DAVID GRANOVSKY

Posts Tagged ‘cancer’

ZEROING IN ON LEUKEMIA SMART BOMBS

In PHARMA AND DRUGS, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on January 31, 2017 at 1:30 pm

A little over a week ago, I posted an article that described:
Of the 100 million BULK CANCER CELLS in a 1-cm cancer tumor, there are about 1,000 to 10,000 CANCER STEM CELLS and those cells are up to 15 times more active and may be the only cells responsible for cancer cell reproduction and metastasis.

Scientists have zeroed in even deeper and targeted a new ‘CD99’ molecule expressed on certain stem cells that drive human leukemia malignancies.  They’ve designed antibodies that can directly kill human acute myeloid leukemia (AML) stem cells.

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protein-sugar molecule, CD99

Researchers design antibody that recognizes and destroys blood cancer stem cells

Published on January 25, 2017 at 9:44 PM ·

Building on this discovery, the study authors designed an antibody that recognizes and destroys CD99-covered leukemia cells while sparing normal blood stem cells, a finding confirmed by experiments in human cells and in mice with AML cells. Antibodies are immune system proteins that stick to a specific target, like a protein on the surface of invading bacterium. In recent years, researchers have become capable of engineering antibodies so that they target disease-related molecules.

“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells,” says corresponding study author, Christopher Y. Park, MD, PhD, associate professor in the Department of Pathology at NYU Langone and its Perlmutter Cancer Center.

“While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing,” says Park.

Direct Cell Killing

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) arise from abnormal stem cells that build up in bone marrow until they interfere with normal blood cell production. Patients struggle with anemia, increased risk for infection, and bleeding.

The study results are based on the understanding that cancers, like normal tissues, contain stem cells that give rise to all the other cells. Such “cancer stem cells” are known to be major drivers of many cancer types. In AML, a small group of leukemic stem cells become incapable of maturing into red or white blood cells as intended. Most leukemias respond initially to standard treatment, but relapse is common as standard treatments fail to kill leukemia stem cells, which continue to multiply.

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The research team became interested in CD99 when they observed that it occurs frequently on AML and MDS cells, and then noted in the literature that CD99 is elevated in a rare bone cancer called Ewing’s Sarcoma. This prompted them to see if CD99 was important in the development of these blood diseases.

When researchers examined stem cell populations from 79 AML and 24 MDS patients, they found that approximately 85 percent of stem cells in both groups expressed high levels of CD99. The levels were so high that diseased stem cells could be cleanly separated from related, normal stem cells in AML patients.

Upon confirming that CD99 was abundant on leukemia stem cells, the research team then made several CD99 antibodies, and chose to focus on the one that most effectively killed those cells. Researchers found that when the study antibody attaches itself to CD99 on the surface of a cancer stem cell, it sends a signal inside the cell that increases the activity of enzymes called SRC-family kinases.

While the team does not yet know why, the binding of their antibody to CD99, and the subsequent activation of these enzymes, causes leukemia stem cells to die. Most cells with genetic mistakes leading to cancer “sense” they are flawed and self-destruct, but CD99, so the theory goes, may be part of a mechanism that prevents this. As the antibody binds to CD99, it appears to undo this block on self-destruction.

“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials,” says Park.

While the most common acute leukemia affecting adults (22,000 new cases each year) and expected to become more prevalent as the population ages, AML it is still relatively rare, accounting for 1.2 percent of U.S. cancer deaths. About 15,000 mostly elderly patients are diagnosed with MDS each year as well.

 

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STEM CELLS FOR CYSTIC FIBROSIS

In DISEASE INFO, HEALTH AND WELLNESS, SCIENCE & STEM CELLS on January 31, 2017 at 10:56 am

“[Bob]  received an infusion of cells called allogeneic human mesenchymal stem cells (hMSC), adult stem cells collected from the bone marrow of healthy volunteers”

“CF’s main effect is on the lungs. They fill with a sticky mucus as a reaction – really an over-reaction – by the body’s immune system to bacteria. The lungs are the source for much of the illness and shortened lifespan seen in CF.”

