“There are over 2.5 million breast cancer survivors in the United States at this time.”
— American Cancer Society
Way too many of my women friends have suffered through breast cancer diagnosis, starting with a close friend who died of breast cancer in her early 30s. Her death inspired me to change careers, in hopes of developing better ways to detect and stage breast cancer. Although the focus of my work has now moved on to other medical imaging areas, I still pay particular attention to new breast cancer research.
It seems like there are reports on breast cancer research in the news daily. But my eye was particularly caught by an article published online on April 28, 2010 in the Journal of the National Cancer Institute. A group of researchers, from UCSF Helen Diller Family Comprehensive Cancer Center, are now able to predict whether women with ductal carcinoma in situ are at high or low risk of developing subsequent invasive cancer.
Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer. The American Cancer Society estimates that about 60,000 women are diagnosed with DCIS in the U.S. each year. This cancer starts in the milk ducts. It is called non-invasive because it hasn’t spread beyond the milk ducts into any normal surrounding breast tissue. DCIS isn’t life-threatening and it rarely leads to death from breast cancer, but having DCIS can increase your risk of developing an invasive breast cancer in the future. Approximately 11 out of 100 women diagnosed with DCIS and treated with a lumpectomy only go on to develop invasive cancer within 8 years, and about the same number go on to develop subsequent DCIS within 8 years. That means that the majority of such women have no further tumors, but these women typically still go through some form of aggressive treatment.
So we really need a way to predict which women with DCIS have a high risk of developing subsequent tumors. The UCSF scientists report that they’ve discovered a method to do just that. They collected and analyzed data for 1162 women aged 40 years or older, who were diagnosed with DCIS and treated with a lumpectomy alone in the San Francisco Bay Area. They followed and measured clinical, histopathologic, and molecular characteristics of subsequent tumors for this large population (from 63 hospitals) for 8 years.
They found that the risk of subsequent invasive cancer was significantly increased among women whose initial DCIS was detected by palpation compared with those detected by mammography. They also found that DCIS lesions that were “triple positive” for the expression of biomarkers p16, COX-2and Ki67 had an even higher risk of subsequent invasive cancer. However, these factors were not associated with increased risk of subsequent DCIS. An independent set of biomarker expression and conditions was identified for increased risk of subsequent DCIS, with the lowest risk group having disease-free surgical margins of 10 mm or larger.
Based on their findings, the UCSF scientist were able to stratify the women into 4 categories for risk of subsequent invasive cancer — Lowest (17%), Low (27%), Intermediate (28%) and High (28%). The lowest risk group had only a 4% risk of developing invasive cancer within 8 years, whereas the high risk group had a 20% risk. A similar stratification was performed for risk of subsequent DCIS with similar results.
Hopefully this new method of predicting risk for subsequent cancers will help women with DCIS chose the proper treatment. Karla Kerlikowske, the lead author, states “It will lead to a more personalized approach to treatment. As many as 44 percent of the patients (i.e., lowest and low risk groups) with DCIS may not require any further treatment, and can rely on surveillance.”
In order to make solar power cost-effective without governmental subsidies, we need to dramatically reduce the manufacturing costs of solar cells. (I discussed solar costs in a previous blog.) A lot of research is underway to do just that. One area of solar research focuses on finding a low-cost alternative to indium tin oxide (ITO), which is an expensive conducting material currently used in standard solar cells. ITO is a rare by-product of mining that is also used in flat-screen televisions, mobile phones, and other devices with display screens. As the demand for these popular devices increases rapidly, the price and availability of ITO for solar cells has become a real problem.
A team of chemical engineers think they’ve found the solution — plastic electronics. This collaboration of chemical engineers from Princeton University, University of Texas, and University of California Santa Barbara reported their latest results in the Proceedings of the National Academy of Sciences on March 30, 2010. Their research focuses on conductive polymers (plastics).
Conductive polymers have been around for a long time, but their ability to conduct electricity degraded when manufactured into devices. Basically the manufacturing process caused their structures to be trapped in a rigid form and that prevented electrical current to travel through them, thus severely limiting device performance.
