Cancer Research

A systematic approach to melanoma mutations

jhalper — Tue, 27 Oct 2015 05:46:17 +0000

A systematic approach to melanoma mutations

Metastatic melanoma tumors. Left exhibits low or absent expression of RASA2 and reduced survival, typical of about 35% of patients. The sample on the right exhibits high RASA2 expression and increased survival

Rates of melanoma are increasing, even as the rates of other common cancers are decreasing. According to the Melanoma Research Alliance, it is the most common cancer diagnosis in young adults 25-29 years old in the United States, the second most common cancer in young people 15-29, and its incidence has tripled in the last 30 years.

What are we doing about it? The Weizmann Institute’s Prof. Yardena Samuels has a database of over 500 samples from melanoma patients, and she is using this information to figure out how mutations drive the cancer. This is easier said than done. The damage to our DNA from the sun’s radiation can be widespread – a single melanoma cell can have hundreds of mutations.

Samuels and her group are going about the process systematically: They looked within a particular subset of melanomas – a group that often has a poor prognosis – for a particular type of gene. The genes known as tumor-suppressors are often mutated or inactivated in cancer. When they work, they protect us from cancer by keeping the brakes on cell growth or telling a cell with cancerous mutations to commit suicide. When they don’t, they not only fail to prevent cancer from growing and spreading, they can be rooked into aiding the process.

The melanoma tumor-suppressor Samuels and her group found interacts with an oncogene that is common to the set of melanomas they were looking at – apparently regulating its activities.

How does one restore the function of a gene that is lost or mutated? That is the question that the group is now addressing. “Now that we have identified the tumor suppressor, we can work out its pathway in the cell and understand how it is meant to function. And that, we hope, may lead to some ideas for treating this subset of melanomas – up to 35 percent of the cases. Among other things, this work highlights the need for more personalized diagnoses and treatment protocols for cancers like melanoma,” says Samuels.

Prof. Yardena Samuels (front left, in white) and her group. Drs. Rand Arafeh and Nouar Qutob (standing to the right and left of Samuels, respectively) led the study

Also online today:

A link between the immune system and obesity: when certain rare immune cells are missing, mice gain weight, even on a regular diet.

A brake on plants' starch production machinery that turns it off at night -- but stays lightly depressed during the day too.

jhalper Tue, 10/27/2015 - 01:46

Tags

basic research

Biological networks

biological regulation

Biomedical

personalized medicine

biological regulation

genes

Crowd Sourced Award Winning Wines Support Prostate Cancer Research

gregladen — Tue, 04 Aug 2015 12:28:48 +0000

Crowd Sourced Award Winning Wines Support Prostate Cancer Research

A guest post by Robet Hollander, Winemaker

2redWinery, makers of the award-winning Ziniphany© Zinfandel and #2red is 38% towards goal on Indiegogo with all proceeds supporting prostate cancer research through the Robert and Susan Hollander Foundation, an IRS approved 501c3 organization. Campaign supporters, in exchange for their tax-deductible support, can secure wine from the 2015 vintage or from the award-winning wine library of 2redWinery.

Robert Hollander, the winemaker and principle of 2redWinery, started small-volume winemaking in 2007 to indulge a long-standing passion. Passion changed to purpose in 2010 after he was diagnosed with prostate cancer at an incurable stage. Dr. Hollander, a highly-regarded clinician/teacher at the Gainesville VA Medical Center, affiliated with the University of Florida, then created the Robert and Susan Hollander Foundation to fund prostate cancer research. “After that, it just made sense to fund the Foundation with my winemaking. It gave my wine a dual purpose, not just to make a great wine I was proud of, but a wine that served a special purpose,” Hollander observed. In the two years the Foundation has been operational, unrestricted grants have been provided to researchers at MD Anderson Center and the Cleveland Clinic.

Dr. Hollander’s campaign goal is $35000 with all proceeds above production costs supporting prostate cancer research through the Foundation. Contributions to the campaign are processed by FirstGiving and are tax deductible. Rewards for campaign supporters include wine from the upcoming 2015 vintage or wines from the award-winning library of 2redWinery. “It’s a win-win-win-wine,” according to Hollander.

See Campaign: http://www.igg.me/at/2redwinery.com

Robert Hollander Winemaker, 2redWinery
President, Robert and Susan Hollander Foundation
doctorbobster@gmail.com
http://www.igg.me/at/2redwinery.com
https://youtu.be/zu7Bf5RubpI
https://www.facebook.com/doctorbobster

gregladen Tue, 08/04/2015 - 08:28

Tags

The puzzle of chemotherapy resistance

jhalper — Wed, 03 Jun 2015 05:12:14 +0000

The puzzle of chemotherapy resistance

What is a breakthrough in cancer research? It is a new piece of a puzzle made up of a million pieces. It may, however, be a piece that allows a picture to start emerging – one that lets us see the shape of the next piece needed to fill in more of the puzzle, or start making changes to rearrange the picture from one of cancerous growth to one of normalcy.

