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Posts tagged "cancer"
How Breast Cancer Genes Work →

Though we may talk of cancer as one disease, it is really many diseases wrapped up under one name. Skin cancer has little in common with pancreatic cancer and breast cancer is something else entirely.

But even breast cancers can differ. The tumor of a woman diagnosed with breast cancer at age 30 is likely very different from that of a woman whose cancer is detected when she is 65. And the causes of their cancers probably vary as well. One may derive from, say, an environmental exposure and the other from an inherited gene mutation. Even two women with the same cancer gene mutation—such as the 185delAG mutation of BRCA1 found in the Hispanic women featured in “The Secret of San Luis Valley”—may experience very different cancers, or no cancer at all.

Women who inherit a mutation in one of the two most common breast cancer genes—BRCA1 or BRCA2—have a 36 percent to 85 percent chance of developing breast cancer during their lives, and they also have a higher risk of developing ovarian and a few other cancers, according to the National Cancer Institute. (Men have an increased risk of developing breast and, possibly, prostate cancers.) By comparison, the average U.S. woman has a 13.2 percent chance of developing breast cancer. Why do these BRCA mutations increase cancer risk?

All cancers are characterized by uncontrolled cell division. These rampantly growing cells usually clump into tumors, though some cells can break free of the tumor and go on to seed more cancers elsewhere in the body (what is known as metastasis). BRCA1 and BRCA2 belong to a class of genes called tumor suppressor genes keep cell division under control. These tumor suppressor genes have many types; BRCA1 and BRCA2 work by repairing damaged DNA.

In their normal state, the BRCA genes produce proteins that piece together breaks in double-stranded DNA that can occur as the DNA is replicated during cell division. Breaks in DNA can cause mutations in other genes. (Cells also produce a host of other proteins that fix mutations caused by sources such as radiation and environmental exposures.)

Scientists have discovered hundreds of different mutations in the BRCA genes—185delAG is just one—but nearly all have the same effect of inactivating the gene. Left with only one copy of the normal gene (or none, in the case of people who inherit two copies of a BRCA gene), the cell cannot fix all the mistakes that occur, so the DNA slowly accumulates mutations. If enough of the wrong genes become mutated, cancer can develop.

According to the National Cancer Institute, Women who have a mutation in one of the BRCA genes can reduce their risk of developing cancer through prophylactic surgery—removal of the breasts, fallopian tubes or ovaries. However, the tissue left may still develop cancer, or cancer may develop in one of the other organs associated with these genes (such as the pancreas). Unfortunately, the mutations in the BRCA genes cannot be repaired.

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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)

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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.

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.

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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.

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.

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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]

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]

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laboratoryequipment: Fungus Has Cancer-Fighting PowerArthrobotrys oligospora doesn’t live a charmed life; it survives on a diet of roundworm.But a discovery by a team led by Mingjun Zhang, an associate professor of biomedical engineering at the Univ. of Tennessee, Knoxville, could give the fungus’s life more purpose—as a cancer fighter. Zhang and his team have discovered that nanoparticles produced by A. oligospora hold promise for stimulating the immune system and killing tumors.Read more: http://www.laboratoryequipment.com/news/2012/12/fungus-has-cancer-fighting-power

laboratoryequipment:

Fungus Has Cancer-Fighting Power

Arthrobotrys oligospora doesn’t live a charmed life; it survives on a diet of roundworm.

But a discovery by a team led by Mingjun Zhang, an associate professor of biomedical engineering at the Univ. of Tennessee, Knoxville, could give the fungus’s life more purpose—as a cancer fighter. Zhang and his team have discovered that nanoparticles produced by A. oligospora hold promise for stimulating the immune system and killing tumors.

Read more: http://www.laboratoryequipment.com/news/2012/12/fungus-has-cancer-fighting-power

(via ikenbot)

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Leukemia-Killing Plasma Beam Could Offer New Cancer Treatments Patients battling the blood cancer leukemia could one day receive a new type of treatment that uses a plasma — a gas of electrically charged particles — to kill cancer cells while keeping the healthy cells intact, according to new research. “We have a really amazing device,” said Mounir Laroussi, director of the laser and plasma engineering institute at Old Dominion University in Norfolk, Va., “We can generate a beam of plasma that is around room temperature. It doesn’t burn anything; it doesn’t destroy or poke holes. You can touch it with your hand.” After 10 minutes of treatment with the cold-plasma blowtorch, over 90 percent of leukemia cells were destroyed, according to the study published by Laroussi and research scientist Nazir Barekzi in October in the Journal of Physics D: Applied Physics.

