Tag Archives: cancer

“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.

Gold nanotubes for treating mesothelioma?

An October 26, 2020 news item on Nanowerk describes some new research that may lead the way to treatments for people with asbestos-related cancers (e.g., mesothelioma), Note: A link has been removed,

Gold nanotubes – tiny hollow cylinders one thousandth the width of a human hair – could be used to treat mesothelioma, a type of cancer caused by exposure to asbestos, according to a team of researchers at the Universities of Cambridge and Leeds.

In a study published in journal Small (“Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells”), the researchers demonstrate that once inside the cancer cells, the nanotubes absorb light, causing them to heat up, thereby killing the cells.

Here`s an image illustrating the research,

Caption: Confocal fluorescence image of gold nanotures (green) in mesothelioma cells. Credit: Arsalan Azad

An October 27, 2020 University of Cambridge press release (also on EurekAlert but published on Oct. 26, 2020), which originated the news item, describes the context for the research and provides a few more technical details,

More than 2,600 people are diagnosed in the UK each year with mesothelioma, a malignant form of cancer caused by exposure to asbestos. Although the use of asbestos is outlawed in the UK now, the country has the world’s highest levels of mesothelioma because it imported vast amounts of asbestos in the post-war years. The global usage of asbestos remains high, particularly in low- and middle-income countries, which means mesothelioma will become a global problem.

“Mesothelioma is one of the ‘hard-to-treat’ cancers, and the best we can offer people with existing treatments is a few months of extra survival,” said Dr Arsalan Azad from the Cambridge Institute for Medical Research at the University of Cambridge. “There’s an important unmet need for new, effective treatments.”

In 2018, the University of Cambridge was awarded £10million from the Engineering and Physical Sciences Research Council to help develop engineering solutions, including nanotech, to find ways to address hard-to-treat cancers.

In a collaboration between the University of Cambridge and University of Leeds, researchers have developed a form of gold nanotubes whose physical properties are ‘tunable’ – in other words, the team can tailor the wall thickness, microstructure, composition, and ability to absorb particular wavelengths of light.

The researchers added the nanotubes to mesothelioma cells cultured in the lab and found that they were absorbed by the cells, residing close to the nucleus, where the cell’s DNA lies. When the team targeted the cells with a laser, the nanotubes absorbed the light and heated up, killing the mesothelioma cell.

Professor Stefan Marciniak, also from the Cambridge Institute for Medical Research, added: “The mesothelioma cells ‘eat’ the nanotubes, leaving them susceptible when we shine light on them. Laser light is able to penetrate deep into tissue without causing damage to surrounding tissue. It then gets absorbed by the nanotubes, which heat up and, we hope in the future, could be used to cause localised cancer-cell killing.”

The team will be developing the work further to ensure the nanotubes are targeted to cancer cells with less effect on normal tissue.

The nanotubes are made in a two-step process. First, solid silver nanorods are created of the desired diameter. Gold is then deposited from solution onto the surface of the silver. As the gold builds-up at the surface, the silver dissolves from the inside to leave a hollow nanotube.

The approach advanced by the Leeds team allows these nanotubes to be developed at room temperature, which should make their manufacture at scale more feasible.

Professor Stephen Evans from the School of Physics and Astronomy at the University of Leeds said: “Having control over the size and shape of the nanotubes allows us to tune them to absorb light where the tissue is transparent and will allow them to be used for both the imaging and treatment of cancers. The next stage will be to load these nanotubes with medicines for enhanced therapies.”

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

Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells by Sunjie Ye, Arsalan A. Azad, Joseph E. Chambers, Alison J. Beckett, Lucien Roach, Samuel C. T. Moorcroft, Zabeada Aslam, Ian A. Prior, Alexander F. Markham, P. Louise Coletta, Stefan J. Marciniak, Stephen D. Evans. Small DOI: https://doi.org/10.1002/smll.202003793 First published: 25 October 2020

This paper is open access.

Gas nanomedicine

This study comes from China and it offers an overview of the state-of-the-art of gas nanomedicine and a roadmap for future research. A May 6, 2020 news item on Nanowerk announces the study,

Cancer is deadly, but available cancer treatment methods are quite limited. The use of therapeutic gas molecules such as H2 [hydrogen gas], NO [nitrogen oxide], CO [carbon monoxide] and H2S [hydrogn sulfide] for cancer treatment is promising owing to their unique properties for selectively killing cancer cells and protecting normal cells from damage from other traditional therapies.

However, these gases and most of their prodrugs lack the abilities of active intratumoral accumulation and controlled gas release, causing limited therapeutic efficacy and potential side effects. The development of precision and intelligent gas delivery nanomedicines can maximize the profits of gas therapy by enhancing the bio-availability and bio-safety of therapeutic gases.

More and more gas-releasing nanomedicines are being developed by virtue of multifunctional nanoplatforms, making it ever-increasingly expectable to make breakthrough in cancer treatment. Even so, there are still many gaps between gas therapy and nanomedicines, needing to be filled.

In a new overview published in the Beijing-based National Science Review, scientists at Shenzhen University, China propose a series of engineering strategies of advanced gas-releasing nanomedicines for augmented cancer therapy from four aspects, 1) stimuli-responsive strategies for controlled gas release, 2) catalytic strategies for controlled gas release, 3) tumor-targeted gas delivery strategies, 4) multi-model combination strategies based on gas therapy.

A May 6, 2020 China Science Press news release on EurekAlert, which originated the news item, provides a little more detail about the overview and about a future application as an assistive therapy in diseases such as coronovirus pneumonia,

“This review systematically dissects the roles of carrier and gas prodrug within nanomedicine for stimuli-responsive gas release, catalytic gas generation routes, tumor-targeted gas delivery approaches and gas therapy-based combination methods, and also provides an insight into their engineering principles and working mechanisms, and correspondingly proposed a series of superior engineering strategies of nanomedicines for gas therapy of cancer to guide the future research.” Dr. Yingshuai Wang said “We believe this review could provide inspiration for constructing advanced gas-releasing nanomedicines.”

