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Killing Cancer by changing body pH from acidic to neutral or basic

 DIY Cancer treatment....baking soda or apple cider vinegar

Killing Cancer by changing body PH from acidic back to neutral or basic with sodium bicarbinate
or baking soda....old wive's tale confirmed by scientists at Cancer Center.

 

Tumor cells engineer acidity to drive cell invasion, Moffitt Cancer Center
researchers say

Using buffers to increase pH may inhibit cancer growth

Researchers at Moffitt Cancer Center and colleagues at Wayne State University School of Medicine investigated the acidity in solid tumors to determine if pH levels play a role in cancer cell
invasion in surrounding tissues. They found that an acidic microenvironment can
drive cancer cells to spread and propose that neutralizing pH would inhibit
further invasion, providing a therapeutic opportunity to slow the progression
of cancers.

Their study appeared in the Jan. 3 online release of Cancer Research, a publication of the
American Association for Cancer Research.

According to the study's corresponding author, Robert J. Gillies, Ph.D., chair of the Department of
Cancer Imaging & Metabolism at Moffitt, acidity in solid tumors is theresult of an increased fermentative metabolism combined with poor delivery of blood to tissues.

In this study, tumor invasion and pH were monitored in immunodeficient laboratory mice hosting a
variety of tumors. "We monitored the test animals over time using
microscopy and found that the highest regions of tumor invasion corresponded to
areas with the lowest pH," Gillies explained. "Tumor invasion did not
occur in regions with normal or near normal pH levels. Furthermore, when we neutralized the acidity with oral sodium bicarbonate, the invasion was halted."

Researchers proposedthat the acidic pH of the tumor microenvironment represents a "niche
engineering" strategy on the part of tumor cells, promoting invasion and
growth of malignant tumors into surrounding tissue. Niche engineering is a
concept in ecology describes how plants and animals alter their environment to
in ways that promote their own growth and survival over their competitors.
"We have long regarded cancers cells as an invading species," said study co-author Robert Gatenby, M.D., chair of the Diagnostic Imaging Services and Integrated Mathematical Oncology departments at
Moffitt.

A key to this process of adaptation and invasion is increased glucose metabolism in
the tumor. "The vast majority of malignant tumors metabolize glucose at
high rates," Gillies said. "We have proposed that there is a direct,
causative link between increased glucose metabolism and the ability of cancer
cells to invade and metastasize."

According to the research, elevated glucose metabolism is the cause of increased acidity in the
tumor microenvironment. Most tumors develop an abnormal vascular network that
tends to be poorly organized and leaky, disrupting blood flow and hampering the
delivery of oxygen.

"This poorly organized vascular system has a two-fold effect on tumor acidity,"
explained Gatenby. "First, it subjects tumor regions to poor perfusion,
which restricts oxygen and increases the rate of glucose fermentation. Second,
the poor perfusion hampers the ability to eliminate the resulting acids,
resulting in very low pH in surrounding tissues."

As tumor cells adapt to increasing acidity, niche engineering through normal cell death and new blood
vessel formation occurs in the tumor and the immune response is suppressed.

"Tumor cells perform niche engineering by creating an acidic environment that is not toxic to
the malignant cells but, through its negative effects on normal cells and
tissues, promotes local invasion of malignant cells," Gatenby said.

The researchers suggested that targeting this activity with buffers and other mechanisms aimed
at increasing pH levels will likely provide a valuable alternative to
traditional therapies focused entirely on killing tumor cells.

###

Funding for this study came from federal grants U54 CA143970; R01 CA 077575; R01 CA 131990S.

About Moffitt Cancer Center

Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's excellence in research, its contributions
to clinical trials, prevention and cancer control. Since 1999, Moffitt has been
listed in U.S. News & World Report as one of "America's Best Hospitals" for
cancer. With more than 4,200 employees, Moffitt has an economic impact on the
state of nearly $2 billion. For more information, visit MOFFITT.org, and follow
the Moffitt momentum on Facebook, twitter and YouTube.

Media release by Florida
Science Communications

Public release date: 25-Jan-2013

http://www.eurekalert.org/pub_releases/2013-01/hlmc-tce012413.php



Contact: Kim Polacek

kim.polacek@moffitt.org

813-745-7408

H. Lee Moffitt Cancer Center &
Research Institute

 

 http://www.eurekalert.org/pub_releases/2013-01/hlmc-tce012413.php

Russian Academy of Sciences (RAS) confirms Ukrainian breakthrough in Alzheimer's treatment with Hydrated Fullerenes or C60-HYFNs or Water Soluble Buckyballs

Russian Academy of Sciences confirms Ukrainian break-though in treating Alzheimer’s
with Carbon 60 or C-60 or hydrated fullerenes (C60HYFns) or Buckeyballs. 

After the discovery of C-60 in 1985 and the awarding of the Nobel prize in 1995 to Kroto, Smalley and Curl, Ukrainian scientists, then discovered a way to make Carbon 60 or C-60 or fullerenes or buckeyballs water soluble about 15 years ago, have made progress on the Alzheimer’s front
treating it with Fullerene Water Solution (FWS) and with conventional treatment.
This was approved as a “dietary supplement” by the Ukrainian Ministry of Health
in 2010, and just several weeks ago they started producing a water drink in
Ukraine with .0002mg/100ml of C-60.