The multi-institutional collaboration has overcome this problem, by treating the conductive polymers with dichloroacetic acid (DCA) after they are processed into the desired form. This “postdeposition solvent annealing” with DCA dramatically rearranges the structure of the polymer, resulting in a smooth film with high conductivity. As a result, they are able to make polymers that are translucent, malleable and highly conductive. These materials could have wide reaching applications as electrodes in transistors, anodes in solar cells, and light-emitting-diodes.
One amazing thing about this research is the simplicity of production. This collaboration made a transistor (a very basic device used to amplify and switch electronic signals) by printing the polymer onto a surface, using a method similar to that used by a standard ink-jet printer. In the future, they hope to distribute the conductive polymers in cartridges like printer ink.
What does this mean for solar power? An important thing for solar is that these conductive polymers are translucent. Although they are less transparent than ITO (e.g., transmissivity of 73% v.s. 84% respectively), they are dramatically cheaper. So the newly developed conductive polymers are still a promising low-cost alternative as anodes for solar cells. Hopefully this research will translate into cheap, commercially available solar cells soon.
“Research is the process of going up alleys to see if they are blind.”
— Marston Bates
My niece has worked in remote developing nations, in places like a tiny village in South Africa where the women have to walk several hours to fetch clean water. In order to travel to such areas, she had to take malaria medication and get a lot of vaccines — such as hepatitis A and B, yellow fever, typhoid, rabies, rubella, and diphtheria vaccines. HIV and Aids can also be prevalent. Unfortunately medical care and resources are often very limited in such isolated villages, where a doctor is many miles away and the villagers may not have access to vehicles or proper roads. To address this critical need, people are using new technology to bring the patients figuratively to the doctors. For example, medical data is acquired and then transmitted to a doctor or medical specialist elsewhere for offline assessment.
This field of telemedicine is growing rapidly. Some telemedical technology relies on the fact that cell phones are now used even in the developing world, as evidenced by extensive cell phone use after the recent earthquake in Haiti. Wireless phone technology has become significantly cheaper and the technical capabilities of cell phones is rapidly improving.
Aydrogan Ozcan, a research engineer at UCLA, has created a tiny microscope that is portable and lensless for telemedicine applications. The microscope attaches using a USB connection to a smart-phone, PDA or computer. This week his group published a paper describing in detail his latest, tiniest microscope. This minature microscope weighs just 46 grams (about the same weight as a large egg) and has dimensions of about 4 cm x 4 cm x 6 cm. It can image sub-cellular structures (with 1-2 micron resolution) over a 24 mm2 imaging area.
Microscopes normally use a lens to magnify the image of an object, where the image is generated by an electromagnetic (in optical microscopes) or electron (in electron microscopes) beam passing through the sample. However, standard microscopes are bulky and expensive, so they are generally used only in laboratories.
Ozcan’s lensless miniature microscope is instead based on digital in-line holography. It uses a simple light-emitting-diode (LED) and a compact digital sensor array to capture holographic images of blood samples or other fluids. A small chip is filled with a fluid sample, such as a blood smear, that is inserted into the microscope. The LED passes incoherent light through the sample, and the interference of the light waves that pass through the cells creates a hologram of each cell. The microscope digitally records these holograms, then rapidly reconstructs images of the cells. A compressed version of each holographic image can then be transmitted to hospitals elsewhere using wireless cellular networks, which have penetrated even the most remote corners of the world.
This portable microscope can accurately identify and count cells, including red blood cells, white blood cells, platelets, and T-cells (white blood cells whose counts are important for accurate diagnosis of AIDS). So this technology could help monitor diseases like malaria, HIV, and tuberculosis. It could also be used to test water quality following a disaster, such as a major earthquake or hurricane.
Ozcan’s microscope is also durable and easy to use. You just need to fill a chip with a sample and slide the chip into the slot in the microscope. The sample doesn’t need to be perfectly aligned in the microscope, so very minimal training is needed. It also uses cheap parts and a standard smart-phone. Plus the images are analyzed automatically by a computer, instead of requiring a trained medical technician. However, this analysis does have a potential down-side. Namely, the computer automatically identifies a cell by comparing the cell’s hologram to a cell hologram library, but I’ve seen little information on the development of this database.
Overall though this new tiny mobile phone microscope has great promise. It could become a very cost-effective tool for telemedicine applications. Next time my niece heads off to a remote village, maybe she can have a tiny microscope to attach to her smart-phone just in case?