Moreover, they have also pointed out current issues and gaps in knowledge, and have envisaged current trends and future prospects of advanced nanomedicines for gas therapy of cancer in this review.

“There are many gaps intriguing me, such as high tissue penetration stimuli-responsive gas release, the local, endless and prodrug-free generation of gases by catalysis, and the super ability of assisting other almost all therapies.” Prof. Qianjun He adds “It is noticeable, in the recent fight of novel coronavirus pneumonia, hydrogen therapy is playing an vitally important role in assisting large numbers of patients to improve oxygen inhalation, relieve hypoxia, and scavenge inflammation. I hope our hydrogen-producing medicines would make bigger contribution to human being in the near future.”

This illustration accompanies the news release,

Caption: Illustration of strategies for engineering advanced nanomedicines for augmented gas therapy of cancer. Credit: ©Science China Press

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

Strategies for engineering advanced nanomedicines for gas therapy of cancer by Yingshuai Wang, Tian Yang, Qianjun He. National Science Review, nwaa034, https://doi.org/10.1093/nsr/nwaa034 Published: 27 February 2020

This appears to be an open access paper in PDF only.

For anyone new to the term, a prodrug is (Note: Links have been removed),

A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug.[1][2] Inactive prodrugs are pharmacologically inactive medications that are metabolized into an active form within the body. Instead of administering a drug directly, a corresponding prodrug might be used instead to improve how a medicine is absorbed, distributed, metabolized, and excreted (ADME).[3][4]

You can find out more in the Prodrug Wikipedia entry.

Trick your kidneys with sugar (molecules, that is)

A February 4, 2020 news item on Nanowerk announces research that makes it possible for kidneys to remove nanoparticles after they’ve been used in therapeutic remedies (Note: A link has been removed),

In the past decade nanomedicine has contributed to better detection and treatment of cancer. Nanoparticles are several 100 times smaller than the smallest grain of sand and can therefore easily travel in the blood stream to reach the tumor.

However, they are still too big to be removed by the kidneys. Since several doses of nanoparticles are necessary to treat a tumor, over time the nanoparticles can accumulate in the kidney and cause irreversible damage.

In a study published in the scientific journal Biomaterials (“Renal clearance of polymeric nanoparticles by mimicry of glycan surface of Viruses”), materials scientists at the University of Freiburg [Germany] led by Prof. Dr. Prasad Shastri from the Institute of Macromolecular Chemistry now present a natural solution to this problem: they built nanoparticles with the carbohydrate polysaccharides, which led to the excretion of the particles.

A February 4, 2020 University of Freiberg press release (also on EurekAlert), which originated the news item, expands on the theme,

In nature viruses such as the herpes simplex virus-1 and the cytomegalovirus, which are able to pass through the kidney filtration apparatus despite their large size compared to nanoparticles. Shastri and his team identified that both viruses presents sugar molecules on their surface. Inspired by this observation, the scientists engineered nanoparticles containing polysaccharides. These carbohydrates are frequently found in the human tissue environment. Using a real-time imaging technique, which they have established in their laboratory, the team investigated in a mouse model the fate of these nanoparticles. They observed that the polysaccharide-enriched nanoparticles readily pass through the kidney and are excreted with the urine within a few hours after intravenous administration. The decisive factor for the researchers was that the nanoparticles continued to act as intended and were still able to target tumors.

“The ability to combine tumor accumulation and kidney clearance in the same nanoparticle represents a tipping point in ensuring that nanomedicines can be safely administered” says Shastri. “Our nature-inspired approach enabled us to trick the kidney environment to let nanoparticles pass through” adds Dr. Melika Sarem who was a co-author of the study.

Prasad Shastri is Professor of Biofunctional Macromolecular Chemistry at the Institute for Macromolecular Chemistry and Professor of Cell Signalling Environments in the Excellence Cluster BIOSS Centre for Biological Signalling Studies and at the University of Freiburg.

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

Renal clearance of polymeric nanoparticles by mimicry of glycan surface of viruses by Pradeep P.Wyss, Surya P.Lamichhane, Ahmed Abed, Daniel Vonwil, Oliver Kretz, Tobias B. Huber, Melika Sarema, V. Prasad Shastri. Biomaterials Volume 230, February 2020, 119643 DOI: https://doi.org/10.1016/j.biomaterials.2019.119643 First published online November 23, 2019

This paper is behind a paywall.

Reading (2 of 2): Is zinc-infused underwear healthier for women?

This first part of this Reading ‘series’, Reading (1 of 2): an artificial intelligence story in British Columbia (Canada) was mostly about how one type of story, in this case,based on a survey, is presented and placed in one or more media outlets. The desired outcome is for more funding by government and for more investors (they tucked in an ad for an upcoming artificial intelligence conference in British Columbia).

This story about zinc-infused underwear for women also uses science to prove its case and it, too, is about raising money. In this case, it’s a Kickstarter campaign to raise money.

If Huha’s (that’s the company name) claims for ‘zinc-infused mineral undies’ are to be believed, the answer is an unequivocal yes. The reality as per the current research on the topic is not quite as conclusive.

The semiotics (symbolism)

Huha features fruit alongside the pictures of their underwear. You’ll see an orange, papaya, and melon in the kickstarter campaign images and on the company website. It seems to be one of those attempts at subliminal communication. Fruit is good for you therefore our underwear is good for you. In fact, our underwear (just like the fruit) has health benefits.