Walter  Derzko

WATER  SOLUBLE C60 FOR DEVELOPING ALZHEIMER'S DISEASE  TREATMENT

I.Ya.Podolskiy1) E.G.Makarova 1) R.Ya.Gordon2) V.V.Vorobev2) L.G.Bobyleva 1) A.G.Bobylev1)
Z.A.Podlubnaya1) , A.B.Geht3) O.A.Mishulina4)


1) Institute of Theoretical and Experimental Biophysics, Pushchino
2) Institute of Cell Biophysics, Pushchino
3) The Russian State Medical University, Moscow
4) National Research Nuclear University MEPI, Moscow


Creation of drugs for the  prevention and treatment of Alzheimer's disease (AD) is the most important
challenge to biomedical research in the XXI century. Synthesis of water-soluble
fullerenes and carbon nanotubes opened a new direction for drug development,
which is growing rapidly in the U.S., Europe and Asia.

* Rationale. One key element in the pathogenesis of Alzheimer's disease is increased formation of aggregated forms in the brain of amyloid β-peptide (1-42) (Aβ1-42). Create antiamiloid drugs is
the main thrust of development of asthma therapy.

^ The project aims to investigate the properties of stable antiamiloidn molecular colloidal aqueous
solution of fullerene C60HyFn.

Results. By transmission electron microscopy in vitro for the first time on a visual level, it was shown that
water-soluble C60 prevent and destroy the beta-amyloid. These findings led to
the conclusion that the fullerene in vitro anti-aggregation has a strong effect
on the β-amyloid peptides. Microinjection C60HyFn (0.46 nmol / μl) into the
hippocampus significantly reduced β-amyloid deposits in the pyramidal neurons of
hippocampal CA1 neurons and warned neurodegeneration. Fluorescence microscopy of
hippocampal pyramidal neurons with acridine orange and microfluoremetric
analysis will provide quantitative data on the restoration protein synthesizing
activity of pyramidal neurons in the hippocampus, impaired Aβ. Microinjection
C60HyFn (0.46 nmol/1μl) to prevent violations of spatial memory, due to the
introduction of the hippocampus Aβ1-42 (1.6 nmol / μl). On surviving hippocampal
slices fullerene increases the activity of pyramidal neurons in rats modified
EEG frontal cortex, impaired Aβ1-42.

Conclusion. Functionalized C60 direction slowly act on one of the key molecular targets of Alzheimer's disease, aggregated amyloid β-peptides, and are of great interest for the development of
Alzheimer's disease therapy. We assume that in the first half of the XXI century
will be based on fullerenes developed an effective prevention and treatment of
Alzheimer's disease.

This work was supported by a grant of the Presidium of RAS "basic sciences Medicine" and the state contract the Ministry of Higher Education and Science of the Russian Federation №
P1052.

http://rudocs.exdat.com/docs/index-417897.html?page=47

More in Russian

http://www.c60water.com/index.php?option=com_content&view=article&id=9&Itemid=33

Ukrainian scientists, who discovered a way to make Carbon 60 or C-60 or fullerenes or buckeyballs
water soluble about 15 years ago, have made progress on the Alzheimer’s front
treating it with Fullerene Water Solution (FWS) and with conventional treatment.
This was approved as a “dietary supplement” by the Ukrainian Ministry of Health
in 2010, and just several weeks ago they started producing a water drink in
Ukraine with .0002mg/100ml of C-60.

Below is a very rough
Google Translation from the Russian original.

Obviously, this
research is not on the radar of most western
researchers.

Walter
Derzko

http://www.c60water.com/index.php?option=com_content&view=article&id=9&Itemid=33

One of the diseases elderly is Alzheimer's disease or senile dementia.
More common after
sixty, but sick and young people. The disease is characterized by a steady
deterioration of memory until the complete disintegration of the personality.
Already in the beginning of the disease, recognizing the gradual loss of memory,
a person experiences great emotionally shaken. This neurodegenerative disease
affects more than thirty million people. Nicholas Sparks romantic drama "The
Notebook" and the same film shows the tragedy of close people who are sick of
this terrible disease.
Unfortunately, at present, has not yet found drugs
that can stop or reverse the development of cause neurodegenerative process.
Search for drugs for the treatment of this disease are engaged in the world. The
Institute of
Theoretical and
Experimental Biophysics studies in experimental models of Alzheimer's disease
are conducted under the direction of Igor Jakovljevic Podolsky. In 2007, he
first discovered the neuroprotective properties of water molecules with the most
beautiful. His work, published in January 2012, revealed the influence of
fullerene water very cause of the neurodegenerative process of memory
loss.
Alzheimer's disease is
associated with a decrease in the water content in the brain and increased
formation of amyloid protein (beta-amyloid peptide Aβ1-42). The threads of this
protein like vines entwine the neurons of the brain, disrupting their work and
worsening memory. In November 2011, Podolsky reported to the Presidium of RAS
results of their work done in accordance with the program "Fundamental science -
medicine." It was shown that the water has a fullerene antiamiloidnymi
properties. Microinjection of water prevents the formation of amyloid by
fullerene and destroyed "threads" of amyloid protein. This led to a reduction of
neurodegenerative changes in the brain of rats and restore lost
memory.
Interview with Igor Yakovlevich under "great discovery" was broadcast
on Channel One Russian TV from 18 to 23 March 2012.

