Cancer Forums and News by PhD's


News | Forums Register

Go Back   Cancer Forums and News by PhD's > Main Category > Main Forum

Reply
 
Thread Tools Display Modes
  #1  
Old 07-20-2012, 08:25 AM
Dross Dross is offline
Moderator
 
Join Date: Nov 2006
Posts: 883
Default Stem cell research aids understanding of cancer

The study, published in the journal Stem Cell, adds to our understanding of the role of stem and next stage progenitor cells in tissue regeneration and in the diagnosis and treatment of cancer. While stem cells are known to reside in organs such as the liver and pancreas, they are difficult to isolate. The new findings show that an antibody developed by the team can be used to capture the stem cells. Professor Pera, program leader for Stem Cells Australia and Chair of Stem Cell Sciences at the University of Melbourne, said the antibody was able to detect progenitor cells in disease states such as cirrhosis of the liver, and in cancers such as pancreatic adenocarcinoma and oesophageal carcinoma. “By being able to identify these cells, we hope to be able to learn more about their role in tissue regeneration and in cancer especially in the diagnosis and treatment of pancreatic cancer,” he said. “Cancers of the liver, pancreas and oesophagus are often very difficult to detect and challenging to treat.”

The large collaboration of scientists from around the world working on this study evolved over many years with research undertaken in Professor Pera’s laboratories at the then Australian Stem Cell Centre and at the University of Southern California Professor Pera and one of the co-authors on the paper, Dr Kouichi Hasegawa, were recently awarded an Australia-India Strategic Research Fund grant to continue their search for novel markers for liver, pancreatic and gut stem cells. Dr Hasegawa, who recently undertook a three month sabbatical at Stem Cells Australia, holds positions at Kyoto University’s Institute for Integrated Cell-Materials Sciences and at the Institute for Stem Cell Biology and Regenerative Medicine at the National Centre for Biological Sciences in Bangalore, India. “This funding will support us to develop more antibodies that can be used to assist in the identification and prospective isolation of stem and progenitor cells in these tissues and lead to the development of novel diagnostic and therapeutic reagents,” said Professor Pera.

Last edited by gdpawel : 07-24-2012 at 11:17 AM. Reason: post full article
Reply With Quote
  #2  
Old 07-20-2012, 10:13 AM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default Cancer Stem Cells Offer New Direction For Treatment

In a review in Science, a University of Rochester Medical Center researcher sorts out the controversy and promise around a dangerous subtype of cancer cells, known as cancer stem cells, which seem capable of resisting many modern treatments.

The article proposes that this subpopulation of malignant cells may one day provide an important avenue for controlling cancer, especially if new treatments that target the cancer stem cell are developed and combined with traditional chemotherapy and/or radiation.

"The fact that these concepts are steadily making their way into the clinic is exciting, and suggests that the recent interest in cancer stem cells may yield beneficial outcomes in potentially unexpected ways," wrote co-authors Craig T. Jordan, Ph.D., professor of Medicine at URMC and director of the James P. Wilmot Cancer Center Translational Research for Hematologic Malignancies program; and Jeffrey Rosen, Ph.D., the C.C. Bell Professor of Molecular and Cellular Biology and Medicine at Baylor College of Medicine.

Cancer stem cells (CSCs) are a hot topic in the scientific community. First identified in 1994 in relation to acute myeloid leukemia, CSCs have now been identified in several solid tumors in mice as well. Scientists who study CSCs believe they have distinct properties from other cancer cells, and may be the first cells to undergo mutations.

Research from the past 10 years suggests that because CSCs may be the root of cancer, they also might provide a new opportunity for a treatment. Jordan and a group of collaborators, for example, are testing a new drug compound based on the feverfew plant that demonstrates great potential in the laboratory for causing leukemia CSCs to self destruct.

Another new approach, the authors said, is the use of chemical screens to search drug libraries for already approved agents that may target CSCs, or make resistant tumor cells more sensitive to chemotherapy and radiation.

