[Source: PRNews Wire] - Systems Medicine LLC (SM), a wholly-owned subsidiary of Cell Therapeutics, Inc. (CTI) , presented data from a preclinical study identifying the genetic markers in patients more likely to respond to treatment with the experimental drug, brostallicin, at the 2008 American Association for Cancer Research (AACR) annual meeting. These findings will be used to guide future development of brostallicin by suggesting which patients are most likely to respond when treated with brostallicin, potentially making the drug's development more efficient. This method of drug development is known as the context of vulnerability approach. The study was co-directed by Jeffrey A. Kiefer, Ph.D., and Holly Yin, Ph.D. in the Translational Genomics Research Institute's Pharmaceutical Genomics Division located in Scottsdale, Arizona.
"This study is an example of using a pharmacogenomic screening approach to find insights that guide the selection of specific contexts of vulnerability for brostallicin. These results provide information on which genetic characteristics to look for in determining whether or not a patient might benefit from treatment with brostallicin. In SM and CTI's continued efforts to make cancer more treatable, results like these broaden our knowledge of brostallicin's context of vulnerability, and bring us closer to being able to offer the right drug to each patient," said Jeffrey Jacob, CEO of SM.
In the study, the NCI-60 cell line panel was profiled for brostallicin response and correlated with specific genomic information derived from the cell line panel. The NCI-60 is a group of 59 human cancer cell lines derived from tumor tissue -- brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate, and skin. Scientists often use cell lines, also called models, in preclinical studies in a laboratory setting. The information learned from preclinical studies helps guide the design of future clinical trials. An integrative knowledge mining strategy was used to identify the genomic and functional consequences of brostallicin response. According to the study abstract, "Gene Set Enrichment Analysis (GSEA) revealed unique associations between cells' sensitivity to brostallicin," and distinct sets of genes, "including significant associations with particular aspects of DNA repair." In addition to correlative genomic analyses on the NCI-60 cell line panel, a high-throughput siRNA (HT-RNAi) screen was conducted to functionally identify those gene products involved in brostallicin response. RNA interference is an experimental technique that allows for the targeted reductions of gene expression. A systematic evaluation
of 7,000 genes was conducted in a cisplatin resistant variant of the ovarian cancer cell line A2780. A number of interesting 'hits' or targets were identified in the screen that modulate the cells sensitivity to brostallicin and represent unique and functionally based contexts of vulnerability.
Knowledge mining of the brostallicin siRNA gene hits revealed enrichment of a number of important molecular concepts and important genes involved in DNA repair. On the basis of these and related studies, a clinical trial will soon be initiated specifically targeting patients with genetic defects in mismatch repair genes such as BRCA1 and 2, which are associated with susceptibility for breast and ovarian cancer.
To review the poster and see more detailed information about
the study, please go to http://www.celltherapeutics.com/investors_news-updates.html
Wednesday, April 16, 2008
Tuesday, April 15, 2008
Clinical trial data and cutting-edge testing give key insights in the fight against basal cell carcinoma and pancreatic cancer
[SOurce: TGen] - Clinical researchers at Scottsdale Healthcare and TGen today announced the results of two clinical trials that show promise for patients battling cancer.
The Phase I clinical trial findings, presented at the this weeks Annual Meeting of the American Association for Cancer Research by Daniel Von Hoff, MD, FACG, focused on basal cell carcinoma (BCC) and pancreatic cancer. The Arizona trials were conducted at TGen's Clinical Research Service (TCRS) at Scottsdale Healthcare, a strategic alliance between TGen and Scottsdale Healthcare’s Clinical Research Institute.
Basal Cell Carcinoma In the first trial, a novel molecule, GDC-0449, shrinks tumors in basal cell carcinoma (BCC) while having limited side effects, including a loss of sense of taste, and a small amount of hair loss and weight loss, suggesting a viable new treatment option. GDC-0449 works by blocking a pathway — a series of chemical reactions within a cell— known as Hedgehog, containing two genes (PTCH and SMO) that lead to a known tumor-promoting gene called GLI1. Alterations in any of these genes have been shown to lead to basal cell carcinoma and other diseases. GDC-0449 is a chemical synthetic designed to replicate the properties of cyclopamine, a chemical found in nature.
“Basal cell carcinoma affects about one million people a year and a proportion of these patients have disease that is not curable with surgery. We currently do not have any treatments that can effectively slow tumor growth in these advanced patients. This finding has potential importance in this population,” said Daniel D. Von Hoff, M.D., Physician in Chief at the Translational Genomics Research Institute (TGen) and Chief Medical Officer for the Scottsdale Clinical Research Institute at Scottsdale Healthcare.
Typically diagnosed with a simple biopsy, the risk of BCC increases for those individuals with a family history, or prolonged exposure to ultraviolet (or UV) rays from the sun. While BCC has an extremely low rate of metastasis, it can lead to scarring and disfigurement if left untreated.
The trial results showed durable clinical benefit —defined as tumor shrinkage visible on X-ray or other physical exam or improvement in symptoms without tumor growth— was observed in eight out of the nine patients evaluated.
The first patient treated in the trial has shown clinical improvement for approximately 450 days and is ongoing, Von Hoff says, with almost no side effects beyond minimal hair loss.
“He came to us short of breath and in pain, but he has had a very dramatic response with this drug,” Von Hoff said.
Further evaluations of the study participants measured the presence of GLI1 in skin cells sampled from the participants. Among all patients tested to date, there was reduction in this marker, indicating that the drug was affecting the hedgehog pathway.
The trial, sponsored by Genentech, also included clinical sites at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland and Karmanos Cancer Institute, Detroit, Michigan.