The obtained results
allow us to begin clinical studies of fullerene water as a means for the
treatment and prevention of Alzheimer's disease. It is assumed that patients
will spray water fullerene as a spray in the nasal passages and to drink a
certain pattern.
Increased production of amyloid protein is the cause of not
only Alzheimer's disease. In addition to degenerative changes in the brain, it
can cause malfunction of other organs such as the pancreas, which is considered
as a possible cause of diabetes type. Amyloid proteins provoke the development
of many serious human diseases, the methods of treatment which at the moment
does not exist.
The Institute of Theoretical and Experimental Biophysics of
amyloidosis research conducted by Professor Zoya Alexandrovna Podlubnaya. Her
studies show that water prevents the formation of fullerene and destroying
amyloids in striated muscle. Antiamiloidnye fullerene properties of water can
allow the creation of new drugs for the treatment of previously incurable
diseases. This stimulates interest in studying biomedical properties of
fullerene water in many research centers. 

Oxygen Chamber Can Boost Brain Repair

Wednesday, January 23, 2013

Hyperbaric treatment has significantly resuscitated activity in damaged brains, TAU researchers find

Stroke, traumatic injury, and metabolic disorder are major causes of brain damage and permanent disabilities, including motor dysfunction, psychological disorders, memory loss, and more. Current therapy and rehab programs aim to help patients heal, but they often have limited success.

Now Dr. Shai Efrati of Tel Aviv University's Sackler Faculty of Medicine has found a way to restore a significant amount of neurological function in brain tissue thought to be chronically damaged — even years after initial injury. Theorizing that high levels of oxygen could reinvigorate dormant neurons, Dr. Efrati and his fellow researchers, including Prof. Eshel Ben-Jacob of TAU's School of Physics and Astronomy and the Sagol School of Neuroscience, recruited post-stroke patients for hyperbaric oxygen therapy (HBOT) — sessions in high pressure chambers that contain oxygen-rich air — which increases oxygen levels in the body tenfold.

Analysis of brain imaging showed significantly increased neuronal activity after a two-month period of HBOT treatment compared to control periods of non-treatment, reported Dr. Efrati in PLoS ONE. Patients experienced improvements such as a reversal of paralysis, increased sensation, and renewed use of language. These changes can make a world of difference in daily life, helping patients recover their independence and complete tasks such as bathing, cooking, climbing stairs, or reading a book.

Oxygen breathes new life into neurons

According to Dr. Efrati, there are several degrees of brain injury. Neurons impacted by metabolic dysfunction have the energy to stay alive, but not enough to fire electric signals, he explains. HBOT aims to increase the supply of energy to these cells.

The brain consumes 20 percent of the body's oxygen, but that is only enough oxygen to operate five to ten percent of neurons at any one time. The regeneration process requires much more energy. The tenfold increase in oxygen levels during HBOT treatment supplies the necessary energy for rebuilding neuronal connections and stimulating inactive neurons to facilitate the healing process, explains Dr. Efrati.

For their study, the researchers sought post stroke patients whose condition was no longer improving. To assess the potential impact of HBOT treatment, the anatomical features and functionality of the brain were evaluated using a combination of CT scans to identify necrotic tissue, and SPECT scans to determine the metabolic activity level of the neurons surrounding damaged areas.

Seventy-four participants spanning 6 to 36 months post-stroke were divided into two groups. The first treatment group received HBOT from the beginning of the study, and the second received no treatment for two months, then received a two-month period of HBOT treatment. Treatment consisted of 40 two-hour sessions five times weekly in high pressure chambers containing oxygen-rich air. The results indicate that HBOT treatment can lead to significant improvement in brain function in post stroke patients even at chronically late stages, helping neurons strengthen and build new connections in damaged regions.

A potential avenue for prevention

Although the study focuses on patients only through three years post-stroke, Dr. Efrati has seen similar improvement in patients whose brain injuries occurred up to 20 years before, belying the concept that the brain has a limited window for growth and change. "The findings challenge the leading paradigm since they demonstrate beyond any doubt that neuroplasticity can still be activated for months and years after acute brain injury, thus revealing that many aspects of the brain remain plastic into adulthood," says Prof. Ben-Jacob.

This study also "opens the gate into a new territory of treatment," adds Dr. Efrati. The researchers are currently conducting a study on the benefits of HBOT for those with traumatic brain injury. This treatment also has potential as an anti-aging therapy, applicable in other disorders such as Alzheimer's disease and vascular dementia at their early stages.

"It is now understood that many brain disorders are related to inefficient energy supply to the brain," explains Dr. Efrati. "HBOT treatment could right such metabolic abnormalities before the onset of full dementia, where there is still potential for recovery."

---

For more neuroscience news from Tel Aviv University, click here.

Keep up with the latest AFTAU news on Twitter: http://www.twitter.com/AFTAUnews.

 

Massive animals may hold secrets of cancer suppression-Peto’s paradox

Theory suggests trade-off between cancer risk and reproductive potential.

• Virginia
       Gewin

21 January 2013

 

Large animals such as humpback whales may have evolved cancer-fighting mechanisms that smaller
animals lack — but one flip-side could be lower rates of reproduction.

Sue Flood / naturepl.com

 

If every living cell had an equal chance of becoming cancerous, whales and elephants should have a
greater risk of developing cancer than do humans or mice. But across species,
the occurrence of cancer does not show a correlation with body mass. According
to a new model, the paradox could be explained if animals were striking a
balance between reducing cancer risk and other priorities, such as maximising
the number of offspring.