Cancer stem cell biologists hypothesize that any treatment that targets the source of origin rather than simply killing all cells, healthy and malignant, would be an improvement over most conventional therapies.

Some scientists, however, are uncertain if CSCs have unique biological properties or any relevance to treatment, the authors noted. What is more likely to fuel cancer, other studies have found, are unfavorable factors in the neighboring cells surrounding the tumor, such as mutated genes, proteins that encourage cell growth, and a poor immune system, for instance.

The most challenging issue facing CSC biologists is that the number and type of cancer stem cells can vary from patient to patient. In some tumor samples, for example, CSCs are rare while in others they constitute a large portion of the tumor mass, the authors said.

To understand why CSCs are so variable, investigators are trying to determine what genes and pathways are responsible for activating cancers that have a poor prognosis, and whether these cancers also have a higher frequency of CSCs.

"Whether the cancer stem cell model is relevant to all cancers or not," they wrote, "it is clear that we need new approaches to target tumor cells that are resistant to current therapies and give rise to recurrence and treatment failure."

An unexpected benefit of so much attention on normal stem cells is that it has stimulated research in areas not previously the focus of cancer therapies, Jordan and Rosen said.

For example, pathways known to be important for normal stem cell self-renewal, such as the Wnt, Notch and Hedgehog(Hh) pathways, are now of increased interest due to their potential role in CSCs. The first clinical trial using an agent to block the Notch pathway in combination with chemotherapy for breast cancer has begun.

The authors conclude by spotlighting the pressing need for preclinical models to test appropriate doses and combinations of CSC therapies before they can move into human clinical trials.

Source: University of Rochester Medical Center

[url]http://cancerfocus.org/forum/showthread.php?t=2883
__________________
Gregory D. Pawelski
Reply With Quote
  #3  
Old 08-12-2012, 11:25 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default Understanding Of Cancer Improved With The Help Of Stem Cell Research

An international team of researchers led by renowned stem cell scientist Professor Martin Pera has discovered a novel marker that plays an important role in our understanding of how cancer develops in the liver, pancreas and oesophagus.

The study, published in the journal Stem Cell, adds to our understanding of the role of stem and next stage progenitor cells in tissue regeneration and in the diagnosis and treatment of cancer.

While stem cells are known to reside in organs such as the liver and pancreas, they are difficult to isolate. The new findings show that an antibody developed by the team can be used to capture the stem cells.

Professor Pera, program leader for Stem Cells Australia and Chair of Stem Cell Sciences at the University of Melbourne, said the antibody was able to detect progenitor cells in disease states such as cirrhosis of the liver, and in cancers such as pancreatic adenocarcinoma and oesophageal carcinoma.

"By being able to identify these cells, we hope to be able to learn more about their role in tissue regeneration and in cancer especially in the diagnosis and treatment of pancreatic cancer," he said.

"Cancers of the liver, pancreas and oesophagus are often very difficult to detect and challenging to treat."

The large collaboration of scientists from around the world working on this study evolved over many years with research undertaken in Professor Pera's laboratories at the then Australian Stem Cell Centre and at the University of Southern California

Professor Pera and one of the co-authors on the paper, Dr Kouichi Hasegawa, were recently awarded an Australia-India Strategic Research Fund grant to continue their search for novel markers for liver, pancreatic and gut stem cells. Dr Hasegawa, who recently undertook a three month sabbatical at Stem Cells Australia, holds positions at Kyoto University's Institute for Integrated Cell-Materials Sciences and at the Institute for Stem Cell Biology and Regenerative Medicine at the National Centre for Biological Sciences in Bangalore, India.

"This funding will support us to develop more antibodies that can be used to assist in the identification and prospective isolation of stem and progenitor cells in these tissues and lead to the development of novel diagnostic and therapeutic reagents," said Professor Pera.

