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Posts tagged "cancer"

biovisual:

THE CELL CYCLE AND ITS SAFEGUARDS AGAINST CANCER
SOURCE: PZ Myers (Pharyngula)

TOP IMAGE
Dividing cells follow a cycle.

  • Most cells are in G1 (Gap 1), doing what cells do.
  • Then under control of clock-like changes in specific genes, they can enter the S (synthesis) phase, when their DNA is replicated,
  • followed by a G2 phase (gap 2),
  • and then an actively dividing mitotic or M phase.

Each of these phases has a checkpoint where a battery of proteins survey the state of the cell and either permit the process to proceed, or block it if there are problems.

In extreme cases, the checkpoint proteins can determine that the cell is so irreparably damaged that the only option is suicide, and the cell will self destruct.

MIDDLE IMAGE
This is the process that cancer needs to disrupt if it is to continue; cancer cells typically have damaged DNA or aberrant signals flying everywhere that ought to be triggering all kinds of alarms in the checkpoint system, and either stopping cell division immediately, or activating repair mechanisms that fix the damage, or just killing the corrupted cell immediately.

One of the most critical points in this cycle is called the R or Restriction point.

  • Prior to the R point, the cell is sensitive to external signals that can induce cell division;
  • after this point, the cell no longer pays attention to those signals, because it is on a rigidly programmed track towards completing cell division.

The R point is that last fateful moment of decision before the cell commits to dividing.

BOTTOM IMAGE
Standing at this point is an essential guardian of the cell cycle, pRb. This protein is an inhibitor of cell division, acting as a tumor suppressor gene. It’s the guard at the gate, and it must be satisfied that all is well in the cell before it will allow division to continue.

pRb’s default mode is to stop cell division, but it receives signals from a wide array of pathways that can tell it to stand down and let the process continue.

Control of this gene is complicated because it is so essential to well-regulated cell division: look at it here, standing sentry just above the yellow R point, with all these other pathways talking to it.

I think you can see how this gene can contribute to cancer when it’s defective. Shoot the guard, open the gate wide, and allow cell divisions to proceed unchecked.

This passage is a part of PZ Myers’ much longer critique of an article on the evolution of cancer by two physicists, Paul Davies and Charles Lineweaver, ‘Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors” (Phys. Biol. 8 015001-015008).

(via azureamaryllis)

laboratoryequipment:

Obama Honors Memory of Girl with Cancer Research BillA 10-year-old girl who died of brain cancer is leaving a legacy for other sick children in a new law signed by President Barack Obama.Obama signed the bipartisan Gabriella Miller Kids First Research Act. It directs $126 million in federal money to be spent over the next decade to research pediatric cancer and other childhood disorders. Her parents and brother watched Obama sign the bill.Read more: http://www.laboratoryequipment.com/news/2014/04/obama-honors-memory-girl-cancer-research-bill

laboratoryequipment:

Obama Honors Memory of Girl with Cancer Research Bill

A 10-year-old girl who died of brain cancer is leaving a legacy for other sick children in a new law signed by President Barack Obama.

Obama signed the bipartisan Gabriella Miller Kids First Research Act. It directs $126 million in federal money to be spent over the next decade to research pediatric cancer and other childhood disorders. Her parents and brother watched Obama sign the bill.

Read more: http://www.laboratoryequipment.com/news/2014/04/obama-honors-memory-girl-cancer-research-bill

candidscience:

Did you know that the human immune system can identify and eliminate precancerous cells before they can cause harm??

 This is called IMMUNE SURVEILLANCE (see ref. from JCI, 2007, for description), and it is essential in preventing the development of B-cell Lymphomas (non-Hodgkin’s lymphomas).  In fact IMMUNE SURVEILLANCE accounts for what researchers at Walter and Eliza Hall Institute call the ‘surprising rarity’ of B-cell lymphomas in the population, given how often these immune cells spontaneously change.  With this information, a test can be developed to identify people with the early stages of this cancer.

Read more: Body kills ‘spontaneous’ Blood Cancers on a Daily Basis

and the original article in Nature Medicine

Image: cells from a lymph node biopsy in a patient with B-cell lymphoma

ucsdhealthsciences:

A confocal micrograph of a human melanoma cell undergoing division or mitosis. The resulting daughter cells are temporarily linked by a bridge of remaining cytoplasm. Green staining labels the endoplasmic reticulum; red colors the mitochondria. Blue indicates the chromosomes. Image courtesy of Wellcome Images.

