy catheter port. The SIRSpheres microspheres distribute non-uniformly in the liver, primarily due to the unique physiological characteristics of the hepatic arterial flow, the tumor to normal liver ratio of the tissue vascularity, and the size of the tumor. The tumor usually gets higher density per unit distribution of SIR-Spheres microspheres than the normal liver. The density of SIR-Spheres microspheres in the tumor can be as high as 5 to 6 times of the normal liver tissue. Once SIR-Spheres microspheres are implanted into the liver, they are not metabolized or excreted and they stay permanently in the liver.
Each device is for single patient use.
Press release: Sirtex receives US FDA approval for FAST clinical trial (.pdf)
Product page: Product Package Insert (PDF)
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Two-Photon Nanoparticles for Tumor Recognition
A porous nanoparticle "capable of absorbing the energy of two photons in the near infrared spectrum, and then re-emitting radiation used for medical imaging by fluorescence" has been developed by an interdisciplinary group of scientists, reports Centre National de la Recherche Scientifique of France:
At present, the medical imaging of tumor cells is based on the fluorescence emitted by chemical groups that can absorb the energy of a photon. These molecules, called fluorophores, are excited in the visible ultraviolet spectrum. Single-photon imaging thus remains relatively imprecise. This obstacle should soon be overcome thanks to work by scientists from CNRS-associated laboratories.These researchers have succeeded in developing organic, two-photon fluorophores (aromatic molecules) that are able simultaneously to absorb two photons in the near infrared spectrum. These were then encapsulated in porous nanoparticles to enable their circulation in a biological medium. The originality of this work resides in the fact that unlike ultraviolet wavelengths, infrared wavelengths penetrate more deeply into tissues and are less energetic, the advantage being that they can explore tumors more profoundly without damaging the tissues. Furthermore, the use of two-photon fluorophores favors access to a 3D spatial resolution, which in the longer term will enable the detection and more targeted treatment of tumor cells. One of the options envisaged may be to encapsulate in the pores of silicon nanoparticles not only the fluorescent agent but also drugs that can locally treat the cancer cells.
The scientists have also been focusing on the functionalization of these nanoparticles in order to create new biological markers capable of interacting with breast and cervical cancer cells. To achieve this, they grafted on the nanoparticles a monolayer made up of a hydrophilic polymer (PEG: polyethylene glycol) and folic acid. The latter forms the ligand recognized by the receptors of HeLa cells (cervical cancer) and MCF7 cells (breast cancer) (see diagram). These results should enable the 3D targeting and imaging of the tumor. Other functionalizations could be envisaged, enabling the detection of other tumors.
Link: Two-photon nanoparticles for the improved detection of tumor cells...
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Monday, March 17, 2008
CellScope for Rural Microscopy On The Go
At the University of California Berkeley, a few handy researchers modified an off-the-shelf camera cellphone to produce a mobile microscope capable of 50x magnification. Coupled with the phone's natural ability to send out images, the device may help to virtually bring dermatologists, pathologists and oncologists to remote areas of the world.
Using Bluetooth, wi-fi and cellular networks, a phone needs no modification itself. Capable of 50x magnification today, the devices could provide twice that. A smaller prototype features its own light source."This could be useful even at home," suggests Fletcher [Associate Professor of Bioengineering at Berkeley --ed.], "where, for example, early warnings of a change in the shape of a mole could be sent to your clinician on a regular basis to monitor."
In addition, cancer patients could conduct their own blood cell counts that today require larger microscopes and particle counters.
Dr. Lam, Pediatric Oncologist at UCSF, is one of the grad students working on CellScope. He adds, "By no means do we think this is going to replace those large particle counters. It's just a good adjunct for the patient to have at home."
More, with video, from ABC...
Project page: Telemicroscopy for Disease Diagnosis...
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Tuesday, March 4, 2008
HistoMag, A Magnetometer for Cancer Cells
Investigators at the University College London developed a miniature magnetic device that is suppose to detect the presence of breast cancer cells labeled with magnetic nanoparticles. This technology, awarded a prestigious Brian Mercer Feasibility Award from the Royal Society, might improve the sensitivity and specificity of diagnosis of not only breast but also other types of cancers:
“Each year 35,000 women are diagnosed with breast cancer in the UK and the testing programme is a massive undertaking,” says Professor Quentin Pankhurst of the London Centre for Nanotechnology and the UCL Department of Physics & Astronomy. “Until now, pathologists had to stain tissue samples with brown dyes to help them determine whether they were normal or cancerous. In terms of streamlining the process, the main problem is that all of the results are open to interpretation and each test has to be individually checked by a specialist.