References: University of Melbourne "Understanding Of Cancer Improved With The Help Of Stem Cell Research." Medical News Today. MediLexicon, Intl., 24 Jul. 2012.
__________________
Gregory D. Pawelski
Reply With Quote
Sponsored Links
Advertisement
  #4  
Old 08-18-2012, 01:24 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default Therapeutic Targeting of Cancer Stem Cells

Front Oncol. 2011; 1: 10. doi: 10.3389/fonc.2011.00010 PMCID: PMC3356019

Therapeutic Targeting of Cancer Stem Cells

Marcello Maugeri-Saccà,1, Ann Zeuner,1, and Ruggero De Maria,1,2

1. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

2. Mediterranean Institute of Oncology, Viagrande, Catania, Italy

Abstract

Recent breakthroughs in translational oncology are opening new perspectives for the treatment of cancer. The advent of targeted therapies has provided the proof-of-concept to selectively turn-off deregulated oncogenic proteins, while the identification and validation of predictive biomarkers of response has allowed to improve, at least in some cases, their performance. Moreover, a subpopulation of tumor-propagating cells has been identified from many solid and hematological tumors. These cells share functional properties of normal stem cells, and are commonly referred to as cancer stem cells (CSCs). It is emerging that CSCs are defended against broadly used anticancer agents by means of different, partly interconnected, mechanisms. However, CSCs rely on specific pathways involved in self-renewal that can be pharmacologically antagonized by experimental molecular targeted agents, some of which have recently entered early phases of clinical development. Here, we discuss the spectrum of pharmacological strategies under clinical or preclinical development for CSCs targeting.

[url]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3356019/
__________________
Gregory D. Pawelski
Reply With Quote
  #5  
Old 01-13-2013, 12:35 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default Cancer Is A Stem Cell Issue, Says European Science Foundation

There is an urgent reason to study stem cells: stem cells are at the heart of some, if not all, cancers. Mounting evidence implicates a clutch of rogue stem cells brandishing ‘epigenetic’ marks as the main culprits in cancer. Wiping out tumours for good, some biologists believe, depends on uprooting these wayward stem cells.

A team in the Netherlands has uncovered a key protein that could stop these stem cells from becoming malignant. “This is a hot topic in the cancer field,” Maarten van Lohuizen of The Netherlands Cancer Institute, Amsterdam told participants at a EuroSTELLS workshop, held in Montpellier, France, 23-24 January. “To be successful in cancer therapy you need to target these stem cells: they are intrinsically resistant to chemotherapy.”

Polycomb proteins have emerged as key players in cancer pathogenesis. They are powerful epigenetic regulators that normally silence genes without altering the cell’s DNA. Compounds that regulate polycomb could result in novel anticancer drugs that shrink malignant tissue, and prevent cancer recurrence, a common problem with most chemotherapies.

That tumours and stem cells have much in common has been known for many years. Both self-renew and both spawn many different types of cells. But only recently, new techniques have enabled biologists to identify stem cells buried in tumours.

Van Lohuizen has found that stem cells in cancerous tissues are locked in an immature state in which they carry on multiplying instead of maturing into specific tissues. “Some resistant cancer cells don’t listen to the ‘stop’ signal any more,” he explains. That stop sign is delivered by the polycomb proteins. They silence several genes at once by affecting the way the DNA is compacted into chromatin fibres, without altering the DNA sequence.

Normally, the main role of the polycomb complex is to repress genes during development or when stem cells are needed for tissue maintenance. But an aberrant polycomb spells trouble. In mice where polycomb proteins have been genetically disabled, van Lohuizen has seen that the cells become invasive and trigger cancerous growth. “This may be why gliomas are such lethal tumours, because these stem cells become highly migratory,” van Lohuizen points out.

The hunt is now on for therapeutic agents that target these budding cancer stem cells. The Dutch researcher is optimistic that used in combination with chemotherapy, such compounds will also prevent cancer reigniting after treatment. “We have to be very careful because [these compounds] will also regulate normal stem cell behaviour. It is a fine balance,” he noted.

