The worst bone tumors not found to be driven by pathways activated in most K9 bone tumors

Main Category: Cancer / Oncology
Also Included In: Bones / Orthopedics
Article Date: 26 Jul 2013 - 0:00 PDT Current ratings for:
The worst bone tumors not found to be driven by pathways activated in most K9 bone tumors

Many cancers show inappropriate activation of a cell signaling pathway called NOTCH. In the developing body, NOTCH tells brain cells to grow and proliferate. It should be quiet in the adult body, but cancers restart NOTCH to drive their own growth, far and beyond the rate of healthy tissues. A Colorado State University and University of Colorado Cancer Center study expected to find NOTCH signaling elevated in K9 osteosarcoma samples, gathered from patients at the CSU Flint Animal Cancer Center. What they found surprised the researchers: overall, NOTCH signaling was elevated in K9 osteosarcoma, but aspects of Notch signaling were noticeably deactivated in the worst cancers.

"We split the samples into two groups: poor responders who had gone less than 100 days after treatment before the progression of their disease, and strong responders who had made it more than 300 days after their treatment without disease progression. Then we could explore the genetic differences between these two groups," says Dawn Duval, PhD, CU Cancer Center investigator and associate professor of molecular oncology at Colorado State University.

Specifically, Duval and colleagues including first author Deanna Dailey, DVM, looked at the expression of a protein called HES1, which is used as a proxy to test for NOTCH activation. High HES1 means that upstream, NOTCH is firing. Low HES1 means it's not firing or that some other pathway is interfering. They expected to find a linear increase in HES1 as cancers and outcomes got worse - more HES1 would have meant more NOTCH signaling and results in other cancers imply that the more NOTCH, the worse the outcomes.

"What we found is that the poor responders had lower HES1. That fit nothing we expected," Duval says.

The osteosarcoma samples from dogs with disease progression in the shortest amount of time, also had the lowest levels of HES1.

"We had to go back and try to figure out what was happening, so we measured HES1 levels in normal bone samples and matched bone tumors. For good measure we also looked at several other Notch pathway markers. What we found was that, in general, Notch signaling was activated in the bone tumors, both good and bad, but that HES1 seemed to be disconnected from Notch signaling in the most aggressive tumors."

They validated the finding by examining HES1 protein expression in over 60 tumors and correlating it with cancer progression. This was the real deal: HES1 was down in the most aggressive K9 osteosarcomas.

"I have many hypotheses why. Here are a couple different ones, most of which have been worked out by Deanna," Duval says. "First, it may be that NOTCH is up due to the proliferation that occurs in most cancers, but that something else is driving the worst ones and this pathway interferes with HES1 expression. For example, another signaling pathway called Hedgehog, which can also affect the level of HES1 is deactivated in these aggressive osteosarcomas and so the level of HES1 may be down because Hedgehog was down. Maybe most interestingly, in the development of neurons, you can see an oscillation of HES1 - it has to go up and then down in order for cells to progress through their cycles. Maybe these osteosarcoma cells have overcome this regulatory pattern to progress?"

For now, the finding of low HES1 signaling in the worst K9 osteosarcomas remains a counterintuitive mystery. Dr. Duval's ongoing work hopes to provide answers to this surprising finding.

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Evidence of 'embryonic-like' cells in marrow of adult mice not found by stanford scientists

Main Category: Stem Cell Research
Article Date: 26 Jul 2013 - 1:00 PDT Current ratings for:
Evidence of 'embryonic-like' cells in marrow of adult mice not found by stanford scientists

Research on human embryonic stem cells has been a political and religious lightning rod for more than a decade.

The cells long have been believed to be the only naturally occurring pluripotent cells. (Under the right conditions, pluripotent cells can become any other cell in the body.) But some people object to the fact that the embryo is destroyed during their isolation. Induced pluripotent stem cells, created by experimentally manipulating an adult cell such as a skin or nerve cell, are much more ethically palatable. But many researchers feel it is important to continue studying both types of cells.

In 2006, a group of researchers led by Mariusz Ratajczak, MD, PhD, at the University of Louisville, described another possible alternative: a special population of very small, pluripotent embryonic-like cells in adult bone marrow of mice and humans. These cells, called VSEL (very small embryonic-like) cells, presumably arise through the self-renewal of embryonic stem cells during the developmental process and, as described, could provide all the benefits of embryonic stem cell research with none of the ethical controversy. However, subsequent research from other labs has provided conflicting results as to the pluripotency - and even the existence - of VSEL cells in bone marrow.

A company, NeoStem, has proposed a human clinical trial of the cells for periodontitis to begin this year.

But scientists in the laboratory of Irving Weissman, MD, a professor of pathology at the Stanford University School of Medicine, say they have been unable to identify any very small, pluripotent cells in the bone marrow of mice, despite exhaustive efforts to duplicate the original experimental procedures.

"It has become important to know to what extent and where these VSEL cells exist to understand how they may affect the field of stem cell research," said Weissman, who directs Stanford's Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford. "We tried as hard as we could to replicate the original published results using the methods described and were unable to detect these cells in either the bone marrow or the blood of laboratory mice."