Split Decision: Stem Cell Signal Linked With Cancer Growth

Researchers at the University of California, San Diego School of Medicine have identified a protein critical to hematopoietic stem cell function and blood formation. The finding has potential as a new target for treating leukemia because cancer stem cells rely upon the same protein to regulate and sustain their growth.

Hematopoietic stem cells give rise to all other blood cells. Writing in the February 2, 2014 advance online issue of Nature Genetics, principal investigator Tannishtha Reya, PhD, professor in the Department of Pharmacology, and colleagues found that a protein called Lis1 fundamentally regulates asymmetric division of hematopoietic stem cells, assuring that the stem cells correctly differentiate to provide an adequate, sustained supply of new blood cells.

Asymmetric division occurs when a stem cell divides into two daughter cells of unequal inheritance: One daughter differentiates into a permanently specialized cell type while the other remains undifferentiated and capable of further divisions.

“This process is very important for the proper generation of all the cells needed for the development and function of many normal tissues,” said Reya. When cells divide, Lis1 controls orientation of the mitotic spindle, an apparatus of subcellular fibers that segregates chromosomes during cell division.

“During division, the spindle is attached to a particular point on the cell membrane, which also determines the axis along which the cell will divide,” Reya said. “Because proteins are not evenly distributed throughout the cell, the axis of division, in turn, determines the types and amounts of proteins that get distributed to each daughter cell. By analogy, imagine the difference between cutting the Earth along the equator versus halving it longitudinally. In each case, the countries that wind up in the two halves are different.”

When researchers deleted Lis1 from mouse hematopoietic stem cells, differentiation was radically altered. Asymmetric division increased and accelerated differentiation, resulting in an oversupply of specialized cells and an ever-diminishing reserve of undifferentiated stem cells, which eventually resulted in a bloodless mouse. 

“What we found was that a large part of the defect in blood formation was due to a failure of stem cells to expand,” said Reya. “Instead of undergoing symmetric divisions to generate two stem cell daughters, they predominantly underwent asymmetric division to generate more specialized cells. As a result, the mice were unable to generate enough stem cells to sustain blood cell production.”

The scientists next looked at how cancer stem cells in mice behaved when the Lis1 signaling pathway was blocked, discovering that they too lost the ability to renew and propagate. “In this sense, the effect Lis1 has on leukemic self-renewal parallels its role in normal stem cell self-renewal,” Reya said.

Reya said the findings shed new light on the fundamental regulators of cell growth both in normal development and in cancer.

“Our work shows that elimination of Lis1 potently inhibits cancer growth, and identifies Lis1 and other regulators of protein inheritance as a new class of molecules that could be targeted in cancer therapy.”

In the long term, Reya noted, it remains to be determined whether inhibiting Lis1 in cancer cells would produce unacceptable consequences in normal cells as well. “A number of commonly used hemotherapy agents target the machinery that controls cell division. Although these agents can be toxic, their effects on cancer cells are much more potent than their effects on normal cells, and so they continue to be used. Agents that target Lis1 might be more specific and less toxic, which would give them significant clinical value.”

ucsdhealthsciences:

A colored scanning electron micrograph of a human T lymphocyte. Image courtesy of the National Institute of Allergy and Infectious Disease

Using microRNA Fit to a T (cell)
Researchers show B cells can deliver potentially therapeutic bits of modified RNA

Researchers at the University of California, San Diego School of Medicine have successfully targeted T lymphocytes – which play a central role in the body’s immune response – with another type of white blood cell engineered to synthesize and deliver bits of non-coding RNA or microRNA (miRNA).

The achievement in mice studies, published in this week’s online early edition of the Proceedings of the National Academy of Sciences, may be the first step toward using genetically modified miRNA for therapeutic purposes, perhaps most notably in vaccines and cancer treatments, said principal investigator Maurizio Zanetti, MD, professor in the Department of Medicine and director of the Laboratory of Immunology at UC San Diego Moores Cancer Center.

“From a practical standpoint, short non-coding RNA can be used for replacement therapy to introduce miRNA or miRNA mimetics into tissues to restore normal levels that have been reduced by a disease process or to inhibit other miRNA to increase levels of therapeutic proteins,” said Zanetti.

“However, the explosive rate at which science has discovered miRNAs to be involved in regulating biological processes has not been matched by progress in the translational arena,” Zanetti added. “Very few clinical trials have been launched to date.  Part of the problem is that we have not yet identified practical and effective methods to deliver chemically synthesized short non-coding RNA in safe and economically feasible ways.”

