Scientists use light scattering to detect cancer and monitor chemotherapeutic efficacy

Angle-resolved low-coherence interferometry for cancer detection

In the latest issue of Cancer Research, scientists at Duke University reported using angle-resolved low coherence interferometry (a/LCI) to detect cellular apoptosis.

light-scatter

The "light scattering fingerprint" of a cell can be used to determine if it's cancerous or pre-cancerous. Recently, scientists at Duke University used angle-resolved low-coherence inteferometry (a/LCI) to measure cellular apoptosis and study chemotherapeutic efficacy. (Credit: Nicolle Rager Fuller, National Science Foundation)

Angle-resolved low-coherence interferometry involves shining a light on a cell sample and using the properties of the resultant scattering of that light to measure certain properties of cells including: cell nuclei size, cell structure sizes, and the presence/absence of precancerous markers. The Duke researchers used a/LCI to examine breast cancer cells after treatment with chemotherapeutic drugs and were able to quickly monitor tumor cell death following drug administration.

Cell imaging techniques that analyze how light scatters off of cells have been around for some time. For instance, flow cytometry has existed since the 1960s. Flow cytometers shine lasers on individual cells from many angles and study the refractive/scattering patterns of those lasers to determine cellular properties. Cellular death and apoptosis can be measured using flow cytometry since as the refractive index of the internal cytoplasm becomes more similar to that of the extracellular medium, the “forward scatter” signal of the laser is reduced. Additionally, intracellular changes and invagination of the cytoplasmic membrane during apoptosis lead to an increase in “side scatter” picked up by the laser sensors.

The problem with flow cytometry is that it typically takes a full day to process cells before they can be examined, and the cells can only be studied one at a time. In contrast, a/LCI can directly screen hundreds of cells in as little as five minutes, making it more desirable for clinical use.

To validate clinical applicability of their work, the Duke team exposed (MCF-7) human breast cancer cells to two common chemotherapy drugs, doxorubicin and paclitaxel. Then, they used a/LCI to look for specific patterns indicating cellular suicide (apoptosis).

Signs of apoptosis were detected shortly after administration of paclitaxel and doxorubicin. When compared to control cells, the paclitaxel-treated cells began showing significant increases in a pattern called “fractal dimension” within 90 minutes, and the doxorubicin-treated cells exhibited the same increases within three hours. Cancer cells typically have a lower fractal dimension than normal cells, and an increase in fractal dimension is a sign of cancer cell death. Notably, the fractal dimensions began decreasing  six hours after drug administration, only to increase again within 12 hours of treatment. Adam Wax, the Duke team’s lead investigator, discussed the significance of their findings:

“The fact that the changes in structure appear over two distinct time scales suggests that multiple mechanisms are involved in these early events in apoptosis…Further analysis showed the early changes we observed were taking place in the mitochondria, while the changes in the structure of the nucleus were responsible for the later ones.”

Most chemotherapy drugs work by damaging cancer cells’ DNA and causing them to undergo apoptosis. As cells undergo this process, structures within the cell, such as the nucleus or mitochondria, go through structural changes; a/LCI can be used to detect these structural changes, and in turn, the presence of certain structural changes are markers for apoptosis.

A principle benefit of a/LCI is the speed with which results can be obtained. Adam Wax noted:

“The new technology allowed us to detect the tell-tale signs of apoptosis in human breast cancer cells in as little as 90 minutes…Currently, it can take between six and eight weeks to detect these changes clinically.”

Julie Ostrander, one of the study’s co-authors, added:

“If we had a way to detect early on in the apoptotic process whether or not a drug was working, patients would not have to wait weeks to months to find out”

Currently, oncologists check if a cancer therapy is working by examining whether or not gross tumor volume diminishes post-therapy. Since tumor shrinkage can take anywhere between weeks to months after drug administration, a/LCI can help physicians determine optimal treatment plans for their patients by allowing them to rapidly assess the efficacy of drugs administered. Angle-resolved low-coherence interferometry is particularly useful since drug efficacy often varies significantly from patient to patient (i.e., different drugs work better for different patients, and with a/LCI patients won’t won’t have to wait months before.

Wax and colleagues at the University of North Carolina at Chapel Hill are currently conducting a pilot clinical trial in humans using a similar technology for early detection of Barrett’s Esophagus.

Want to read more about tumor cell imaging techniques?

At MIT, physics professor Michael Feld has used light scattering systems (Raman spectroscopy, tri-modal spectroscopy, and optical interferometry [of which a/LCI is an application of]) to study cellular morphology and to diagnose dysplasia (pre-cancer) since the 1980s. To date, Feld’s team has used light scattering spectroscopy to detect Barrett’s esophagus and dysplasia in the colon, bladder, cervix, and esophagus.

Source Used:

(1) Kevin J. Chalut, Julie Hanson Ostrander, Michael G. Giacomelli, and Adam Wax. “Light Scattering Measurements of Subcellular Structure Provide Noninvasive Early Detection of Chemotherapy-Induced Apoptosis” Cancer Research 69, 1199-1204, February 1, 2009. Published Online First January 13, 2009; <http://cancerres.aacrjournals.org/cgi/content/abstract/69/3/1199>

(2) Duke University. “Scattered Light Rapidly Detects Tumor Response To Chemotherapy.” ScienceDaily 7 February 2009. 7 February 2009 <http://www.sciencedaily.com­ /releases/2009/02/090202074847.htm>

Hormone replacement therapy increases risk for breast cancer

A new study suggests that hormone replacement therapy may significantly increase one's risk for breast cancer.

