Chemists find help from nature in fighting cancer

Inspired by a chemical that fungi secrete to defend their territory, MIT chemists have synthesized and tested several dozen compounds that may hold promise as potential cancer drugs.

A few years ago, MIT researchers led by associate professor of chemistry Mohammad Movassaghi became the first to chemically synthesize 11,11’-dideoxyverticillin, a highly complex fungal compound that has shown anti-cancer activity in previous studies.

In the new study, recently published online in the journal Chemical Science, Movassaghi and colleagues at MIT and the University of Illinois at Urbana-Champaign (UIUC) designed and tested 60 compounds for their ability to kill human cancer cells.

“What was particularly exciting to us was to see, across various cancer cell lines, that some of them are quite potent,” Movassaghi says.

Lead author of the paper is MIT postdoc Nicolas Boyer. Other authors are MIT graduate student Justin Kim, UIUC chemistry professor Paul Hergenrother and UIUC graduate student Karen Morrison.

Many of the compounds tested in this study, known as epipolythiodiketopiperazine (ETP) alkaloids, are naturally produced by fungi. Scientists believe these compounds help fungi prevent other organisms from encroaching on their territory.

The compounds that kill cancer cells appear to be very selective, destroying them 1,000 times more effectively than they kill healthy blood cells.

The researchers also identified sections of the compounds that can be altered without discernably changing their activity. This is useful because it could allow chemists to use those points to attach the compounds to a delivery agent such as an antibody that would target them to cancer cells, without impairing their cancer-killing ability.

Larry Overman, a professor of chemistry at the University of California at Irvine, says the new study is an impressive advance.The research was funded by the National Institute of General Medical Sciences.

Source: http://web.mit.edu/newsoffice/2013/chemists-find-help-from-nature-in-fighting-cancer-0227.html

Indian Plant Compound Could Play Role In Cancer Cell Death

Gedunin, an extract of the Indian neem tree that has been used for centuries in Asia as a natural remedy to treat inflammation, fever, and malaria, may also be used to help kill cancer cells.

 Cancer cells typically avoid death by hijacking molecular chaperones that guide and protect the proteins that ensure normal cellular function and then tricking them into helping mutated versions of those proteins stay alive, says Dr. Ahmed Chadli, a researcher at the GRU Cancer Center and senior author of the study.

Drug development has focused on the chaperone Hsp90 (heat shock protein 90) because it plays a key role in assisting mutated proteins, making it an attractive cancer drug target. But small molecules targeting Hsp90 have inadvertently resulted in the expression of proteins that protect cancer cells from programmed cell death, compromising the Hsp90 inhibitors in the clinic.

Chadli and his team found that gedunin attacks a co-chaperone, or helper protein, of Hsp90 called p23. Hence, gedunin leads to the inactivation of the Hsp90 machine and the killing of cancer cells without the production of anti-apoptotic proteins.

Source:
http://www.asianscientist.com/in-the-lab/gedunin-indian-plant-compound-cancer-cell-death-2013/
http://www.jbc.org/content/early/2013/01/25/jbc.M112.427328

Nanoscale capsule kills cancer cells without harming healthy cells

A degradable nanoscale shell to carry proteins to cancer cells and stunt the growth of tumors without damaging healthy cells has been developed by a team led by researchers from the UCLA Henry Samueli School of Engineering and Applied Science.

The process does not present the risk of genetic mutation posed by gene therapies for cancer, or the risk to healthy cells caused by chemotherapy, which does not effectively discriminate between healthy and cancerous cells, said Yi Tang, a professor of chemical and biomolecular engineering and a member of the California NanoSystems Institute at UCLA.

The research was funded by the David and Lucille Packard Foundation and a breast cancer research grant from the Congressionally Directed Medical Research Program.

Source: http://www.kurzweilai.net/nanoscale-capsule-kills-cancer-cells-without-harming-healthy-cells

New world-record efficiency for thin-film silicon solar cells

EPFL’s Institute of Microengineering has reached a remarkable 10.7% efficiency for a single-junction microcrystalline silicon solar cell, surpassing the previous world record of 10.1% held by the Japanese company Kaneka Corporation since 1998.

The efficiency increase was also achieved with with only 1.8 microns of photovoltaic active material — 100 times less material than with standard wafer-based crystalline silicon PV technology.

Thin-film silicon technology indeed offers the advantages of saving up on raw material and offering low energy payback time, thus allowing module production prices as low as 35 €/m2 (47 $/m2), reaching the price level of standard roof tiles.

