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Inovio Biomedical Corporation (AMEX:INO), a leader in enabling the development of DNA vaccines using electroporation-based DNA delivery, announced that the team of Dr. Christian H. Ottensmeier, MD, PhD, Cancer Research UK Senior Clinical Research Fellow at the University of Southampton, will present interim data from a clinical study of an experimental DNA-based prostate cancer vaccine at the American Association for Cancer Research meeting in San Diego, USA, April 12 – 16, 2008. The data indicates that the combination of this DNA vaccine and electroporation DNA delivery was safe and well-tolerated. Patients treated using electroporation also displayed higher levels of antibody and anti-DOM CD4 responses.

This academic study is a phase I/II study in 30 HLA A2+ patients with biochemical failure of prostate cancer. The study is testing a DNA fusion vaccine developed at Southampton. The vaccine encodes an immunostimulant sequence from tetanus linked to a sequence from prostate specific membrane antigen (PSMA27). PSMA is an attractive antigen as it is found in the vast majority of prostate cancers and its expression is increased after standard anti-androgen treatment. The study is also evaluating electroporation as a novel delivery strategy for DNA vaccines compared to DNA delivered without electroporation.

The study has completed recruitment of 30 patients and vaccination is ongoing at the third (highest) dose level. Monitoring of antibody responses has been completed for the 20 patients at the first and second dose levels to week 16. Monitoring of CD4 cellular immunity has been completed for the 10 patients at the lowest dose. These 10 patients have additionally been assessed for CD8 T-cell responses. Interim results to date include:

– Vaccination with and without electroporation has been safe and well tolerated.

– The tetanus sequence induced strong antibody responses and cellular immunity. The PSMA27 antigen induced CD8+ cytotoxic T-cells in a substantial number of the patients.

- 13 of 20 patients developed increases in anti-DOM (the immunostimulant sequence from tetanus) antibody by week 16 after three vaccinations. Of these increased responses, 4 of 10 were in the DNA arm; 9 of 10 were in the electroporation arm.
- In 9 of 10 patients in the low dose cohort, increases in CD4 responses were observed.
- 6 of 10 subjects in the low dose cohort developed PSMA27-specific CD8 responses not detected before vaccination.

– Antibody responses were generally higher in patients treated using electroporation compared to those treated with the DNA vaccine alone (without electroporation). The use of electroporation-based DNA delivery appears to also increase the level of anti-DOM CD4 responses.

“We are extremely pleased with these observations that our electroporation delivery technology is enhancing the level of antibody and T-cell responses from this novel DNA vaccine against prostate cancer,” said Avtar Dhillon, MD, president and CEO of Inovio. “Apart from assessing the safety and tolerability of electroporation, being able to also detect increased levels of immune response is one of the important outcomes that we are aiming to achieve with all of our five current clinical studies for DNA-based immunotherapies and DNA vaccines that are being advanced by our partners.”

The development of this DNA vaccine was supported by the UK cancer charities the Leukemia Research Fund and Cancer Research UK, and rights to the vaccine are owned by Cancer Research Technology Limited. The study was supported by Cancer Research UK funding, the Allan Willett Foundation, Inovio Biomedical Corporation, and the Experimental Cancer Medicine Centre in Southampton. The clinical study is a collaborative project between the University of Southampton/Southampton University Hospitals and the Institute of Cancer Research/Royal Marsden Hospital, Sutton, Surrey.

An abstract of the presentation (Abstract Number 2843) including CD8+ response data for the first three patients is now available at aacr. The presentation during the conference will include the data from the first ten patients referenced above.

About Inovio’s Immunotherapy Products

DNA-based immunotherapy products have the potential to by-pass inherent scientific obstacles of conventional vaccines that prevent their development for cancer and chronic infectious diseases such as HIV and hepatitis C. Pre-clinical and clinical data have indicated the potential ability of Inovio’s technologies to safely and effectively deliver and significantly enhance the potency of such immunotherapies.