 

The lack of correlation between body mass and cancer risk is known as Peto’s paradox, after epidemiologist Richard Peto of Oxford University in the UK, who noted it in the 1970s.
Evolutionary biologists think that it results from larger animals using
protective mechanisms that many smaller animals do not¹.

In an attempt to identify how greater body mass might foster such mechanisms, evolutionary biologist Benjamin Roche at the Institute of Research for Development in Montpellier, France, and
his colleagues created a theoretical model to simulate which of 100 possible
genetic-mutation strategies would become most prevalent over 4,000 generations.

The model included two gene types: proto-oncogenes, which can cause normal cells to become cancerous, and tumour-suppressor genes, which repair cellular damage that could otherwise lead
to cancer. For carcinogenesis to occur, the team assumed that proto-oncogenes
must be activated and tumour-suppressor genes must be rendered inactive.

“We found that tumour-suppressor genes and proto-oncogenes react differently along a gradient of body masses,” says Roche. “Their evolutionary dynamics are linked.” Proto-oncogene activation
decreased steadily with increasing body mass, the team found.

Cost–benefit ratio

In their model, evolution did not
always favour tumour-suppressor genes. Although these mechanisms could reduce
cancer mortality in any animal, they may come at a cost — reduced fertility, in
the case of the team's model. The result was that for intermediate-sized
animals, the evolutionary cost of having many tumour suppressor genes was
greater than the benefits of cancer protection they offered.

As a consequence, mutations would arise to keep tumour-suppressors in check.
“At this point, it is better for the population, evolutionarily, to tolerate
more deaths from cancer rather than investing in more costly mechanisms to
avoid cancer development,” says Roche.

The results, published in a special issue of Evolutionary Applications focused on cancer biology², could explain why, for example, the incidence of
cancer in humans stands at one in three, whereas it is only 18% in beluga whales³.

Roche and colleagues' is not the
only proposed explanation for Peto’s paradox. “There are a number of different
hypotheses,” says Carlo Maley, director of the Center for Evolution and Cancer
at the University of California, San
  Francisco. “For example, rather than body mass
influencing the number of tumour suppressors and oncogenes, maybe there are
less reactive oxygen species in larger organisms due to their lower metabolic
rate."

Maley and his colleagues are
sequencing the humpback whale genome, which they plan to compare with others,
including the elephant genome, to determine which hypotheses might be valid —
and whether nature has already come up with cancer-prevention mechanisms that
could be translated to the clinic.

Still, some biologists question
whether there is a paradox at all, saying that variations in cancer rates
across species — which range between 20% and 46% — are more similar than
different. “All species get cancer at about the same rate, typically in the
latter part of life span,” says James DeGregori, a molecular biologist at the University of Colorado
in Denver. “We
simply don’t have the data yet to back up the notion that larger animals have
come up with a way to avoid oncogenic mutations.”

Journal name:

Nature

DOI:

doi:10.1038/nature.2013.12258

References

1. 
   Caulin
   A.F., & Maley, C.C., Trends
   Ecol Evol 26, 175–182 (2011).

1.  
   • Article
   • ISI

Show context

1. 
   Roche, B., et
   al., Evo Appl. DOI: 10.1111/eva.12025 (2013).

Show context

1. 
   Martineau, D. et
   al. Environ Health Perspect. 110, 285–292 (2002).

1.  
   • Article
   • PubMed
   • ISI

Show context

 

 

La Jolla Institute identifies molecular switch enabling immune cells to better fight disease

Finding on killer cells opens new avenue for combating AIDS, cancer and other diseases

SAN DIEGO – (January 20th, 2013) A research team led by the La Jolla Institute for Allergy & Immunology has discovered the mechanism that enables CD4 helper T cells to assume the more aggressive role of killer T cells in mounting an immune attack against viruses, cancerous tumors and other damaged or infected cells.   The finding, made in collaboration with researchers from the RIKEN Institute in Japan, could enable the development of more potent drugs for AIDS, cancer and many other diseases based on using this mechanism to trigger larger armies of killer T cells against infected or damaged cells. 

CD4 helper T cells, which normally assist other cells of the immune system during an infection, and CD8 killer T cells, which directly attack and eliminate infected cells, are two of the body's most important immune cells for defending against diseases.  Earlier research studies have shown that helper T cells can become killer cells in some instances.  However, the specific mechanism of action that allowed this to occur was not known until now.

"We have identified the molecular switch that enables CD4 T cells to override their programming as helper cells and transform into cytolytic (killer) cells," said La Jolla Institute scientist and study co-leader Hilde Cheroutre, Ph.D.  "Our team also showed that these transformed helper T cells represent a separate and distinct population of cells.  They are not a subset of TH-1 helper cells as previously thought."

Jay A. Berzofsky, M.D., Ph.D., chief of the Vaccine Branch at the National Cancer Institute's Center for Cancer Research, called the finding "a major advance" that provides new understanding about the cell's lineage and basic mechanisms.  Dr. Berzofsky was among the researchers whose work in the 1980s first demonstrated that helper cells could convert to killer cells.  "Understanding how these cells derive and what causes them to switch from helper T cells to cytolytic T cells is an important step to learning how to manipulate them in disease," he said, noting it could lead to novel approaches "either to turn these cells off in autoimmune disease or turn them on in infectious diseases."