Pancreatic Cancer In the second trial, Von Hoff and colleagues showed that a novel combination of two drugs (nanoparticle albumin-bound paclitaxel, or “nab-pacilitaxel” and gemcitabine) showed a significant clinical benefit in more than 80 percent of pancreatic cancer patients. “Unfortunately, most patients with pancreatic cancer have a very poor survival, and until now, the only option has been gemcitabine alone or in combination with erlotinib,” said Von Hoff.
The researchers utilized the Target Now™ tumor profiling analysis, a cutting-edge oncology testing service performed by Caris Dx and Caris MPI, to better understand the characteristics expressed in patient’s tumors. In this ongoing research program, Von Hoff and colleagues found the SPARC (Secreted Protein Acidic and Rich in Cysteine) protein to be commonly found in pancreatic cancer specimens. The SPARC protein is being investigated by Abraxis BioScience in this trial as a potential target for nab-paclitaxel. A test for SPARC, developed at Abraxis and Caris MPI and applied by Caris MPI under contract with Abraxis, was utilized to analyze SPARC in the pancreatic cancer patients in the trial.
The finding of SPARC protein in pancreatic cancer patients, also described by other investigators, was the basis for this phase I clinical trial that Von Hoff presented at AACR.
“Chemotherapy often means combining more than one drug, and we do not want to just take the next thing off the shelf. We want to know as much about a tumor as possible going in,” Von Hoff said.
Researchers reported on the first 20 patients of what will eventually be a 42-patient trial.
“This was a phase I trial, and phase I trials are usually designed to test safety, hoping it will also determine efficacy. The fact that we saw this kind of activity in a phase I trial is dramatic,” Von Hoff said.
“The rationale behind the combination of Gemcitabine plus Abraxane was based on careful science and was designed and executed by some of the leading experts in pancreas cancer in the world. While the data is preliminary and longer follow-up will be important, the biochemical and radiographic responses look very encouraging”, says Dr. Laheru of Johns Hopkins Kimmel Cancer Center.
The trial, sponsored by Abraxis BioScience, also included clinical sites at South Texas Oncology and Hematology, P.A., San Antonio, Texas, University of Alabama at Birmingham, Birmingham, Alabama, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
The Phase I clinical trial findings, presented at the this weeks Annual Meeting of the American Association for Cancer Research by Daniel Von Hoff, MD, FACG, focused on basal cell carcinoma (BCC) and pancreatic cancer. The Arizona trials were conducted at TGen's Clinical Research Service (TCRS) at Scottsdale Healthcare, a strategic alliance between TGen and Scottsdale Healthcare’s Clinical Research Institute.
Basal Cell Carcinoma In the first trial, a novel molecule, GDC-0449, shrinks tumors in basal cell carcinoma (BCC) while having limited side effects, including a loss of sense of taste, and a small amount of hair loss and weight loss, suggesting a viable new treatment option. GDC-0449 works by blocking a pathway — a series of chemical reactions within a cell— known as Hedgehog, containing two genes (PTCH and SMO) that lead to a known tumor-promoting gene called GLI1. Alterations in any of these genes have been shown to lead to basal cell carcinoma and other diseases. GDC-0449 is a chemical synthetic designed to replicate the properties of cyclopamine, a chemical found in nature.
“Basal cell carcinoma affects about one million people a year and a proportion of these patients have disease that is not curable with surgery. We currently do not have any treatments that can effectively slow tumor growth in these advanced patients. This finding has potential importance in this population,” said Daniel D. Von Hoff, M.D., Physician in Chief at the Translational Genomics Research Institute (TGen) and Chief Medical Officer for the Scottsdale Clinical Research Institute at Scottsdale Healthcare.
Typically diagnosed with a simple biopsy, the risk of BCC increases for those individuals with a family history, or prolonged exposure to ultraviolet (or UV) rays from the sun. While BCC has an extremely low rate of metastasis, it can lead to scarring and disfigurement if left untreated.
The trial results showed durable clinical benefit —defined as tumor shrinkage visible on X-ray or other physical exam or improvement in symptoms without tumor growth— was observed in eight out of the nine patients evaluated.
The first patient treated in the trial has shown clinical improvement for approximately 450 days and is ongoing, Von Hoff says, with almost no side effects beyond minimal hair loss.
“He came to us short of breath and in pain, but he has had a very dramatic response with this drug,” Von Hoff said.
Further evaluations of the study participants measured the presence of GLI1 in skin cells sampled from the participants. Among all patients tested to date, there was reduction in this marker, indicating that the drug was affecting the hedgehog pathway.
The trial, sponsored by Genentech, also included clinical sites at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland and Karmanos Cancer Institute, Detroit, Michigan.
Pancreatic Cancer In the second trial, Von Hoff and colleagues showed that a novel combination of two drugs (nanoparticle albumin-bound paclitaxel, or “nab-pacilitaxel” and gemcitabine) showed a significant clinical benefit in more than 80 percent of pancreatic cancer patients. “Unfortunately, most patients with pancreatic cancer have a very poor survival, and until now, the only option has been gemcitabine alone or in combination with erlotinib,” said Von Hoff.
The researchers utilized the Target Now™ tumor profiling analysis, a cutting-edge oncology testing service performed by Caris Dx and Caris MPI, to better understand the characteristics expressed in patient’s tumors. In this ongoing research program, Von Hoff and colleagues found the SPARC (Secreted Protein Acidic and Rich in Cysteine) protein to be commonly found in pancreatic cancer specimens. The SPARC protein is being investigated by Abraxis BioScience in this trial as a potential target for nab-paclitaxel. A test for SPARC, developed at Abraxis and Caris MPI and applied by Caris MPI under contract with Abraxis, was utilized to analyze SPARC in the pancreatic cancer patients in the trial.
The finding of SPARC protein in pancreatic cancer patients, also described by other investigators, was the basis for this phase I clinical trial that Von Hoff presented at AACR.
“Chemotherapy often means combining more than one drug, and we do not want to just take the next thing off the shelf. We want to know as much about a tumor as possible going in,” Von Hoff said.