Inovio’s DNA-based immunotherapy products consist of DNA plasmids and its electroporation-based intratumoral and intramuscular DNA delivery systems. A DNA plasmid is designed to express an antigen that can induce an immune response specific to a cancer or infectious disease-causing organism. The plasmid is synthetically created and readily manufactured using well-established bacterial fermentation and purification technology. After a plasmid is delivered into tumor or muscle cells, production of the antigen may then induce a preventive or therapeutic immune response against the targeted disease. Inovio’s advanced electroporation devices facilitate delivery and expression of such immunotherapies and have been shown in primate and human studies to safely and efficiently generate immune responses. Breast cancer, prostate cancer, melanoma, HIV and hepatitis C virus are among the current targets of therapies employing Inovio technology.

Inovio is poised to deliver advanced DNA-based immunotherapies, devices and know-how in this rapidly advancing field. The company is actively licensing its technology to pharmaceutical and biotechnology companies and supporting early stage clinical studies arising from its own research efforts or through academic collaborations.

About the University of Southampton

The University of Southampton is a leading UK teaching and research institution with a global reputation for leading-edge research and scholarship. It is one of the UK’s top 10 research universities, offering first-rate opportunities and facilities for study and research across a wide range of subjects in humanities, health, science and engineering. The University has over 22,000 students and 5000 staff. Its annual turnover is in the region of ВЈ325 million. soton.ac

About Royal Marsden Hospital

The Royal Marsden Hospital was the first hospital in the world dedicated to cancer treatment and research into the causes of cancer. Today the hospital with its academic partner, The Institute of Cancer Research, forms the largest comprehensive cancer centre in Europe with over 40,000 patients from the UK and abroad seen each year. It provides inpatient, day care and outpatient services for all areas of cancer treatment.

About Cancer Research Technology

Cancer Research Technology Limited (CRT) is a specialist commercialization and development company, which aims to develop new discoveries in cancer research for the benefit of cancer patients. CRT works closely with leading international cancer scientists and their institutes to protect intellectual property arising from their research and to establish links with commercial partners. CRT facilitates the discovery, development and marketing of new cancer therapeutics, vaccines, diagnostics and enabling technologies. CRT is wholly owned by Cancer Research UK, the largest independent funder of cancer research in the world. Further information about CRT can be found at cancertechnology.

About Cancer Research UK

Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer. The charity carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer. It ensures that its findings are used to improve the lives of all cancer patients. Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make. The charity works in partnership with others to achieve the greatest impact in the global fight against cancer. For further information about Cancer Research UK’s work or to find out how to support the charity, visit cancerresearchuk.

About Leukaemia Research

Leukaemia Research is the only national UK charity devoted exclusively to improving treatments, finding cures and learning how to prevent leukaemia, Hodgkin’s lymphoma and other lymphomas, myeloma and the related blood disorders. Leukaemia Research receives no government grants and urgently needs to raise over ВЈ100 million in the next five years to commit to new research. From basic laboratory research to clinical trials with patients, Leukaemia Research is committed to saving lives by funding high quality, carefully selected research throughout the UK. Further information, including patient information booklets, is available at lrf.

Leukaemia Research currently supports 30 Specialist Programmes in which the groups undertake long-term intensive research into relevant areas of leukaemia and the related diseases, often working closely with diagnosis and treatment; more than 200 project grants, which provides short-term funding, usually two-three years, for work on a specific problem; 25 clinical fellowships for the training of outstanding junior doctors in both the treatment and research of leukaemia and more than 20 studentships, lectureships and senior fellowships.

About Inovio Biomedical Corporation

Inovio Biomedical (AMEX: INO)is focused on developing multiple DNA-based immunotherapies and DNA vaccines. Inovio is a leader in developing human applications of electroporation using brief, controlled electrical pulses to increase cellular uptake of a useful biopharmaceutical. Human data has shown that Inovio’s electroporation-based DNA delivery technology can significantly increase gene expression and immune responses from DNA vaccines. Immunotherapy partners include Merck, Wyeth, Vical, University of Southampton, Moffitt Cancer Center, the U.S. Army, National Cancer Institute, and International Aids Vaccine Initiative. Inovio’s technology is protected by an extensive patent portfolio covering in vivo electroporation. More information is available at inovio.