He added that the finding could also have important implications in cancer. "We need all of the cytolytic machinery that we can get to try to destroy cancers," he said. "If we can learn to turn them on, I think it's reasonable to believe that these cytolytic T cells can play an important role in controlling cancer."

The findings were published today in Nature Immunology in a paper entitled "Transcriptional reprogramming of mature CD4 helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes."  Dr. Cheroutre is co-senior author on the study together with Dr. Ichiro Taniuchi of the RIKEN Research Center for Allergy and Immunology in Yokohama, Kanagawa, Japan.  First authors on the paper are: Mohammad Mushtaq Husain, Ph.D., of the La Jolla Institute; Daniel Mucida, Ph.D., formerly of the La Jolla Institute, now at Rockefeller University; Femke van Wijk, Ph.D., formerly of the La Jolla Institute, now at the University Medical Center Utrecht, The Netherlands, and Sawako Muroi, of the RIKEN Institute.

Mitchell Kronenberg, Ph.D., La Jolla Institute president & chief scientific officer, said the study reflects the very successful collaboration between the La Jolla Institute and RIKEN in Japan, which have joined efforts on a number of projects over the years.

In the study, the researchers found that a certain transcription factor, which are molecules in the cell nucleus that control  the activity of cells, continually suppresses the killer T cell lineage in helper T cells.  Using mice, the team showed that turning off this transcription factor (ThPOK) enabled the helper cells in the body's peripheral areas, like the blood, spleen and the intestine, to override their original programming and to become killer T cells.  "While our work focused on the intestines, we found that helper T cells in all tissues of the body have the potential to become killer cells in response to recognition of viral, tumor or other antigens in the context of cytokines such as IL-15," said Dr. Cheroutre.

Jonathan Braun, M.D., chair of the Department of Pathology and Laboratory Medicine at UCLA's David Geffen School of Medicine, praised the study as laying the groundwork for using T helper cells in a much more aggressive manner.  "Helper T cells are mainly understood for their role in regulating other immune cells," he said.  "This work reveals how they themselves can be triggered to become the action cells in the immune response.  This opens new possibilities for how to manipulate them therapeutically in disease."

Dr. Cheroutre said the transformation of CD 4 helper T cells into killer cells already occurs in the body naturally.  "Our finding could help to explain a number of occurrences that we haven't really understood up to this point, such as why some people can be chronically infected with HIV without developing AIDS."  In these instances, Dr. Cheroutre is convinced that CD4 helper T cells must be taking over the role of killer cells after the CD8 T cells become exhausted.  "It's like the helper cells can come in as reinforcements to keep the virus under control.  If we can develop ways to artificially trigger that process, we may be able to significantly help people with HIV and other chronic infections." 

While scientists would want to trigger a larger army of virus-specific killer cells in the case of infections, the opposite would be true in inflammation-fueled autoimmune diseases, like rheumatoid arthritis or multiple sclerosis, said Dr. Cheroutre.  "The CD4 T cells are the bad wolves in inflammatory diseases because they often trigger more pro-inflammatory cells which worsen these conditions," she said.  "With this knowledge, we may be able to prevent that by coaxing the CD4 killer cells to become regulatory cells instead, which is another one of their potential functions.  In regulatory mode, the CD4 T cells suppress the immune system.  This suppression reduces inflammatory cells, which is what we want to do in autoimmune diseases." 

However in cancer, the CD4 T cell's regulatory function becomes problematic because they inhibit the killer T cells from destroying cancerous cells.  This is because of their built-in mechanism to keep T cells from attacking the body's own cells, said Dr. Cheroutre.   "Cancer cells develop from our own cells and only look a little different from healthy cells," she explained.  "The killer T cells can sense that they are different and decide to eliminate them.  However, the CD4 regulatory T cells frequently suppress the killer T cells and prevent them from destroying the cancerous cells.  This is often how cancer cells can escape the immune system's normal action of stamping out bad cells."

Dr. Cheroutre said she believes it may be possible, using the newly discovered mechanism, to turn the CD4 regulatory T cells into killer cells that would aid, rather than block, the immune system's attack on cancerous cells.

 

###

 

Scripps Research Institute Chemists Devise Inexpensive, Benchtop Method for Marking and Selecting Cells

LA JOLLA, CA – January 8, 2013 - Chemists at The Scripps Research Institute (TSRI) have found an easier way to perform one of the most fundamental tasks in molecular biology. Their new method allows scientists to add a marker to certain cells, so that these cells may be easily located and/or selected out from a larger cell population.

The technique, which is described in a recent issue of the chemistry journal Angewandte Chemie International Edition,makes use of the tight binding of two proteins that are cheaply obtainable but are not found in human or other mammalian cells. As such, it has advantages over existing cell-marking techniques.

“This new technique is cheap, easy and sensitive,” said TSRI Institute Professor Richard A. Lerner, who is the senior author of the new report. “The method should be useful in a variety of applications that require separating out certain types of cells.”

Looking for a Better Way

The best-known cell marker in use today is GFP (green fluorescent protein), a jellyfish protein that emits a distinctive green light when illuminated by certain other light wavelengths. When scientists want to add a new gene to cells, for example to produce a therapeutic protein, they often construct a genetic sequence that also includes the GFP gene. Thus the cells that successfully produce the new protein will also produce GFP, whose fluorescence allows these cells to be identified and even sorted out from a larger population.