For a deeper dive into the world of semiotics, there’s the ‘be fruitful and multiply’ stricture which is found in more than one religious or cultural orientation and is hard to dismiss once considered.

There is no reason to add fruit to the images other than to suggest benefits from nature and fertility (or fruitfulness). They’re not selling fruit and these ones are not particularly high in zinc. If all you’re looking for is colour, why not vegetables or puppies?

The claims

I don’t have time to review all of the claims but I’ll highlight a few. My biggest problem with the claims is that there are no citations or links to studies, i.e., the research. So, something like this becomes hard to assess,

Most women’s underwear are made with chemical-based, synthetic fibers that lead to yeast and UTI [urinary tract infection] infections, odor, and discomfort. They’ve also been proven to disrupt human hormones, have been linked to cancer, pollute the planet aggressively, and stay in landfills far too long.

There’s more than one path to a UTI and/or odor and/or discomfort but I can see where fabrics that don’t breathe can exacerbate or cause problems of that nature. I have a little more difficulty with the list that follows. I’d like to see the research on underpants disrupting human hormones. Is this strictly a problem for women or could men also be affected? (If you should know, please leave a comment.)

As for ‘linked to cancer’, I’m coming to the conclusion that everything is linked to cancer. Offhand, I’ve been told peanuts, charcoal broiled items (I think it’s the char), and my negative thoughts are all linked to cancer.

One of the last claims in the excerpted section, ‘pollute the planet aggressively’ raises this question.When did underpants become aggressive’?

The final claim seems unexceptional. Our detritus is staying too long in our landfills. Of course, the next question is: how much faster do the Huha underpants degrade in a landfill? That question is not addressed in Kickstarter campaign material.

Talking to someone with more expertise

I contacted Dr. Andrew Maynard, Associate Director at Arizona State University (ASU) School for the Future of Innovation in Society, He has a PhD in physics and longstanding experience in research and evaluation of emerging technologies (for many years he specialized in nanoparticle analysis and aerosol exposure in occupational settings),.

Professor Maynard is a widely recognized expert and public commentator on emerging technologies and their safe and responsible development and use, and has testified before [US] congressional committees on a number of occasions. 

None of this makes him infallible but I trust that he always works with integrity and bases his opinions on the best information at hand. I’ve always found him to be a reliable source of information.

Here’s what he had to say (from an October 25, 2019 email),

I suspect that their claims are pushing things too far – from what I can tell, professionals tend to advise against synthetic underwear because of the potential build up of moisture and bacteria and the lack of breathability, and tend to suggest natural materials – which indicating that natural fibers and good practices should be all most people need. I haven’t seen any evidence for an underwear crisis here, and one concern is that the company is manufacturing a problem which they then claim to solve. That said, I can’t see anything totally egregious in what they are doing. And the zinc presence makes sense in that it prevents bacterial growth/activity within the fabric, thus reducing the chances of odor and infection.

Pharmaceutical grade zinc and research into underwear

I was a little curious about ‘pharmaceutical grade’ zinc as my online searches for a description were unsuccessful. Andrew explained that the term likely means ‘high purity’ zinc suitable for use in medications rather than the zinc found in roofing panels.

After the reference to ‘pharmaceutical grade’ zinc there’s a reference to ‘smartcel sensitive Zinc’. Here’s more from the smartcel sensitive webpage,

smartcel™ sensitive is skin friendly thanks to zinc oxide’s soothing and anti-inflammatory capabilities. This is especially useful for people with sensitive skin or skin conditions such as eczema or neurodermitis. Since zinc is a component of skin building enzymes, it operates directly on the skin. An active exchange between the fiber and the skin occurs when the garment is worn.

Zinc oxide also acts as a shield against harmful UVA and UVB radiation [it’s used in sunscreens], which can damage our skin cells. Depending on the percentage of smartcel™ sensitive used in any garment, it can provide up to 50 SPF.

Further to this, zinc oxide possesses strong antibacterial properties, especially against odour causing bacteria, which helps to make garments stay fresh longer. *

I couldn’t see how zinc helps the pH balance in anyone’s vagina as claimed in the Kickstarter campaign and smartcel, on its ‘sensitive’ webpage, doesn’t make that claim but I found an answer in an April 4, 2017 Q&A (question and answer) interview by Jocelyn Cavallo for Medium,

What women need to know about their vaginal p

Q & A with Dr. Joanna Ellington

A woman’s vagina is a pretty amazing body part. Not only can it be a source of pleasure but it also can help create and bring new life into the world. On top of all that, it has the extraordinary ability to keep itself clean by secreting natural fluids and maintaining a healthy pH to encourage the growth of good bacteria and discourage harmful bacteria from moving in. Despite being so important, many women are never taught the vital role that pH plays in their vaginal health or how to keep it in balance.

We recently interviewed renowned Reproductive Physiologist and inventor of IsoFresh Balancing Vaginal Gel, Dr. Joanna Ellington, to give us the low down on what every woman needs to know about their vaginal pH and how to maintain a healthy level.

What is pH?

Dr. Ellington: PH is a scale of acidity and alkalinity. The measurements range from 0 to 14: a pH lower than 7 is acidic and a pH higher than 7 is considered alkaline.

What is the “perfect” pH level for a woman’s vagina?

Dr. E.: For most women of a reproductive age vaginal pH should be 4.5 or less. For post-menopausal women this can go up to about 5. The vagina will naturally be at a high pH right after sex, during your period, after you have a baby or during ovulation (your fertile time).

Are there diet and environmental factors that affect a women’s vaginal pH level?

Dr. E.: Yes, iron zinc and manganese have been found to be critical for lactobacillus (healthy bacteria) to function. Many women don’t eat well and should supplement these, especially if they are vegetarian. Additionally, many vegetarians have low estrogen because they do not eat the animal fats that help make our sex steroids. Without estrogen, vaginal pH and bacterial imbalance can occur. It is important that women on these diets ensure good fat intake from other sources, and have estrogen and testosterone and iron levels checked each year.