Although other groups have seemingly confirmed the existence of these cells as defined by size and the expression of key cell-surface molecules, Weissman's study is the first to evaluate the biological potency of the cells.

The research was published online in Stem Cell Reports. Weissman, who is also the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research and a member of the Stanford Cancer Institute, shares senior authorship of the study with instructor Jun Seita, MD, PhD. Postdoctoral scholars Masanori Miyanishi, PhD, and Yasuo Mori, MD, PhD, are the lead authors.

Using a variety of methods, the researchers found that most of the very small (less than 5 micrometers in diameter) particles in mouse-bone marrow were not cells, but were in fact cell debris or dead cells with a less-than-normal complement of DNA. Because it can be difficult to determine actual cell size, they opted to include even larger cells in their subsequent analysis.

Another way the cells are defined is by the expression, or lack of expression, of a combination of key molecules on their surface. Specifically, the cells are defined as CD45-/intLin-SCA-1+. Weissman and his colleague found that cells from the mouse-bone marrow meeting this criteria, or phenotype, failed to express the stem-cell-specific marker Oct-4, were unable to form spheres in culture (a hallmark of pluripotent cells) and could not differentiate into any cells of the hematopoietic, or blood-forming, system.

"A true pluripotent cell would be able to differentiate into any tissue type," said Weissman. "But we couldn't confirm that cells of that size or phenotype could generate hematopoietic cells with any reliability."

Weissman has previously proposed three key tenets necessary to prove the accuracy of a scientific result: The original finding must be published in a peer-reviewed journal; the experiment must be repeatable, as published, by many independent laboratories; and the finding as described should be detected by multiple experimental methods. Although the original research was peer-reviewed and published, the difficulty experienced by other labs attempting to replicate the findings has led the Weissman group to conclude in the paper that "the existence of adult mouse VSELs in the bone marrow remains dubious."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our stem cell research section for the latest news on this subject.

Other Stanford researchers involved in the work were graduate student James Chen; Seth Karten, MD, an academic research and program officer; and postdoctoral scholar Charles Chan, PhD.

The study was supported by fellowships from the Toyobo Biotechnology Foundation, the Uehara Memorial Foundation, Human Frontier Science Program, the Japan Society for the Promotion of Science, the National Institutes of Health (grants R01CA086065 and U01HL099999), the California Institute for Regenerative Medicine and the Leukemia & Lymphoma Society.

Hiromitsu Nakauchi is a shareholder and a member of the scientific advisory board of ReproCELL Inc. and Megakaryon Inc., and a member of the scientific advisory board of Shionogi Inc. Weissman is a member of the scientific advisory board and is a director of StemCells Inc.

Stanford University Medical Center

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Superbug Infections Found During Admission Screenings In Virginia

Main Category: MRSA / Drug Resistance
Also Included In: Infectious Diseases / Bacteria / Viruses;  Public Health
Article Date: 11 Jul 2013 - 1:00 PDT Current ratings for:
Superbug Infections Found During Admission Screenings In Virginia

Antibiotic-resistant superbugs like carbapenem-resistant Enterobacteriaceae (CRE) present a challenge to healthcare professionals as patients move from different care settings and facilities, unknowingly spreading healthcare-associated infections. In a new study, researchers screened all patients for CRE at admission to a long-term acute care hospital (LTACH). They found patients colonized with CRE coming into the LTACH from hospitals, but they also found transmission occurring among patients in the LTACH. LTACHs provide similar care as hospitals but focus on patients who, on average, stay more than 25 days.

The findings of this study provide an indication of the prevalence of CRE in hospitalized patients in one specific region, as well as the frequency of transmission based on transitions between healthcare facilities. The study is published in the August issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

"Identification of asymptomatic CRE carriers admitted to LTACHs may help identify patients who could benefit from interventions that reduce risks for subsequent CRE transmission and break cycles of resistance that develop when patients move between healthcare facilities," said Costi Sifri, MD, an author of the study.

Recent research has shown that LTACHs can play important roles in the regional transmission of CRE. These facilities are reservoirs of healthcare-associated infections, since patients admitted to these facilities are highly susceptible to CRE colonization due to risk factors such as complex medical conditions, extended hospitalizations, invasive medical devices and unnecessary antibiotic use.

Researchers at the University of Virginia Health System prospectively screened patients admitted to a 40-bed central Virginia LTACH for CRE colonization. Additionally, weekly surveillance for CRE was performed on all patients in the facility. During the 24-month study period, 262 patients received care at the LTACH and 20 had positive CRE cultures.

The investigators identified six patients positive for CRE on admission who had no known history of CRE infection or colonization. Two of these patients were admitted from the affiliated academic hospital and four were admitted from four separate regional hospitals.

Additionally, six patients had a prior history of CRE colonization or infection and seven patients had no known history of CRE infection or colonization, but tested positive during hospitalization.