Leukemia-Killing Plasma Beam Could Offer New Cancer Treatments

Patients battling the blood cancer leukemia could one day receive a new type of treatment that uses a plasma — a gas of electrically charged particles — to kill cancer cells while keeping the healthy cells intact, according to new research.

“We have a really amazing device,” said Mounir Laroussi, director of the laser and plasma engineering institute at Old Dominion University in Norfolk, Va., “We can generate a beam of plasma that is around room temperature. It doesn’t burn anything; it doesn’t destroy or poke holes. You can touch it with your hand.”

After 10 minutes of treatment with the cold-plasma blowtorch, over 90 percent of leukemia cells were destroyed, according to the study published by Laroussi and research scientist Nazir Barekzi in October in the Journal of Physics D: Applied Physics.

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biocanvas: A growing fibrosarcoma tumor in mouse skin triggers neoangiogenesis, the generation of new blood vessels that supply the tumor with nourishment. Tumor cells are labeled yellow and red, blood vessels are in green, and collagen fibers are in blue. Image by Stephanie Alexander and Peter Friedl, University of Texas, MD Anderson Cancer Center.

biocanvas:

A growing fibrosarcoma tumor in mouse skin triggers neoangiogenesis, the generation of new blood vessels that supply the tumor with nourishment. Tumor cells are labeled yellow and red, blood vessels are in green, and collagen fibers are in blue.

Image by Stephanie Alexander and Peter Friedl, University of Texas, MD Anderson Cancer Center.

(via ikenbot)

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biocanvas: A growing fibrosarcoma tumor in mouse skin triggers neoangiogenesis, the generation of new blood vessels that supply the tumor with nourishment. Tumor cells are labeled yellow and red, blood vessels are in green, and collagen fibers are in blue. Image by Stephanie Alexander and Peter Friedl, University of Texas, MD Anderson Cancer Center.

biocanvas:

A growing fibrosarcoma tumor in mouse skin triggers neoangiogenesis, the generation of new blood vessels that supply the tumor with nourishment. Tumor cells are labeled yellow and red, blood vessels are in green, and collagen fibers are in blue.

Image by Stephanie Alexander and Peter Friedl, University of Texas, MD Anderson Cancer Center.

(via ikenbot)

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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)

(via ikenbot)

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biocanvas: A HeLa cell dividing on a fibronectin micropattern at 100-times magnification. Image by Dr. Manuel Thery, CEA Grenoble.

biocanvas:

A HeLa cell dividing on a fibronectin micropattern at 100-times magnification.

Image by Dr. Manuel Thery, CEA Grenoble.

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8bitfuture: KickStarter campaign hopes to fund an anti-cancer virus. The campaign is hoping to raise US$1,000,000 to fund the development of potential treatment for neuroendocrine tumours, or NET - the same cancer that killed Steve Jobs. The potential therapy, a cancer-busting virus, is currently sitting in a freezer in Sweden – but it can’t be tested for lack of just £2million. Without the money, the research will cease and the virus will be thrown away, placing in jeopardy a therapy that could significantly extend the lives of thousands of NET cancer sufferers. Big business won’t stump up the £2million needed to fund the first stage of clinical trials, because there is no money to be made. The Swedish research team, led by Prof Magnus Essand from Uppsala University, were so keen to collaborate and share the findings they published the research. But now it is out in the public domain it can’t be protected by the patent that would have enabled business backers to make a profit. We want to raise enough money to enable Prof Essand and his team to conduct clinical trials on their groundbreaking cancer eating virus. £1 million will enable him to do it - £2 million will enable him to do it really well. Check out the campaign here.

8bitfuture:

KickStarter campaign hopes to fund an anti-cancer virus.

The campaign is hoping to raise US$1,000,000 to fund the development of potential treatment for neuroendocrine tumours, or NET - the same cancer that killed Steve Jobs.

The potential therapy, a cancer-busting virus, is currently sitting in a freezer in Sweden – but it can’t be tested for lack of just £2million.

Without the money, the research will cease and the virus will be thrown away, placing in jeopardy a therapy that could significantly extend the lives of thousands of NET cancer sufferers.

Big business won’t stump up the £2million needed to fund the first stage of clinical trials, because there is no money to be made. The Swedish research team, led by Prof Magnus Essand from Uppsala University, were so keen to collaborate and share the findings they published the research.

But now it is out in the public domain it can’t be protected by the patent that would have enabled business backers to make a profit.