Do clothing and underwear affect vaginal pH?

Dr. E.: Yes, tight clothing and thong underwear [emphasis mine] have been shown in studies to decrease populations of healthy vaginal bacteria and cause pH changes in the vagina. Even if you wear these sometimes, it is important for your vaginal ecosystem that loose clothing or skirts be worn some too.

Yes, Dr. Ellington has the IsoFresh Balancing Vaginal Gel and whether that’s a good product should be researched but all of the information in the excerpt accords with what I’ve heard over the years and fits in nicely with what Andrew said, zinc in underwear could be useful for its antimicrobial properties. Also, note the reference to ‘thong underwear’ as a possible source of difficulty and note that Huha is offering thong and very high cut underwear.

Of course, your underwear may already have zinc in it as this research suggests (thank you, Andrew, for the reference),

Exposure of women to trace elements through the skin by direct contact with underwear clothing by Thao Nguyen & Mahmoud A. Saleh. Journal of Environmental Science and Health, Part A Toxic/Hazardous Substances and Environmental Engineering Volume 52, 2017 – Issue 1 Pages 1-6 DOI: https://doi.org/10.1080/10934529.2016.1221212 Published online: 09 Sep 2016

This paper is behind a paywall but I have access through a membership in the Canadian Academy of Independent Scholars. So, here’s the part I found interesting,

… The main chemical pollutants present in textiles are dyes containing carcinogenic amines, metals, pentachlorophenol, chlorine bleaching, halogen carriers, free formaldehyde, biocides, fire retardants and softeners.[1] Metals are also found in textile products and clothing are used for many purposes: Co [cobalt], Cu [copper], Cr [chromium] and Pb [lead] are used as metal complex dyes, Cr as pigments mordant, Sn as catalyst in synthetic fabrics and as synergists of flame retardants,Ag [silver] as antimicrobials and Ti [titanium] and Zn [zinc] as water repellents and odor preventive agents.[2–5] When present in textile materials, the toxic elements mentioned above represent not only a major environmental problem in the textile industry but also they may impose potential danger to human health by absorption through the skin.[6,7] [emphasis mine] Chronic exposure to low levels of toxic elements has been associated with a number of adverse human health effects.[8–11] Also exposure to high concentration of elements which are considered as essential for humans such as Cu, Co, Fe [iron], Mn [manganese] or Zn among others, can also be harmful.[12] [emphasis mine] Co, Cr, Cu and Ni [nitrogen] are skin sensitizers,[13,14] which may lead to contact dermatitis, also Cr can lead to liver damage, pulmonary congestion and cancer.[15] [emphasis mine] The purpose of the present study was to determine the concentrations of a number of elements in various skin-contact clothes. For risk estimations, the determination of the extractable amounts of heavy metals is of importance, since they reflect their possible impact on human health. [p. 2 PDF]

So, there’s the link to cancer. Maybe.

Are zinc-infused undies a good idea?

It could go either way. (For specifics about the conclusions reached in the study, scroll down to the Ooops! subheading.) I like the idea of using sustainable Eucalyptus-based material (TencelL) for the underwear as I have heard that cotton isn’t sustainably cultivated. As for claims regarding the product’s environmental friendliness, it’s based on wood, specifically, cellulose, which Canadian researchers have been experimenting with at the nanoscale* and they certainly have been touting nanocellulose as environmentally friendly. Tencel’s sustainability page lists a number of environmental certifications from the European Union, Belgium, and the US.

*Somewhere in the Kickstarter campaign material, there’s a reference to nanofibrils and I’m guessing those nanofibrils are Tencel’s wood fibers at the nanoscale. As well, I’m guessing that smartcel’s fabric contains zinc oxide nanoparticles.

Whether or not you need more zinc is something you need to determine for yourself. Finding out if the pH balance in your vagina is within a healthy range might be a good way to start. It would also be nice to know how much zinc is in the underwear and whether it’s being used antimicrobial properties and/or as a source for one of minerals necessary for your health.

How the Kickstarter campaign is going

At the time of this posting, they’ve reached a little over $24,000 with six days left. The goal was $10,000. Sadly, there are no questions in the FAQ (frequently asked questions).

Reading tips

It’s exhausting trying to track down authenticity. In this case, there were health and environmental claims but I do have a few suggestions.

  1. Look at the imagery critically and try to ignore the hyperbole.
  2. How specific are the claims? e.g., How much zinc is there in the underpants?
  3. Who are their experts and how trustworthy are the agencies/companies mentioned?
  4. If research is cited, are the publishers reputable and is the journal reputable?
  5. Does it make sense given your own experience?
  6. What are the consequences if you make a mistake?

Overblown claims and vague intimations of disease are not usually good signs. Conversely, someone with great credential may not be trustworthy which is why I usually try to find more than one source for confirmation. The person behind this campaign and the Huha company is Alexa Suter. She’s based in Vancouver, Canada and seems to have spent most of her time as a writer and social media and video producer with a few forays into sales and real estate. I wonder if she’s modeling herself and her current lifestyle entrepreneurial effort on Gwyneth Paltrow and her lifestyle company, Goop.

Huha underwear may fulfill its claims or it may be just another pair of underwear or it may be unhealthy. As for the environmentally friendly claims, let’s hope that the case. On a personal level, I’m more hopeful about that.

Regardless, the underwear is not cheap. The smallest pledge that will get your underwear (a three-pack) is $65 CAD.

Ooops! ETA: November 8, 2019:

I forgot to include the conclusion the researchers arrived at and some details on how they arrived at those conclusions. First, they tested 120 pairs of underpants in all sorts of colours and made in different parts of the world.