This press release contains certain forward-looking statements relating to our plans to develop our electroporation drug and gene delivery technology. Actual events or results may differ from our expectations as a result of a number of factors, including the uncertainties inherent in clinical trials and product development programs (including, but not limited to, the fact that pre-clinical results referenced in this release may not be indicative of results achievable from testing in humans and that results from one study may necessarily not be reflected or supported by the results of other similar studies), the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of Inovio’s technology as a delivery mechanism, the availability or potential availability of alternative therapies or treatments for the conditions targeted by Inovio or its collaborators, including alternatives that may be more efficacious or cost-effective than any therapy or treatment that Inovio and its collaborators hope to develop, evaluation of potential opportunities, issues involving patents and whether they or licenses to them will provide Inovio with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether Inovio can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2006, our 10-Q for the nine months ended September 30, 2007,and other regulatory filings from time to time. There can be no assurance that any product in our product pipeline will be successfully developed or manufactured, that final results of clinical studies will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proved accurate.

Inovio Biomedical Corporation

Changes in Medicare reimbursement policy might have prompted more beneficiaries to undergo surgical castration to treat prostate cancer rather than a less invasive alternative, according to a study published Monday on the Web site of the journal Cancer, USA Today reports. Castration — either through surgery or hormone injections — is a common treatment for certain forms of prostate cancer.

In the 1990s and early 2000s, hormone injections became “far more popular … with patients and doctors,” in part because of high Medicare reimbursement rates for the treatment, but “doctors gave far fewer hormone injections after Medicare slashed what it paid them by half,” according to USA Today. The study, led by J. Stephen Jones of the Cleveland Clinic, found that the number of hormone injections decreased by 14% from 2003 to 2005 and that the number of surgical castrations increased by 4% during the same period. Jones attributed the shifts to the changes in Medicare reimbursement policy.

However, Ethan Basch of Memorial Sloan-Kettering Cancer Center, who was not involved in the study, said that physicians have begun to administer hormone injections intermittently, rather than continuously, a shift that might account for the decrease in hormone injections. According to Otis Brawley, chief medical officer at the American Cancer Society, the shift resulted because of studies released around 2005 that found hormone injections can increase risk for osteoporosis and other health problems (Szabo, USA Today, 4/7).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Recent studies have suggested an association between chronic inflammation and cancers of the prostate, colon, stomach and liver. Now scientists at Northwestern University Feinberg School of Medicine report success in blocking an early step in metastasis of prostate cancer cells by interrupting the communication between the cancer cells and other cells that promote inflammation.

Their success suggests new ways to control cancer spread and metastasis. The findings also provide an impetus to look more closely at existing inflammation-controlling drugs including non-steroidal anti-inflammatory drugs, cyclooxygenase inhibitors, antioxidants and statins. It is possible, says Dr. Paul Lindholm, that these widely available drugs could be used to control aggressive cancer cell growth and spread for these and other inflammation-associated cancers.

Dr. Lindholm presented results of the study on April 8 at the Experimental Biology 2008 meeting in San Diego. The presentation was part of the scientific program of the American Society for Investigative Pathology.

In earlier studies, Dr. Lindholm and his colleagues at Northwestern found that when compared to benign prostate tissues, prostate cancer tissue has a higher density of macrophages and the monocytes from which these immune system cells derive. These scavenger cells are vital to the regulation of immune responses and the development of inflammation. High grade and high stage prostate cancer tissues showed significantly increased numbers of macrophages compared to low grade and low stage tumors. When the researchers added monocyte-like cell lines or monocytes obtained from the blood of normal people to less aggressive prostate cancer cell lines, these cancer cells became more invasive, indicating that the cancer cells and the monocytes were indeed communicating with each other. But how?