But fluorescence-based cell sorting is relatively expensive and cumbersome. Alternative cell-marking techniques use marker molecules to which antibodies or metals will bind tightly, but these are apt to have unwanted side effects on the cells that they mark. Lerner’s team, led by first author Yingjie Peng, a postdoctoral fellow, set out to invent a better method.

The new method exploits a special property of chitinase enzymes, which evolved to break down chitin—a tough, sugar-derived material found, for example, in crab shells, squid beaks and the cell walls of fungi. In addition to a main chitin-breaking domain, chitinases have another active structure, a “chitin binding domain”(ChBD). “It makes a super-strong bond with chitin,” said Peng. In recent years, scientists have begun to use this high-affinity binding of ChBD and chitin as a marker system, typically for selecting ChBD-tagged proteins in a lab dish. The new method uses ChBD to mark and select cells.

A Powerful Tool

In the basic technique, a new gene can be added to cells within a larger DNA vector that also includes the genetic sequences for ChBD and GFP. The ChBD molecule will be produced in such a way that it ends up being held on the outer surface of its host cell’s plasma membrane—and the GFP molecule will sit just inside the membrane. The GFP serves as a visual beacon, while the ChBD serves as a handy gripping point for cell selection.

After exposing a culture of test cells to this experimental ChBD-containing vector, the scientists was able to see, via the GFP tags, which cells were expressing them, and was able to select them out easily, with high sensitivity, using magnetic beads coated with chitin. “This is a relatively easy benchtop method,” Peng said. Importantly, these selected cells could produce progeny cells that seemed normal and healthy.

Because the ChBD marker, in the vector, is produced in a way that anchors it to a cell’s membrane, it also can serve as a powerful tool for selecting just the membrane fraction of a sample of cellular material. Peng and his colleagues demonstrated this using chitin beads to quickly isolate a pure fraction of membrane material from ChBD-marked test cells.

Cellulase enzymes, which break down the ubiquitous plant compound cellulose, also have a high-affinity cellulase-binding domain, which can be employed in the same way as the ChBD.

The scientists expect that the new cell-marking method will help to streamline another major molecular biology technique, which was pioneered by the Lerner laboratory in parallel with the group of Sir Gregory Winter at the Laboratory of Molecular Biology in Britain. This technique allows scientists to produce very large and diverse libraries of antibody arms, and to sift through them, or“pan”—as gold miners pan for nuggets—for those that might be of use, for example in therapies. ChBD-based markers should be useful in boosting the efficiency of this panning process, said Peng.

The Lerner laboratory is also investigating the potential use of ChBD-based cell marking in living animals, for example to track the fates of selected cell types throughout an animal’s lifespan.

Those interested in using the new technology are invited to contact TSRI’s Office of Technology Development, at (858) 784-8140 or through the department’s webpage at http://www.scripps.edu/research/technology/contactus.html.

Other contributors to the study, “Engineering Cell Surfaces for Orthogonal Selectability,”were Teresa M. Jones and Diana I. Ruiz of the TSRI Department of Chemistry, and Dae Hee Kim of the Scripps Korea Antibody Institute. For more information on the paper, see http://onlinelibrary.wiley.com/doi/10.1002/anie.201201844/abstract

The research was supported by a grant from Scripps Korea Antibody Institute.

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, TSRI has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.

# # #

For information:
Office of Communications
Tel: 858-784-8134
Fax: 858-784-8136
press@scripps.edu

Researchers discover how underground rodent wards off cancer

 

Second mole rat species has different mechanism for resisting
cancer

Biologists at the University of Rochester have determined how blind mole
rats fight off cancer—and the mechanism differs from what they discovered three
years ago in another long-lived and cancer-resistant mole rat species, the
naked mole rat.

The team of researchers, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, found that abnormally growing cells in blind mole rats secrete the interferon beta
protein, which causes those cells to rapidly die. Seluanov and Gorbunova hope
the discovery will eventually help lead to new cancer therapies in humans.
Their findings are being published this week in the Proceedings of the
National Academy of Sciences.

Blind mole rats and naked mole rats—both subterranean rodents with long life spans—are the only
mammals never known to develop cancer. Three years ago, Seluanov and Gorbunova
determined the anti-cancer mechanism in the naked mole rat. Their research found
that a specific gene—p16—makes the cancerous cells in naked mole rats
hypersensitive to overcrowding, and stops them from proliferating when too many
crowd together.

"We expected blind mole rats to have a similar mechanism for stopping the spread of cancerous
cells," said Seluanov. "Instead, we discovered they've evolved their
own mechanism."

Gorbunova and Seluanov made their discovery by isolating cells from blind mole rats and forcing them
to proliferate in culture beyond what occurs in the animal. After dividing
approximately 15-20 times, all of the cells in the culture dish died rapidly.
The researchers determined that the rapid death occurred because the cells
recognized their pre-cancerous state and began secreting a suicidal protein,
called interferon beta. The precancerous cells died by a mechanism which kills
both abnormal cells and their neighbors, resulting in a "clean
sweep."

"Not only were the cancerous cells killed off, but so were the adjacent cells, which may also be
prone to tumorous behavior," said Seluanov.