The Institute’s Prof. Yosef Yarden’s recent research provides a vital piece for the puzzle of resistance – how cancer cells, especially those in recurring cancers, stop responding to chemotherapy. His answer is specific to a kind of lung cancer, one that has a certain mutation in the gene for a growth receptor on the cell’s outer membrane. So his findings point to the need for both a personalized approach to treating cancer and a new general approach to understanding the lengths that certain cancer cells will go to in order to keep dividing and spreading.

The particular puzzle was that the chemotherapy used to treat these lung cancers almost always sends them into what appears to be complete remission. But they invariably come back, often with a second mutation in the same receptor; and the new cancer is not only resistant to the original chemotherapy, it is also resistant to a second drug that should, by all scientific reckoning, block the re-mutated growth receptor and thus stop the cancer’s spread.

Lung cancer cells (green) cultured together with normal lung cells (red). The triple-antibody combination EGFR, HER2 and HER3 strongly impairs the survival of tumor cells while sparing normal cells. Modified confocal microscopy image: Maicol Mancini, lab of Prof. Yosef Yarden

Yarden and his group found that the resistant cancer cells had actually rewired a main internal communications line, ultimately putting several “sibling” receptors on the cell’s outer surface. These siblings can take in the growth signal but are impervious to the drugs that block the original signal.

With this piece of the puzzle in hand, he and his team were able to design antibodies to block the two other receptors, and they applied these together with the original antibody that “should have worked.” This “triple treatment” was very effective against resistant lung cancers – in lab dishes and in mice.

Since lung cancer is the leading cause of cancer death, worldwide, this is a little piece of the puzzle that could, conceivably, have pretty large implications in the future. But not just for lung cancer: The emerging picture, say Yarden, is one in which drugs that target just one receptor, for example, the cancer cell’s growth receptor, can activate a chain reaction that turns the cell resistant and possibly even more ready to divide and spread than before. Yarden had previously shown in collaboration with Prof. Michael Sela of the Institute, that certain breast cancers arising from specific mutations can be treated with a combination of receptor-blocking drugs. In other words, this mechanism of chemotherapy resistance is likely to be present in many cancers, suggesting that more than a few more pieces of the puzzle might now be within reach.

jhalper Wed, 06/03/2015 - 01:12

Tags

biological regulation

chemotherapy resistance

growth factor receptor

Michael Sela

Yosef Yarden

biological regulation

breast cancer

I’m surprised at the title and substance of this article, especially for this website.
I’m puzzled by the eight uses of the word “puzzle”.

There is NO “puzzle.”
You ALREADY KNOW what the answer is: Chemotherapy resistance EVOLVED.
As with all of evolution theory, the rest is just details to be worked out later. I mean to be theorized later.

See Noeve, if you go back to the article this links to, you will see that the resistance did not evolve in the way they thought it would. Believe it or not, there are still a lot of puzzles out there.

Guest post: Dr. Gabriele D’Uva: How to Grow New Heart Cells

jhalper — Mon, 13 Apr 2015 06:10:12 +0000

Guest post: Dr. Gabriele D’Uva: How to Grow New Heart Cells

Dr. Gabriele D'Uva is finishing up his postdoctoral research at the Weizmann Institute. Here is his account of three years of highly successful research on regenerating heart cells after injury. Among other things, it is the story of the way that different ideas from vastly different research areas can, over the dinner table or in casual conversation, provide the inspiration for outstanding research:

Three years ago, when I joined the lab of Prof. Eldad Tzahor, the emerging field of cardiac regeneration was totally obscure to me. My scientific track at that time was mainly focused on normal and cancer stem cells: cells that build our bodies during development and adulthood. The deregulation of these cells can lead to cancer. I have to admit that I didn’t know even the shape of a cardiac cell when my postdoc journey started…

Eldad’s lab was also switching fields -- well, not drastically, like me, but still it was a transition from a basic research on the development of the heart to the challenge of heart regeneration during adult life.

Two neonatal cardiomyocytes (staining in red) undergoing cell division after treatment with NRG1

In contrast to most tissues in our body, which renew themselves throughout life using our pools of stem cells, the renewal of heart cells in adulthood is extremely low; it almost doesn’t exist. Just to give an approximate picture of renewal and regeneration processes: Every day we produce billions of new blood cells that completely replace the old ones in a few months. In contrast, heart cells renewal is so low that, many cardiac cells remain with us for our entire life, from birth to death! Consequently, heart injuries cannot be truly repaired, leading to (often lethal) cardiovascular diseases. This might appear somewhat nonsensical, since the heart is our most vital organ: No (heart) “beat” no life.