Zanetti and colleagues transfected primary B lymphocytes, a notably abundant type of white blood cell (about 15 percent of circulating blood) with engineered plasmid DNA (a kind of replicating but non-viral DNA), then showed that the altered B cells targeted T cells in mice when activated by an antigen – a substance that provokes an immune system response.

“This is a level-one demonstration for this new system,” said Zanetti. “The next goal will be to address more complex questions, such as regulation of the class of T cells that can be induced during vaccination to maximize their protective value against pathogens or cancer. 

More here

(via contaminatedbreastcheese)

scipak:

Bundled RNA Balls Attack Brain Tumors

Spherical nucleic acids, or SNAs, are balls of RNA with a gold nanoparticle core that can slip into brain tumors and block cancer gene expression, reports a new study in mice. The technology may be an effective treatment for glioblastoma, a deadly form of brain cancer.

This video shows a 3D reconstruction of magnetic resonance images after intracranial injection of Gd(III)-functionalized spherical nucleic acids.

Read more about this research from the 30 October issue of Science Translational Medicine here.

[Video courtesy of Science Translational Medicine/AAAS]

© 2013 American Association for the Advancement of Science. All Rights Reserved.

(via afro-dominicano)

laboratoryequipment:

Nanoparticle Fights Cancer in Two WaysUniv. of New South Wales chemical engineers have synthesized a new iron oxide nanoparticle that delivers cancer drugs to cells while simultaneously monitoring the drug release in real time.The result, published online in the journal ACS Nano, represents an important development for the emerging field of theranostics – a term that refers to nanoparticles that can treat and diagnose disease.Read more: http://www.laboratoryequipment.com/news/2013/10/nanoparticle-fights-cancer-two-ways

laboratoryequipment:

Nanoparticle Fights Cancer in Two Ways

Univ. of New South Wales chemical engineers have synthesized a new iron oxide nanoparticle that delivers cancer drugs to cells while simultaneously monitoring the drug release in real time.

The result, published online in the journal ACS Nano, represents an important development for the emerging field of theranostics – a term that refers to nanoparticles that can treat and diagnose disease.

Read more: http://www.laboratoryequipment.com/news/2013/10/nanoparticle-fights-cancer-two-ways

thenewenlightenmentage:

One-two punch knocks out aggressive tumors

New nanoparticles weaken tumor-cell defenses, then strike with chemotherapy drug.

An aggressive form of breast cancer known as “triple negative” is very difficult to treat: Chemotherapy can shrink such tumors for a while, but in many patients they grow back and gain resistance to the original drugs.

To overcome that resistance, MIT chemical engineers have designed nanoparticles that carry the cancer drug doxorubicin, as well as short strands of RNA that can shut off one of the genes that cancer cells use to escape the drug. This “one-two punch” disables tumors’ defenses and makes them much more vulnerable to chemotherapy.

Continue Reading

bpod-mrc:

23 October 2013

Moving Out

One major reason why cancer is so difficult to cure is because it can spread from one location to other organs, in a process known as metastasis. Cancer cells move around the body by invading blood vessels and travelling down them, before leaving to proliferate in new tissues. How they are able to move out of the bloodstream is still poorly understood, so researchers have designed an artificial set-up that mimics blood vessels to study this final step in their journey. Tumour cells are injected into the system, and their behaviour can be observed under the microscope. From left to right and top to bottom, these images, taken at half-hour intervals, show a cancer cell (in green) squeezing its way out after it becomes trapped in a vessel. This new technique should eventually allow drugs to be tested for their ability to interfere with this process, and so hinder metastasis.

Written by Emmanuelle Briolat

Roger D. Kamm
Department of Biological Engineering, Massachusetts Institute of Technology
Royal Society of Chemistry
Integr. Biol., 2013, 5, 1262

laboratoryequipment:

Coffee Reduces Risk of Liver Cancer

Coffee consumption reduces risk of hepatocellular carcinoma (HCC), the most common type of liver cancer, by about 40 percent, according to an up-to-date meta-analysis published in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association. Further, some data indicate that three cups of coffee per day reduce liver cancer risk by more than 50 percent.

"Our research confirms past claims that coffee is good for your health, and particularly the liver," says Carlo La Vecchia, study author from the department of epidemiology, Istituto di Ricerche Farmacologiche Mario Negri. "The favorable effect of coffee on liver cancer might be mediated by coffee’s proven prevention of diabetes, a known risk factor for the disease, or for its beneficial effects on cirrhosis and liver enzymes."