We want to raise enough money to enable Prof Essand and his team to conduct clinical trials on their groundbreaking cancer eating virus. £1 million will enable him to do it - £2 million will enable him to do it really well.

Check out the campaign here.

(via 8bitfuture)

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seeinnovation: A team of scientists has developed a simple electronic device that detects a prostate cancer biomarker—prostate-specific membrane antigen (PSMA)—in biological relevant fluids. The device contains an array of nanowires composed of PSMA-binding viruses embedded inside a conducting polymer. This technology offers an excellent opportunity to create an in-home detection system for prostate cancer markers with the hopes that lives will be saved by continual monitoring and early detection. Here you see hybrid nanowire with diagram of nanowire preparation. Image credit: Reginald M. Penner and Ruqian Yu, UC Irvine

seeinnovation:

A team of scientists has developed a simple electronic device that detects a prostate cancer biomarker—prostate-specific membrane antigen (PSMA)—in biological relevant fluids. The device contains an array of nanowires composed of PSMA-binding viruses embedded inside a conducting polymer. This technology offers an excellent opportunity to create an in-home detection system for prostate cancer markers with the hopes that lives will be saved by continual monitoring and early detection. Here you see hybrid nanowire with diagram of nanowire preparation. Image credit: Reginald M. Penner and Ruqian Yu, UC Irvine

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fuckyeahmolecularbiology:

Rogue Response: Chemotherapy Undermines Itself

A new study, published in Nature Medicine, has suggested that chemotherapy used to treat metastatic cancers can cause a rogue response in healthy cells, which helps to explain why people become resistant to the treatment. Chemotherapy has been shown to lose effectiveness in a large number of patients (approximately 90%) with secondary cancers - those that started out as solid cancers in areas such as the breast, lung, and colon, and metastasised, or spread to a different area of the body. The new research shows that the cause of this resistance could be hidden in fibroblasts - wound-healing cells around tumours discovered to create a protein that may teach the cancerous cells how to evade the treatment.

Researchers at the Fred Hutchinson Cancer Research Center in Seattle looked at the damage chemotherapy was causing to the fibroblast cells surrounding tumours. Because the radiation caused DNA damage, the fibroblasts produced up to 30 times more of a specific protein, Wnt16B, than they should. The protein fuels cancer cells to invade and attack surrounding tissues and evade chemotherapy treatments.

It was already known that Wnt16B was involved in the development of cancers, but not in treatment resistance. The researchers hope they can put a stop to the protein response, and greatly improve the effectiveness of chemotherapy, especially for those patients with multiple cancers. 

Professor Fran Balkwill, a Cancer Research UK expert on the microenvironment around tumours, said: “This work fits with other research showing that cancer treatments don’t just affect cancer cells, but can also target cells in and around tumours. Sometimes this can be good - for instance, chemotherapy can stimulate surrounding, healthy immune cells to attack tumours. But this work confirms that having healthy cells around the tumour can help the tumour become resistant to treatment. 

“The next step is to find ways to target these resistance mechanisms to help make chemotherapy more effective.”

Top image: A human fibroblast cell. Bottom image: Mouse fibroblast cells.

The original paper was published in Nature Medicine. A brief synopsis, and link to the full paper, can be found here.

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sciencenote: HeLa Cervical Carcinoma Cells Labeled with Alexa Fluor Dyes and TO-PRO-3 Immunofluorescence with mouse anti-alpha-tubulin was employed to visualize details of the microtubule network in a log phase monolayer culture of HeLa adenocarcinoma cells. The secondary antibody (goat anti-mouse IgG) was conjugated to Alexa Fluor 488 and mixed with Alexa Fluor 546 conjugated to phalloidin to simultaneously image tubulin and the actin cytoskeleton. Nuclei were counterstained with TO-PRO-3, a carbocyanine monomer with long-wavelength red fluorescence.

sciencenote:

HeLa Cervical Carcinoma Cells Labeled with Alexa Fluor Dyes and TO-PRO-3

Immunofluorescence with mouse anti-alpha-tubulin was employed to visualize details of the microtubule network in a log phase monolayer culture of HeLa adenocarcinoma cells. The secondary antibody (goat anti-mouse IgG) was conjugated to Alexa Fluor 488 and mixed with Alexa Fluor 546 conjugated to phalloidin to simultaneously image tubulin and the actin cytoskeleton. Nuclei were counterstained with TO-PRO-3, a carbocyanine monomer with long-wavelength red fluorescence.

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