Roche XCELLigence System For Cell Analysis To Provide Predictive Mechanistic Information For Small Molecule Compounds - Uncategorized

The extent to which protein targets are modulated by drugs or small molecule compounds depends on a number of factors, including the expression levels of the target, the effective concentration of the compound, and the time needed for the compound to perturb the target. One of the limitations of current multidimensional phenotypic profiling approaches is that typically a single time point is chosen to assess the effect of compounds. The conclusion, regarding the compounds mechanism of action, is based on the time point at which the samples are processed.

To address these restrictions, researchers Abassi et al. (1) have devised a live cell morphological profiling approach for dynamic monitoring of the effect of small molecule compounds that was based on impedance measurement of cells with the xCELLigence RTCA System of Roche Applied Science (SIX: RO, ROG; OTCQX: RHHBY). The approach was tested by screening a library containing FDA approved drugs, experimental compounds, and natural compounds. Compounds with similar activity produced similar impedance-based Time-dependent Cell Response Profiles (TCRPs). The compounds were clustered then based on TCRP similarity.

The researchers identified novel mechanisms for existing drugs, confirmed previously reported calcium modulating activity for COX-2 inhibitor celecoxib, and discovered an additional mechanism for the experimental compound monastrol. They also recognized and characterized a new antimitotic agent. This approach will also help to detect the off target effect of a given compound.

The TCRP technique described by Abassi et al. can overcome the limitations of current approaches, because the profile generated is time dependent. In combination with measurement of cell number, morphology, and adhesion, the TCR technique allows greater expansion of the ”biological space” at which compounds are screened. It provides ample opportunity to detect and identify biological activity associated with small molecules.

In conclusion, these findings indicate that the time-dependant resolution, provided by the TCRP approach, can be used in conjunction with phenotypic profiling approaches to obtain additional data associated with small molecule compounds. TCRP approach provides predictive mechanistic information for small molecule compounds.

The non-invasive and label-free xCELLigence analysis method, originally invented by ACEA Biosciences in San Diego, USA is based on measuring the impedance of cells. The technique utilizes an electronic readout of impedance to non-invasively quantify cellular status in real-time. Cells are seeded in E-Plate microtiter plates, which are integrated with microelectronic sensor arrays. The interaction of cells with the microelectrode surface generates a cell-electrode impedance response, which not only indicates cell viability but also correlates with the number of the cells seeded in the well. In conjunction with its user-friendly data collection and analysis capabilities, the xCELLigence System makes a unique platform for continuous, real-time cell-based assays and provides a huge opportunity for cellular and molecular biology.

For more information on the technology, please visit http://www.roche-applied-science.com.

Literature:
(1) Abassi YA et al.: Kinetic cell-based morphological screening: prediction of mechanism of compound action and off-target effects. Chem Biol 2009; 16:712-723

Source
Roche

Roche XCELLigence System For Cell Analysis To Provide Predictive Mechanistic Information For Small Molecule Compounds

Originally from:
http://www.medicalnewstoday.com/articles/162257.php

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Diagnosed at birth with Sickle Cell Anemia, Joseph Davis Jr. was saved by the stem cell rich cord blood of his newborn brother Isaac. Watch the story and read others at cordblood.com under the Real People Real Stories section.

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Researchers at the Keck School of Medicine of the University of Southern California (USC) have been awarded $2.9 million in grants from the California Institute for Regenerative Medicine (CIRM) to support research into stem cell discoveries that lay the foundation for future therapies.

The Basic Biology Awards received formal approval Thursday from the Independent Citizens Oversight Committee (ICOC), the 29-member governing board of the institute. The state’s stem cell agency awarded a total $16 million to researchers at five institutions in the first annual round of funding for Basic Biology Awards. The grants are intended to lead to advances in understanding the basic mechanisms underlying stem cell biology, cellular plasticity, and cellular differentiation.

Keck School of Medicine faculty members Martin Pera, PhD., director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, and Wange Lu, assistant professor of biochemistry & molecular biology, were among the 12 award recipients. Pera’s grant of approximately $1.4 million will fund studies into key processes involved with stem cell renewal. Lu’s grant of approximately $1.4 million will look into the molecular mechanisms of induced pluripotent stem (iPS) cells-cells that can be programmed to become any kind of tissue in the body.

“The research will provide new insights into how embryonic stem cells multiply in the laboratory and how they take the first steps into becoming specialized tissues,” says Pera. “The scientists will also learn more about the reverse of this process, specifically how cells from adult tissues can undergo conversion to a state resembling early embryonic cells. These findings will help in large scale production of various specialized cells for use in research or the treatment of disease.”

“Our research ultimately will allow us to improve methods to create patient-specific iPS cells for individualized cell replacement therapy, and disease-specific iPS cells which will help in research of the cause of diseases and screening for drugs to treat those diseases,” Lu says.
Alan Trounson, CIRM President, said these grants to fund basic biology will maintain the flow of new ideas entering the research pipeline. “These basic biology grants will generate new ideas for future therapies and also provide information to help overcome barriers in bringing therapies to patients,” he said.

Funding basic research is also a good economic investment, according to Trounson. Former acting NIH director Raynard Kington estimated that each dollar invested by the NIH stimulates $2.50 in associated economic activity.