Hence a challenge for many scientists is to understand how to induce heart regeneration Scientists have been trying different strategies, for example, the injection of stem cells. We decided to adopt a different strategy – one that mimics the natural regenerative process of healing the heart in such “regenerative” organisms as amphibians and fish, and even newly-born mice. In all these cases the regeneration of the heart involves the proliferation of heart muscle cells called cardiomyocytes. Therefore the challenge before us was: “How can we push cardiomyocytes to divide?”

We adopted a team strategy. Cancer turned out to be a somewhat useful model for a “strategy.” After all, the hallmark of this disease is continuous self-renewal and cell proliferation. Starting from this thought, Prof. Yossi Yarden, a leading expert in the cancer field, suggested: “Why don’t you try an oncogene, such as ERBB2, whose deregulation can lead to uncontrolled cellular growth and tumour development?” The idea was that cardiomyocytes could be pushed into a proliferative state by this cancer-promoting agent. To Eldad, this was a nice “life” circle closing, since Eldad, when he was a PhD student in Yossi’s lab, focused exactly on the ERBB2 mechanism of action in cancer progression. I must admit, the idea sounded very intriguing and I really liked it.

Eldad, as a developmental biologist, had a different approach. Based on his field of expertise, his tactic was to apply proliferative (and regenerative) strategies learned from the embryos, when heart cells normally proliferate to form a functional organ. It turned out that a key player in driving embryonic heart growth is again… ERBB2!

So, Yossi and Eldad, from different fields of expertise, had the same idea: Look to ERBB2, which is a receptor on the cell surface that amplifies and transmits growth factor signals. It looked, back then, like a challenging idea; I was very happy to take the dare.

So this is exactly how my three and half years of post doc research started. At that stage, ERBB2 looked like a perfect candidate for cardiac regeneration. The idea to bring together cancer and developmental knowledge doubled the percentage of our success. The odds were on my side!

A first rule to starting a project regarding the role of any protein is to check for its expression. Therefore I started to analyse the kinetic of expression of ERBB2 in a normal heart during post-natal development. Interestingly, I noticed a dramatic reduction in ERBB2 levels in the heart during the first week of post-natal life. I have to mention that mouse cardiomyocytes stop dividing soon after birth, in about a week. It’s probably a residual proliferative ability of their embryonic life. My initial results revealed a strong reduction in ERBB2 expression, exactly coincident with the period in which heart cells lose their proliferative and regenerative capabilities.

I was very intrigued by this result, which immediately opened a very important question: “Is the loss of the regenerative ability of the heart in mice due to the decline of ERBB2 expression after birth?” After hundreds of experiments I can confidently answer: Yes. ERBB2 levels are reduced in cardiomyocytes shortly after birth, and this down-regulation limits the proliferative and regenerative ability of cardiac muscle cells.

To prove that, we first generated mice in which we deleted the Erbb2 gene specifically in heart cells. Loss of the ERBB2 gene (and protein) led to reduced cardiomyocyte proliferation and consequently to a very thin and poorly contracting heart. In the absence of ERBB2, the heart at birth was so weak that it could not tolerate the blood pressure and became dilated, a cardiac disease in humans known as dilated cardiomyopathy. The conclusion was that EBB22 is required for proper proliferation and growth of heart during embryonic development and its expression is physiologically reduced soon after birth to allow maturation of the cardiomyocytes.

Cardiomegaly (giant heart) in adult mice upon induction of Erbb2 (heart on the right) compared to normal mice (heart on the left)

Because of its major role in cancer, the only way to study ERBB2 involvement during heart regeneration was to search for a sophisticated system to finely, and transiently, increase its levels in the heart, within defined time windows. For this, we generated mice in which we could switch ERBB2 ON or OFF in cardiomyocytes. The results were amazing. Persistent ERBB2 induction led to a giant heart, two to three times bigger than normal in just a week or two. The analysis of the mechanism demonstrated that ERBB2 gets muscle cell to “rejuvenate” to an earlier stage (a phenomenon called “dedifferentiation”) and to reacquire the ability to proliferate -- similar to what happens during embryonic development. In addition, ERBB2 increases the size of the cardiomyocytes (a phenomenon called “hypertrophy”).

Thus far, the project had been proceeding in the right direction. However we soon realized that a bigger team could improve the project’s success. A very talented master’s student, Alla Aharonov, joined me in this effort. Alla’s help was precious in many ways. In particular, she contributed to our resolving the specific molecular pathways that are mediated by ERBB2 activation. Precious help in the analyses of cardiac functions were obtained from the lab of Profs. Jonathan Leor and Michal Neeman. Very important were also the “dinner discussions” with my wife, Mattia Lauriola (who was conducting a parallel postdoc in Yossi Yarden’s lab), in addition to Yossi’s scientific support and help from the beginning of the project. At certain point Eldad also involved Prof. Richard Harvey, a good friend of his and a leading scientist in heart development, whose suggestions turned out to be very effective. The project and the team were blooming.