Researchers reported on the first 20 patients of what will eventually be a 42-patient trial.
“This was a phase I trial, and phase I trials are usually designed to test safety, hoping it will also determine efficacy. The fact that we saw this kind of activity in a phase I trial is dramatic,” Von Hoff said.
“The rationale behind the combination of Gemcitabine plus Abraxane was based on careful science and was designed and executed by some of the leading experts in pancreas cancer in the world. While the data is preliminary and longer follow-up will be important, the biochemical and radiographic responses look very encouraging”, says Dr. Laheru of Johns Hopkins Kimmel Cancer Center.
The trial, sponsored by Abraxis BioScience, also included clinical sites at South Texas Oncology and Hematology, P.A., San Antonio, Texas, University of Alabama at Birmingham, Birmingham, Alabama, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
Monday, April 14, 2008
PET's Targeted Imaging May Lead to Earlier, More Accurate Diagnosis of Dementia and Alzheimer's Disease
[Source: Barbara Kram, DonMed] - Researchers involved in a large, multi-institutional study using positron emission tomography (PET) imaging with the radiotracer fluorodeoxyglucose (FDG) were able to classify different types of dementia with very high rates of success, raising hopes that dementia diagnoses may one day be made at earlier stages.
"Previously, scientists have been able to look only at the surface of the brain to differentiate various types of dementia," said Lisa Mosconi, Ph.D., assistant professor of psychiatry at the New York University School of Medicine. "With FDG PET, we were able to develop standardized disease-specific patterns from which we could correctly classify dementia more than 94 percent of the time."
The study, which was reported in the March issue of the Journal of Nuclear Medicine, measured the cerebral metabolic rate of glucose (CMRglc)-the amount of sugar the brain uses to fuel its activities-in various areas of the organ. A decrease in this rate is indicative of a loss of nerve cells and of dysfunction associated with dementia. Because FDG behaves like glucose when injected into the body, its location in the PET scans pinpointed the specific area where glucose utilization had fallen below normal levels as compared to an age-appropriate control group.
"Each type of dementia examined-Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB)-affects a different area of the brain. Based on where in the brain this decrease occurred, we were able to determine which type of dementia a patient had," Mosconi explained.
For instance, only AD patients have severe CMRglc reductions in the hippocampus (a part of the brain located deep in the organ and, prior to this study, unreachable for examination), whereas FTD patients have only mild abnormalities in the area and DLB patients have no hippocampal hypometabolism. "We believe that the ability to measure this embedded area in the brain will be important in identifying AD at an early stage," added Mosconi.
This is also the first study to use FDG PET to compare an early stage of dementia known as mild cognitive impairment (MCI) with dementing diseases other than AD. According to the researchers, the results suggest that the ability to detect differentiated uptake of glucose may result in earlier and more accurate diagnoses of MCI and better disease management.
"Because the incidence of these disorders is expected to increase dramatically as the baby-boomer generation ages, accurate diagnosis is extremely important-particularly at the early and mild stages of dementia when life-style changes and therapeutic interventions would be most effective," said Mosconi.
AD and other forms or dementia can take several years to progress to a debilitating stage, and a diagnosis based on FDG-PET assessments at the first sign of onset may improve the prognosis of MCI patients. "Early diagnosis may enable earlier treatment and empower people to plan for their future sooner, including financial and legal matters. It is also important for individuals at risk to take care of treatable risk factors, such as hypertension and high cholesterol levels," said Mosconi. "By changing their diet and increasing exercise, many MCI patients may deter dementia for years-perhaps even until more effective treatments are developed."
The study comprised 548 subjects and is the largest FDG PET study measuring brain metabolism in different dementing disorders to date. Researchers from PET centers in the United States and Europe were able to apply and share objective image analysis procedures easily, opening up the possibility that this diagnostic procedure could be adapted to a clinical setting.
Dementia is a general term for a progressive brain dysfunction that results in the loss of memory and other intellectual abilities serious enough to interfere with daily life. MCI patients demonstrate a decline of cognitive performance that is more pronounced than expected from age but not severe enough to meet criteria for dementia. The clinical course of these patients is challenging to forecast on the basis of clinical measures alone. Many diseases can result in a form of dementia, the most common one being AD, a progressive and fatal brain disease. According to the Alzheimer's Association, more than five million people in the United States have AD, and by 2050, that number could triple. Currently it is the seventh leading cause of death in the United States.
Co-authors of "Multicenter Standardized 18F-FDG PET Diagnosis of Mild Cognitive Impairment, Alzheimer's Disease, and Other Dementias" include Wai H. Tsui, New York University School of Medicine and the Nathan Kline Institute, New York, N.Y.; Karl Herholz, University of Manchester, Manchester, U.K.; Alberto Pupi, University of Florence, Florence, Italy; Alexander Drzezga, University of Munich, Munich, Germany; Giovanni Lucignani, University of Milan, Milan, Italy; Eric M. Reiman, Good Samaritan Banner Center, University of Arizona, Phoenix, Ariz.; Vjera Holthoff, University Hospital of Dresden, Dresden, Germany; Elke Kalbe, Medical Faculty, University of Cologne, Cologne, Germany; Sandro Sorbi, University of Florence, Florence, Italy; Janine Diehl-Schmid, University of Munich, Munich, Germany; Robert Perneczky University of Munich, Munich, Germany; Francesca Clerici, University of Milan, Milan, Italy; Richard Caselli, Arizona Center for Alzheimer's Disease Research, Phoenix, Ariz.; Bettina Beuthien-Baumann, PET-Center Dresden-Rossendorf and University Hospital of Dresden, Dresden, Germany; Alexander Kurz, University of Munich, Munich, Germany; and Satoshi Minoshima, University of Washington, Seattle, Wash.