EuroSTELLS is the European Collaborative Research (EUROCORES) programme on “Development of a Stem Cell Tool Box” developed by the European Science Foundation.

The European Science Foundation (ESF) provides a platform for its Member Organisations to advance European research and explore new directions for research at the European level.

Established in 1974 as an independent non-governmental organisation, the ESF currently serves 75 Member Organisations across 30 countries.

European Science Foundation
__________________
Gregory D. Pawelski
Reply With Quote
Sponsored Links
Advertisement
  #6  
Old 01-13-2013, 12:37 PM
gdpawel gdpawel is offline
Moderator
 
Join Date: Feb 2007
Location: Pennsylvania
Posts: 4,354
Default Tissue culture: unlocking the mysteries of viruses and cancer

Tissue culture methods have made gene therapy and stem cell research possible. The ability to transfect cultured cells with DNA gene sequences has allowed us to assign functions to different genes and understand the mechanisms that activate or redress their function. By the 1960s, cell culture technology was well established in cancer research. The time was right for the interaction between cell biology and genetics that gave birth to molecular biology. Without cell culture, gene therapy and the use of stem cells to repopulate damaged organs would be beyond imagination.

The study of Cell Function Analysis tells us that even when the disease is the same type, different patients' tumors respond differently to the same agents. So it doesn't matter if there is a "target" molecule in the cell that the "targeted" drug is going after, if the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial.

Over the past few years, gene expression profiling has been suggested as the best or only way of determining ex vivo drug sensitivity. However, the clinical applicaton of these DNA content assays have been shown to correlate only with response and not survival. And due to almost all patients being treated with combination chemotherapy, this methodology cannot even be calibrated without the use of Cell Function Analysis. This analysis can actually integrate all the gene expression into one convenient test result.

In obtaining information from gene mutations (DNA content assays) and/or gene expression (RNA content) it must be realized that DNA structure is only important insofar as it predicts for RNA content, which is only important insofar as it predicts for protein content, which is only important insofar as it predicts for protein function, which is important only insofar as it predicts for cell response, which is only important insofar as it predicts for tumor response and function. In other words, it correlates only with response and not survival, in entirely retrospective (not prospective) studies.

What are the data supporting the use of testing DNA, RNA and Protein expression? Two retrospective studies from two Harvard-affiliated hospitals, showing response, but not survival advantages, with a grand total of twenty six correlations. And a subsequent study, presented in the July 14, 2005 issue of the New England Journal of Medicine from another laboratory that did not show correlations between gene mutations and patient survival (Volume 353:133-144 Number 2).

There is Cell Function Analysis (functional profiling) that shows data indicating a near doubling in the survival of patients with platinum resistant ovarian cancer, striking correlations between platinum activity and patient survival in previously-untreated ovarian cancer, and a comprehensive meta-analysis of scores of studies reporting response and survival correlations in thousands of patients.

Plus a recent study using an angiogenesis assay describing correlations between cell culture assay results and survival in patients with non-small cell lung cancer. These correlations were based on the actual assay results which had been reported, in real time, prospectively to the doctors who had ordered the assay laboratory tests. There were striking correlations between test results and patient survival, not just response.

Not only is cellular profiling a very important predictive test, but it is a unique tool for identifying newer, better drugs, testing drug combinations, and serving as a "gold standard" to develop new DNA, RNA, and protein-based tests of drug activity.

BMJ 2007;334(suppl_1):s18 (6 January), doi:10.1136/bmj.39034.719942.94

[url]http://www.bmj.com/cgi/content/full/334/suppl_1/s18
__________________
Gregory D. Pawelski
Reply With Quote
Sponsored Links
Advertisement
Reply


Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

vB code is On
Smilies are On
[IMG] code is On
HTML code is Off
Forum Jump


All times are GMT -5. The time now is 05:49 PM.