The main findings, which we are happy to report, are that transient activation of ERBB2 (ranging from 10 days to 3 weeks) can trigger cardiomyocyte dedifferentiation and proliferation. These two processes in turn are critical to achieving cardiac regeneration after the injury that we had induced in mice to mimic human heart attacks. (termed myocardial infarction). Therefore, the activation of ERBB2 is one strategy to promote heart regeneration. It’s important to mention that one of the therapies currently being tested in clinical trials is a growth factor stimulus called Neuregulin1 (NRG1), which activates ERBB2 signalling. However, since we uncovered the fact that that ERBB2 levels are very low in adult mouse cardiomyocytes, we suggest that the efficacy of NRG1 therapy might be limited in adulthood. Further experiments in cardiomyocytes derived from human patients could answer this question.

The good news is that, according to our results, heart patients will definitely improve if we can, in the future, find a way to fine-tune ERBB2 levels. We need to find a way to control the expression of this receptor, or its signalling partners, for a short time to repair the damaged heart. How? That’s the next challenge; but it which could help millions patients worldwide!

Our findings point to a central role of ERBB2 in cardiomyocyte cell division and regeneration.

jhalper Mon, 04/13/2015 - 02:10

Tags

basic research

biological regulation

Biomedical

Cancer Research

Embryonic development

heart disease

scientific collaboration

dedifferrntiation

Eldad Tzahor

Gabriele D'Uva

growth factor receptor

heart cell regenertation

basic research

biological regulation

scientific collaboration

This was such an interesting read! I am amazed by the continuous progress being made under the radar. Is it possible to manipulate the heart from birth to ensure that levels of ERBB2 never decrease? I am looking forward to see how these results will alter the treatment of heart conditions.

[15044922]

What are the chances of succeeding in finding a way to fine-tune ERBB2 levels and a way to control the expression of this receptor, or its signalling partners, for a short time to repair the damaged heart in the future?and is it guaranteed that when you succeed in these findings heart patients will improve?

Wow that is amazing! More research should definitely be done on the subject. I am confident that these findings will help to ensure that heart diseases will be treated easily and that people with weak hearts will have a chance to live a normal life. (15001548)

what is the difference between cardiac and tissue cell that give rise the high frequent renewal of the tissue cells but extremely low to the cardiac cell?

That is excelent work indeed.I claim with no doubt that these findings can extend to other interesting researches about the heart.

I find this research ground-breaking and indicates that science is one step closer to finding the life-saving therapy and treatment that patients with cardiovascular disease need. It is enlightening to also know how heart cell stop regenerating from birth which highlights the importance not taking one's heart health for granted. It would be great if similar research can be done on the regeneration of neuron cells in the body which like this research, will cure other various degenerative diseases.

I find this research very remarkable and proves that science is one step closer to finding a cure for patients suffering from various cardiovascular diseases. Can the same approach be used to treat other damaged tissues such as the in the brain when a patient has suffered a stroke?

It is incredible to turn something negative into something positive. Can the same cancer growth idea be used for other organs as well? I would love to see how this idea can be used in the brain or nervous system to cure auto immune degenerative diseases. It is unbelievable to imagine where the medical research will be in 20 years from now. The life expectancy can increase drastically.

with such groundbreaking studies it would now seem that soon the world would be populated by older and older people. Is there no possible way of programming the heart cells to function like those of the liver?

i would pose the same question as you danielle, can it also be used for other organs? so that finally we can get a cure for cancer not a guarantee of losing a loved as soon as they have cancer, this would help a lot of people in different ways.Excelent work being down by our scientist and physicians

excellent work being done by our scientist and physicians i meant

The fact that this discovery has been made could have unlimited possibilities! would it be possible to synthesize ERBB2 that is might be possible in humans to utilize it when it is needed, for example in patients with failing hearts? Or perhaps a way unto which the production of ERBB2 could be increased to an extent that humans continue to produce it only to regenerate heart cells without the side effect of an enlarged heart as seen by the mouse heart three times the size of a normal mouse heart. Very interesting read though and cannot wait for further advancements in this field. u15016677

If these ERBB2 cells are known to stimulate growth, could it not also be used in other areas of the body where for example there is a cell deficiency, or maybe with diabetes where there is a low production of the necessary components. There should be a way to use ERBB2 in other areas of the body as well.

I find this research very interesting, I can even see myself doing perhaps something similar in the future. This research not only have the potential to change the way we look at the human heart but also the way we look at various degenerative diseases. It will change the medical world drastically. One thing I am wondering about is why the heart has such a low renewal rate?