Work leading to this result was supported by the Swiss Federal Office of Energy (SFOE), the EU-FP7 program, the Swiss National Science Foundation (SNSF), and the Commission for Technology and Innovation (CTI).

Source: http://www.kurzweilai.net/new-world-record-efficiency-for-thin-film-silicon-solar-cells

Cancer battle: Scientists engineer new tumor-killing virus

A new genetically-engineered virus has been developed to kill cancer tumors and prevent the growth of new ones, according to a study. It was tested in 30 terminally-ill liver cancer patients and proved to significantly prolong their lives.
The study, which was recently published in the journal Nature Medicine, describes a four-week trial of the vaccine Pexa-Vec or JX-594 marking a step forward towards a successful treatment of solid tumors, AFP reports.

Sixteen out of 30 patients who were given a high dosage of therapy lived for 14.1 months on average, while the other 14 patients were given a low dosage and survived for 6.7 months.
"For the first time in medical history we have shown that a genetically-engineered virus can improve survival of cancer patients," study co-author David Kirn from California-based biotherapy company Jennerex told AFP.
The results of the study indicate that "Pexa-Vec treatment at both doses resulted in a reduction of tumor size and decreased blood flow to tumors," Jennerex said in a statement. “This is the first randomized clinical trial of an oncolytic immunotherapy demonstrating significantly prolonged overall survival.”

The new treatment uses oncolytic immunotherapy, which is a genetically modified type of virus that attacks tumors to induce a systemic immune response to cancer. It selectively replicates in tumor cells to achieve an antitumor effect.
The new virus "is designed to multiply in and subsequently destroy cancer cells, while at the same time making the patients' own immune defense system attack cancer cells also," added Kirn.

This trial shows concrete progress and proves that “Pexa-Vec treatment induces an immune response against the tumor."

Source: http://rt.com/news/new-virus-battles-cancer-888/

Some cancer mutations slow tumor growth

A typical cancer cell has thousands of mutations scattered throughout its genome and hundreds of mutated genes. However, only a handful of those genes, known as drivers, are responsible for cancerous traits such as uncontrolled growth. Cancer biologists have largely ignored the other mutations, believing they had little or no impact on cancer progression.

But a new study from MIT, Harvard University, the Broad Institute and Brigham and Women’s Hospital reveals, for the first time, that these so-called passenger mutations are not just along for the ride. When enough of them accumulate, they can slow or even halt tumor growth.

The findings, reported in this week’s Proceedings of the National Academy of Sciences, suggest that cancer should be viewed as an evolutionary process whose course is determined by a delicate balance between driver-propelled growth and the gradual buildup of passenger mutations that are damaging to cancer, says Leonid Mirny, an associate professor of physics and health sciences and technology at MIT and senior author of the paper.

In computer simulations, the researchers tested the possibility of treating tumors by boosting the impact of deleterious mutations. In their original simulation, each deleterious passenger mutation reduced the cell’s fitness by about 0.1 percent. When that was increased to 0.3 percent, tumors shrank under the load of their own mutations.

The same effect could be achieved in real tumors with drugs that interfere with proteins known as chaperones, Mirny suggests. After proteins are synthesized, they need to be folded into the correct shape, and chaperones help with that process. In cancerous cells, chaperones help proteins fold into the correct shape even when they are mutated, helping to suppress the effects of deleterious mutations.

Several potential drugs that inhibit chaperone proteins are now in clinical trials to treat cancer, although researchers had believed that they acted by suppressing the effects of driver mutations, not by enhancing the effects of passengers.

In current studies, the researchers are comparing cancer cell lines that have identical driver mutations but a different load of passenger mutations, to see which grow faster. They are also injecting the cancer cell lines into mice to see which are likeliest to metastasize.

The research was funded by the National Institutes of Health/National Cancer Institute Physical Sciences Oncology Center at MIT.

Source: http://web.mit.edu/newsoffice/2013/some-cancer-mutations-slow-tumor-growth-0204.html

Mercedes engineers expect autonomous cars by 2020

German ingenieurs from Mercedes expect that by 2020 series models can at least partially drive themselves.

Source: http://www.zeit.de/auto/2013-01/auto-autonom

Will we ever... grow synthetic organs in the lab?

Grow synthetic organs in the lab

Growing synthetic windpipes, artificial skin and replacement blood vessels is now a reality, but scientists are now turning their attention to their ultimate goal: growing new human kidneys or hearts.

