Three Reasons You Should Test Your CRC Patients’ MSI Status

Posted on by Jordan Nutting

Oncologists, do you know your colorectal cancer patients’ MSI status?

High-frequency microsatellite instability (MSI-H) in tumors is a form of genomic instability where mismatch repair (MMR) proteins fail to properly correct errors in microsatellite regions of the genome. When a patient’s tumor tissue is determined to have MSI-H markers, it’s strongly recommended that they be further tested for Lynch syndrome, a hereditary condition that puts them and their family at a higher risk of developing colorectal and other cancers (1).

Though as many as 1 in 279 people might be carriers for the mutations associated with Lynch syndrome (2), 95% of them don’t know it (3). Furthermore, people with Lynch syndrome have an approximately 80% increased lifetime risk of developing colorectal cancer, compared to a risk of only ~4% for the general population (4, 5).  

On Lynch Syndrome Awareness Day, here are three key reasons why you should test all your colorectal cancer patients’ MSI status.

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T Cells Newly Discovered Role in Alzheimer’s and Related Diseases Could Offer Another Therapeutic Approach

Posted on by Kelly Grooms

Alzheimer’s disease is a devastating, progressive degenerative brain condition that starts with mild   dementia symptoms like memory issues and gradually worsens to the point where you can no longer communicate or care for yourself. For anyone with personal experience with it, Alzheimer’s looms like a specter over the natural process of aging.

In the beginning phase of Alzheimer’s, abnormal plaques of the protein, amyloid-β, develop. These protein clumps can accumulate for decades with no detectable impact on cognitive ability or brain health. Eventually, a second protein, tau, begins to gather and form intercellular, fibrous, tangles. It is with the formation of these tau tangles that symptoms first appear. The combined presence of these extracellular plaques and intercellular tangles are the hallmarks of Alzheimer’s disease.

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The Largest Maxprep Liquid Handler Installation Ever: Kigali Rwanda, 2022

Posted on by Jordan Villanueva

“It was just a sea of Promega everywhere,” says Rebecca Roberts, a Promega Field Applications Scientist. “Floor to ceiling, piled up with Maxwell instruments, Maxprep Liquid Handlers, all the accessories and consumables…”

In her role on the Field Application Scientists team, Rebecca travels the United States installing the Maxprep Liquid Handler in customer labs and training scientists to operate the system and incorporate it into their workflow. This instrument automates the pre- and post-processing steps in a nucleic acid purification workflow. It’s a large and sophisticated instrument that takes up roughly four feet of lab bench space and weighs up to 220 pounds. It is intended for research use only, but during the COVID-19 pandemic, the Maxprep Liquid Handler, Maxwell RSC 48 Instrument, and several Maxwell purification kits were recommended for nucleic acid extraction protocols in the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel Emergency Use Authorization (EUA).  

When an instrument is sold, Rebecca and a Service Engineer spend three days on-site installing it and training a small group of staff to use it. One Maxprep instrument at a time is typical. On rare occasions, Rebecca might install two on a single trip. However, in 2022, Rebecca joined a multinational team of Promega scientists and engineers in Kigali, Rwanda for an order that was anything but typical.

Promega field applications scientists install a Maxprep Liquid Handler in a small room that already holds two more liquid handlers.
Field Application Scientists Rebecca Roberts, Ben Cooley and Lucy Swithenbank install a Maxprep Liquid Handler in Kigali, Rwanda

“We knew a large order from this customer was a possibility,” Rebecca says, “But I certainly wasn’t expecting an order of ten.”

This was the largest installation of Maxprep instruments Promega has ever seen from a single order. The customer also had a hard deadline that required delivery, installation and training to be complete in only six weeks – half the time usually quoted for a single instrument.

In the end, ten Maxprep instruments were installed at the National Reference Laboratory in Kigali, and more than twenty people were trained to use the systems for RNA extraction to support COVID-19 testing at a major international meeting. The order was a success, but that six week journey was a wild ride that depended on the hard work and dedication of Promega teams on both sides of the Atlantic.

And the impact of this work is still growing.

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3.14 Ways to Make Pi Day a Piece of Cake!

Posted on by Riley Bell

Celebrated each year on March 14th (3.14), Pi Day commemorates the irrational, transcendent, and never-ending ratio that’s used to represent a mathematical constant. This infinite number is crucial when describing circles because no matter how big or small, the ratio of a circle’s circumference to its diameter will always equal to pi.

In 2009, pi day, also written π or 3.14, was declared an official national holiday–one that’s worth celebrating! We’ll help you kick things off with 3 fun facts, 1 joke, and 4 activities that are certain to get you in the Pi Day spirit.

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Conversations: Nerve-Tumor Crosstalk in the Tumor Microenvironment

Posted on by Michele Arduengo
Cancer cells are characterized by features such as metabolic reprogramming and uncontrolled proliferation all of which are supported by underlying genomic instability, inflammation and the tumor microenvironment.

Cancer cells can be distinguished from normal cells by a variety of features including their ability to inappropriately activate signals for cell proliferation, evade growth suppression from contact inhibition or tumor suppressor activity, evade cell death signals, replicate DNA continually, induce angiogenesis, invade new tissues, reprogram their metabolism to provide energy for rapid proliferation, and evade immune detection (1) . Several biological processes are responsible for these features including genomic instability, inflammation, and the creation of a tumor microenvironment.