Second, some underpants showed excessive levels of metals. Cotton was the most likely material to show excess although nylon and polyester can also be problematic. To put this into proportion and with reference to zinc, “Zn exceeded the limit in 4% of the tested samples
and was found mostly in samples manufactured in China.” [p. 6 PDF] Finally, dark colours tested for higher levels of metals than light colours.

While it doesn’t mention underpants as such, there’s a November 8, 2019 article ‘Five things everyone with a vagina should know‘ by Paula McGrath for BBC news online. McGrath’s health expert is Dr. Jen Gunter, a physician whose specialties are obstetrics, gynaecology, and pain.

Skin-based vaccination delivery courtesy of nanotechnology

A May 28, 2019 news item on Nanowerk announced research targeting Langerham cells and the immune system (Note: A link has been removed),

Researchers at the Max Planck Institute of Colloids and Interfaces in Potsdam developed targeted nanoparticles that are taken up by certain immune cells of the human skin (ACS Central Science, “A specific, glycomimetic Langerin ligand for human Langerhans cell targeting”). These so-called Langerhans cells coordinate the immune response and alert the body when pathogens or tumors occur.

This new nanoparticle technology platform enables targeted drug delivery of vaccines or pharmaceuticals to Langerhans cells, triggering a controlled immune response to naturally eradicate the pathogen or tumor.

Internalized nanoparticles (red) in a Langerhans cell (green membrane marker). Specific targeting of these skin immune cells may lead to novel approaches for skin vaccination [weniger] © Langerhans Zellforschung Labor an der Medizinischen Universität Innsbruck Courtesy: Max Planck Institute

A May 28,2019 Max Planck Institute (MPI) press release, which originated the news item, provides further explanations,

The skin is a particularly attractive place for the application of many drugs that affect the immune system, as the appropriate target cells lie directly beneath the skin. These Langerhans cells are able to elicit an immune reaction in the entire body of the patient after local application of an active substance.

Langerhans Cells – Experts of pathogen defense

To develop a targeted drug delivery system, which guides drugs directly to Langerhans cells, one can make use of their natural function: as professional, antigen-presenting cells they detect pathogens, internalize them and present components of these pathogens to effector cells of the immune system (T cells). For detection and uptake, Langerhans cells use receptors on their surface that search the environment for microbes. They especially recognize pathogens by the unique coating of sugar structures on their surface. Langerin, a protein of the C-type lectins family, is such a receptor on Langerhans cells that can detect viruses and bacteria. The specific expression of Langerin on Langerhans cells allows a targeted drug delivery encapsulated in nanoparticleswhile minimizing the side effects.

The research team of Dr. Christoph Rademacher at the Max Planck Institute of Colloids and Interfaces has now been able to exploit the knowledge of the underlying detection mechanisms with atomic resolution: “Based on our insight how immune cells recognize sugars, we developed a synthetic, sugar-like substance that enables nanoparticles to specifically bind to Langerhans cells”, says Dr. Christoph Rademacher. In collaboration with a scientific team from the Laboratory for Langerhans Cell Research of the Medical University of Innsbruck, nanoparticles have been developed that can be incorporated into Langerhans cells of the human skin through this interaction. The researchers thus lay the foundation for further developments, for example to deliver vaccines directly through the skin to the immune cells. “Imagine avoiding needles for vaccination in the future or directly activating the body’s immune system against infections and maybe even cancer”, adds Dr. Christoph Rademacher. Langerhans cells are responsible for activating the immune system systemically. Based on these findings, it may be possible in the future to develop novel vaccines against infections or immunotherapies for the treatment of cancer or autoimmune diseases.

The starting points for this work were the pioneering contributions from Ralph M. Steinman (Nobel Prize 2011) and other scientists who showed the potential of dendritic cells. Langerhans cells are one subset of these cells and are able to trigger an immune response. These findings were subsequently refined for use in cancer therapy. It has been shown that an immune response can be achieved via artificially introduced antigens. Later work confirmed these findings and also demonstrated that human Langerhans cells are also able to activate the immune system, which is particularly interesting for skin vaccination. Targeted delivery of immunomodulators to Langerhans cells would thus be desirable. However, this is often hindered or even prevented by the complex environment of the skin, especially by competing phagocytes in this tissue, such as macrophages. Consequently, pharmaceuticals not taken up by the Langerhans cells, but internalized into bystander cells may lead to unwanted side effects.

Recognition through synthetic sugars

Based on insights on the interaction between Langerin and its natural sugar ligands Christoph Rademacher and his team developed a synthetic ligand, which binds specifically to the receptor on Langerhans cells. For this purpose, synthetic sugars were produced in the laboratory and their interactions with the receptor were examined by nuclear magnetic resonance spectroscopy. With this method the researchers were able to determine which atoms of the ligand interact with which parts of the receptor. By using this structure-based approach they found out that a compound can be anchored and tested on these nanoparticles. These particles are liposomes, which have been used for many years in the clinic in the absence of such targeting ligands as a carrier for various drugs. The difference with existing systems is that the sugar-like ligand now allows specific binding to Langerhans cells. The investigations on these immune cells were carried out in collaboration with the research group of Assoz. Prof. Patrizia Stoitzner at the Langerhans Cell Research Laboratory of the Medical University of Innsbruck. Together they could show that the specific uptake of liposomes is possible even in the complex environment of human skin. The scientists used different methods such as flow cytometry and confocal microscopy for their findings.

These liposomal particles may now provide a common platform for researchers at the MPI of Colloids and Interfaces to work on the development of novel vaccines in the future.