"Previously, scientists have been able to look only at the surface of the brain to differentiate various types of dementia," said Lisa Mosconi, Ph.D., assistant professor of psychiatry at the New York University School of Medicine. "With FDG PET, we were able to develop standardized disease-specific patterns from which we could correctly classify dementia more than 94 percent of the time."
The study, which was reported in the March issue of the Journal of Nuclear Medicine, measured the cerebral metabolic rate of glucose (CMRglc)-the amount of sugar the brain uses to fuel its activities-in various areas of the organ. A decrease in this rate is indicative of a loss of nerve cells and of dysfunction associated with dementia. Because FDG behaves like glucose when injected into the body, its location in the PET scans pinpointed the specific area where glucose utilization had fallen below normal levels as compared to an age-appropriate control group.
"Each type of dementia examined-Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB)-affects a different area of the brain. Based on where in the brain this decrease occurred, we were able to determine which type of dementia a patient had," Mosconi explained.
For instance, only AD patients have severe CMRglc reductions in the hippocampus (a part of the brain located deep in the organ and, prior to this study, unreachable for examination), whereas FTD patients have only mild abnormalities in the area and DLB patients have no hippocampal hypometabolism. "We believe that the ability to measure this embedded area in the brain will be important in identifying AD at an early stage," added Mosconi.
This is also the first study to use FDG PET to compare an early stage of dementia known as mild cognitive impairment (MCI) with dementing diseases other than AD. According to the researchers, the results suggest that the ability to detect differentiated uptake of glucose may result in earlier and more accurate diagnoses of MCI and better disease management.
"Because the incidence of these disorders is expected to increase dramatically as the baby-boomer generation ages, accurate diagnosis is extremely important-particularly at the early and mild stages of dementia when life-style changes and therapeutic interventions would be most effective," said Mosconi.
AD and other forms or dementia can take several years to progress to a debilitating stage, and a diagnosis based on FDG-PET assessments at the first sign of onset may improve the prognosis of MCI patients. "Early diagnosis may enable earlier treatment and empower people to plan for their future sooner, including financial and legal matters. It is also important for individuals at risk to take care of treatable risk factors, such as hypertension and high cholesterol levels," said Mosconi. "By changing their diet and increasing exercise, many MCI patients may deter dementia for years-perhaps even until more effective treatments are developed."
The study comprised 548 subjects and is the largest FDG PET study measuring brain metabolism in different dementing disorders to date. Researchers from PET centers in the United States and Europe were able to apply and share objective image analysis procedures easily, opening up the possibility that this diagnostic procedure could be adapted to a clinical setting.
Dementia is a general term for a progressive brain dysfunction that results in the loss of memory and other intellectual abilities serious enough to interfere with daily life. MCI patients demonstrate a decline of cognitive performance that is more pronounced than expected from age but not severe enough to meet criteria for dementia. The clinical course of these patients is challenging to forecast on the basis of clinical measures alone. Many diseases can result in a form of dementia, the most common one being AD, a progressive and fatal brain disease. According to the Alzheimer's Association, more than five million people in the United States have AD, and by 2050, that number could triple. Currently it is the seventh leading cause of death in the United States.
Co-authors of "Multicenter Standardized 18F-FDG PET Diagnosis of Mild Cognitive Impairment, Alzheimer's Disease, and Other Dementias" include Wai H. Tsui, New York University School of Medicine and the Nathan Kline Institute, New York, N.Y.; Karl Herholz, University of Manchester, Manchester, U.K.; Alberto Pupi, University of Florence, Florence, Italy; Alexander Drzezga, University of Munich, Munich, Germany; Giovanni Lucignani, University of Milan, Milan, Italy; Eric M. Reiman, Good Samaritan Banner Center, University of Arizona, Phoenix, Ariz.; Vjera Holthoff, University Hospital of Dresden, Dresden, Germany; Elke Kalbe, Medical Faculty, University of Cologne, Cologne, Germany; Sandro Sorbi, University of Florence, Florence, Italy; Janine Diehl-Schmid, University of Munich, Munich, Germany; Robert Perneczky University of Munich, Munich, Germany; Francesca Clerici, University of Milan, Milan, Italy; Richard Caselli, Arizona Center for Alzheimer's Disease Research, Phoenix, Ariz.; Bettina Beuthien-Baumann, PET-Center Dresden-Rossendorf and University Hospital of Dresden, Dresden, Germany; Alexander Kurz, University of Munich, Munich, Germany; and Satoshi Minoshima, University of Washington, Seattle, Wash.
Data Confirming Anti-Cancer Effect of Naturally Occurring Heart Hormones Presented at Experimental Biology 2008 Symposium
[Source: Pr-Inside.com] - Kalos Therapeutics, a privately held biopharmaceutical company developing the Atrial Natriuretic Peptide (ANP) family for the treatment of human cancers, announced that David L. Vesely, M.D.,Ph.D., (University of South Florida) presented additional positive xenograft data today at the Experimental Biology 2008 Symposium on Heart Hormones. The data confirmed and expanded pre-clinical studies establishing the anti-cancer effect of this family of peptides naturally expressed in the human heart.
Dr. Vesely had shown that the ANP family of peptides has very broad activity in animal models, inhibiting the growth of all of the cancers examined to date: human pancreatic, lung, and breast cancers. The additional studies reported at the Symposium were performed by TD2, an oncology drug development contract research organization affiliated with the Translational Genomics Research Institute (TGen, Scottsdale, AZ), and focused on the most active member of the ANP peptide family that is designated KT-220. These studies were designed to extend Dr. Vesely's previous findings by using a more challenging pancreatic tumor model system and including an additional, more aggressive type of pancreatic cancer. The results showed that KT-220 also has significant activity in these models.