In June 2011, an Eritrean man entered an operating theatre with a cancer-ridden windpipe, but left with a brand new one. People had received windpipe transplants before, but Andemariam Teklesenbet Beyene’s was different. His was the first organ of its kind to be completely grown in a lab using the patient's own cells.

The practicalities are, as you can imagine, less straightforward. Take the example I have already described. The process began with researchers taking 3D scans of Beyene’s windpipe, and from these scans Alexander Seifalian at University College London built an exact replica from a special polymer and a glass mould. This was flown to Sweden, where surgeon Paolo Macchiarini seeded this scaffold with stem cells taken from Beyene’s bone marrow. These stem cells, which can develop into every type of cell in the body, soaked into the structure and slowly recreated the man’s own tissues. The team at Stockholm’s Karolinska University Hospital incubated the growing windpipe in a bioreactor – a vat designed to mimic the conditions inside the human body.

Two days later, Macchiarini transplanted the windpipe during a 12-hour operation, and after a month, Beyene was discharged from the hospital, cancer-free. A few months later, the team repeated the trick with another cancer patient, an American man called Christopher Lyles.

“A good way to think about it is that there are four levels of complexity,” says Anthony Atala from the Wake Forest Institute for Regenerative Medicine, one of the leaders of the field. The first level includes flat organs like skin, which comprise just a few types of cells. Next up are tubes, like windpipes or blood vessels, with slightly more complex shapes and more varied collections of cells. The third level includes hollow sac-like organs, like the bladder or stomach. Unlike the tubes, which just act as pipes for fluid, these organs have to perform on demand – secreting, expanding or filtering as the situation arises.

Even after scientists successfully devise ways of growing organs, there are many logistical challenges to overcome before these isolated success stories can become everyday medical reality. “Can you manufacture them and grow them on large scales?” asks Robert Langer, a pioneer in the field. “Can you create them reproducibly? Can you preserve them [in the cold] so they have a reasonable shelf-life? There are a lot of very important engineering challenges to overcome.”

Source: http://www.bbc.com/future/story/20120223-will-we-ever-create-organs

Printing a human kidney

Surgeon Anthony Atala demonstrates an early-stage experiment that could someday solve the organ-donor problem: a 3D printer that uses living cells to output a transplantable kidney. Using similar technology, Dr. Atala's young patient Luke Massella received an engineered bladder 10 years ago.

Anthony Atala asks, "Can we grow organs instead of transplanting them?" His lab at the Wake Forest Institute for Regenerative Medicine is doing just that - engineering over 30 tissues and whole organs. Anthony Atala is the director of the Wake Forest Institute for Regenerative Medicine, where his work focuses on growing and regenerating tissues and organs. His team engineered the first lab-grown organ to be implanted into a human - a bladder - and is developing experimental fabrication technology that can "print" human tissue on demand.

In 2007, Atala and a team of Harvard University researchers showed that stem cells can be harvested from the amniotic fluid of pregnant women. This and other breakthroughs in the development of smart bio-materials and tissue fabrication technology promises to revolutionize the practice of medicine.

Source: http://www.bbc.com/future/story/20120621-printing-a-human-kidney

Epigenetic reveal clues to ageing

Why do we develop wrinkles and why do our muscles waste away? Why do our brains and immune systems become less effective with time?

Epigenetics is all about changing the way our genes function by turning them off or making them more active.

Genes are the blueprint for building the human body. There's a copy of the whole blueprint in nearly every cell in the body, but clearly you don't need to use all of it all of the time. Bone cells will use different bits of the blueprint to nerve cells or light sensing cells in the eye.

Manel Esteller's team, at the Bellvitge Biomedical Research Institute, has shown that this control over the blueprint decays over time.

Adding small chemicals, methyl groups, to specific points of DNA is one of the main ways of turning a gene off.

Longer or healthier life?

It is possible to change a person's epigenome. Studies have already shown how a pregnant mother's diet can affect her child's risk of obesity epigenetically.

Prof Tim Spector, the author of a book on epigenetics, Identically Different, said: "There are epigenetic drugs in development, four for cancer. In terms of lifestyle, we know that exercise can switch off the main obesity genes epigenetically.

"Apart from stem cells, this is the hot area of ageing at the moment, finding ways of encouraging our genes to remain healthy is going to be a top priority in the next few years."

Source: http://www.bbc.co.uk/news/health-18400219