Read more: http://www.laboratoryequipment.com/news/2013/10/coffee-reduces-risk-liver-cancer

Cancer checkpoint
Mitochondrial metabolic regulator SIRT4 guards against DNA damage
Healthy cells don’t just happen. As they grow and divide, they need checks and balances to ensure they function properly while adapting to changing conditions around them.
Researchers studying a set of proteins that regulate physiology, caloric restriction and aging have discovered another important role that one of them plays. SIRT4, one of seven sirtuin proteins, is known for controlling fuel usage from its post in the mitochondria, the cell’s energy source. It responds to stressful changes in the availability of nutrients for the cell.
New research reveals that SIRT4 is also extremely sensitive to a different form of stress: DNA damage. This unsuspected response by the metabolic checkpoint means SIRT4 doubles as a sentry guarding against cancer, which is spurred by genetic abnormalities.
Sirtuins have become familiar for their connection to longevity and to resveratrol, the red-wine compound that activates SIRT1, but less attention has been focused on SIRT3, SIRT 4 and SIRT5, all of which are found in mitochondria. Marcia Haigis, HMS associate professor of cell biology, led a team that has uncovered SIRT4 as an important player in the DNA damage response pathway, coordinating a sequence of events that normally result[s] in tumor suppression. They published their results April 4 in Cancer Cell.
"When we started studying SIRT4, we were focused only on its metabolic role, looking for functions related to diabetes and obesity," said Haigis. "What we found, to our surprise, was that SIRT4 was responsive to DNA damage, so that led us to investigate the metabolic response to DNA damage and how SIRT4 controls the metabolic response to genotoxic stress."
To see how SIRT4 normally functions, Haigis and her colleagues induced DNA damage by exposing cells in a lab dish to ultraviolet light. This damage triggered a halt in glutamine metabolism, limiting the amount of nutrients the cell could use as it goes through a cycle of division and growth.
Blocking the cell cycle at this juncture is important. If cell growth after DNA damage goes unchecked, proliferation of impaired cells can lead to cancer. When SIRT4 works properly, this chain of events is broken before bad cells and their abnormal genes multiply. SIRT4 blocks glutamine metabolism, arrests the cell cycle and suppresses tumor formation.
The scientists tested this SIRT4 response in mice. Bred to lack the gene that encodes the SIRT4 protein but otherwise normal, the mice spontaneously developed lung cancer by 15 months.
"When SIRT4 is missing, you don’t have this metabolic checkpoint involving glutamine, which is important because glutamine is an amino acid required for proliferation in the cell," Haigis said. "Without SIRT4, the cell keeps dividing even in the face of DNA damage, so the cell accumulates more damage."
The scientists also analyzed data showing SIRT4 gene expression levels are low in several human cancers, including small-cell lung carcinoma, gastric cancer, bladder carcinoma, breast cancer and leukemia.
While they cannot say if SIRT4 loss alone will initiate cancer, its absence appears to create an environment in which tumor cells survive and grow.
"Our findings suggest that SIRT4 may be a potential target against tumors," they conclude.
A healthy mitochondrion contains the metabolic regulator SIRT4, which responds to DNA damage and other stress. (Credit: National Institute on Aging)

Cancer checkpoint

Mitochondrial metabolic regulator SIRT4 guards against DNA damage

Healthy cells don’t just happen. As they grow and divide, they need checks and balances to ensure they function properly while adapting to changing conditions around them.

Researchers studying a set of proteins that regulate physiology, caloric restriction and aging have discovered another important role that one of them plays. SIRT4, one of seven sirtuin proteins, is known for controlling fuel usage from its post in the mitochondria, the cell’s energy source. It responds to stressful changes in the availability of nutrients for the cell.

New research reveals that SIRT4 is also extremely sensitive to a different form of stress: DNA damage. This unsuspected response by the metabolic checkpoint means SIRT4 doubles as a sentry guarding against cancer, which is spurred by genetic abnormalities.

Sirtuins have become familiar for their connection to longevity and to resveratrol, the red-wine compound that activates SIRT1, but less attention has been focused on SIRT3, SIRT 4 and SIRT5, all of which are found in mitochondria. Marcia Haigis, HMS associate professor of cell biology, led a team that has uncovered SIRT4 as an important player in the DNA damage response pathway, coordinating a sequence of events that normally result[s] in tumor suppression. They published their results April 4 in Cancer Cell.