Kalos Therapeutics holds an exclusive, worldwide license to a 2005 patent resulting from the pioneering work of Dr. Vesely, at the University of South Florida's Cardiac Hormone Center. The patent covers the use of this family of cardiac hormones as cancer therapeutics. Dr. Vesely now serves on Kalos' Scientific Advisory Board.
Dr. Norrie Russell, president and CEO of Kalos, said, "We are very encouraged by these study results, particularly in light of the National Cancer Institute analysis showing that an anti-cancer compound's breadth of activity in xenograft animal models is the best predictor of activity in human clinical studies. Based on these findings, and on the previous safe administration of KT-220 and other ANP family members to humans for another indication, we can confidently move forward with clinical development. Kalos is currently raising capital from institutional investors and qualified private individuals to initiate clinical trials of KT-220 in cancer."
KT-220 and the other peptides of the ANP family exert their anti-cancer effects through a novel mechanism involving the inhibition of the Mitogen Activated Protein Kinase (MAPK) signaling pathway, a key mechanism in cancer cell proliferation. These peptide hormones selectively shut off the proliferative effects of this kinase pathway in cancer cells but not in normal cells.
About the ANP Family of Peptides
The ANP family of peptides consists of four peptides derived from the pro-ANP gene, and includes ANP itself. These peptides, which share certain structural features, act through cell surface receptors to produce their antiproliferative effects. These peptides occur at the highest concentration in the heart, and much lower levels throughout the body. High natural levels of ANP peptides in the heart may be responsible for the low incidence of metastatic as well as primary cardiac tumors.
More information can be found on Kalos' web site at www.kalostherapeutics.com. For further information contact Dr. Russell at nrussell@kalostpx.com or 858-552-6890 or Linda Press of FD at Linda.press@fd.com or 213-452-6453.
Dr. Vesely had shown that the ANP family of peptides has very broad activity in animal models, inhibiting the growth of all of the cancers examined to date: human pancreatic, lung, and breast cancers. The additional studies reported at the Symposium were performed by TD2, an oncology drug development contract research organization affiliated with the Translational Genomics Research Institute (TGen, Scottsdale, AZ), and focused on the most active member of the ANP peptide family that is designated KT-220. These studies were designed to extend Dr. Vesely's previous findings by using a more challenging pancreatic tumor model system and including an additional, more aggressive type of pancreatic cancer. The results showed that KT-220 also has significant activity in these models.
Kalos Therapeutics holds an exclusive, worldwide license to a 2005 patent resulting from the pioneering work of Dr. Vesely, at the University of South Florida's Cardiac Hormone Center. The patent covers the use of this family of cardiac hormones as cancer therapeutics. Dr. Vesely now serves on Kalos' Scientific Advisory Board.
Dr. Norrie Russell, president and CEO of Kalos, said, "We are very encouraged by these study results, particularly in light of the National Cancer Institute analysis showing that an anti-cancer compound's breadth of activity in xenograft animal models is the best predictor of activity in human clinical studies. Based on these findings, and on the previous safe administration of KT-220 and other ANP family members to humans for another indication, we can confidently move forward with clinical development. Kalos is currently raising capital from institutional investors and qualified private individuals to initiate clinical trials of KT-220 in cancer."
KT-220 and the other peptides of the ANP family exert their anti-cancer effects through a novel mechanism involving the inhibition of the Mitogen Activated Protein Kinase (MAPK) signaling pathway, a key mechanism in cancer cell proliferation. These peptide hormones selectively shut off the proliferative effects of this kinase pathway in cancer cells but not in normal cells.
About the ANP Family of Peptides
The ANP family of peptides consists of four peptides derived from the pro-ANP gene, and includes ANP itself. These peptides, which share certain structural features, act through cell surface receptors to produce their antiproliferative effects. These peptides occur at the highest concentration in the heart, and much lower levels throughout the body. High natural levels of ANP peptides in the heart may be responsible for the low incidence of metastatic as well as primary cardiac tumors.
More information can be found on Kalos' web site at www.kalostherapeutics.com. For further information contact Dr. Russell at nrussell@kalostpx.com or 858-552-6890 or Linda Press of FD at Linda.press@fd.com or 213-452-6453.
Wednesday, April 2, 2008
Retired NFL Players At Increased Risk For Heart Problems, Mayo Clinic Finds
[Source: ScienceDaily ] - Screening for cardiovascular problems in elite-level football players should begin in high school and continue throughout the lives of college and professional players. Mayo Clinic physicians based that conclusion on the results of their new study of the cardiovascular health of 233 retired National Football League (NFL) players.
The Mayo data showed that 82 percent of NFL players under age 50 had abnormal narrowing and blockages in arteries, compared to the general population of the same age. This finding suggests that the former athletes face increased risk of experiencing high blood pressure, heart attack or stroke. The report on research conducted by the Mayo Clinic Arizona group will be presented next week at the American College of Cardiology Annual Scientific Session in Chicago.
Significance of the Mayo Clinic Study
This is the first and largest study to measure comprehensive cardiovascular performance measures on retired NFL athletes, ages 35 to 65. Its findings add to the emerging portrait of poor heart health among this group of retired athletes. The findings also suggest that players as young as high school age who are engaged in serious competitive-conference level of training and play may benefit from regular cardiovascular screening. "What we hope to emphasize with our findings is that all NFL players -- retired or not -- need to undergo cardiovascular health evaluation because they may have changes in heart and vessel conditions that we can treat so they don't experience problems later in life," says Robert Hurst, M.D., Mayo Clinic cardiologist and lead researcher.
Adds chair of cardiovascular diseases at Mayo Clinic in Arizona and researcher Bijoy Khandheria, M.D.: "Cardiovascular screening is readily available and needs to become a routine part of serious football players' health care, beginning at the high school level for those who are engaged in a highly competitive and rigorous level of training and play."