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CYSTIC FIBROSIS The_fluorescent_microscopy_image_of_CFTR_tagged_with_EYFP

First stem cell study could lead to development of therapy to reduce inflammation caused by CF

Published on January 31, 2017 at 3:24 AM · 

A 39-year-old man with cystic fibrosis (CF) made history by becoming the first person to receive human adult stem cells in a new research study that researchers hope will someday lead to the development of a therapy to reduce the inflammation and infection caused by CF.

The pioneering subject in the study is Bob Held from Alliance, Ohio, who on Jan. 26 received an infusion of cells called allogeneic human mesenchymal stem cells (hMSC), adult stem cells collected from the bone marrow of healthy volunteers. Mr. Held was diagnosed with CF when he was 16 months old.

Currently, there is no cure for CF, and life expectancy for patients who survive into adulthood is approximately 41 years of age.

“It was a very exciting day for us with the very first participant in the first stem cell trial for cystic fibrosis,” said James Chmiel, MD, the principal investigator of the study at University Hospitals Rainbow Babies & Children’s Hospital.

The Phase 1 trial will assess the safety and tolerability of hMSCs in adult patients with CF.

“This is an early phase trial, and the most important thing is to ensure safety,” said Dr. Chmiel. “This study consists of a single infusion of stem cells. We will follow the study participants for a year to make sure it’s safe. Before applying any therapy on a broad basis, we want to make sure that it’s safe.”

While the goal of the study is safety, Dr. Chmiel hopes this is a first step towards the ultimate goal of developing a therapy to reduce lung inflammation and infection, resulting in longer and healthier lives for people with CF.

“While there’s been a tremendous increase in survival for people with CF from when I entered the field in the 1990s, that’s still not good enough,” said Dr. Chmiel, Director of the Cystic Fibrosis Therapeutics Development Center at UH Rainbow Babies & Children’s Hospital and Professor of Pediatrics at Case Western Reserve University School of Medicine. “While we’ve made great progress, we still have a long way to go.”
The stem cells that Mr. Held received were collected from the bone marrow of a healthy adult volunteer. UH is a national leader in the use of stem cell therapy with hMSCs. Researchers from UH, along with the CWRU School of Medicine, discovered hMSCs. The hMSCs possess many properties that are ideal for the treatment of inflammatory and degenerative diseases, and they possess natural abilities to detect changes in their environment, such as inflammation. The hope is that hMSCs can reduce the inflammation in the lungs caused by CF.

CF’s main effect is on the lungs. They fill with a sticky mucus as a reaction – really an over-reaction – by the body’s immune system to bacteria. The lungs are the source for much of the illness and shortened lifespan seen in CF.

“One of the issues in CF is that people with the disease get bacterial infections in their lungs, and these bacteria incite a vigorous and excessive inflammatory response,” explained Dr. Chmiel. “It’s actually the body’s inflammatory response that damages the lungs. The inflammatory response tries to eliminate the bacteria, but it’s not successful. Instead, the inflammatory system releases molecules that damage the individual’s own airways. The lung disease causes much of the illness and is responsible for the majority of the mortality of the disease.”

The stem cells are donated by healthy adult volunteers who go through a rigorous screening process. The stem cells are cultured in the UH stem cell facility. Volunteers with CF who are in the study receive an infusion through an IV.
“Once in the patient’s body, the stem cell tracks to the area where there’s a significant amount of inflammation, and they take up residence there. The stem cells then respond to the environment, and hopefully reverse some of the abnormalities,” said Dr. Chmiel. “We hope in future studies to demonstrate that the stem cells reduce the infection and inflammation and return the lungs to a more normal state.”

“This therapy aims to turn down the inflammatory response, not eliminate it because we still have to keep the bacteria in check. We want to reduce inflammation and the subsequent lung damage caused by inflammation without allowing the bacteria to proliferate,” said Dr. Chmiel.

A total of 15 clinically stable adults with CF will be enrolled in the study. Support for the study is from the Cystic Fibrosis Foundation.

The patient, Mr. Held, considers himself fortunate to be close to 40 with CF. When he was growing up, he said he’d miss 50 days of school each year because of the disease. Every day, he needs to breathe in aerosols for about two hours in the morning and 1-1/2 hours before bed to keep his lungs functioning. While he hasn’t been sick from the illness since his late teens, he does check himself into the hospital a couple of times a year for precautionary measures and to prevent himself from “getting into a valley” with CF.