In the study reported at Experimental Biology, the researchers demonstrated that the monocyte-like cells stimulate the cancer cells’ Nuclear Factor-kappaB, a gene regulating transcription factor able to stimulate gene activity. To test whether NF-kappaB activity was increasing the cancer cells’ movement and invasive activity, the researchers then introduced into the cancer cells biological inibitors that blocks NF-kappaB activity. The treatments that block NF-kappaB activity reduced the cancer cell movement and invasion through the basement membrane (a thin, delicate layer of connective tissue underlying the epithelium of many organs).

The researchers now plan to study the effects of macrophages and inflammation and NF-kappaB inhibiting treatments in vivo, in a specially designed mouse model of invasive prostate cancer. They also plan to extend these experiments to include drugs currently used in humans to control inflammation. If anti-inflammatory drugs block cancer cell NF-kappaB activity and spreading movement, as the researchers hope, these drugs may prove useful for patients whose cancers are discovered early but who are at risk for cancer spread. The results also could help identify biomarkers of early cancer, before it can be detected by current technology, and to monitor response to treatments designed to prevent cancer spread.

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Dr. Lindholm’s colleagues on the study presented at Experimental Biology are Dr. Yi Lu, Dr. Borko D. Jovanovic, Dr. Neela Sivapurapu, and Dr. Chung Lee. The study was supported in part by the National Institutes of Health, the U.S. Department of Defense, and the Department of Pathology of Northwestern University.

Source:
Sylvia Wrobel
Federation of American Societies for Experimental Biology

Cell Genesys, Inc. (Nasdaq:CEGE) announced data from a completed Phase 1/2 clinical trial (G-9802) of GVAX immunotherapy for prostate cancer in men with recurrent prostate cancer who had not yet received treatment with hormone replacement therapy following relapse after prostate cancer surgery and/or radiation therapy. Data from the trial, which enrolled 19 patients, indicate that GVAX immunotherapy for prostate cancer results in a statistically significant increase in median PSA (prostate-specific antigen) doubling time as well as the formation of prostate cancer-associated antibodies in 79 percent of patients who received GVAX immunotherapy. These data will be presented today by Kristen Hege, M.D., vice president of Clinical Research and Development at Cell Genesys, at the annual meeting of the Tumor Vaccine and Cell Therapy Working Group being held in San Diego, California, in conjunction with the American Association for Cancer Research (AACR) annual meeting.

Data from the trial indicate a favorable increase in PSA doubling time from 28.7 weeks before receiving GVAX immunotherapy to 57.1 weeks after receiving the product (p=0.0095). In addition, 16 patients (84 percent) experienced a decline in PSA slope, a potential measure of the rate of disease progression, after receiving GVAX immunotherapy (p=0.018). PSA levels in eight of 19 patients (42 percent) remained stable during the six-month treatment period, with a median time to PSA progression of 9.7 months. Additionally, analysis of patient sera taken before and after receiving GVAX immunotherapy showed that 15 of the 19 patients (79 percent) developed new or enhanced antibody responses against either PC-3 or LNCaP, the two prostate cancer cell lines that comprise GVAX immunotherapy for prostate cancer. The product was generally well tolerated, with the most common side effects being injection site reactions in most patients and mild flu-like symptoms in some patients. No dose-limiting toxicities were observed.

“These data suggest that GVAX immunotherapy for prostate cancer may have clinical activity for men with early stage, recurrent prostate cancer,” stated Robert J. Dow, MBChB, senior vice president of Medical Affairs and chief medical officer of Cell Genesys. “We are now planning a larger randomized trial to further examine the potential application of GVAX immunotherapy in this patient population and also look forward to learning more from a study currently under way that is evaluating the product in combination with docetaxel as a preoperative therapy in men with high-risk prostate cancer.”