Football and Heart Problems
Previous research by various institutions and investigators in recent years showed concerning health trends:
- Retired NFL players are more prone to obesity and obstructive sleep apnea than the general population.
Retired NFL players have an increased rate of metabolic syndrome, a condition increasingly linked to excess weight and lack of activity, which can lead to type 2 diabetes.
Higher mortality is reported in linemen, as compared to people in the general population of the same age who are not professional football players.
Research is needed to determine the causes.
Observing these serious trends, the Mayo Clinic researchers undertook the study to define vascular health and, by association, cardiovascular risk in retired NFL players. To determine vascular health, the Mayo team conducted multisite screening events with the help of players' associations. Investigators measured the internal diameter of the carotid artery. They also assessed plaque deposits which can block blood flow.
The most striking results showed that:
In players less than 50 years old, 82 percent had either plaque or carotid narrowing greater than the 75th percentile of the population, adjusted for age, sex and race. This represents a dangerous level of narrowing that could lead to a catastrophic reduction of blood flow resulting in heart attack or stroke.
Heart disease had not been previously diagnosed in these players. Nor had they experienced symptoms of heart disease, such as chest pain upon exertion.
As a result, the players did not know that they were at serious risk of heart attack or stroke, or that they needed to make lifestyle changes or start medical therapy to improve the capacity of their cardiovascular systems to maintain blood flow.
The Mayo research team concluded that because test results showed evidence of asymptomatic narrowing of the arteries -- called atherosclerosis -- the retired NFL players are at abnormally high risk for an adverse cardiovascular event, as compared with people of the same age in the general population. In addition, the high incidence of plaque found in players' vessels suggests that the increased narrowing is not solely due to increased body mass index. Further research is needed to explain this. In the meantime, football players will benefit from regular cardiovascular screening. "Effective therapies are available to help players avoid serious cardiovascular problems later in life, but players need to take that first step of seeking out screening programs to identify those at risk," Dr. Khandheria says.
Collaboration and Support
Other Mayo Clinic researchers are Erik Wissner, M.D.; Robert Burke, M.D.; and Chris Kendall, all of Mayo Clinic, Scottsdale/Phoenix, Ariz. Their work was supported by Mayo Foundation for Medical Education and Research.
Adapted from materials provided by Mayo Clinic.
Dung Happens And Helps Scientists: Scoop On Poop And Climate Change
[Source: ScienceDaily] - When scientists around the world think of dung, they think of Jim Mead.
Mead, a researcher at Northern Arizona University, is one of the world's foremost authorities on animal dung, and he's got the poop to prove it.
"You have got to laugh at this bizarre resource," says Mead, director of NAU's Laboratory of Quaternary Paleontology. "Although I don't think anyone is keeping track, I suspect we have the largest comparative animal dung collection in the world. If someone needs to identify dung, they send it to me."
The lab, part of the university's Center for Environmental Sciences and Education, has row after row of cabinets with thousands of dung pieces used by scientists to get accurate data on an array of topics, including the environmental changes that took place on the Colorado Plateau during the last 100,000 years.
"Dung is accurate for carbon dating," Mead explains. "It's a data set that typically disappears in the fossil record. All we typically get are bones, but with dung we get biochemistry. We can tell a lot about the climate by analyzing what plants the animal ate."
Through the digested plants, scientists can tell what was going on in the environment at the time, such as the amount of rainfall that was occurring. The data help researchers pinpoint when different changes in the environment took place.
"The plant remains in the dung allow us to determine the mosaic of plants in the local plant community. The community structure changes with changes in climate," he says.
Mead's research includes tracking and comparing ancient dung DNA samples to learn about an animal's gender, food and water sources, air pollen, parasites and community structure during the Ice Age. The data allow him to determine when and how an animal evolved and became extinct.
The collection includes dung from modern animals to prehistoric ground sloths and 40,000-year-old mammoths.
Molecular biologists in Denmark, Australia and Canada are using pieces from NAU's dung collection to compare its DNA to dung they are finding. "To understand ancient dung, one must have a modern comparative collection, and we have one of the best there is," Mead notes. "It is extremely rare to have preserved fossil dung—yet we have the best and most there are in any collection—from Siberia to Tierra del Fuego to Argentina—we have it."
Most of NAU's dung collection is dried and stored wrapped in tissue inside sturdy, archival cardboard boxes.
Mead opens a box of chunky 14,000-year-old mammoth dung and a slight scent of musty grass escapes. He points to the chomped blades of grass fossilized into the brown dried dung and surmises that the mammoth ate about 600 pounds of grass a day.
Mead currently is working with the National Park Service to figure out when bison were introduced to the plateau region. Previous research suggests bison dispersed into the Grand Canyon area more than 11,000 years ago, but with dating from dung, Mead knows that they roamed the plateau at least 23,000 years ago.
He also curates dung and skeletal collections for 22 national parks. Dung from the NAU collection also finds its way into public displays in museums, including the International Wildlife Museum in Tucson, Mesa Southwest Museum in Mesa and at the National Museum in Paris.
"It's no coincidence this dung collection is here," Mead says. "The Colorado Plateau is arid and replete with shelters and caves that are perfect for dung collection. Most other places in the world stay moist and the bacteria break down the dung."
Mead began collecting dung during his research at the University of Arizona in the 1970s. When he came to teach at NAU in 1985, Mead brought the collection with him and has since grown it by gathering dung from zoos and remote regions throughout United States and in places such as Africa, Canada, Mexico, South America, Australia and Siberia.
"Although our research is humorous," Mead says, "the data from dung is nothing to laugh about."
Adapted from materials provided by Northern Arizona University.
Mead, a researcher at Northern Arizona University, is one of the world's foremost authorities on animal dung, and he's got the poop to prove it.
"You have got to laugh at this bizarre resource," says Mead, director of NAU's Laboratory of Quaternary Paleontology. "Although I don't think anyone is keeping track, I suspect we have the largest comparative animal dung collection in the world. If someone needs to identify dung, they send it to me."