His late wife, Michelle, died of CF seven years ago. They had met when they were kids, but didn’t get married until 2012. She died from the disease suddenly 28 days after they married.

“My only regret is that I didn’t ask her out sooner,” said Mr. Held.
He is participating in the study to carry on Michelle’s legacy, and “I am hoping the future generations of CF patients can get better treatments and that eventually a cure will be found for them,” he said.

WHY SMOKING CAUSES CANCER

In DISEASE INFO, HEALTH AND WELLNESS, SCIENCE & STEM CELLS on January 30, 2017 at 7:30 pm
Lung stem cells cultured in the laboratory. The green, blue and purple colors emerging from behind the orbs are a protein expressed by lung basal stem cells. Photo: Clare Weeden, Walter and Eliza Hall Institute of Medical Research

For four years straight medical researcher Clare Weeden would go on alert whenever lung surgery was underway anywhere across Melbourne. No matter the time, she would have to be ready in her lab to receive samples of fresh tissue as part of a project to isolate and research the stem cells that repair our lungs as they constantly breathe in contaminants from air pollution to cigarette smoke.

She didn’t know it at the time, but she was hot on the trail of the lung’s basal stem cells that now appear to be the likely culprits that trigger a major lung cancer closely tied to smoking – squamous cell carcinoma. It is the second most common form of lung cancer.

Basal stems cells are very quick at repairing DNA damage caused by inhaled chemicals such as those from cigarette smoke, but they are prone to making mistakes. It means that the more repair work they have to do, the greater the chance of a cancer-causing mutation.

“What we have found is a genetic fingerprint in squamous cell carcinoma that has been left from basal stem cells in the lung whose repair work has gone awry and led to the cancer,” says Weeden, from the Walter and Eliza Hall Institute of Medical Research and a PhD candidate at the University of Melbourne.

“It isn’t definitive but the evidence is that lung basal stem cells are the likely cells of origin.”

The unmasking of basal stem cells, published in the Public Library of Science: Biology, is the culmination of years of painstaking laboratory work and data-crunching that has now provided a crucial new target for developing drugs that may be able to turn off the progress of the cancer.

Weeden was sometimes up until to 3am at the Institute isolating and processing cells from the freshly operated-on lung tissue, especially when there was a flurry of samples in one day. It is a complex process that took up to six hours for each of the eventual 140 samples.

The Clue

But one day she came across a sample that she could barely get to grow at all.

Intrigued, she contacted the Victorian Cancer Biobank for basic information on the donor. It was likely that the donor was a smoker or ex-smoker since most people having lung surgery have a history of smoking. But this patient had never smoked. Sensing a possible link she went back to the Biobank to get information on all the previous tissue donors, and over that weekend plotted out a chart.

The correlation was stark. Samples from those that had never smoked had low basal cell growth, and the more heavily a patient had smoked, the higher the growth rate.

“It completely grabbed my curiosity,” she says. “I remember on Monday morning going straight into my supervisor’s office (Marie-Liesse Asselin-Labat) and putting the chart down in front of her. We both realized we were onto something significant. The question was what?”

By using the same process that Weeden had developed to accurately isolate lung stem cells, she and Asselin-Libat set to examine how the basal stem cells worked.

They discovered that basal stem cells were very efficient at repairing damaged DNA but that the process the cells use, called non-homologous repair, is prone to making errors that can lead to cancer-causing mutations. In non-homologous repair the break in a damaged DNA chain is simply closed over rather than copied. They also found evidence of the accumulation of mutations in the basal stem cells of the smokers.

“While we need more experimentation, this gave us a model of what may be happening,” says Weeden. “Our lungs are constantly being exposed to what we inhale. When we breathe in something like cigarette smoke that causes lung damage, these basal cells receive a signal to grow and repair the damage.

But they have to first repair their own DNA damage and the process they use is very quick. The advantage is that it helps the cells to survive, but the disadvantage is that they are prone to making errors that can lead to cancer.”

To test that model they turned to Institute bioinfomaticians Professor Gordon Smyth and Yunshun (Andy) Chen who used statistics and computer science to extract a genetic “signature” for lung basal stem cells. They then compared that signature with the genetics of various lung cancers.

clear evidence

They discovered that this same signature was highly correlated with lung squamous cell carcinoma, the second most common form of lung cancer and the most closely linked to smoking – some 96 per cent of people with lung squamous cell carcinoma are either smokers or ex-smokers. It was clear evidence that basal stem cells are the likely culprits in how the cancer is triggered.