A new study suggests that hormone replacement therapy may significantly increase one's risk for breast cancer.

A new study published just two days ago in the New England Journal of Medicine suggests that the hormone replacement therapy (HRT) many women use to alleviate discomfort often experienced during menopause may significantly increase their risk for breast cancer.

The study followed up on a previous 2002 Women’s Health Initiative study which found that women taking HRT had higher rates of breast cancer, stroke and heart disease. In the years following the 2002 study, HRT sales plummeted and breast cancer rates for those who were once on HRT dropped significantly. Many have argued that the drop in breast cancer rates was due to a decline in mammogram screening. (Women on HRT tend to go more frequently to mammogram screenings which increases their chance of finding tumors.) Dr. Marcia Stefanick, one of the HRT study’s co-authors and a professor at Stanford Medical School, said that while women on HRT are more likely to have mammogram screenings, HRT use can also make it harder to find small tumors because it changes the composition of the breast.  Thus, just because the women on HRT are getting more frequent screenings doesn’t mean that their rates of cancer diagnosis are elevated. Ultimately, the study rebuffed critics and concluded that the HRT-breast cancer relationship is real:

“The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography…the difference in frequency of mammography use of 2% between 2002 and 2003 for women using hormones is insufficient to account for the 43% reduction in the incidence of breast cancer.”

-Chlebowski et al. (2)

Some are still skeptical of the HRT study’s results. The International Menopause Society released a statement shortly after the study’s publication arguing that the HRT-breast cancer link was inconclusive at best:

“The decline in breast cancer rates started at least 3 years before the Women’s Health Initiative study was halted…Breast cancer takes years to develop and, to reach the stage where it is detectable, it takes at least a decade. If HRT use causes breast cancer, then the drop in breast cancer rates would not be seen for some time yet.”

-International Menopause Society (4)

Hormone replacement therapy involves giving menopausal women estrogen & progesterone. Estrogen is a potent mitogen (increases cell division) and has been listed by the National Institute of Environmental Heath Sciences as a known cancer-causing compound. The exact mechanism behind estrogen’s role in increasing cancer risk is still under study, but  the fact that it plays a role in breast cancer is undisputed; inhibitors of the estrogen receptor and estrogen-producing enzymes have been used successfully as a method for treating breast cancer. Whether or not progesterone increases one’s risk of breast cancer is still a debated topic, and the answer is likely extremely complex (e.g., it might increase or decrease risk of breast cancer depending on a number of other factors).

Bottom line: If you or someone you know is currently taking hormone replacement therapy for menopausal/post-menopausal symptoms, you/they should consider cutting use or reducing dose taken. If you are considering starting HRT, you should consult your doctor about the possible benefits and risks of hormone replacement therapy.

Sources Used:

(1) Lange CA, Yee D (“Progesterone and breast cancer” Womens Health (Lond Engl). 2008 Mar;4(2):151-62  Abstract available online: http://www.ncbi.nlm.nih.gov/pubmed/19072517?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pub med.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

(2) Chlebowski, Rowan T., Kuller, Lewis H., Prentice, Ross L., Stefanick, Marcia L., Manson, JoAnn E., Gass, Margery, Aragaki, Aaron K., Ockene, Judith K., Lane, Dorothy S., Sarto, Gloria E., Rajkovic, Aleksandar, Schenken, Robert, Hendrix, Susan L., Ravdin, Peter M., Rohan, Thomas E., Yasmeen, Shagufta, Anderson, Garnet, the WHI Investigators. (“Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women.” N Engl J Med Volume 360, Number 6, pages 573-587, February 5, 2009. Available online: http://content.nejm.org/cgi/content/short/360/6/573)

(3) Catharine Paddock (“Another Study Confirms HRT Breast Cancer Link” Available online: http://www.medicalnewsto day.com/articles/137915.php Last Accesed: 2/6/2009)

(4) International Menopause Society “NEJM Article on Breast Cancer and HRT – Comment by International Menopause Society” Available online: http://www.imsociety.org/pages/comments_and_press_statements/ims_press_stateme nt_04_02_09.html?SESSID=cgfaus4gkbej95g0rod8r4no81  Last Accessed:2/6/09

(5) Susan Conova (“Estrogen-induced Cancer” Available online: http://www.cumc.columbia.edu/news/in-vivo/Vol2_Iss10_may26_03/index.html


First three pages up!

Hello World!

The first three pages of this blog are up! One talks about the history of fever as a cancer therapy, and in true correlatingcancer format, the page segue’s into a discussion about how the practice of deliberately introducing an infection/fever response in patients has evolved to modern immunotherapies and hyperthermia therapy. One of the better-known stories of modern hyperthermia cancer that is that of John Kanzius, who invented a machine which emits radiowaves and heats up tumors. His idea isn’t that unique, and as you’ll find from the article, several other approaches to locally heat tumors exist. The fact that he used radiofrequency waves, however, is particularly interesting since it correlates with an ongoing debate about just how harmful radiofrequency waves (like the ones given off by cell phones) are.

From now on, this blog will be updated daily with a post on some cancer-related stories that I’ve come across and weekly with an illustrated page like the one I’ve posted on cell phone use and cancer.

Please post a comment or send an email if you’d like to hear my thoughts on any particular cancer topic or have a question you’d like to ask.

Happy Readings,

Justin

First Post

Thanks for visiting! This blog is currently under construction. Please check back Mid-February.

-Justin