Tag Archives: liquid biopsy

“How genome research is influencing our understanding of B-cell lymphomas” at Simon Fraser University (SFU) Café Scientifique on November 25, 2021 from 5:00 pm – 6:30 pm PST

This is from a November 8, 2021 SFU Café Scientifique notice (received via email),

We are excited to announce our next virtual SFU Café Scientifique!

NOW OPEN FOR REGISTRATION

Thursday November 25, 2021  5:00-6:30pm

Dr. Ryan Morin, SFU Department of Molecular Biology and Biochemistry

“How genome research is influencing our understanding of B-cell lymphomas”

Zoom invites will be sent to those registered, closer to the date.

Register here:

https://www.eventbrite.ca/e/how-genome-research-is-influencing-our-understanding-of-b-cell-lymphomas-tickets-203977471107

We hope to see you then!

There’s a little more of a topic description on the event registration webpage,

Every cancer arises following the accumulation of genetic changes known as mutations. Dr. Ryan Morin will discuss how genomics can allow us to understand how specific mutations influence the onset of lymphoma (and other common cancers) and can lead to new and more effective therapies.

There’s a little more detail about Morin’s work on his profile page on the BC Cancer Research Institute website,

Dr. Ryan Morin has been studying the genetic nature of lymphoid cancers using genomic methods for more than a decade. During his doctoral training at the University of British Columbia and BC Cancer, he pioneered the use of transcriptome and whole genome sequencing to identify driver mutations in non-Hodgkin lymphomas. Over the course of his training, he published a series of papers describing some of the most common genetic features of diffuse large B-cell (DLBCL) and follicular lymphomas including EZH2, KMT2D, CREBBP and MEF2B. Following his transition to an independent position at SFU, Dr. Morin has continued to identify genetic features of these and other aggressive lymphomas including non-coding (silent) regulatory drivers of cancer. His laboratory has implemented novel assays for the sensitive detection and genetic characterization of circulating tumour DNA (ctDNA). These “liquid biopsy” approaches continue to be developed as non-invasive methods for monitoring treatment response and resistance. Using these and other modern genomics tools and bioinformatics techniques, his team continues to explore the genetics of relapsed and refractory DLBCL with an ultimate goal of identifying novel biomarkers that predict treatment failure on specific therapies. This work has helped refine our understanding of genetic and gene expression differences that predict poor outcome in DLBCL.

Hopefully, Morin will be talking about the liquid biopsies and other non-invasive methods he and his team use in their work.

Liquid biopsy chip that uses carbon nanotubes in place of microfluidics

They’re calling this a breakthrough technology in a Dec. 15, 2016 news item on ScienceDaily,

A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) [UK] can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more effective in trapping cancer cells than the microfluidic approach employed in many existing devices.

The WPI device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they selectively bind to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). This “liquid biopsy,” described in a recent issue of the journal Nanotechnology, could become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified.

A Dec. 15, 2016 WPI press release (also on EurekAlert), which originated the news item, explains the breakthrough in more detail (Note: Links have been removed),

Metastasis is the process by which a cancer can spread from one organ to other parts of the body, typically by entering the bloodstream. Different types of tumors show a preference for specific organs and tissues; circulating breast cancer cells, for example, are likely to take root in bones, lungs, and the brain. The prognosis for metastatic cancer (also called stage IV cancer) is generally poor, so a technique that could detect these circulating tumor cells before they have a chance to form new colonies of tumors at distant sites could greatly increase a patient’s survival odds.

“The focus on capturing circulating tumor cells is quite new,” said Balaji Panchapakesan, associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, tens of thousands of white blood cells, and, perhaps, only a small number of tumor cells floating among them. We’ve shown how those cells can be captured with high precision.”

The device developed by Panchapakesan’s team includes an array of tiny elements, each about a tenth of an inch (3 millimeters) across. Each element has a well, at the bottom of which are antibodies attached to carbon nanotubes. Each well holds a specific antibody that will bind selectively to one type of cancer cell type, based on genetic markers on its surface. By seeding elements with an assortment of antibodies, the device could be set up to capture several different cancer cells types using a single blood sample. In the lab, the researchers were able to fill a total of 170 wells using just under 0.3 fluid ounces (0.85 milliliter) of blood. Even with that small sample, they captured between one and a thousand cells per device, with a capture efficiency of between 62 and 100 percent.

In a paper published in the journal Nanotechnology [“Static micro-array isolation, dynamic time series classification, capture and enumeration of spiked breast cancer cells in blood: the nanotube–CTC chip”], Panchapakesan’s team, which includes postdoctoral researcher Farhad Khosravi, the paper’s lead author, and researchers at the University of Louisville and Thomas Jefferson University, describe a study in which antibodies specific for two markers of metastatic breast cancer, EpCam and Her2, were attached to the carbon nanotubes in the chip. When a blood sample that had been “spiked” with cells expressing those markers was placed on the chip, the device was shown to reliably capture only the marked cells.

In addition to capturing tumor cells, Panchapakesan says the chip will also latch on to tiny structures called exosomes, which are produced by cancers [sic] cells and carry the same markers. “These highly elusive 3-nanometer structures are too small to be captured with other types of liquid biopsy devices, such as microfluidics, due to shear forces that can potentially destroy them,” he noted. “Our chip is currently the only device that can potentially capture circulating tumor cells and exosomes directly on the chip, which should increase its ability to detect metastasis. This can be important because emerging evidence suggests that tiny proteins excreted with exosomes can drive reactions that may become major barriers to effective cancer drug delivery and treatment.”

Panchapakesan said the chip developed by his team has additional advantages over other liquid biopsy devices, most of which use microfluidics to capture cancer cells. In addition to being able to capture circulating tumor cells far more efficiently than microfluidic chips (in which cells must latch onto anchored antibodies as they pass by in a stream of moving liquid), the WPI device is also highly effective in separating cancer cells from the other cells and material in the blood through differential settling.

While the initial tests with the chip have focused on breast cancer, Panchapakesan says the device could be set up to detect a wide range of tumor types, and plans are already in the works for development of an advanced device as well as testing for other cancer types, including lung and pancreas cancer. He says he envisions a day when a device like his could be employed not only for regular follow ups for patients who have had cancer, but in routine cancer screening.

“Imagine going to the doctor for your yearly physical,” he said. “You have blood drawn and that one blood sample can be tested for a comprehensive array of cancer cell markers. Cancers would be caught at their earliest stage and other stages of development, and doctors would have the necessary protein or genetic information from these captured cells to customize your treatment based on the specific markers for your cancer. This would really be a way to put your health in your own hands.”

“White blood cells, in particular, are a problem, because they are quite numerous in blood and they can be mistaken for cancer cells,” he said. “Our device uses what is called a passive leukocyte depletion strategy. Because of density differences, the cancer cells tend to settle to the bottom of the wells (and this only happens in a narrow window), where they encounter the antibodies. The remainder of the blood contents stays at the top of the wells and can simply be washed away.”

Here’s a link to and a citation for the paper,

Static micro-array isolation, dynamic time series classification, capture and enumeration of spiked breast cancer cells in blood: the nanotube–CTC chip by Farhad Khosravi, Patrick J Trainor, Christopher Lambert, Goetz Kloecker, Eric Wickstrom, Shesh N Rai, and Balaji Panchapakesan. Nanotechnology, Volume 27, Number 44 DOI http://dx.doi.org/10.1088/0957-4484/27/44/44LT03 Published 29 September 2016

© 2016 IOP Publishing Ltd

This paper is open access.