The tumor microenvironment is the network of non-malignant cells, connective tissue and blood vessels that surround and infiltrate the tumor. These surrounding “normal” cells interact with each other and the cancer cells and are important players in tumorigenesis. One cell type that is often found in the tumor microenvironment are nerve cells. In fact, cancer cells often express proteins that encourage nerve growth into the tumor microenvironment such as growth factors and axon-guidance molecules (2). Crosstalk between nerve cells and tumor cells can facilitate development of several cancer types (2) including pancreatic, head and neck, oral, prostate, and colorectal cancers.

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Shifting Gears: Repurposing Instruments for Changing Needs

Posted on by AnnaKay Kruger
Sarah Teter operates the Tecan Freedom EVO 150 liquid handler
Sarah Teter operates the Tecan Freedom EVO 150

The thought of an expensive instrument falling out of use and gathering dust on the shelf is enough to bring a tear to any lab manager’s eye. An instrument that once served a key purpose and now functions only as a “paperweight” is a tragic waste of valuable resources. Fortunately, it is sometimes possible to breathe new life into neglected tools and to retrofit or repurpose equipment to meet the new needs that will inevitably arise in a changing lab environment.  

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Monoclonal Antibody (mAb) Therapy to Delay the Onset of Type 1 Diabetes

Posted on by Ken Doyle

On November 18, 2022, the US Food and Drug Administration (FDA) announced the approval of the first drug to delay the onset of stage 3 type 1 diabetes (T1D). The monoclonal antibody (mAb) drug, teplizumab, was approved for use in adults and pediatric patients 8 years and older.

3D illustration of a monoclonal antibody

The road to approval has been a bumpy one for the manufacturer, Provention Bio. In 2020, the FDA rejected the application for teplizumab due to several concerns, including the small size of the clinical trial. With the current approval, based on new clinical trial results, Provention Bio confirmed a co-promotion agreement with Sanofi US. The agreement included a $35 million Sanofi equity investment in the company.

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New Vaccine for Honeybees Could Take the Sting Out of Devastating American Foulbrood Disease

Posted on by Kelly Grooms

Our world is a complex, interdependent system, and invertebrate pollinators such as honeybees play a pivotal role in its survival. Threats to populations numbers of pollinators like honeybees can be equated to threats to the overall health and survival of the ecosystem in which they live. Of the over 20,000 known bee species, one—the western honeybee (Apis mellifera)—acts as the single most frequent pollinator for crops worldwide (1). Found on every continent except Antarctica, the western honeybee owes its status as a top pollinator to its widespread geographic distribution, generalist foraging behavior and competence as pollinators (1).

Deadly American Foulbrood Disease

Honeybees are the most economically valuable pollinators and are threatened by several pathogens (2). Perhaps the biggest threat to honeybee colony health and survival is the bacterial disease, American Foulbrood (AFB; (3). Caused by the spore-forming, Gram+ bacteria, Paenibacillus larvae, the highly contagious AFB disease affects the young brood of colonies.  When newly hatched larvae are fed spore-contaminated food, the spores germinate and replicate causing septicemia and death. P. larvae spores are incredibly resilient and can remain viable for decades (3). Each infected larva can produce over 1 billion new spores.  Thus, a colony can produce large numbers of spores with just a few cases of symptomatic brood (4).

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Scaling Up to Measure 40,000 Data Points a Day with GloMax® Microplate Readers

Posted on by Jordan Nutting

Traditional approaches for protein degrader compound screening like Western blotting can be laborious, time consuming and cannot be streamlined with automation. By implementing a high-throughput, automated workflow that uses our CRISPER/Cas9 knock-in cell lines, live-cell bioluminescent assays and sensitive GloMax® Discover microplate readers, our custom assay services offer protein degradation profiling at an accelerated rate.  

To do this, we collaborated with HighRes® Biosolutions, to develop an automated system that can screen up to 100 384-well plates each day, generating roughly 40,000 data points with minimal hands-on work.

Learn how bioluminescent tools like HiBiT and NanoBRET™ technology can help you answer key questions in your targeted protein degradation research.

An important step of building this system is to integrate four GloMax® Discover microplate readers into the automated system using instrument’s built-in SiLA2 communication driver. The driver software makes it easy to connect the microplate readers with HighRes® Biosolution’s robotic components.

Check out our setup in the video below.

See how we’ve integrated GloMax® Discover microplate readers into a high-throughput automated system for profiling protein degraders in live cells.
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suPAR: A New Approach to Treating Cardiovascular Disease

Posted on by Riley Bell

Cardiovascular disease (CVD), continues to be the leading cause of death in the United States and worldwide. Many patients with CVD have signs of chronic kidney disease (CKD), and those with CKD are often times disproportionately affected by CVD.

This interconnectedness was further explored in a recent study published in the Journal of Clinical Investigation that identified a new immune target, suPAR, as a protein that causes kidney disease and atherosclerosis, the most common form of CVD. Unlike traditional approaches to treating CVD such as controlling blood pressure and lowering cholesterol, this breakthrough research offers a new approach to treatment from an entirely different perspective.

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