Well done on the research conducted and progress made in the field of cardiac regeneration. It truly made for a very informative read and it was interesting to note about the almost non-existing renewal of heart cells. The research provides hope that damaged hearts could be repaired in the near future. Keep up the good work! (04648685)

It is amazing! More research ought to certainly be done on the subject. I am certain that these discoveries will help to guarantee that heart sicknesses will be dealt with effectively and that individuals with frail hearts will have an opportunity to carry on with a typical life

This is amazing, to think that researchers has come this far in a matter of a few years. The regeneration of heart cells is maybe one of the most important medical fields to explore to ensure that people with heart damage can live a full life despite their condition.
14010926

Since ERBB2 seems to be triggered in all the cardiac tissue, leading to hypertrophy, which in itself is potentially fatal, how would one limit its action or generation to specific areas affected by myocardial infarction, which are necrotic? Put another way, how would one achieve a patch effect?

This research is so inspirational and very interesting. I can't wait to see how damaged hearts will be repaired in the future. It is amazing how medical science has improved.

Well done to medical science! It is amazing how the world of medicine has improved.

This is very interesting. I can not wait to see how damaged heart will be repaired in the future. This is outstanding work done by scientists and physicians. Science just keep improving our lives day by day.

I found this article not only interesting but inspiring, To take the concept and idea of what cancer does to the cell, then to apply it to an organ where regenerative capabilities are needed?. My only question is are we able to control ERBB2 receptors and the growth of the heart cells? and as asked in comment #8 can this be applied to other internal organs??

What are the chances of cardiac regeneration in baby's born with holes in their hearts,especially baby's born with down syndrome? Will this research project be of any help to them?

This is truly fascinating. I had no idea that heart cells could not be renewed or repaired. An interesting point to acknowledge however is why try to repair an organ that is destined to fail at some point? Why not replace the organ with a more reliable, longer lasting piece of equipment? I believe further studies should be focused on cybertronics.
u15001319

15008160

I'm really impressed with this research and hope to one day partake in this exciting search to cure the heart!!!

WOW hopefully by the time my heart gives in this research would have been completed and my heart saved ;)

To all you South African commenters: sorry if your comments did not appear immediately. I was on vacation, but tried to get them up as soon as I could.

Please keep up your interest in this site and in science!

Getting the Whole Picture

jhalper — Thu, 12 Feb 2015 08:02:53 +0000

Getting the Whole Picture

What's in a picture?

Prof. Benny Shilo knows the value of a good picture. We recently mentioned his book: Life’s Blueprint, which uses photographs of things like bread dough and yeast cells to illustrate the process of biological development. Here is the image from the most recent piece we have uploaded on his research:

This is an individual Islet of Langerhans, as you’ve never seen it before. The white dots are the insulin-containing vesicles inside the beta cells, which both sense glucose levels and secrete insulin. Shilo and his team managed to get “close-up shots” of the individual cell membranes, and found that they have straight edges where both sensing and secretion functions are located.

We love the images in this new article on the work of Prof. Talila Volk because, aside from their eye-catching colors, these ones really do illustrate the story her work tells.

Volk’s work investigates how muscle fibers get renewed through exercise. It may all come down to a protein that senses muscle contraction and tells the DNA in the cell nucleus to make more muscle proteins.

In this image, red is muscle fiber in fruit fly larvae, green is nuclei (muscle fibers are large cells with multiple nuclei) (A) shows normal muscle fiber, the others show what happens when the protein is missing.

How does it work? This image says it all:

In the left image you can see how the protein structure encircles the cell nucleus. At the other end of its arms (red) it connects to the cell’s skeletal structure – the cytoskeleton. On the right, in green, you can see the protein structure. Its arms are springy – so that a pull on the end transmits a signal to the middle.

Volk and her group refer to the protein as a biological “mechanosensor,” and, indeed, there is something rather mechanical about the right-hand image.

Assuming that form follows function, Volk has surmised that similarly-shaped proteins in human muscle fibers do the same thing.

Third, we have some cancer research images from the lab of Prof. Lea Eisenbach:

These tell the story of anti-cancer immune activity. Tissue and tumor cells appear in blue, pink shows immune cells that attack the cancer cells. When tumor cells appear in the back, there are many immune cells (left); but in the brain (middle) the same tumor cells attract relatively few immune cells. In fact, the normal brain tissue (in the same brain) on the right has no immune cells. If you first inject the tumor into the rat’s back, where there is immune activity, and then inject the tumor cells from the back into the brain, the brain will be protected from the cancer.