CIRM was established when voters passed Proposition 71 in 2004 to borrow and spend $3 billion over 10 years to support stem cell research. To date, USC faculty members working at the USC Health Sciences Campus and its affiliate Childrens Hospital Los Angeles have secured more than $60 million in funding. USC is also part of the Southern California Stem Cell Scientific Collaboration (SC3), which is an agreement among six research institutions in Southern California allowing members to share training programs, scientific core facilities and expertise, and to team up on a wide range of research programs.

For more information on USC’s stem cell programs, please visit http://stemcell.usc.edu.

Source
University of Southern California

USC Researchers Receive $2.9 Million In Stem Cell Research Funding

Originally from:
http://www.medicalnewstoday.com/articles/162133.php

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For those of us who ride the metro regularly, knowing when the next train will arrive before you enter the station is a major convenience.

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Scientists in Switzerland have discovered a way to block the growth of human colon cancer cells, preventing the disease from reaching advanced stages and the development of liver metastases. The research, published today in EMBO Molecular Medicine, shows that blocking the so-called Hedgehog-GLI pathway can prevent the growth of tumours, metastatic lesions and cancer stem cells, the cells thought to lie at the root of cancer growth.

Colon cancer often begins in a treatable form when it is confined to the bowel wall, but in frequent cases it can develop to an incurable metastatic stage. A Geneva-based research team has discovered the essential role played by HH-GLI in the progression of colon cancer to these late and incurable stages. HH-GLI is a signalling pathway used by cells to communicate with each other, often used to determine position, growth and survival.

“Previous works hinted at the possible role of HH-GLI in colon cancer, but this was denied by other studies, so its involvement was never entirely clear,” said lead researcher Professor Ariel Ruiz i Altaba of Geneva University. “In this study we have proven that HH-GLI is essential for the development and growth of colon cancers. The research demonstrates the active presence of HH-GLI signalling in epithelial cells of colon cancers. Moreover, we find that metastatic tumours rely on this pathway for sustained growth. This identifies HH-GLI as a target for novel anti-cancer therapies against so far incurable forms of colon cancer in distant organs, such as the liver.”

This research opens the possibility of new anti-cancer therapies, specifically the use of RNA interference and of Cyclopamine, a plant product known to block Hedgehog pathway activity. This and other similar molecules can now be considered for future research as a treatment for terminal patients with metastatic disease and to fight resurgent forms of the disease.

“Recurrence is a major problem in cancer treatment. Even after a patient has displayed an apparent complete recovery from a primary tumour, recurrence at nearby or distal locations has a poor prognosis,” said Ruiz i Altaba. “While monitoring recovering mice we noted that tumours began to recur in all cases except for those treated with Cyclopamine for a short period of time after tumour disappearance. The treated mice were kept for up to one year after the treatment and remained healthy and tumour free.”

Using these genetic or pharmacologic methods to block HH-GLI activity also prevents cancer stem cell self-renewal. Using a new in vivo assay to test the participation of cancer stem cells in a growing tumour, the research team demonstrated the essential role of this pathway for the maintenance and survival of cancer stem cells.

“This work firmly establishes the critical action of HH-GLI in human colon cancer cells, providing the platform for preclinical and future clinical work.” concluded Ruiz i Altaba. “The finding that a blockade of HH-GLI for a relatively short period was sufficient to eliminate the tumour and prevent recurrence, without negatively affecting the health of the mice, opens the possibility for the use of a therapeutic window to eradicate the tumour without major side effects.”

Source:
Ben Norman

Wiley-Blackwell

Research Into The Role Of Pathway Gene Could Provide Novel Method To Treat Cancer Metastases

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Suze Orman discusses the benefits of cord blood storage and stem cell research!

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Scientist and Medical researchers believe that stem cell treatments have the potential to cure any known human diseases. This type of cell therapy introduces new cells into the damaged tissue to treat a disease or injury. Because stem cells are the master cells of the human body, they can produce copies of themselves and many other types of cells. This ability for stem cells to self-renew or regenerate offers a large potential to replace diseased and damaged human tissues in the body without the risk of rejection.

Stem cell treatment is considered to be the revolution of cellular medicine in the 21st century. Thousands of patients around the globe have already benefitted from using stem cell delivered safely by skilled and certified physicians. Diseases once considered incurable are responding well to stem cell treatment and are restoring hope to patients who thought they had lost their lives forever.

Some of the diseases that can be treated using stem cell treatment include brain damage, cancer, spinal cord injury, heart damage, haematopoiesis (blood cell formation), diabetes, orthopedics, deafness, blindness or vision impairment, neural and behavioral birth defects, Crohns disease and many more.

Though the benefits of stem cell treatment are a major breakthrough in the field of biotechnology, it is very expensive and only few physicians are licensed to do the procedure, especially in the Philippines. Only a handful of surgeons and physicians in the country are certified and have a broad experience in stem cell treatment.

For interested individuals who wish to submit in stem cell treatment, careful consideration and selection of the surgeon and physician to do the procedure should be a priority. They can ask the help and assistance of Asian Medical Tourism which have lists of certified and well-experienced physicians and surgeons specializing in stem cell treatment in the Philippines.

Asian Medical Tourism will also chaperone their clients through each health consultations so that they will have the opportunity of making an informed choice which will later lead into greater attainment and personal fulfillment in life.

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Article Source:http://www.articlesbase.com/health-articles/stem-cell-treatment-the-21st-century-medical-breakthrough-1159427.html