The multicenter, open-label, Phase 1/2 clinical trial reported on today was designed to evaluate the safety and activity of GVAX immunotherapy for prostate cancer in men with early stage, recurrent prostate cancer. All of the 19 enrolled had non-castrate (hormone-sensitive) prostate cancer with PSA recurrence following prostatectomy and/or radiation therapy, and no radiologic evidence of metastases. Patients were administered an initial dose of GVAX immunotherapy for prostate cancer followed by bi-weekly injections for a six-month period. Patients were monitored for an additional six months following the last injection for adverse events, PSA response, changes in PSA kinetics, and the induction of prostate cancer-associated antibodies. Long term safety monitoring was conducted and at a median follow up of six years, 17 of the 19 patients remained alive.

The results reported build upon the previously reported findings in an initial study (G-9705) of GVAX immunotherapy for prostate cancer in patients with early stage, non-castrate disease. These results, which were published in the July 2006 issue of Clinical Cancer Research showed that 16 (76 percent) of the 21 patients enrolled in the trial had a statistically significant decline in PSA slope after receiving GVAX immunotherapy for prostate cancer compared to the five patients who did not (p

The University of Texas Health Science Center at Houston has received a $412,500 federal stimulus grant for Parkinson’s disease research, the university announced today. It is the university’s first federal stimulus grant.

Parkinson’s disease is an incurable brain disorder. Its symptoms include trembling, stiffness and problems with balance. An estimated one million Americans are diagnosed with the neurological disorder.

The two-year grant will support efforts by researchers in the university’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) to develop a therapeutic vaccine.

Rowen Chang, Ph.D, an IMM professor of protein chemistry, is the principal investigator on the grant that comes from The National Institute of Neurological Disorders and Stroke through the American Recovery and Reinvestment Act of 2009. Chuantao Jiang, M.D., Ph.D., an assistant research professor at the IMM, is co-principal investigator.

Chang plans to add one or two researchers to the team of scientists in his lab with the funds. The grant extends through April 30, 2011.

“We are excited about receiving this grant, which will support our research and help the economy by employing more scientists,” Chang said.

Chang believes he may be able to slow the progression of Parkinson’s disease and possibly even prevent it by targeting a protein associated with the disease called alpha-synuclein.

If successful, Chang’s vaccine would work by strengthening the immune system’s ability to suppress the activity of alpha-synuclein through the production of antibodies. The effectiveness of this vaccine will be tested in transgenic mice expressing human alpha-synuclein.

The American Recovery and Reinvestment Act was passed by Congress to jumpstart the economy and create jobs.

“The focus of the research has been on creating ‘locked structures’ of proteins by internal cross linking,” said C. Thomas Caskey, M.D., IMM Director/CEO. “The application of this technology to creation of therapeutic antibodies for Parkinson’s disease is a creative approach to new therapies for a challenging disease.”

Chang has been on the faculty of the Institute of Molecular Medicine for about a decade and was one of the initial appointments. He obtained his master’s of science degree from the National Taiwan University in Taipei and his doctorate from the Australian National University at Canberra.

Source:
Robert Cahill
University of Texas Health Science Center at Houston

The use of MRI without endorectal coil can detect prostate cancer and provide undistorted images with diagnostic image quality and accurate tumor localization, according to a recent study conducted by researchers from The Ohio State University in Columbus, OH.

“The 3T MRI datasets were acquired without an endorectal coil and were used during robotic surgery,” said Steffen Sammet, MD, PhD, lead author of the study. “Since the use of an endorectal coil leads to deformation of the prostate and potentially altered microcirculation, our goal was to assess the capability of detecting prostate cancer areas by dynamic contrast enhanced MRI without endorectal coil at 3T validated by correlation with surgical pathology,” he said.

The study included 13 patients with prostate cancer who were scheduled for prostatectomy and were imaged on a 3T MRI. The researchers noted suspicious areas, tumor location, extracapsulation (the extent of the tumor outside the capsule of the prostate and is a associated with a unfavorable prognosis), and seminal vesicle involvement. Once this was complete, 3D reconstruction of the prostate, tumor neurovascular bundle and surrounding tissue was performed and used as an intra-operative “roadmap”.