And, oh yes, they are pretty too. This image, again from Talila Volk, of a 3-D computer model of a fruit fly larva muscle fiber was the inspiration for a sewing project:

jhalper Thu, 02/12/2015 - 03:02

Creating Smarter Life-Saving Drugs and Gene Therapy Through Nanobiotechnology with Dr. Jordan Green

carlyo — Thu, 13 Nov 2014 17:48:03 +0000

Creating Smarter Life-Saving Drugs and Gene Therapy Through Nanobiotechnology with Dr. Jordan Green

The ‘Nifty Fifty (times 4)’, a program of Science Spark, presented by InfoComm International, are a group of 200 noted science and engineering professionals who will fan out across the Washington, D.C. area in the 2014-2015 school year to speak about their work and careers at various middle and high schools.

Meet Nifty Fifty Speaker Dr. Jordan Green

As a researcher, Jordan Green, Ph.D. is on the front lines of creating innovative technologies and therapeutics that can directly benefit human health.

Specifically, this involves employing techniques in cellular engineering and nanobiotechnology to develop effective drug and gene therapies to treat cancer and other medical conditions.

¨The research findings and technologies developed by my research group are applied in the fields of ophthalmology, oncology, stem cell research and regenerative medicine,¨ says Jordan, Associate Professor of Biomedical Engineering, Ophthalmology, Neurosurgery, and Materials Science & Engineering at the Translational Tissue Engineering Center of Johns Hopkins University School of Medicine.

¨At Johns Hopkins, we seek out collaborations where we can combine our technologies with a clinical need to hopefully be able to make a difference to patients," he explains. ¨One of the areas where there is a great need for improved therapeutics is cancer. One and a half million Americans develop cancer each year and over 550,000 Americans tragically die from it annually.¨

Nanobiotechnology (the merger of biological research with various fields of nanotechnology), Jordan says, can improve cancer therapy by enabling smarter targeting of tumors and reduced off-target side effects in healthy cells.

Research by Jordan and his laboratory (the Green Group) are yielding promising results. For instance in 2014, through studies in mice, the lab demonstrated that "nanoparticles" can be created via nanotechnology to carry genetic material to cancer cells left in the brain after surgery. In such situations, Jordan's studies suggest that these nanoparticles could one day be especially successful in treating glioblastoma, the most common and most aggressive malignant primary brain tumor in humans.

In another pivotal study using nanotechnology, his lab reported success in creating flattened, football-shaped artificial particles that impersonate, or mimic, immune cells. These artificial particles, he says, seem to be better than traditional basketball-shaped particles at teaching immune cells to recognize and destroy cancer cells in mice.

Says Jordan, ¨One of the greatest challenges in the field of cancer medicine is tracking down and killing tumor cells once they have metastasized, or spread, and escaped from a tumor mass.¨ One strategy, he explains, has been to create tiny artificial capsules that stealthily carry toxic drugs throughout the body so that they can reach the escaped tumor cells.

"Unfortunately, traditional chemotherapy drugs do not know healthy cells from tumor cells, but immune system cells recognize this difference. We wanted to enhance the natural ability of T-cells to find and attack tumor cells.¨

Jordan is the author of numerous scientific journal articles in his field. He holds a Ph.D. in Biological Engineering from the Massachusetts Institute of Technology (MIT), and a Bachelors of Science degree in Chemical Engineering and Biomedical Engineering from Carnegie Mellon University.

Click here for more information.

carlyo Thu, 11/13/2014 - 12:48

Tags

Regenerative Medicine

STEM

stem cell research

STEM Education

STEM Education Outreach

USA Science & Engineering Festival

USASEF

Resetting Our Biological Clocks

jhalper — Tue, 21 Oct 2014 07:48:03 +0000

Resetting Our Biological Clocks

To all bits of clockwork that are adjusted in our bodies according to our day-night timetable, we can now add two more: cancer growth and the schedules of our internal complements of bacteria.

Cancer, according to a new Weizmann Institute study, may grow and spread more at night. In this scenario, our cells are getting messages left and right, day and night, and taking them in through the specialized receptors on their outer membranes. During the daytime, our bodies produce natural “wake-up” hormones, and these apparently, take precedence over other incoming messages, their receptors overriding those receiving growth factor messages. At night, when the wake-up hormones have gone to bed, the growth receptor messages are heard in the cell loud and clear, especially in cancer cells that tend to amplify growth signals.

The message: Certain anti-cancer drugs that target the growth factor receptors could be more effective if given at night.

How does a population of internal bacteria, which sit in the deepest intestinal dark, tell day from night? The scientists who brought us the news on the connection between artificial sweeteners, gut bacteria and glucose intolerance are back with a new study on our close relationship with our microbiome. This time, they have shown that our gut bacteria change and adapt throughout the day in synchronization with our eating schedule. So jet lag, for example, does not just screw with your head; it can temporarily upset the balance of bacteria in your gut. And constant upsets in that balance, as we know from their previous study, can lead to metabolic disorders. Indeed, the gut bacteria from a jet-lagged person implanted in the intestines of a sterile mouse caused weight gain and a rise in blood sugar levels.