The lab, part of the university's Center for Environmental Sciences and Education, has row after row of cabinets with thousands of dung pieces used by scientists to get accurate data on an array of topics, including the environmental changes that took place on the Colorado Plateau during the last 100,000 years.
"Dung is accurate for carbon dating," Mead explains. "It's a data set that typically disappears in the fossil record. All we typically get are bones, but with dung we get biochemistry. We can tell a lot about the climate by analyzing what plants the animal ate."
Through the digested plants, scientists can tell what was going on in the environment at the time, such as the amount of rainfall that was occurring. The data help researchers pinpoint when different changes in the environment took place.
"The plant remains in the dung allow us to determine the mosaic of plants in the local plant community. The community structure changes with changes in climate," he says.
Mead's research includes tracking and comparing ancient dung DNA samples to learn about an animal's gender, food and water sources, air pollen, parasites and community structure during the Ice Age. The data allow him to determine when and how an animal evolved and became extinct.
The collection includes dung from modern animals to prehistoric ground sloths and 40,000-year-old mammoths.
Molecular biologists in Denmark, Australia and Canada are using pieces from NAU's dung collection to compare its DNA to dung they are finding. "To understand ancient dung, one must have a modern comparative collection, and we have one of the best there is," Mead notes. "It is extremely rare to have preserved fossil dung—yet we have the best and most there are in any collection—from Siberia to Tierra del Fuego to Argentina—we have it."
Most of NAU's dung collection is dried and stored wrapped in tissue inside sturdy, archival cardboard boxes.
Mead opens a box of chunky 14,000-year-old mammoth dung and a slight scent of musty grass escapes. He points to the chomped blades of grass fossilized into the brown dried dung and surmises that the mammoth ate about 600 pounds of grass a day.
Mead currently is working with the National Park Service to figure out when bison were introduced to the plateau region. Previous research suggests bison dispersed into the Grand Canyon area more than 11,000 years ago, but with dating from dung, Mead knows that they roamed the plateau at least 23,000 years ago.
He also curates dung and skeletal collections for 22 national parks. Dung from the NAU collection also finds its way into public displays in museums, including the International Wildlife Museum in Tucson, Mesa Southwest Museum in Mesa and at the National Museum in Paris.
"It's no coincidence this dung collection is here," Mead says. "The Colorado Plateau is arid and replete with shelters and caves that are perfect for dung collection. Most other places in the world stay moist and the bacteria break down the dung."
Mead began collecting dung during his research at the University of Arizona in the 1970s. When he came to teach at NAU in 1985, Mead brought the collection with him and has since grown it by gathering dung from zoos and remote regions throughout United States and in places such as Africa, Canada, Mexico, South America, Australia and Siberia.
"Although our research is humorous," Mead says, "the data from dung is nothing to laugh about."
Adapted from materials provided by Northern Arizona University.
New Resuscitation Approach For Out-of-hospital Cardiac Arrest Associated With Increased Survival, Study Shows
[Source: ScienceDaily ] - Patients who had cardiac arrests outside of the hospital setting and were treated with a resuscitation approach designed to limit interruption of chest compressions, termed minimally interrupted cardiac resuscitation (MICR), were more likely to survive than those patients who received standard treatments, according to a new study.
"Out-of-hospital cardiac arrest is a major public health problem and a leading cause of death," the authors write. "Although early defibrillation with automated external defibrillators improves survival, early defibrillation is rare and few patients with out-of-hospital cardiac arrest survive. In 2004, the average survival of patients with out-of-hospital cardiac arrest was 3 percent in the state of Arizona."
MICR, previously referred to as cardiocerebral resuscitation, is a new approach to out-of-hospital cardiac arrest for emergency medical services (EMS) personnel. MICR focuses on maximizing blood flow to the heart and brain through a series of coordinated interventions, and includes an initial series of 200 uninterrupted chest compressions, rhythm analysis with a single shock, 200 immediate post-shock chest compressions before pulse check or rhythm re-analysis, early administration of epinephrine (adrenaline, used to stimulate the heart), and delayed endotracheal intubation (placement of a flexible plastic tube into the trachea for the purpose of ventilating the lungs).
Bentley J. Bobrow, M.D., of Mayo Clinic, Scottsdale, Ariz., and colleagues investigated whether MICR would improve survival from out-of-hospital cardiac arrest. Patients with out-of-hospital cardiac arrests in two metropolitan cities in Arizona before and after MICR training of fire department emergency medical personnel were assessed. In a second analysis of protocol compliance, patients from the two metropolitan cities and 60 additional fire departments in Arizona who actually received MICR were compared with patients who did not receive MICR but received standard advanced life support.
Among the 886 patients with cardiac arrest in the two metropolitan cities, survival-to-hospital discharge increased from 4 of 218 patients (1.8 percent) in the before MICR training group to 36 of 668 patients (5.4 percent) in the after MICR training group. In the subgroup of 174 patients with a witnessed cardiac arrest and ventricular fibrillation (chaotic, irregular heart rhythm that results in little or no circulation but that may respond to defibrillation), survival increased from 2 of 43 patients (4.7 percent) in the before MICR training group to 23 of 131 patients (17.6 percent) in the after MICR training group.
For the protocol compliance analysis, overall survival-to-hospital discharge occurred in 69 of 1,799 patients (3.8 percent) who did not receive MICR and in 60 of 661 (9.1 percent) who received MICR. Survival with witnessed ventricular fibrillation and cardiac arrest occurred in 46 of 387 patients (11.9 percent) who did not receive MICR and in 40 of 141 patients (28.4 percent) who received MICR.