By identifying a cell of origin Weeden says we now have a drug target to aim at that has the potential to stop the progress of the cancer. Previous Institute research in 2009 lead by Professor Jane Visvader and Professor Geoff Lindeman had similarly identified a likely cell of origin for inherited breast cancer, and last year that same team identified an existing drug, denosumab, that in laboratory models could switch off the problematic cell growth and curtail the cancer. Clinical trials are now underway.

“In the breast cancer research they similarly used correlations to identify a cell of origin like we have and now further work has solidified that,” says Weeden.

Does this mean that at some point in the future smokers could breathe easier by taking a drug that could stop the cancer being triggered? No. Weeden points out that if someone took such a drug and continued to smoke the damage could be even worse than the cancer.

“Basal stem cells have a job to do in the lung, they repair any damage. If a person was treated with a drug that turned off basal cells and continued to smoke, I would imagine that other lung problems may develop due to the inability of the stem cell to repair the lung airways from cigarette smoke-induced damage,” says Weeden. She points out that smoking also causes other lung cancers that don’t arise from basal stem cells.

She says the biggest beneficiaries of any such drug could be ex-smokers. “This is particularly relevant as lung squamous cell carcinoma can occur in ex-smokers who have quit perhaps 20 or 30 years ago.

“But the best way to reduce the risk of lung cancer is to simply quit smoking because no matter how long you’ve smoked for, the risk of lung cancer is reduced when you quit.”

NON SMOKERS GET LUNG CANCER

In DISEASE INFO, HEALTH AND WELLNESS, SCIENCE & STEM CELLS on January 26, 2017 at 2:00 pm

‘Lung cancer is almost always fatal because it is asymptomatic. “Symptoms of lung cancer (chronic cough, shortness of breath, phlegm in lungs) are very similar to common respiratory illnesses”’

Can people get lung cancer if they don’t smoke?

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Lung cancer is responsible for almost one-quarter of all cancer deaths in the nation.

Although this type is especially common in people who smoke cigarettes, it is possible for the disease to occur in non-smokers and yes, sometimes even in those who aren’t often breathing secondhand smoke.

A Texas A&M College of Medicine Radiation Oncologist breaks down the science behind lung cancer and the environmental hazards that could result in a diagnosis.

The American Cancer Society (ACS) estimates 224,000 new cases of lung cancer will be diagnosed in 2016.

“This means up to 13 percent of all projected cancers this year could be lung cancer,” said Niloy J. Deb, MD, Assistant Professor of radiology with the Texas A&M College of Medicine and Chairman.

“The leading cause of diagnosis is due to smoking cigarettes, but there are other instances where the cancer can occur.”

Secondhand smoke—like breathing car exhaust into your lungs

Do you live with friends or family who smoke cigarettes? If so, you’re at a much higher risk for developing lung cancer.

“Exposure to secondhand smoke is the number one cause of lung cancer in non-smokers,” Deb said. “Non-smokers who are constantly exposed to secondhand smoke increase their likelihood of getting lung cancer by 20 percent.”

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So, how exactly does secondhand smoke up your chances for lung cancer? Deb said even smoke indirectly inhaled from a cigarette is damaging to the lungs.

“Chronic smoking impairs the tiny alveoli (small sacs that move oxygen and carbon dioxide between the lungs and bloodstream) in our lungs, and these alveoli start ‘trapping’ air,” he said.

“Cigarette smoke, with all the dissolved carcinogens, will then ‘sit’ in the alveoli, which causes the genetic mutations (changes) that cause cancerous transformation.”

Important to know: The most harmful part of cigarette smoke comes from the burning paper. This is because compounds are added to the wrapping to allow the tobacco and paper to burn at the same rate.

“To do this, companies add tar and other petroleum derivatives to the paper around cigarettes,” Deb said. “So, when you inhale smoke from a cigarette, it’s essentially like breathing car exhaust directly into your lungs.”

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Carcinogens activate the ‘switch’ for cancer cell mutation

Cancer happens when a cell’s DNA is changed, and there are certain known substances and exposures that can lead to cancer; these are called carcinogens.