The message: If you are gaining too much weight while rotating through shift work or flying around the world, blame it on your gut bacteria. Eventually, according to the scientists, we might be able to develop ways of “tricking” our gut bacteria into revising their schedules to fit the unnatural ones we adopt.

jhalper Tue, 10/21/2014 - 03:48

Tags

basic research

Biological networks

biological regulation

biological regulation

circadian clocks

obesity

A Visit to the fMRI

jhalper — Tue, 29 Apr 2014 04:16:17 +0000

A Visit to the fMRI

I’ve heard that for some the experience of undergoing an MRI scan is claustrophobic, but I find it oddly comfy and cocoon-like. OK, there are those gear-grinding screeches and thumps interrupting the music in the earphones. And the cumbersome set-up for imaging breasts, along with the usual admonition to keep perfectly still, does not leave me in a position I would choose for a nap. Still, I’m on the verge of dropping off when the whole table starts shaking under me. They had warned me about this before I climbed onto the apparatus, but for a second I’m not sure whether to laugh (without moving) or jump off.

The fMRI machine I’m visiting is located in the center of campus. I’m taking part in an experiment on breast imaging for cancer detection. This experiment couldn’t be more timely: One scholarly article after another is calling into question the blanket use of current screening methods, as well as for better methods for early breast cancer detection. Indeed, one of the goals of the experiment was to develop a method that could image the breasts of women of all ages and at various hormonal stages, with a completely safe, non-invasive method, while avoiding some of the frequent false positives that plague the usual types of screening.

Dr. Noam Nissan

PhD research student Noam Nissan, MD, who led this study, talked with me afterwards. Noam is supervised by Prof. Hadassa Degani of the Biological Regulation Department and Prof. Lucio Frydman of the Chemical Physics Department. Those two groups converge on the MRI equipment: Degani developed a highly sensitive, MRI-based method of breast cancer diagnosis called 3TP, which is in clinical use, and more recently she also developed the new, completely non-invasive method based on diffusion measurements; while Frydman is a pioneer in developing novel NMR and MRI techniques.

“I knew I wanted to research cancer, for personal reasons as well as scientific ones,” says Noam. “I had contacted Hadassa almost by mistake, but minutes into our first talk I was introduced to her work in breast cancer research, and I immediately recognized that she would be my supervisor, even though, at the time, I knew almost nothing about the methodology of MRI. ”

Prof. Hadassa Degani

For the experiment, volunteers from three different groups were recruited: Young, premenopausal women; older, postmenopausal women; and lactating women. Detection of cancer in each of these groups, Noam explains, presents a different diagnostic challenge. For the young, premenopausal women, hormonal cycles can get in the way when the current standard MRI method that uses injection of a contrast material is used, thus restricting the scanning to a limited time of the month. Hormone replacement therapy in older women is also problematic for the standard MRI method and it is generally recommended to discontinue it a few months prior the scan, which, again, may lead to delayed diagnosis. There are also problems with using this method in lactating women and pregnant women. In addition, mammography – the standard screening method – is less effective in young women and women treated with hormonal replacement therapy who have unusually dense breast tissue. Although rare, pregnancy-associated breast cancer is not unknown, says Noam and because of the diagnostic challenge with conventional imaging methods, it is often diagnosed late and thus carries a less favorable outcome.

Degani’s new method, Diffusion-Tension Imaging (DTI), does not require any injection of contrast materials, and the experiment showed that it is not sensitive to hormonal changes, so it can potentially be used for all of the above. Part of the method relies on using diffusion gradients in multiple directions, which causes the feeling of shaking in the MRI bed. The other part is computerized analysis of the data. Call it extreme photoshopping: The algorithms they developed begin working immediately after the scanning – while the subject may still be in the fMRI scanner – and provides very fast answers. It consists of analyzing each pixel in the some 60 thin slices of each breast produced in the scan to find any in which the normal, relatively fast diffusion of water is reduced and becomes disordered – a sign of cancer, especially if the neighboring pixels show a similar reduction and disorder. The result is a 3-D, “searchable” image of the breasts that in normal breasts appear in cold colors (purple and blue), while any cancer is highlighted in living color (red and yellow).

The results were published in Radiology, a clinical journal, and the researchers hope that breast DTI will make a relatively quick transition from lab to clinic. According to Noam, DTI can complement the other breast screening methods, giving clinicians a valuable choice in non-standard situations. In the meantime, the lab team is working to apply the method to screening for other forms of cancer, particularly pancreatic cancer, which is often discovered only in the later stages of the disease.

From Radiology Nissan, et al. [0033-8419] 2014

When I asked Noam about the experiment, itself, he told me that I was not alone in my keenness to volunteer. The lab was flooded with calls, including quite a few lactating women. (The experimental setup was not suitable for pregnant women – otherwise they would likely have volunteered as well.) Clearly, he says, there is quite a bit of awareness of the problem as well as willingness to help find a solution.