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

A Specific, Glycomimetic Langerin Ligand for Human Langerhans Cell Targeting by Eike-Christian Wamhoff, Jessica Schulze, Lydia Bellmann, Mareike Rentzsch, Gunnar Bachem, Felix F. Fuchsberger, Juliane Rademacher, Martin Hermann, Barbara Del Frari, Rob van Dalen, David Hartmann, Nina M. van Sorge, Oliver Seitz, Patrizia Stoitzner, Christoph Rademacher. ACS Cent. Sci.201955808-820 DOI: https://doi.org/10.1021/acscentsci.9b00093 Publication Date: May 10, 2019 Copyright © 2019 American Chemical Society

This paper appears to be open access.

Art/science and a paintable diagnostic test for cancer

One of Joseph Cohen’s painting incorporating carbon nanotubes photographed in normal light. Photo courtesy of Joseph Cohen. [downloaded from https://news.artnet.com/art-world/carbon-nanotube-cancer-paint-1638340?utm_content=from_&utm_source=Sailthru&utm_medium=email&utm_campaign=Global%20September%202%20PM&utm_term=artnet%20News%20Daily%20Newsletter%20USE%20%2830%20Day%20Engaged%20Only%29]

The artist credited with the work seen in the above, Joseph Cohen, has done something remarkable with carbon nanotubes (CNTs). Something even more remarkable than the painting as Sarah Cascone recounts in her August 30, 2019 article for artnet.com (Note: A link has been removed),

Not every artist can say that his or her work is helping in the fight against cancer. But over the past several years, Joseph Cohen has done just that, working to develop a new, high-tech paint that can be used not only on canvas, but also to detect cancers and medical conditions such as hypertension and diabetes.

Sloan Kettering Institute scientist Daniel Heller first suggested that Cohen come work at his lab after seeing the artist’s work, which is often made with pigments that incorporate diamond dust and gold, at the DeBuck Gallery in New York.

“We initially thought that in working with an artist, we would make art to shed a little light on our science for the public,” Heller told the Memorial Sloan Kettering blog. “But the collaboration actually taught us something that could help us shine a light on cancer.”

For Cohen, the project was initially intended to develop a new way of art-making. In Heller’s lab, he worked with carbon nanotubes, which Heller was already employing in cancer research, for their optical properties. “They fluoresce in the infrared spectrum,” Cohen says. “That gives artists the opportunity to create paintings in a new spectrum, with a whole new palette of colors.”

Because human eyesight is limited, we can’t actually see infrared fluorescence. But using a special short-wave infrared camera, Cohen is able to document otherwise invisible effects, revealing the carbon nanotube paint’s hidden colors.

“What you’re perceiving as a static painting is actually in motion,” Cohen says. “I’m creating paintings that exist outside of the visible experience.”

Art Supplies—and a Diagnostic Tool

That same imaging technique can be used by doctors looking for microalbuminuria, a condition that causes the kidneys to leak trace amounts of albumin into urine, which is an early sign of of several cancers, diabetes, and high blood pressure.

Cohen helped co-author a paper published this month in Nature Communications about using the nanosensor paint in litmus paper tests with patient urine samples. The study found that the paint, when viewed through infrared light, was able to reveal the presence of albumin based on changes in the paint’s fluorescence after being exposed to the urine sample.

“It’s easy to detect albumen with a dipstick if there’s a lot of levels in the urine, but that would be like looking at stage four cancer,” Cohen says. “This is early detection.”

What’s more, a nanosensor paint can be easily used around the world, even in poor areas that don’t have access to the best diagnostic technologies. Doctors may even be able to view the urine samples using an infrared imaging attachments on their smartphones.

One of Joseph Cohen’s painting incorporating carbon nanotubes shown in both the visible light (left) and in UV fluorescence (right). Photo courtesy of Joseph Cohen. [downloaded from https://news.artnet.com/art-world/carbon-nanotube-cancer-paint-1638340?utm_content=from_&utm_source=Sailthru&utm_medium=email&utm_campaign=Global%20September%202%20PM&utm_term=artnet%20News%20Daily%20Newsletter%20USE%20%2830%20Day%20Engaged%20Only%29]

Amazing, eh? If you have the time, do read Cascone’s article in its entirety and should your curiosity be insatiable, there’s also an August 22, 2019 posting by Jim Stallard on the Memorial Sloan Kettering Cancer Center blog,

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

Synthetic molecular recognition nanosensor paint for microalbuminuria by Januka Budhathoki-Uprety, Janki Shah, Joshua A. Korsen, Alysandria E. Wayne, Thomas V. Galassi, Joseph R. Cohen, Jackson D. Harvey, Prakrit V. Jena, Lakshmi V. Ramanathan, Edgar A. Jaimes & Daniel A. Heller. Nature Communicationsvolume 10, Article number: 3605 (2019) DOI: https://doi.org/10.1038/s41467-019-11583-1 Published: 09 August 2019

This paper is open access.

Joseph Cohen has graced this blog before in a May 3, 2019 posting titled, Where do I stand? a graphene artwork. It seems Cohen is very invested in using nanoscale carbon particles for his art.

Breakthrough with Alpaca nanobodies

Caption: Bryson and Sanchez, two alpacas who produce unusually small antibodies. These ‘nanobodies’ could help highly promising CAR T-cell therapies kill solid tumors, where right now they work only in blood cancers. Credit: Courtesy of Boston Children’s Hospital

Bryson and Sanchez are not the first camelids to grace this blog. ‘Llam’ me lend you some antibodies—antibody particles extracted from camels and llamas, a June 12, 2014 posting, and Llama-derived nanobodies are good for solving crystal structure, a December 14, 2017 posting, both feature news about medical breakthroughs with regard to the antibodies found in Llamas, camels, and other camelids (including alpacas) could enable.