I want to let my Bay Area readers know about an upcoming cool science lecture for the general public. Berkeley Lab presents “Just Say No To Carbon Emissions” on April 26 from 7-9 pm at the Berkeley Repertory Theatre. Admission is free. There will be three dynamic speakers from Berkeley Labs discussing renewable energy topics. Ramamoorthy Ramesh, a material scientist, will describe current research efforts to make cheap solar. Nan Zhou will discuss efforts to increase energy efficiency and reduce carbon dioxide emissions in China. Lastly, the geologist Curt Oldenbury will explain a strategy to reduce carbon emissions from coal and natural gas, by storing it deep underground. This event is co-sponsored by “Friends of Berkeley Lab” and “Berkeley Energy and Resources Collaboration.” For more information, check out their website.
My mother died of Alzheimer’s at the age of 69, so I can personally attest to the horror of this disease. I can think of few things worse than slowly watching your cognitive abilities decline, particularly if you are aware of the progressive deterioration as my mother was. So I’m keeping a close watch on the latest Alzheimer’s research, including the research of my colleague William Jagust who is a neuroscientist at UC Berkeley.
Dr. Jagust is participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which is large multicenter project supported by NIH, private pharmaceutical companies and nonprofit organizations. The primary goal of ADNI is to discover indicators (biomarkers) that can track disease progression and hopefully diagnose Alzheimer’s early on. Basically, they want to help speed up and streamline drug and clinical trials by developing biomarkers that track Alzheimer’s more reliably.
The initial ADNI five-year research project completed last fall. It studied cognition, function, brain structure and biomarkers for 800 subjects (200 elderly controls, 400 subjects with mild cognitive impairment, and 200 subjects with Alzheimer’s). The clinical data from the patients went into a large database, including MRI scans, PET scans, blood tests, neuropsychological tests, and genetic tests. The truly unique thing is that this database can be accessed by the public through a website. Basically the raw data (with patient personal information removed) is made available for everyone to use, in hopes that this will help scientists more rapidly understand and treat Alzheimer’s. This ADNI project just received the second phase of funding, so the studies will be expanded.
Although the cause and progression of Alzheimer’s disease is not fully understood, current research indicates that the disease is associated with the formation of “amyloid plaques” and “neurofibrillary tangles” in the brain that damage nerve cells. What does this mean? Amyloid plaques are protein fragments that the body produces naturally. In a healthy brain, these protein fragments are broken down and eliminated. In a brain with Alzheimer’s, the fragments instead accumulate to form hard, insoluble plaques between nerve cells. This excess amyloid buildup occurs before clinical Alzheimer’s symptoms, so it may be used as a predictor of disease. Neurofibrillary tangles are insoluble twisted fibers found inside the brain’s cells. These tangles mainly consist of a protein called tau, which helps form microtubules that transport nutrients from one part of the nerve cell to another. In an Alzheimer’s brain, the tau protein is abnormal and the tangles collapse this important transport system.
Dr. Jagust and other researchers are studying this beta-amyloid buildup using medical imaging, including PET imaging with a new drug called [11C]Pittsburg Compound B. This new PET drug binds to beta-amyloid plaques and indicates their size and position. “With PET, we’re able to study the biochemistry of the brain, and with MRI we can study both the anatomy and structure of the brain,” Jagust said. “We can also study some of the function of the brain to see what parts of the brain are active during different cognitive tests. So when you put all this information together, you can get a very detailed picture of how the brain is functioning and how function and structure might change with age.” Last fall Jagust published an article on the relationships between biomarkers in aging and dementia. The group found that the confluence of three factors — beta-amyloid deposition, atrophy of the hippocampus (part of the brain that stores and sorts memories), and episodic memory loss — signals early stage of Alzheimer’s. Hopefully this new understanding will ultimately provide early and more accurate diagnosis.
I don’t have room here to summarize all the results from the Jagust lab, let alone all the other labs doing Alzheimer’s research. But I must say that I’m optimistic given the recent progress they have made in understanding the disease. There are also many clinical trials underway for new Alzheimer’s drugs, including ones that hope to stop cognitive deterioration instead of just reducing symptoms. I’m encouraged but I still tell my friends who are doing the research that they need to find a cure within the next 10 years, because I do not want to suffer through this frightening disease like my mother did.