“At UCL we’ve been working in the relatively new area of biomagnetics to develop a technique which provides more quantitative and reliable results, whilst also enabling pathologists to identify abnormal tissue sections much more quickly.
“Cancerous cells have a protein on their surface called HER2. We use a solution of HER2 antibodies, tagged with magnetic nanoparticles, to stain the tissue sample. Using the HistoMag we can detect the quantity of tagged antibodies which attach themselves to the HER2 protein, which in turn provides us with an accurate picture of the spread of cancerous cells.”
By automating the process through which cancerous cells are detected and quantified, HistoMag will not only ease the pressure on pathologists but also help to identify the 15-30% of patients who are likely to benefit from being treated with the drug Herceptin. At a cost of £30,000 per patient per annum it is essential to target Herceptin at those women who will respond positively to it.
The team, led by Professor Pankhurst and LCN systems engineer Simon Hattersley, works closely with Professor Kai Stoeber and Dr Keith Miller of the UCL Department of Pathology. They form one of only seven groups to receive a Brian Mercer Feasibility Award from the Royal Society this year. The £25,000 award will enable the team to re-engineer the HistoMag, increasing its sensitivity before it goes on to clinical trials. Their goal is to make the device generally available to pathologists in 2010.
UCL: Biomagnetics developed for use in new breast cancer tests...
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Friday, February 29, 2008
Artificial Antigen-Presenting Cells (aAPCs) Boost T-cell Mediated Immunity
Biomedical engineering professor Tarek Fahmy and graduate student Erin Steenblock from Yale are reporting in the upcoming issue of Molecular Therapy the development of biodegradable microparticles specially designed "for attaching both recognition ligands and co-stimulatory ligands to a biodegradable core encapsulating the cytokine interleukin-2 (IL-2)". The particles, constructed from polymer poly(lactide-co-glycolide) (PLGA), have been shown in the group's experiments to produce a 45-fold enhancement of T cell activation and expansion:
The artificial cells, developed by Tarek Fahmy, assistant professor of biomedical engineering at Yale and his graduate student Erin Steenblock, are made of a material commonly used for biodegradable sutures. The authors say that the new method is the first “off-the-shelf” antigen-presenting artificial cell that can be tuned to target a specific disease or infection.“This procedure is likely to make it to the clinic rapidly,” said senior author Fahmy. “All of the materials we use are natural, biodegradable already have FDA approval.”
Cancer, viral infections and autoimmune diseases have responded to immunotherapy that boosts a patient’s own antigen-specific T cells. In those previous procedures, a patient’s immune cells were harvested and then exposed to cells that stimulate the activation and proliferation of antigen-specific T-cells. The “boosted” immune cells were then infused back into the patient to attack the disease.
Limitations of these procedures include costly and tedious custom isolation of cells for individual patients and the risk of adverse reaction to foreign cells, according to the Yale researchers. They also pointed to difficulty in obtaining and maintaining sufficient numbers of activated T-cells for effective therapeutic response.
In the new system, the outer surface of each particle is covered in universal adaptor molecules that serve as attachment points for antigens — molecules that activate the patient’s T-cells to recognize and fight off the targeted disease — and for stimulatory molecules. Inside of each particle, there are slowly released cytokines that further stimulate the activated T-cells to proliferate to as much as 45 times their original number.
“Our process introduces several important improvements,” said lead author Steenblock. “First, the universal surface adaptors allow us to add a span of targeting antigen and co-stimulatory molecules. We can also create a sustained release of encapsulated cytokines. These enhancements mimic the natural binding and signaling events that lead to T-cell proliferation in the body. It also causes a fast and effective stimulation of the patient’s T-cells — particularly T-cells of the cytotoxic type important for eradicating cancer.”
“Safe and efficient T-cell stimulation and proliferation in response to specific antigens is a goal of immunotherapy against infectious disease and cancer,” said Fahmy. “Our ability to manipulate this response so rapidly and naturally with an “off the shelf” reproducible biomaterial is a big step forward.”