The latest camelid-oriented medical research story is in an April 11, 2019 news item on phys.org (Note: A link has been removed),

In 1989, two undergraduate students at the Free University of Brussels were asked to test frozen blood serum from camels, and stumbled on a previously unknown kind of antibody. It was a miniaturized version of a human antibody, made up only of two heavy protein chains, rather than two light and two heavy chains. As they eventually reported, the antibodies’ presence was confirmed not only in camels, but also in llamas and alpacas.

Fast forward 30 years. In the journal PNAS [Proceedings of the National Academy of Science] this week [April 8 – 12, 2019], researchers at Boston Children’s Hospital and MIT [Massachusetts Institute of Technology] show that these mini-antibodies, shrunk further to create so-called nanobodies, may help solve a problem in the cancer field: making CAR T-cell therapies work in solid tumors.

An April 11, 2019 Boston Children’s Hospital news release on EurekAlert, which originated the news item, explores the technology,

Highly promising for blood cancers, chimeric antigen receptor (CAR) T-cell therapy genetically engineers a patient’s own T cells to make them better at attacking cancer cells. The Dana-Farber/Boston Children’s Cancer and Blood Disorders Center is currently using CAR T-cell therapy for relapsed acute lymphocytic leukemia (ALL), for example.

But CAR T cells haven’t been good at eliminating solid tumors. It’s been hard to find cancer-specific proteins on solid tumors that could serve as safe targets. Solid tumors are also protected by an extracellular matrix, a supportive web of proteins that acts as a barrier, as well as immunosuppressive molecules that weaken the T-cell attack.

Rethinking CAR T cells

That’s where nanobodies come in. For two decades, they largely remained in the hands of the Belgian team. But that changed after the patent expired in 2013. [emphases mine]

“A lot of people got into the game and began to appreciate nanobodies’ unique properties,” says Hidde Ploegh, PhD, an immunologist in the Program in Cellular and Molecular Medicine at Boston Children’s and senior investigator on the PNAS study.

One useful attribute is their enhanced targeting abilities. Ploegh and his team at Boston Children’s, in collaboration with Noo Jalikhani, PhD, and Richard Hynes, PhD at MIT’s Koch Institute for Integrative Cancer Research, have harnessed nanobodies to carry imaging agents, allowing precise visualization of metastatic cancers.

The Hynes team targeted the nanobodies to the tumors’ extracellular matrix, or ECM — aiming imaging agents not at the cancer cells themselves, but at the environment that surrounds them. Such markers are common to many tumors, but don’t typically appear on normal cells.

“Our lab and the Hynes lab are among the few actively pursuing this approach of targeting the tumor micro-environment,” says Ploegh. “Most labs are looking for tumor-specific antigens.”

Targeting tumor protectors

Ploegh’s lab took this idea to CAR T-cell therapy. His team, including members of the Hynes lab, took aim at the very factors that make solid tumors difficult to treat.

The CAR T cells they created were studded with nanobodies that recognize specific proteins in the tumor environment, bearing signals directing them to kill any cell they bound to. One protein, EIIIB, a variant of fibronectin, is found only on newly formed blood vessels that supply tumors with nutrients. Another, PD-L1, is an immunosuppressive protein that most cancers use to silence approaching T cells.

Biochemist Jessica Ingram, PhD of the Dana-Farber Cancer Institute, Ploegh’s partner and a coauthor on the paper, led the manufacturing pipeline. She would drive to Amherst, Mass., to gather T cells from two alpacas, Bryson and Sanchez, inject them with the antigen of interest and harvest their blood for further processing back in Boston to generate mini-antibodies.

Taking down melanoma and colon cancer

Tested in two separate melanoma mouse models, as well as a colon adenocarcinoma model in mice, the nanobody-based CAR T cells killed tumor cells, significantly slowed tumor growth and improved the animals’ survival, with no readily apparent side effects.

Ploegh thinks that the engineered T cells work through a combination of factors. They caused damage to tumor tissue, which tends to stimulate inflammatory immune responses. Targeting EIIIB may damage blood vessels in a way that decreases blood supply to tumors, while making them more permeable to cancer drugs.

“If you destroy the local blood supply and cause vascular leakage, you could perhaps improve the delivery of other things that might have a harder time getting in,” says Ploegh. “I think we should look at this as part of a combination therapy.”

Future directions

Ploegh thinks his team’s approach could be useful in many solid tumors. He’s particularly interested in testing nanobody-based CAR T cells in models of pancreatic cancer and cholangiocarcinoma, a bile duct cancer from which Ingram passed away in 2018.

The technology itself can be pushed even further, says Ploegh.

“Nanobodies could potentially carry a cytokine to boost the immune response to the tumor, toxic molecules that kill tumor and radioisotopes to irradiate the tumor at close range,” he says. “CAR T cells are the battering ram that would come in to open the door; the other elements would finish the job. In theory, you could equip a single T cell with multiple chimeric antigen receptors and achieve even more precision. That’s something we would like to pursue.”

So, the Belgian researchers have a patent for two decades and, after it expires, more researchers could help to take the work further. Hmm …

Moving on, here’s a link to and a citation for the paper,

Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice by Yushu Joy Xie, Michael Dougan, Noor Jailkhani, Jessica Ingram, Tao Fang, Laura Kummer, Noor Momin, Novalia Pishesha, Steffen Rickelt, Richard O. Hynes, and Hidde Ploegh. PNAS DOI: https://doi.org/10.1073/pnas.1817147116
First published April 1, 2019

This paper is behind a paywall

The CRISPR ((clustered regularly interspaced short palindromic repeats)-CAS9 gene-editing technique may cause new genetic damage kerfuffle

Setting the stage

Not unexpectedly, CRISPR-Cas9  or clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 can be dangerous as these scientists note in a July 16, 2018 news item on phys.org,

Scientists at the Wellcome Sanger Institute have discovered that CRISPR/Cas9 gene editing can cause greater genetic damage in cells than was previously thought. These results create safety implications for gene therapies using CRISPR/Cas9 in the future as the unexpected damage could lead to dangerous changes in some cells.

