Oh Yeah, Developmental Biology!

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Posts tagged with "Cancer"

Quadruple helix' DNA discovered in human cells

In 1953, Cambridge researchers Watson and Crick published a paper describing the interweaving ‘double helix’ DNA structure - the chemical code for all life. Now, in the year of that scientific landmark’s 60th Anniversary, Cambridge researchers have published a paper proving that four-stranded ‘quadruple helix’ DNA structures - known as G-quadruplexes - also exist within the human genome. They form in regions of DNA that are rich in the building block guanine, usually abbreviated to ‘G’.

The findings mark the culmination of over 10 years investigation by scientists to show these complex structures in vivo - in living human cells - working from the hypothetical, through computational modelling to synthetic lab experiments and finally the identification in human cancer cells using fluorescent biomarkers.

Read more at: http://phys.org/news/2013-01-quadruple-helix-dna-human-cells.html#jCp

Physics not biology may be key to beating cancer

Billions of dollars spent on cancer research have yielded no great breakthrough yet. There are other ways to attack the problem, says physicist Paul Davies

AS THE US faces up to its “fiscal cliff” of massive spending cuts, a major issue is burgeoning health costs. High on the list of those costs is cancer therapy, with the clamour for hugely expensive drugs - many of which have little or no clinical benefit - set to grow as baby boomers age.

Cancer research swallows billions of dollars a year, but the life expectancy for someone diagnosed with cancer that has spread to other parts of the body has changed little over several decades. Therapy is often a haphazard rearguard action against the inevitable. And the search for a general cure remains as elusive as ever.

Recognising this depressing impasse, the US National Cancer Institute (NCI) took a bold step in 2008 by deciding that the field might benefit from the input of mathematicians and physical scientists, whose methods and insights differ markedly from those of cancer biologists.

After all, the history of science teaches us that major advances come when a subject’s conceptual foundations are revised. Maybe progress is slow because we are looking at the problem in the wrong way? So the NCI created 12 centres for physical science and oncology. Four years on, they are starting to bear fruit, for example, by showing how the elastic properties of cells change as cancer progresses.

In the 19th century, living organisms were widely regarded as machines infused by vital forces. Biologists eventually came to realise that cells are not some sort of magic matter, but complex networks of chemical reaction pathways. Then came the genetics revolution, which describes life in the informational language of instructions, codes and signalling. Mainstream research today focuses almost exclusively on chemical pathways or genetic sequencing. For example, drugs are designed to block reaction pathways implicated in cancer. The cancer genome atlas is amassing terabytes of data in which people hope to spot some sort of mutational pattern. But while of great scientific interest, such projects have not led to the much-anticipated breakthrough.

Why? There are fundamental obstacles: living cells, including cancer cells, are a bottomless pit of complexity, and cancer cells are notoriously heterogeneous. A reductionist approach that seeks to unravel the details of every pathway of every cancer cell type might employ researchers for decades and consume billions of dollars, with little impact clinically. Linear chains of cause and effect rarely work in biology, which is dominated by elaborate networks of interactions such as feedback and control loops.

There is, however, another way of looking at cells. In addition to being bags of chemicals and information processing systems, they are also physical objects, with properties such as size, mass, shape, elasticity, free energy, surface stickiness and electrical potential. Cancer cells contain pumps, levers, pulleys and other paraphernalia familiar to physicists and engineers. Furthermore, many of these properties are known to change systematically as cancer progresses in malignancy.

First, though, we need to get away from the notion of a cure, and think of controlling or managing cancer. Like ageing, cancer is not so much a disease as a process. And just as the effects of ageing can be mitigated without a full understanding of the process, the same could be true of cancer.

Many accounts misleadingly describe cancer as rogue cells running amok. In fact, once cancer is triggered, it is usually very deterministic in its behaviour. Primary tumours are rarely the cause of death. It is when cancer spreads around the body and colonises other organs that the patient’s prospects deteriorate sharply.