According to the ACS, carcinogens don’t always cause cancer in every case, but they may predispose to cancer in other ways.

“Some environmental carcinogens like asbestos, silica, benzene, ethylene oxide, and exposure to nickel compounds and by-products of petroleum distillation from vehicle exhaust and fossil fuels, can lead to lung cancer,” Deb said.

“These substances flip the genetic switches in our body by turning on a cancer activator or turning off a cancer suppressor.”

For example: For a cancer cell to form in our lungs, there must be an on/off switch flipped in the genetic code of the lung cells. “When a carcinogen flicks the ‘on’ switch, it turns on a gene that converts a normal cell into a cancer cell,” Deb said.

“When a carcinogen hits the ‘off’ switch, it’s turning off a gene that has been preventing a cancerous process or cancer cell formation. These switches can be flipped because of exposure to environmental carcinogens.”

Why lung cancer is a killer

Lung cancer is almost always fatal because it is asymptomatic. “Symptoms of lung cancer (chronic cough, shortness of breath, phlegm in lungs) are very similar to common respiratory illnesses,” Deb said.

“Most patients (both smokers and non-smokers) do not know their symptoms may be caused by cancer instead of a relatively benign illness.”

Most people who are diagnosed with lung cancer live with symptoms for years before seeking any medical opinion, and by then, it’s too late.

“This is why most lung cancers are diagnosed at Stage 3 or Stage 4 and the reason approximately 158,000 people die from lung cancer each year,” Deb said.

“The death rate increases when you can’t catch the cancer at an earlier stage, when there are more treatment options available.”

WITH CANCER, AIM ONLY FOR FURTHER GROWTH

In PHARMA AND DRUGS, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on January 22, 2017 at 10:16 am

Did we just figure out which cells actually cause the creation of more cancer cells?

  • A 1-cm cancer tumor has about 100 million BULK CANCER CELLS.
  • A 1-cm cancer tumor has about 1,000 to 10,000 CANCER STEM CELLS.
  • We know that cancer cells may pass through blood vessel walls to metastasize Moses-stem-cell-pathways-and-maybe-metastatic-cancers/
  • We know that long telomeres increase risk of cancer in cells.

Scientists found that cancer stem cells which have the enzyme called Telomeras, were found to be up to 15 times more active and may be the only cells responsible for cancer cell reproduction and metastasis.
“We can now begin to think of cancer stem cells as being at the heart of tumour regrowth and turn our efforts away from ‘bulk cancer cells’, which don’t really drive tumour recurrence and metastasis.”

Now, we know how to aim at the cells responsible for tumor growth we can change how we fight cancer!

Puts a whole new spin on the Niki Lauda quote:

Stem cell ‘marking’ study offers alterative hypothesis of cancer metastasis

Date:January 18, 2017- Source: University of Salford – Summary: Stem cells are among the most energetically activated, migratory and proliferative sub-populations of tumour cells, according to observations by scholars at the Biomedical Research Centre at the University of Salford.

Cancerous stem cells are often left behind after chemotherapy with the potential to create new tumours — a process called recurrence and metastasis.

In research published in the journal Oncotarget, the Salford team conclude that stem cell characteristics and behaviour are instrumental in metastasis and believe the key to their reactivation is an enzyme called Telomerase, or hTERT.

Using lung, breast and ovarian cancer cells, the team set out to identify which cells are cancerous by their levels of Telomerase, an enzyme which endows cells with the ability to multiply.

To achieve this, they followed Telomerase activity with a fluorescent protein, GFP, more commonly found in jellyfish, effectively colouring each cells to mark it either ‘active’ or ‘inactive’.

Cells highlighted ‘fluorescent’ (hTERT-high) were found to be up to 15 times more active than others with an vastly increased capacity for migration and cell proliferation.

Michael Lisanti, Professor of Translational Medicine at the University of Salford said: “We reasoned that if we could spot the telomerase activity, we could identify which cells were cancerous.

“What we had not expected was to find the very rapid rate of proliferation of the cancer stem cells.

“Clearly, this contradicts the accepted view that stem cells do not proliferate quickly, and offers an alternative view of the process of metastasis, and moreover, a method of identifying, isolating and potentially killing tumour-forming cells.”