Press release: Yale Scientists Create Artificial "Cells" that Boost the Immune Response to Cancer...
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Tuesday, February 19, 2008
First Patient Undergoes Volumetric Modulated Arc Therapy Treatment
Elekta AB, a Swedish firm, is reporting that its new radiation therapy system has been successfully implemented by docs on the first patient in General Hospital Vienna:
VMAT technology provides a simultaneous control of the linear accelerator gantry position and speed, the leaves and angle of the multileaf collimator and dose rate. This flexibility enables highly conformal cancer treatments, as well as optimal sparing of the healthy tissue around the target. In addition, VMAT significantly reduces patient treatment times, leading to greater patient comfort and stillness for a more efficient and precise treatment.Dietmar Georg, Ph.D., head of the Division of Medical Radiation Physics at General Hospital Vienna (Medical University Vienna, Vienna, Austria) says the first patient was treated for glioblastoma, a serious brain tumor that was positioned near vital structures such as the brain stem and optical lenses and nerves. The treatment consisted of three non-coplanar VMAT arcs with collimator rotation. The entire treatment took just 10 minutes, including creation and evaluation of the patient’s brain images and treatment positioning.
“This therapy is applied in very complex situations where the localization and form of the tumor requires tailored intensity modulated treatment,” says Dr. Georg.
General Hospital Vienna used its existing Elekta Synergy® S system to perform the VMAT treatment, along with Elekta’s next generation linear accelerator control software. Elekta’s VMAT solution also includes ERGO++ treatment planning system for rotational therapy, and MOSAIQ™ image-enabled oncology Electronic Medical Records (EMR) system. This complete VMAT solution is now available in upgrades to existing Elekta accelerators.
Product page: Elekta Synergy ...
Press release: First Clinical Volumetric Modulated Arc Therapy Treatment Completed with Elekta Synergy® S at General Hospital Vienna ...
Brochure: Volumetric Intensity Modulated Arc Therapy (.pdf)...
Flashbacks: Elekta Compact™ Linear Accelerator ; Leksell Gamma Knife® PERFEXION™ System
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Friday, February 1, 2008
Genetic Barcoding to Aid with Drug Cancer Targeting
In two papers published in the latest Science, scientists from Howard Hughes Medical Institute describe a way of identifying genes that are critical to colon and breast cancer cell growth. The technique should help with developing new therapeutic methods to target these common cancers.
The method exploits a powerful cellular mechanism called RNA interference. Discovered just a decade ago, RNA interference likely evolved to help cells fight viruses. The cellular machinery involved in RNA interference first identifies short segments of suspicious-looking RNA, and then destroys all identical copies of that RNA. The result: None of the protein that the RNA encodes for gets made.While RNA interference prevents viruses from replicating inside cells, scientists discovered that they could exploit the process to squelch individual gene products. To do so, they introduce a short segment of RNA that looks like one of the cell's normal genes. The RNA interference machinery grinds into action and shuts down production of the protein made from that gene.
Six years ago, Elledge and Hannon began making a library of RNAs, called short hairpin RNAs, which trigger the RNA interference mechanism. They've now made short hairpin RNAs that can squelch every gene in the human and mouse genomes.
For their new experiments, the pair first identified about 3,000 genes important in cell signaling, growth, and other essential processes. Next, they inserted a gene sequence coding for short hairpin RNAs targeting these genes into retroviruses. Then they infected dishes of normal and tumor cells with the retroviruses, which added instructions to each cell's genome telling it to produce a short hairpin RNA. These short RNAs then triggered the RNA interference mechanism. In effect, each virus halts production of a single protein in a single cell.
In the past, researchers deployed this method to study the effects of turning off one particular gene. But to study the effects of thousands of genes, researchers had to run thousands of separate experiments with thousands of plates of cells.
Instead, Hannon and Elledge developed a “barcoding” method to track a diverse pool of short hairpin RNAs in parallel. In the barcoding method, every short hairpin RNA that is made carries a unique genetic tag. This tag lets the researchers track the effect of thousands of the RNAs in a single pool of cells in a single lab dish.
“We get a mixture of cells where each individual cell has one of these genes knocked down,” says Hannon.
If RNA interference knocks down a gene important for cell growth and survival, the cell fails to thrive or dies. At the end of t