In a commentary published alongside the study, L. Silvia Munoz-Price, MD, Associate Professor of Medicine at University of Miami notes "healthcare professionals who work in this field are concerned with the inter-facility, inter-regional, and inter-continental spread of CREs. However, we are attempting to solve a population health problem by using snapshots of what occurs in our own hospitals or within a limited set of facilities where we have professional networks - over simplifications are hindering us from determining the extent in which all the contributing factors are affecting this dynamic population model."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our mrsa / drug resistance section for the latest news on this subject.

Jessica D. Lewis, Matthew Bishop, Brenda Heon, Amy J. Mathers, Kyle B. Enfield, Costi D. Sifri. "Admission Surveillance for Carbapenamase-Producing Enterobacteriaceae at a Long-TermAcute Care Hospital." Infection Control and Hospital Epidemiology 34:8 (August 2013).

Society for Healthcare Epidemiology of America

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'Superbug Infections Found During Admission Screenings In Virginia'

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Superbug Infections Found During Admission Screenings In Virginia

Main Category: MRSA / Drug Resistance
Also Included In: Infectious Diseases / Bacteria / Viruses;  Public Health
Article Date: 11 Jul 2013 - 1:00 PDT Current ratings for:
Superbug Infections Found During Admission Screenings In Virginia

Antibiotic-resistant superbugs like carbapenem-resistant Enterobacteriaceae (CRE) present a challenge to healthcare professionals as patients move from different care settings and facilities, unknowingly spreading healthcare-associated infections. In a new study, researchers screened all patients for CRE at admission to a long-term acute care hospital (LTACH). They found patients colonized with CRE coming into the LTACH from hospitals, but they also found transmission occurring among patients in the LTACH. LTACHs provide similar care as hospitals but focus on patients who, on average, stay more than 25 days.

The findings of this study provide an indication of the prevalence of CRE in hospitalized patients in one specific region, as well as the frequency of transmission based on transitions between healthcare facilities. The study is published in the August issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

"Identification of asymptomatic CRE carriers admitted to LTACHs may help identify patients who could benefit from interventions that reduce risks for subsequent CRE transmission and break cycles of resistance that develop when patients move between healthcare facilities," said Costi Sifri, MD, an author of the study.

Recent research has shown that LTACHs can play important roles in the regional transmission of CRE. These facilities are reservoirs of healthcare-associated infections, since patients admitted to these facilities are highly susceptible to CRE colonization due to risk factors such as complex medical conditions, extended hospitalizations, invasive medical devices and unnecessary antibiotic use.

Researchers at the University of Virginia Health System prospectively screened patients admitted to a 40-bed central Virginia LTACH for CRE colonization. Additionally, weekly surveillance for CRE was performed on all patients in the facility. During the 24-month study period, 262 patients received care at the LTACH and 20 had positive CRE cultures.

The investigators identified six patients positive for CRE on admission who had no known history of CRE infection or colonization. Two of these patients were admitted from the affiliated academic hospital and four were admitted from four separate regional hospitals.

Additionally, six patients had a prior history of CRE colonization or infection and seven patients had no known history of CRE infection or colonization, but tested positive during hospitalization.

In a commentary published alongside the study, L. Silvia Munoz-Price, MD, Associate Professor of Medicine at University of Miami notes "healthcare professionals who work in this field are concerned with the inter-facility, inter-regional, and inter-continental spread of CREs. However, we are attempting to solve a population health problem by using snapshots of what occurs in our own hospitals or within a limited set of facilities where we have professional networks - over simplifications are hindering us from determining the extent in which all the contributing factors are affecting this dynamic population model."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our mrsa / drug resistance section for the latest news on this subject.

Jessica D. Lewis, Matthew Bishop, Brenda Heon, Amy J. Mathers, Kyle B. Enfield, Costi D. Sifri. "Admission Surveillance for Carbapenamase-Producing Enterobacteriaceae at a Long-TermAcute Care Hospital." Infection Control and Hospital Epidemiology 34:8 (August 2013).

Society for Healthcare Epidemiology of America

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Society for Healthcare Epidemiology of America. "Superbug Infections Found During Admission Screenings In Virginia." Medical News Today. MediLexicon, Intl., 11 Jul. 2013. Web.
11 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Superbug Infections Found During Admission Screenings In Virginia'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

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All opinions are moderated before being included (to stop spam)

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Summer Hairstyles That Won't Fall Flat? We Found Them!

Mad Men's resident vixen, Christina Hendricks, incorporates lots of long layers into her curly bob, which prevents the hairstyle from feeling bottom-heavy. For similarly soft waves, curl 2-in. sections using a medium-shaft iron, alternating direction from section to section.

Try a layered haircut on yourself using our Virtual Makeover tool.

View the original article here

Summer Hairstyles That Won't Fall Flat? We Found Them!

Mad Men's resident vixen, Christina Hendricks, incorporates lots of long layers into her curly bob, which prevents the hairstyle from feeling bottom-heavy. For similarly soft waves, curl 2-in. sections using a medium-shaft iron, alternating direction from section to section.

Try a layered haircut on yourself using our Virtual Makeover tool.

View the original article here