"Why should MICR be associated with improved outcomes after out-of-hospital cardiac arrest" One major contributor to the poor survival rates of patients with out-of-hospital cardiac arrest is prolonged inadequate myocardial and cerebral perfusion. During resuscitation efforts, the forward blood flow produced by chest compressions is so marginal that any interruption of chest compressions is extremely [harmful], especially for favorable neurological outcomes. Excessive interruptions of chest compressions by pre-hospital personnel are common. Therefore, MICR emphasizes uninterrupted chest compressions," the authors write.
"In this study, survival-to-hospital discharge of patients with an out-of-hospital cardiac arrest improved significantly after implementation of MICR as an alternate EMS protocol. These findings require confirmation in randomized trials."
Journal reference: JAMA. 2008;299[10]:1158-1165.
Editorial: Progress in Resuscitation
In an accompanying editorial, Mary Ann Peberdy, M.D., and Joseph P. Ornato, M.D., of Virginia Commonwealth University, Richmond, comment on the findings of Bobrow and colleagues.
"Although the concept of MICR needs further scientific evaluation, perhaps in the form of a randomized, controlled, clinical trial with precise documentation of protocol compliance, these details are likely not important factors to the numerous additional survivors who are back home with their families after the implementation of this new protocol. Progress in improving survival after cardiac arrest is most commonly made by a gradual evolution of science and its translation into clinical medicine rather than single, earth-shattering revolutions. This study ... represents confirmation that the quality of CPR, particularly the need for minimally interrupted chest compression and the lesser importance of positive pressure ventilation [receiving oxygen under pressure by a mechanical respirator], is a meaningful development in the evolution of resuscitation science."
Editorial reference: JAMA. 2008;299[10]:1188-1190.
Adapted from materials provided by JAMA and Archives Journals.
"Out-of-hospital cardiac arrest is a major public health problem and a leading cause of death," the authors write. "Although early defibrillation with automated external defibrillators improves survival, early defibrillation is rare and few patients with out-of-hospital cardiac arrest survive. In 2004, the average survival of patients with out-of-hospital cardiac arrest was 3 percent in the state of Arizona."
MICR, previously referred to as cardiocerebral resuscitation, is a new approach to out-of-hospital cardiac arrest for emergency medical services (EMS) personnel. MICR focuses on maximizing blood flow to the heart and brain through a series of coordinated interventions, and includes an initial series of 200 uninterrupted chest compressions, rhythm analysis with a single shock, 200 immediate post-shock chest compressions before pulse check or rhythm re-analysis, early administration of epinephrine (adrenaline, used to stimulate the heart), and delayed endotracheal intubation (placement of a flexible plastic tube into the trachea for the purpose of ventilating the lungs).
Bentley J. Bobrow, M.D., of Mayo Clinic, Scottsdale, Ariz., and colleagues investigated whether MICR would improve survival from out-of-hospital cardiac arrest. Patients with out-of-hospital cardiac arrests in two metropolitan cities in Arizona before and after MICR training of fire department emergency medical personnel were assessed. In a second analysis of protocol compliance, patients from the two metropolitan cities and 60 additional fire departments in Arizona who actually received MICR were compared with patients who did not receive MICR but received standard advanced life support.
Among the 886 patients with cardiac arrest in the two metropolitan cities, survival-to-hospital discharge increased from 4 of 218 patients (1.8 percent) in the before MICR training group to 36 of 668 patients (5.4 percent) in the after MICR training group. In the subgroup of 174 patients with a witnessed cardiac arrest and ventricular fibrillation (chaotic, irregular heart rhythm that results in little or no circulation but that may respond to defibrillation), survival increased from 2 of 43 patients (4.7 percent) in the before MICR training group to 23 of 131 patients (17.6 percent) in the after MICR training group.
For the protocol compliance analysis, overall survival-to-hospital discharge occurred in 69 of 1,799 patients (3.8 percent) who did not receive MICR and in 60 of 661 (9.1 percent) who received MICR. Survival with witnessed ventricular fibrillation and cardiac arrest occurred in 46 of 387 patients (11.9 percent) who did not receive MICR and in 40 of 141 patients (28.4 percent) who received MICR.
"Why should MICR be associated with improved outcomes after out-of-hospital cardiac arrest" One major contributor to the poor survival rates of patients with out-of-hospital cardiac arrest is prolonged inadequate myocardial and cerebral perfusion. During resuscitation efforts, the forward blood flow produced by chest compressions is so marginal that any interruption of chest compressions is extremely [harmful], especially for favorable neurological outcomes. Excessive interruptions of chest compressions by pre-hospital personnel are common. Therefore, MICR emphasizes uninterrupted chest compressions," the authors write.
"In this study, survival-to-hospital discharge of patients with an out-of-hospital cardiac arrest improved significantly after implementation of MICR as an alternate EMS protocol. These findings require confirmation in randomized trials."
Journal reference: JAMA. 2008;299[10]:1158-1165.
Editorial: Progress in Resuscitation
In an accompanying editorial, Mary Ann Peberdy, M.D., and Joseph P. Ornato, M.D., of Virginia Commonwealth University, Richmond, comment on the findings of Bobrow and colleagues.
"Although the concept of MICR needs further scientific evaluation, perhaps in the form of a randomized, controlled, clinical trial with precise documentation of protocol compliance, these details are likely not important factors to the numerous additional survivors who are back home with their families after the implementation of this new protocol. Progress in improving survival after cardiac arrest is most commonly made by a gradual evolution of science and its translation into clinical medicine rather than single, earth-shattering revolutions. This study ... represents confirmation that the quality of CPR, particularly the need for minimally interrupted chest compression and the lesser importance of positive pressure ventilation [receiving oxygen under pressure by a mechanical respirator], is a meaningful development in the evolution of resuscitation science."
Editorial reference: JAMA. 2008;299[10]:1188-1190.
Adapted from materials provided by JAMA and Archives Journals.
Subscribe to:
Posts (Atom)