- Judy Halper

jhalper Tue, 04/29/2014 - 00:16

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Diffusion-Tension Imaging

A Genetic Balance of Terror

jhalper — Sun, 29 Sep 2013 05:17:51 +0000

A Genetic Balance of Terror

Cancer, we are told, is a disease of the genes. It originates in mutations in the DNA. But a paper published by a Weizmann Institute group in Cell Reports flips that idea sideways by about 90 degrees: For at least some types of the disease, the healthy, non-mutated version of a gene is no less of a driving force behind the development of cancer than its mutated form.

Prof. Yoram Groner, who led the research, describes the situation as a “balance of terror.” Until now, researchers have assumed that, when a mutation causes cancer it becomes dominant in the cell, overriding the second copy of that gene. But a search through genetic databases for a particular type of mutation suggested that in a number of cases, that second copy is not only functional, it is quite active. The study was mainly conducted by postdoctoral fellow Dr. Oren Ben-Ami in Groner’s lab, together with the group of Dr. Amos Tanay of the Computer Science and Applied Mathematics Department and Dena Leshkowitz of the Israeli National Center for Personalized Medicine.

Groner and his team are interested in the gene RUNX1, which regulates the expression of many other genes, especially those involved in the differentiation of stem cells in the bone marrow into blood cells. Specific mutations in this gene are responsible for several types of leukemia.

Sure enough, when the research team created cells in which just the mutated version of RUNX1 was active, the cells died. Only when both copies – mutated and non-mutated – were present did the cells act like cancer cells: aggressive and long-lived. Further research revealed exactly at which point in the cell cycle the healthy version steps in to keep the cancer cell alive.

Pre-leukemic stem cells (top) with both mutated and healthy copies of the RUNX1 gene already display some of the characteristics of acute myeloid leukemia (AML). When the non-mutated copy of the gene is inactivated, disruptions in the spindle-assembly-checkpoint phase of cell division trigger cell death

As Groner describes the process, mutated RUNX1, because it controls other genes, actively promotes the progression of further mutations that turn the cell into an all-out cancer cell. It does this so well that the end result, if it is allowed to continue, is all-consuming burnout. The standoff between the two versions of the gene is what saves it in the end. As Groner puts it: “The leukemia cells are addicted to the normal RUNX1 gene.”

That implies, over and above the obvious relevance of these findings to diagnostics, that the path to a cure might lie in addressing the addiction.

jhalper Sun, 09/29/2013 - 01:17

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Overturning Ideas on Cancer

jhalper — Sun, 24 Feb 2013 06:29:43 +0000

Overturning Ideas on Cancer

Another advance in cancer research is featured on our website this week. Among other things, this one highlights the dangers of assuming causation from correlation. Prof. Dov Zipori and his team were looking at adult stem cells in the bone marrow. These hold a lot of potential for treating many kinds of disease but, like many kinds of stem cells, there is a risk of these cells differentiating into cancer instead of the intended normal tissue replacement. The idea was to find a marker that could tell which cells were more likely to turn cancerous, thus making the use of these stem cells safer.

Polyploidy in an adult stem cell. From the lab of Prof. Dov Zipori

What the team discovered – to their great surprise – is that a major change in chromosome number that has been associated with cancer is actually found in stem cells that are less likely to become cancerous. This change is called polyploidy: a multiplication of the entire set of chromosomes such that three, four or even more sets appear in the adult stem cells. Up to now, it has been obvious to everyone that the excess chromosomes in polyploidy can lead to the excess growth of cancer.

When the facts tell a different story, the explanation must change as well, and Zipori has an explanation: Polyploidy may be a cell’s way of avoiding cancer. Adding more genes can dilute the effect of a potentially harmful mutation in one. The fact that some cancer cells are polyploid simply means that the strategy doesn’t always work.

This insight, by the way, led Zipori and his team to a gene that is about a thousand times more active in diploid than polyploid cells. The analysis of this gene turns out to be a good predictor of cancer risk in adult stem cells.

jhalper Sun, 02/24/2013 - 01:29

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basic research

biological regulation

biological regulation

genes

Why exactly is this a surprise..?

At least as a superficial analysis.. at least some of the mutations that lead to cancer will involve genes becoming broken (some may involve over-expression which polyplody will not help much). If you have 4 copies of a gene then it requires 4 mutations to completely remove the functionality, which is exponentially harder than 2.

Furthermore, it becomes that much harder to knock out the apotosis mechanisms.

Obviously, there would be side effects.. but if an organism could be engineered for quardroploiy, surely the cancer rate would be lower.

It is a surprise exactly because polyploidy has been associated with cancer. And it is a somewhat risky strategy, because doubling chromosomes with certain mutations could accelerate the cancer process, rather than inhibit it.