"While people don't use the same cancer-killing mechanism as blind mole rats, we may be able
to combat some cancers and prolong life, if we could stimulate the same clean
sweep reaction in cancerous human cells," said Gorbunova.

The research team also included Christopher Hine, Xiao Tian, and Julia Ablaeva in Rochester,
Andrei Gudkov at Roswell Park Cancer Institute in Buffalo,
NY, and Eviatar Nevo at the University of Haifa
in Israel.

Gorbunova and Seluanov say they next want to find out exactly what triggers the secretion of
interferon beta after cancerous cells begin proliferating in blind mole rats.

Gorbunova believes the anti-cancer mechanism is an adaptation to subterranean life. "Blind mole
rats spend their lives in underground burrows protected from predators,"
said Gorbunova. "Living in this environment, they could perhaps afford to
evolve a long lifespan, which includes developing efficient anti-cancer
defenses."

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Breast milk contains more than 700 bacteria

Microbes taken from breast milk by the infant are identified

Spanish researchers have traced the bacterial microbiota map in breast milk, which is the main source of nourishment for newborns. The study has revealed a larger microbial diversity than originally thought: more than 700 species.

The breast milk received from the mother is one of the factors determining how the bacterial flora will develop in the newborn baby. However, the composition and the biological role of these bacteria in infants remain unknown.

A group of Spanish scientists have now used a technique based on massive DNA sequencing to identify the set of bacteria contained within breast milk called microbiome. Thanks to their study, pre- and postnatal variables influencing the micriobial richness of milk can now be determined.

Colostrum is the first secretion of the mammary glands after giving birth. In some of the samples taken of this liquid, more than 700 species of these microorganisms were found, which is more than originally expected by experts. The results have been published in the 'American Journal of Clinical Nutrition'.

"This is one of the first studies to document such diversity using the pyrosequencing technique (a large scale DNA sequencing determination technique) on colostrum samples on the one hand, and breast milk on the other, the latter being collected after one and six months of breastfeeding," explain the coauthors, María Carmen Collado, researcher at the Institute of Agrochemistry and Food Technology (IATA-CSIC) and Alex Mira, researcher at the Higher Public Health Research Centre (CSISP-GVA).

The most common bacterial genera in the colostrum samples were Weissella, Leuconostoc, Staphylococcus, Streptococcus and Lactococcus. In the fluid developed between the first and sixth month of breastfeeding, bacteria typical of the oral cavity were observed, such as Veillonella, Leptotrichia and Prevotella.

"We are not yet able to determine if these bacteria colonise the mouth of the baby or whether oral bacteria of the breast-fed baby enter the breast milk and thus change its composition," outline the authors.

The heavier the mother, the fewer the bacteria

The study also reveals that the milk of overweight mothers or those who put on more weight than recommended during pregnancy contains a lesser diversity of species.

The type of labour also affects the microbiome within the breast milk: that of mothers who underwent a planned caesarean is different and not as rich in microorganisms as that of mothers who had a vaginal birth. However, when the caesarean is unplanned (intrapartum), milk composition is very similar to that of mothers who have a vaginal birth.

These results suggest that the hormonal state of the mother at the time of labour also plays a role: "The lack of signals of physiological stress, as well as hormonal signals specific to labour, could influence the microbial composition and diversity of breast milk," state the authors.

Help for the food industry

Given that the bacteria present in breast milk constitute one of initial instances of contact with microorganisms that colonise the infant's digestive system, the researchers are now working to determine if their role is metabolic (it helps the breast-fed baby to digest the milk) or immune (it helps to distinguish beneficial or foreign organisms).

For the authors, the results have opened up new doors for the design of child nutrition strategies that improve health. "If the breast milk bacteria discovered in this study were important for the development of the immune system, its addition to infant formula could decrease the risk of allergies, asthma and autoimmune diseases," conclude the authors.

 

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References:

Referencia bibliográfica:

Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. "The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery".  American Journal of Clinical Nutrition 96(3):544-551, 2012.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

UCSB researchers perform pioneering research on Type 2 diabetes

		IMAGE:This is Jamey Marth.Click here for more information.

(Santa Barbara, Calif.) –– While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others.

Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.

		IMAGE:This is Frank Doyle.Click here for more information.

The current work is based on a previous major finding by UCSB's Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.

"By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells," said Marth. UCSB is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.

The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.

"Even in the post-genomic era, after the human genome has been sequenced, we're beginning to realize that diseases aren't always in our genes –– that the environment is playing a major role in many of the common diseases," said Marth.

		IMAGE:This image shows four types of macromolecules in cells. The nucleic acids DNA and RNA and proteins are on the left and glycans and lipids are on the right.Click here for more information.

Normally, beta cells in the pancreas sense a rise in blood sugar and then secrete insulin to regulate blood glucose levels. But in Type 2 diabetes, the beta cells fail to execute this important function and blood sugar rises, a trend that can reach life-threatening levels. The researchers identified a "tipping point," or metabolic threshold, that when crossed results in the failure of beta cells to adequately sense glucose in order to properly secrete insulin.

Obesity has long been linked to Type 2 diabetes, but the cellular origin of the disease due to beta cell failure has not been described until now. "In obesity there's a lot of fat in the system," said Marth. "When the cell is exposed to high levels of fat or lipids, this mechanism starts, and that's how environment plays a role, among large segments of the population bearing 'normal' genetic variation. We're trying to understand what actually causes disease, which is defined as cellular dysfunction. Once we understand what causes disease we can make a difference by devising more rational and effective preventative and therapeutic approaches."