As part of the study, the team found that FDA-approved drugs, such as doxycycline and palbociclib, were effective at halting cancer stem cell propagation. Palbociclib blocks the activity of proteins known as cyclin-dependent kinases (CDK) and inhibits the division of cancer cells, but until now hadn’t been shown to effectively block cancer stem cell reproduction.

“The use of these FDA-approved drugs may provide a mechanism for treating metastatic disease on a larger scale and certainly opens the way for new Phase II clinical trials in multiple cancer types,” adds Professor Lisanti.

Dr Federica Sotgia, Reader of Translational Medicine at the University of Salford said: “We can now begin to think of cancer stem cells as being at the heart of tumour regrowth and turn our efforts away from ‘bulk cancer cells’, which don’t really drive tumour recurrence and metastasis.”


Story Source:

Materials provided by University of Salford. Note: Content may be edited for style and length.


Journal Reference:

  1. Gloria Bonuccelli, Maria Peiris-Pages, Bela Ozsvari, Ubaldo E. Martinez-Outschoorn, Federica Sotgia, Michael P. Lisanti. Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity. Oncotarget, 2016; DOI: 10.18632/oncotarget.14196

TZAP! GOES THE TELOMERE FUSE

In DISEASE INFO, HEALTH AND WELLNESS, OFF THE BEATEN PATH, PHARMA AND DRUGS, SCIENCE & STEM CELLS on January 21, 2017 at 9:44 am

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EVERY TIME A CELL DIVIDES, A TELOMERE LOSES IT’S WINGS

  • The length of a telomere controls cell age.
  • Each time a cell splits, the telomere gets smaller.
  • Too long and cancer risk increases.
  • Too short and no more cell division.

Scripps Research Institute discovered the TZAP that controls telomere length.  “TZAP: a Telomere-Associated Protein involved in telomere length control”

Master regulator of cellular aging discovered

Date: January 12, 2017 – Source: Scripps Research Institute – Summary: Scientists have discovered a protein that fine-tunes the cellular clock involved in aging.
Cell culture under microscope (stock image).
Credit: © sinitar / Fotolia
 Scientists at The Scripps Research Institute (TSRI) have discovered a protein that fine-tunes the cellular clock involved in aging.

This novel protein, named TZAP, binds the ends of chromosomes and determines how long telomeres, the segments of DNA that protect chromosome ends, can be. Understanding telomere length is crucial because telomeres set the lifespan of cells in the body, dictating critical processes such as aging and the incidence of cancer.

“Telomeres represent the clock of a cell,” said TSRI Associate Professor Eros Lazzerini Denchi, corresponding author of the new study, published online today in the journal Science. “You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore.”

Naturally, researchers are curious whether lengthening telomeres could slow aging, and many scientists have looked into using a specialized enzyme called telomerase to “fine-tune” the biological clock. One drawback they’ve discovered is that unnaturally long telomeres are a risk factor in developing cancer.

“This cellular clock needs to be finely tuned to allow sufficient cell divisions to develop differentiated tissues and maintain renewable tissues in our body and, at the same time, to limit the proliferation of cancerous cells,” said Lazzerini Denchi.

In this new study, the researcher found that TZAP controls a process called telomere trimming, ensuring that telomeres do not become too long.

“This protein sets the upper limit of telomere length,” explained Lazzerini Denchi. “This allows cells to proliferate — but not too much.”

For the last few decades, the only proteins known to specifically bind telomeres is the telomerase enzyme and a protein complex known as the Shelterin complex. The discovery TZAP, which binds specifically to telomeres, was a surprise since many scientists in the field believed there were no additional proteins binding to telomeres.

“There is a protein complex that was found to localize specifically at chromosome ends, but since its discovery, no protein has been shown to specifically localize to telomeres,” said study first author Julia Su Zhou Li, a graduate student in the Lazzerini Denchi lab.

“This study opens up a lot of new and exciting questions,” said Lazzerini Denchi.

In addition to Lazzerini Denchi and Li, authors of the study, “TZAP: a telomere-associated protein involved in telomere length control,” were Tatevik Simavorian, Cristina Bartocci and Jill Tsai of TSRI; Javier Miralles Fuste of the Salk Institute for Biological Studies and the University of Gothenburg; and Jan Karlseder of the Salk Institute for Biological Studies.