This so-called metastasis is a well characterised, if poorly understood, physical process. Cells migrate from the primary tumour to blood vessels, which they enter through spaces in the vessel walls. Then, swept along in the torrent, they circulate in the blood system, sometimes individually, sometimes “rafting” in gangs like Lilliputian raiders, stuck together by blood platelets. A fraction of these migrants get jammed in tiny blood vessels called venules or, more spectacularly, roll along the vessel wall and fling out little molecular grappling hooks called cadherins. Thus anchored against the blood flow, they inveigle their way into the nearest organ.

During this process, the physical properties and shape of the cells can change dramatically. Generally, cancer cells are soft and misshapen compared with healthy cells of the same type, a transformation that may affect their motility and increase their invasive potential. Cancer cells are adept at building nests in foreign tissue, by altering the structure and physical properties of the host organ’s supporting extracellular matrix, and recruiting local healthy cells. There are also hints that a primary tumour may send out chemical signals ahead of time to prepare the physical and chemical ground for the colonists.

Although metastasis seems fiendishly efficient, most disseminated cancer cells never go on to cause trouble. The vast majority die, and the survivors may lie dormant for years or even decades, either as individual, quiescent, cells in the bone marrow, or as micro-metastases in tissues, before erupting into proliferating secondary tumours. Hence the many cases of “cancer survivors” who die when the same cancer returns with enhanced malignancy years or even decades after a primary tumour has been removed.

The spread of cancer presents many possibilities for clinical intervention once the dream of a cure has been abandoned. For example, if the period of dormancy can be extended by, say, a factor of five, many breast, colon and prostate cancers would cease to be a health issue. How could this be achieved?

Evolutionary roots

We do not need to know the intricate details of the cancer cells’ innards to figure out how their overall behaviour might be controlled. It is well known that cells regulate the action of genes not just as a result of chemical signals, but because of the physical properties of their micro-environment. They can sense forces such as shear stresses and the elasticity of nearby tissue. They are also responsive to temperature, electric fields, pH, pressure and oxygen concentration. All these variables offer opportunities for intervening and stabilising widespread cancer cells. For example, a few doctors are attempting to treat cancer using hyperbaric oxygen therapy, where the patient is placed in a chamber of high-pressure pure oxygen, which affects cancer cell metabolism.

We also need to involve other kinds of biologists in cancer research - after all, cancer is widespread among mammals, fish, reptiles, even plants. Clearly it is an integral part of the evolutionary story of multicellular life over the last billion years.

Most normal cells seem to come pre-loaded with a “cancer subroutine” that can be triggered by a variety of insults, and we need to understand the evolutionary origin of this just as much as the triggering mechanisms. In addition, it has long been recognised that there are many similarities between cancer and embryo development, and evidence is mounting that some genes expressed during embryogenesis get re-awakened in cancer.

Right now, the huge cancer research programme is long on technical data, but short on understanding. By reshaping the conceptual landscape, we may at last see how to make serious inroads into tackling a much- feared disease that touches every family on the planet.

Nov 6
frontal-cortex:

Pamela Itkin-Ansari’s Research Report
“We are interested in identifying the master regulators of growth control in pancreatic ductal adenocarcinoma (PDA). We found that the transcriptional repressor Id3 is profoundly upregulated in human PDA.
We are now studying Id3 interacting genes in order to identify optimal targets for drug discovery efforts for PDA.” (SanfordBurnham.org)
Above : Id3 (green) is strikingly upregulated in murine pancreatic intraepithelial neoplasia (mucin, red) and in human pancreatic ductal adenocarcinoma (PDA)

frontal-cortex:

Pamela Itkin-Ansari’s Research Report

“We are interested in identifying the master regulators of growth control in pancreatic ductal adenocarcinoma (PDA). We found that the transcriptional repressor Id3 is profoundly upregulated in human PDA.

We are now studying Id3 interacting genes in order to identify optimal targets for drug discovery efforts for PDA.” (SanfordBurnham.org)

Above : Id3 (green) is strikingly upregulated in murine pancreatic intraepithelial neoplasia (mucin, red) and in human pancreatic ductal adenocarcinoma (PDA)

neurosciencestuff:

Colorful But Deadly: Images of Brain Cancer

Folded DNA becomes Trojan horse to attack cancer

IT WORKED for the ancient Greeks, so why shouldn’t it work for us? Some cancers are resistant to chemotherapy, but we can attack them successfully by hiding drugs inside folded-up DNA.