"When we started studying SIRT4, we were focused only on its metabolic role, looking for functions related to diabetes and obesity," said Haigis. "What we found, to our surprise, was that SIRT4 was responsive to DNA damage, so that led us to investigate the metabolic response to DNA damage and how SIRT4 controls the metabolic response to genotoxic stress."

To see how SIRT4 normally functions, Haigis and her colleagues induced DNA damage by exposing cells in a lab dish to ultraviolet light. This damage triggered a halt in glutamine metabolism, limiting the amount of nutrients the cell could use as it goes through a cycle of division and growth.

Blocking the cell cycle at this juncture is important. If cell growth after DNA damage goes unchecked, proliferation of impaired cells can lead to cancer. When SIRT4 works properly, this chain of events is broken before bad cells and their abnormal genes multiply. SIRT4 blocks glutamine metabolism, arrests the cell cycle and suppresses tumor formation.

The scientists tested this SIRT4 response in mice. Bred to lack the gene that encodes the SIRT4 protein but otherwise normal, the mice spontaneously developed lung cancer by 15 months.

"When SIRT4 is missing, you don’t have this metabolic checkpoint involving glutamine, which is important because glutamine is an amino acid required for proliferation in the cell," Haigis said. "Without SIRT4, the cell keeps dividing even in the face of DNA damage, so the cell accumulates more damage."

The scientists also analyzed data showing SIRT4 gene expression levels are low in several human cancers, including small-cell lung carcinoma, gastric cancer, bladder carcinoma, breast cancer and leukemia.

While they cannot say if SIRT4 loss alone will initiate cancer, its absence appears to create an environment in which tumor cells survive and grow.

"Our findings suggest that SIRT4 may be a potential target against tumors," they conclude.

A healthy mitochondrion contains the metabolic regulator SIRT4, which responds to DNA damage and other stress. (Credit: National Institute on Aging)

Lung Cancer Cell Dividing

This is a scanning electron micrograph (STEM), coloured by Steve Gscheissner, of a lung cancer cell dividing. The two daughter cells remain temporarily joined at the cytoplasmic bridge.

positive-press-daily:

Cancer-killing cells grown by Japanese scientists in major breakthrough; the white blood cell known as a cytotoxic T-cell is produced in small numbers in the body and could be reinjected to fight off cancer

Cancer-killing cells have been grown in a lab by Japanese researchers, possibly a major breakthrough in treatments for the illness.

The white blood cell known as a cytotoxic T-cell is produced in small numbers in the body and could possibly be reinjected to fight off cancer. Researchers at the RIKEN Research Centre for Allergy and Immunology were able to grow the cells in the lab and hope then to put them into a patient to bolster the immune system.

Prior research into creating the killer T lymphocytes has been fruitless. Previous efforts have not been able to create long-lasting cells, which has limited their use as an effective treatment.

The Daily Mail reported that the new research takes these cytotoxic (killer - in a good way) immune cells and uses a technique called “induced pluripotent stem-cell” to make them grow and divide. These cells then can revert back to their original form after becoming stem cells (which can multiply) but in much larger numbers.

BBC reported that so far the scientists have only been able to create these cells. It is still unclear whether the cells can be reinjected or if they will attack the right diseased cells.

“The next step will be to test whether these T-cells can selectively kill tumour cells, but not other cells in the body,” said study co-author Hiroshi Kawamoto, according to BBC.

“If they do, these cells might be directly injected into patients for therapy. This could be realized in the not-so-distant future.”

The findings were published in the journal Cell Stem Cell.

(via exclusively-positive-press)

brilliantbotany:

Merry Christmas!

Did you know that mistletoe extract has the potential to treat cancer? According to a study in 1999, mistletoe extract increased immune system activities in cell cultures, which could be beneficial to cancer patients (Hajto, Pharmacological Effects of Mistletoe Therapy, Clinical Toxicology, 1999). This was only a study, however, and much more research would be required to perfect a treatment. More recent studies have found that mistletoe extract induces apoptosis (cell death) in melanoma cells (Struh, A Novel Tripetertene Extract from Mistletoe Induces Rapid Apoptsosis in Murine B16.F10 Melanoma Cells, Phytotheraphy Research, 2012). This is because chemicals in the extract encourage cells to produce more cytokines, which help with immune response. [x]