The study was supported by the American Cancer Society (grant RSG-14-186-01), the Swedish Research Council International (grant D0730801) and the National Institutes of Health (grant R01GM087476 and R01CA174942).


Story Source:

Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.


Journal Reference:

  1. Julia Su Zhou Li, Javier Miralles Fuste, Tatevik Simavorian, Cristina Bartocci, Jill Tsai, Jan Karlseder, Eros Lazzerini Denchi. TZAP: A telomere-associated protein involved in telomere length control. Science, 2017; DOI: 10.1126/science.aah6752

MOSES, STEM CELL PATHWAYS AND MAYBE METASTATIC CANCERS

In ALL ARTICLES, DISEASE INFO, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS on January 20, 2017 at 9:32 am

When white blood cells leave a vessel through the vessel wall, they contort their shape to pass through.  But when stem cells exit a blood vessel, they don’t change their shape.  They just pass on through the wall and the endothelial cells lining the vessel do the work by stretching around them and then actively expelling them.   In other words, the stem cells are the Moses to the parting of the cells of the blood vessels:
“…when we looked at therapeutic stem cells… the endothelial cells not only changed their shape in order to surround the stem cell, they actually pushed the stem cells out of the blood vessel. We’ve named this process angiopellosis, and it represents an alternative way for cells to leave blood vessels.”  Which begs the question…is this how cancer cells move around too?

Stem Cell Finding May Improve Understanding of Metastatic Cancers

  • A stem cell exits the bloodstream through angiopellosis. [Alice MacGregor Harvey, North Carolina State University]

  • Researchers at North Carolina State University have discovered that therapeutic stem cells exit the bloodstream in a different manner than was previously thought. This process, called angiopellosis by the researchers, has implications for improving our understanding of not only intravenous stem cell therapies, but also metastatic cancers.

    When white blood cells need to get to the site of an infection, they can exit the bloodstream via a process known as diapedesis. In diapedesis, the white blood cell changes its shape to squeeze between or through the epithelial cells that form the walls of the blood vessel. Diapedesis is a well-understood process, and researchers believed that other types of cells, like therapeutic stem cells or even metastatic cancer cells, exited blood vessels in a similar way, with the cells pushing or squeezing themselves out.

    But a group of researchers led by Ke Cheng, Ph.D., associate professor of molecular biomedical sciences at NC State with a joint appointment in the NC State/University of North Carolina (UNC)-Chapel Hill Department of Biomedical Engineering, found that these stem cells behaved differently. Their study (“Angiopellosis as an Alternative Mechanism of Cell Extravasation”) appears online in Stem Cells.

    Therapeutic stem cells share the same ability to exit the bloodstream and target particular tissues that white blood cells do. But the precise way that they did so was not well understood, so Dr. Cheng and his team used a zebrafish model to study the process. The genetically modified zebrafish embryos were transparent and had fluorescently marked green blood vessels. Researchers injected the embryos with white blood cells and cardiac stem cells from humans, rats, and dogs. These cells had all been marked with a red fluorescent protein.

    Through time-lapse, three-dimensional, light sheet microscopic imaging, Dr. Cheng and his team could trace the progress of these cells as they left the blood vessel. The white blood cells exited via diapedesis, as expected. When stem cells exited the blood vessel, however, the endothelial cells lining the vessel actively expelled them. Membranes surrounding the endothelial cells on either side of the stem cell stretched themselves around the stem cell, then met in the middle to push the stem cell out of the vessel.

    “When you’re talking about diapedesis, the white blood cell is active because it changes its shape in order to exit. The endothelial cells in the blood vessel are passive,” Dr. Cheng says. “But when we looked at therapeutic stem cells, we found the opposite was true—the stem cells were passive—and the endothelial cells not only changed their shape in order to surround the stem cell, they actually pushed the stem cells out of the blood vessel. We’ve named this process angiopellosis, and it represents an alternative way for cells to leave blood vessels.”

    The researchers found two other key differences between angiopellosis and diapedesis: one, that angiopellosis takes hours, rather than minutes, to occur and two, that angiopellosis allows more than one cell to exit at a time.

    “Angiopellosis is really a group ticket for cells to get out of blood vessels,” notes Dr. Cheng. “We observed clusters of cells passing through in this way. Obviously, this leads us to questions about whether other types of cells, like metastatic cancer cells, may be using this more effective way to exit the bloodstream, and what we may need to do to stop them.”