DNA origami involves folding a single strand of DNA into a complex pattern, creating a 3D structureBaoquan Ding at the National Center for Nanoscience and Technology in Beijing, China, and colleagues loaded a tubular piece of folded DNA with doxorubicin, a chemotherapy drug. The DNA Trojan horse delivered a dose of the drug that proved lethal to human breast-cancer cells, even though they had developed resistance to doxorubicin (Journal of the American Chemical Society, DOI: 10.1021/ja304263n).

"This is the first study to demonstrate that DNA origami can be used to circumvent drug resistance," says Hao Yan at Arizona State University in Tempe, who jointly led the work. The cancer cells may not recognise the DNA origami as a threat in the way that free doxorubicin is, he suggests. The folded DNA might also alter the pH inside the cells, increasing the drug’s activity.

New cancer drug sabotages tumour's escape route

Some untreatable cancers could soon be held in check by an experimental drug that targets not only the tumour itself, but also how it evolves to spread through the body.

The new drug, Cabozantinib, or cabo for short, simultaneously neutralises two mechanisms cancers need to survive. First, it chokes each tumour’s blood supply by blocking a molecule on the surface of its blood vessels, called vascular endothelial growth factor receptor (VEGFR). There is evidence in animals that cancers can respond to this kind of attack by invading new tissues, where they may be able to generate secondary tumours. Importantly, cabo foils this strategy by blocking a second receptor called c-MET that would otherwise help cancer cells spread to new tissue.

Read more.

'Immortal' Tasmanian devil brings vaccine hope

A bizarre facial cancer threatening to wipe out the Tasmanian devil probably evolved from a single female about 16 years ago, new scans of the cancer reveal. The scans are also helping to identify gene mutations found in the cancer but not healthy tissue, which might provide targets for a vaccine to rescue the endangered species.

Devil facial tumour disease is unusual in that the cancer cells themselves act as infectious agents. The cells spread between animals through biting during fights or mating. A vaccine could prime uninfected animals against the cancer if they are subsequently bitten.

"Now we know which genes are mutated, we can begin assessing which ones might be good antigens for a vaccine," says Elizabeth Murchison of the Wellcome Trust Sanger Institute in Hinxton, UK, who led the team.

'DNA robot' targets cancer cells

Scientists have developed and tested a “DNA robot” that delivers payloads such as drug molecules to specific cells.

The container was made using a method called “DNA origami”, in which long DNA chains are folded in a prescribed way.

Then, so-called aptamers - which can recognise specific cell types - were used to lock the barrel-shaped robot.

New Article

Original Paper

Feb 2

Colourful cancer cells snag micro-photography prize.
An ovarian cancer researcher found the beauty in a horrific disease to win the 2011 IN Cell Analyzer Image Competition. Geoffrey Grandjean from the MD Anderson Cancer Center in Houston, Texas captured this image of human cancer cells to win the prize.
The cells’ kaleidoscope of colours come from stains that show DNA in red and microtubules in green. Images of this type help the researchers identify areas to attack in cancer therapies.
This image will be shown off with the other category winners on the big screen in New York’s Times Square on April 20-22. If you can’t make it to the Big Apple this spring, you can still check out all the winners in GE Healthcare’s online gallery.
Ovarian cancer cells have also been made to fluoresce to help doctors remove them more accurately.

Colourful cancer cells snag micro-photography prize.

An ovarian cancer researcher found the beauty in a horrific disease to win the 2011 IN Cell Analyzer Image Competition. Geoffrey Grandjean from the MD Anderson Cancer Center in Houston, Texas captured this image of human cancer cells to win the prize.

The cells’ kaleidoscope of colours come from stains that show DNA in red and microtubules in green. Images of this type help the researchers identify areas to attack in cancer therapies.

This image will be shown off with the other category winners on the big screen in New York’s Times Square on April 20-22. If you can’t make it to the Big Apple this spring, you can still check out all the winners in GE Healthcare’s online gallery.

Ovarian cancer cells have also been made to fluoresce to help doctors remove them more accurately.