The research was based on a unique approach. "This project illustrates the power of systems biology; namely, how a network perspective combined with computational modeling can shed new light on biophysical circuits, such as this beta-cell glucose transport system," said co-author Frank Doyle. "It cannot be done by molecular biology alone, nor computational modeling alone; rather, it requires the uniquely interdisciplinary approach that is second-nature here at UCSB." Doyle is associate dean for research of the College of Engineering; director of UCSB's Institute for Collaborative Biotechnologies; professor of chemical engineering; and the Mellichamp Chair in Process Control.

"We are excited to bring our 20 years of expertise on Type 1 diabetes and systems biology methods to look at the networks responsible for the onset of Type 2 diabetes," said Doyle.

According to the American Diabetes Association, 8.3 percent of the U.S. population has diabetes. The disease can lead to nerve loss, blindness, and death.

The first author of the paper is Camilla Luni, who was a UCSB postdoctoral researcher at the time of the study, and is now with the University of Padova, in Italy. The research was funded by a grant from the U.S. Army Research Office to UCSB's Institute for Collaborative Biotechnologies, and a grant from the U.S. National Institutes of Health.

 

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Shifting the balance between good fat and bad fat> study on p62's role in fat metabolism

by Bruce Lieberman on January 4, 2013  at 10:39 am  | 1 comment

Sanford-Burnham Professors Jorge Moscat, Ph.D., and Maria Diaz-Meco, Ph.D. co-authored a study on p62's role in fat metabolism

Sanford-Burnham researchers show that protein p62 balances metabolism in fat tissue—making it an attractive target for anti-obesity therapies

 In many cases, obesity is caused by more than just overeating and a lack of exercise. Something in the body goes haywire, causing it to store more fat and burn less energy. But what is it? Sanford-Burnham researchers have a new theory—a protein called p62. According to a study the team published December 21 in the Journal of Clinical Investigation, when p62 is missing in fat tissue, the body’s metabolic balance shifts—inhibiting “good” brown fat, while favoring “bad” white fat. These findings indicate that p62 might make a promising target for new therapies aimed at curbing obesity.

“Without p62 you’re making lots of fat but not burning energy, and the body thinks it needs to store energy,” said Jorge Moscat, Ph.D., Sanford-Burnham professor. “It’s a double whammy.” Moscat led the study with collaborators at Helmholtz Zentrum München in Germany and the University of Cincinnati.

p62 and obesity

Moscat’s team had previously produced mice that completely lack the p62 protein everywhere in their bodies. As a result, the animals were obese. They also had metabolic syndrome. In other words, as compared to mice with p62, mice lacking p62 weighed more, expended less energy, had diabetes and had a hyper-inflammatory response that’s characteristic of obesity.

While those results showed that the lack of p62 leads to obesity, “we didn’t know which tissue was responsible for these effects, because p62 was missing in all of them,” Moscat said.

Some researchers believe that muscle tissue, where energy is expended, controls obesity. Others suspect the liver is a key player, or that the brain’s appetite control center is most responsible for obesity.

But then there’s fat itself—both white fat and brown fat. White fat is the type we think of as unwanted body fat. Brown fat, on the other hand, is beneficial because it burns calories. Many researchers now believe that brown fat somehow malfunctions in obesity, but the details are unclear.

p62 shifts the balance between white fat and brown fat

In their latest study, Moscat and colleagues set out to pinpoint the specific tissue responsible for obesity when p62 is missing. They made several different mouse models, each missing p62 in just one specific organ system, such as the central nervous system, the liver, or muscle. In every case, the mice were normal. They weren’t obese like the mice lacking p62 everywhere.

Then they made a mouse model lacking p62 only in their fat tissue. These mice were obese, just like the mice missing p62 in all tissues. Upon further study, the researchers found that p62 blocks the action of an enzyme called ERK while activating another enzyme called p38. When p62 is missing, the enzyme p38 is less active in brown fat, while ERK is more active in white fat. As a result, Moscat said, p62 is “a master regulator” in normal fat metabolism.

According to Moscat, the discovery of p62’s role in brown fat tissue is encouraging, because fat tissue is much more accessible than other parts of the body—the brain, for example—for potential drug therapies. “This makes it easier to think about new strategies to control obesity,” he said.

New methods for preventing or treating obesity, a major epidemic in the United States, are urgently needed. Drug therapies designed to minimize the intake of food have had limited success and also produce considerable side effects.

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This study was funded by the National Institutes of Health -  National Institute of Allergy and Infectious Diseases grant DK088107 and National Cancer Institute grants CA132847 and CA134530.

Original paper:

Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S, Divanovic S, Endele M, Finan B, Gao Y, Habegger KM, Hembree J, Heppner KM, Hofmann S, Holland J, Küchler D, Kutschke M, Krishna R, Lehti M, Oelkrug R, Ottaway N, Perez-Tilve D, Raver C, Walch AK, Schriever SC, Speakman J, Tseng YH, Diaz-Meco M, Pfluger PT, Moscat J, & Tschöp MH (2013). p62 Links β-adrenergic input to mitochondrial function and thermogenesis. The Journal of clinical investigation, 123 (1), 469-78 PMID: 23257354