 

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LATE STAGE OVARIAN CANCER CURED WITH STEM CELLS

In ALL ARTICLES, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on July 7, 2014 at 1:03 pm

ovarian-cancer-symptoms
Hue Hospital Succeeds in Treating Cancer with Stem Cell

Saigon – Doctors of Hue Central Hospital have used stem cell transplantation to successfully treat a cancer patient of the last stage. The Hue Central Hospital announced on June 26 that its doctors have cured Le Thi Sau, 52, who was suffering ovarian cancer in the last stage, with stem cell transplant. The operation is the success of the scientific project “Using stem cell in breast cancer and cervical cancer” managed by Professor Nguyen Duy Thang, deputy head of the hospital. Adult stem cells have been used to treat certain cancers through bone marrow transplants. In this therapy, the stem cells that give rise to the different blood cells in the body are transplanted into the bone marrow of the patient, where they regenerate the blood. The project was given green light to carry out in the Hue Central Hospital by the Ministry of Science and Technology. Professor Nguyen Duy Thang said the success of this method will pave the way for next operations on breast and ovarian cancer patients. In the time ahead, the hospital continues to treat two other cancer female patients with the stem cell treatment. It is hoped that the treatment will save many cancer patients. (www.saigon-gpdaily.com.vn June 27)

DO ADULT STEM CELLS CAUSE CANCER?

In ALL ARTICLES, SCIENCE & STEM CELLS, STEM CELLS IN THE NEWS, VICTORIES & SUCCESS STORIES on July 1, 2014 at 4:31 pm

NO!

cancer-free-zone

What do you get when you add 1,100 ADULT STEM CELL PATIENTS studied over 5 years,

plus another 1,873 ADULT STEM CELL PATIENTS studied over an average 12.5 years,

plus another ~7,000 ADULT STEM CELL PATIENTS in studies and FDA clinical trials data?

~10,000 ADULT STEM CELL TREATMENT PATIENTS showing NO CANCER!

 

“A total of 1873 patients were treated from 1990 to 2006 with bone marrow-derived concentrated cells. Patients were monitored for cancer incidence from the date of the first operation (1990) until death, or until December 31, 2011. The mean follow-up time was 12.5 years (range, five to twenty-two years)…No tumor formation was found at the treatment sites on the 7306 magnetic resonance images and 52,430 radiographs among the 1873 patients…This study found no increased cancer risk in patients after application of autologous cell-based therapy using bone marrow-derived stromal progenitor cells either at the treatment site or elsewhere in the patients after an average follow-up period of 12.5 years.

The upshot? This most recent study, as well as others, FDA clinical trials data, and the data we have published now amounts to about 10,000 patients who have been treated with adult stem cells and extensively tracked for this issue. There is no evidence that adult stem cells cause cancer. There is no rational reason for the fear, other than a completely different type of cell (ESC) that happens to have a similar name (stem cell) can cause teratomas – hence the confusion!”

Tumors, cancers and teratomas may result from Embryonic stem cell (ESC) treatments or Induced Pluripotent stem cell (iPSC) treatments

but NOT FROM ADULT STEM CELL TREATMENTS.

Sources:

RADIATION AND CANCER (MUST READ)

In ALL ARTICLES, DISEASE INFO on June 29, 2014 at 12:23 pm

RADIATION AND CANCER (MUST READ)

radiotherapy_malignancy

“Researchers from the Department of Radiation Oncology at the UCLA Jonsson Comprehensive Cancer Center report that radiation treatment TRANSFORMS CANCER CELLS INTO TREATMENT-RESISTANT BREAST CANCER STEM CELLS, even as it kills half of all tumor cells.”

“…In some cases, CANCER STEM CELLS ARE GENERATED by the therapy…”

“… if tumors are challenged by certain stressors that threaten them (such as radiation), they generate iBCSCs that may, along with surviving cancer stem cells, PRODUCE MORE TUMORS…”

For more info: http://www.greenmedinfo.com/blog/study-radiation-therapy-can-make-cancers-30x-more-malignant
Study: http://onlinelibrary.wiley.com/doi/10.1002/cncr.27701/full

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