Reported today (16 July 2018) in the journal Nature Biotechnology, the study also revealed that standard tests for detecting DNA changes miss finding this genetic damage, and that caution and specific testing will be required for any potential gene therapies.

This CRISPR-Cas9 image reminds me of popcorn,

CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)[ downloaded from https://phys.org/news/2018-07-genome-crisprcas9-gene-higher-thought.html#jCp]

A July 16, 2018 Wellcome Sanger Institute press release (also on EurekAlert), which originated the news item, offers a little more explanation,

CRISPR/Cas9 is one of the newest genome editing tools. It can alter sections of DNA in cells by cutting at specific points and introducing changes at that location. Already extensively used in scientific research, CRISPR/Cas9 has also been seen as a promising way to create potential genome editing treatments for diseases such as HIV, cancer or sickle cell disease. Such therapeutics could inactivate a disease-causing gene, or correct a genetic mutation. However, any potential treatments would have to prove that they were safe.

Previous research had not shown many unforeseen mutations from CRISPR/Cas9 in the DNA at the genome editing target site. To investigate this further the researchers carried out a full systematic study in both mouse and human cells and discovered that CRISPR/Cas9 frequently caused extensive mutations, but at a greater distance from the target site.

The researchers found many of the cells had large genetic rearrangements such as DNA deletions and insertions. These could lead to important genes being switched on or off, which could have major implications for CRISPR/Cas9 use in therapies. In addition, some of these changes were too far away from the target site to be seen with standard genotyping methods.

Prof Allan Bradley, corresponding author on the study from the Wellcome Sanger Institute, said: “This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now. It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects.”

Michael Kosicki, the first author from the Wellcome Sanger Institute, said: “My initial experiment used CRISPR/Cas9 as a tool to study gene activity, however it became clear that something unexpected was happening. Once we realised the extent of the genetic rearrangements we studied it systematically, looking at different genes and different therapeutically relevant cell lines, and showed that the CRISPR/Cas9 effects held true.”

The work has implications for how CRISPR/Cas9 is used therapeutically and is likely to re-spark researchers’ interest in finding alternatives to the standard CRISPR/Cas9 method for gene editing.

Prof Maria Jasin, an independent researcher from Memorial Slone Kettering Cancer Centre, New York, who was not involved in the study said: “This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site. While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically.”

For anyone who’d like to better understand the terms gene editing and CRISPR-Cas9, the Wellcome Sanger Institute provides these explanatory webpages, What is genome editing? and What is CRISPR-Cas9?

For the more advanced, here’s a link and a citation for the paper,

Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements by Michael Kosicki, Kärt Tomberg, & Allan Bradley. Nature Biotechnology DOI: https://doi.org/10.1038/nbt.4192 Published 16 July 2018

This paper appears to be open access.

The kerfuffle

It seems this news has affected the CRISPR market. From a July 16, 2018 article by Cale Guthrie Weissman for Fast Company,

… CRISPR could unknowingly delete or alter non-targeted genes, which could lead to myriad unintended consequences. This is especially frightening, since the technology is going to be used in human clinical trials.

Meanwhile, other scientists working with CRISPR are trying to downplay the findings, telling STAT [a life sciences and business journalism website] that there have been no reported adverse effects similar to what the study describes. The news, however, has brought about a market reaction–at least three publicly traded companies that focus on CRISPR-based therapies are in stock nosedive. Crispr Therapeutics is down by over 6%; Editas fell by over 3%; and Intellia Therapeutics dropped by over 5%. [emphasis mine]

Damage control

Gaetan Burgio (geneticist, Australian National University)  in a July 16, 2018 essay on phys.org (originating from The Conversation) suggests some calm (Note: Links have been removed),

But a new study has called into question the precision of the technique [CRISPR gene editing technology].

The hope for gene editing is that it will be able to cure and correct diseases. To date, many successes have been reported, including curing deafness in mice, and in altering cells to cure cancer.

Some 17 clinical trials in human patients are registered [emphasis mine] testing gene editing on leukaemias, brain cancers and sickle cell anaemia (where red blood cells are misshaped, causing them to die). Before implementing CRISPR technology in clinics to treat cancer or congenital disorders, we must address whether the technique is safe and accurate.

There are a few options for getting around this problem. One option is to isolate the cells we wish to edit from the body and reinject only the ones we know have been correctly edited.

For example, lymphocytes (white blood cells) that are crucial to killing cancer cells could be taken out of the body, then modified using CRISPR to heighten their cancer-killing properties. The DNA of these cells could be sequenced in detail, and only the cells accurately and specifically gene-modified would be selected and delivered back into the body to kill the cancer cells.

While this strategy is valid for cells we can isolate from the body, some cells, such as neurons and muscles, cannot be removed from the body. These types of cells might not be suitable for gene editing using Cas9 scissors.

Fortunately, researchers have discovered other forms of CRISPR systems that don’t require the DNA to be cut. Some CRISPR systems only cut the RNA, not the DNA (DNA contains genetic instructions, RNA convey the instructions on how to synthesise proteins).

As RNA [ribonucleic acid] remains in our cells only for a specific period of time before being degraded, this would allow us to control the timing and duration of the CRISPR system delivery and reverse it (so the scissors are only functional for a short period of time).

This was found to be successful for dementia in mice. Similarly, some CRISPR systems simply change the letters of the DNA, rather than cutting them. This was successful for specific mutations causing diseases such as hereditary deafness in mice.

I agree with Burgio’s conclusion (not included here) that we have a lot more to learn and I can’t help wondering why there are 17 registered human clinical trials at this point.