According to the study, cancer was correctly localized in 11 of the 13 patients. There was an agreement with pathology in 10 of the 13 patients regarding extracapsulation and 11 of 13 regarding seminal vesicle involvement. The study showed that 3D reconstruction was useful for the surgical roadmap in all 13 cases.

“High field MRI enables the acquisition of undistorted prostate images without endorectal coil. The high signal to noise ratio and the image quality of the prostate and the surrounding tissue may, in the future, allow us to detect prostate cancer at an earlier stage,” said Dr. Sammet.

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The full results of this study will be presented as an electronic exhibit beginning today, Monday, April 14, 2008 during the American Roentgen Ray Society’s annual meeting in Washington, DC.

Source: Necoya Tyson

American Roentgen Ray Society

Scott & White has begun recruiting patients with recurring prostate cancer to participate in a clinical trial that uses a PSA (prostate specific antigen) activated chemical injected into the prostate that attaches to prostate cancer cells and causes cell death.

“This is an important and exciting step in this process,” said Dr. Scott Coffield, the principal investigator, a urologist and professor of surgery at Scott & White. “We are trying to determine if this agent is effective in destroying cancer cells in the prostate using varying doses of the agent, which has demonstrated safety in an earlier trial.”

To be eligible to participate in this study, a patient must have been diagnosed with prostate cancer that has recurred after completing treatment by external beam radiation therapy or radioactive seed implant.

Protox Therapeutics, Inc., a Canadian company, developed the drug and has received clearance from the U.S. Food and Drug Administration to proceed with a Phase IIa clinical trial. According to Protox officials, PRX302, as the agent is currently called, is injected into the prostate where it turns into a potent cell-killing toxin when it comes in contact with PSA-producing cells.

The purpose of this study is to determine therapeutic activity of different concentrations of PRX302 at increasing volumes as well as the safety and tolerance among study subjects after injection into the prostate. The study is expected to enroll 30 subjects.

Scott & White’s Genitourinary Cancer Team/Scott & White Cancer Center in Temple is the primary study site for this trial. Participants will receive screening, laboratory testing, a procedure to administer the agent, and up to nine follow-up visits.

According to American Cancer Society data, prostate cancer strikes more than 230,000 men in the U.S. each year, resulting in approximately 30,000 deaths.

In a Phase IIa clinical trial, an investigational drug is tested in a small group of people to evaluate the drug’s safety, determine what the range of safe dosage is, and to identify side effects. An investigational drug is one that is under study but does not have permission from the U.S. Food and Drug Administration or any regulatory authority to be legally marketed and sold. If approved by regulators, additional clinical trials may be conducted on larger groups for further evaluation and to gather more information, to help determine safe use of the drug, and if it will eventually be approved for general use.

In addition to the recurrent prostate cancer, other requirements must also be met to be considered for participation in this clinical trial. For more information on enrolling in this clinical trial, contact research coordinators Nancy Bowman or Richard Castillo at 866-226-3534, or visit the study’s Web site protox.sw.

About Scott & White

Scott & White Healthcare is a three-hospital health care system established in 1897. Recognized among the nation’s 100 Top Hospitals, Scott & White is the principal teaching facility affiliated with the Texas A&M Health Science Center College of Medicine. Along with its flagship hospital and clinic facility in Temple, Texas, Scott & White also includes its Continuing Care Hospital on Temple’s West Campus and the 72-bed acute care hospital at the University Medical Campus in Round Rock. With more than 650 physicians and scientists, Scott & White has become one of the nation’s largest multi-specialty group practice systems.

Scott & White Healthcare

Prostate tumors grew more quickly in mice who exercised than in those who did not, leading to speculation that exercise may increase blood flow to tumors, according to a new study by researchers in the Duke Comprehensive Cancer Center (DCCC) and the Duke Prostate Center.

“Our study showed that exercise led to significantly greater tumor growth than a more sedentary lifestyle did, in this mouse model,” said Lee Jones, Ph.D., a researcher in the DCCC and senior investigator on this study. “Our thought is that we may, in the future, be able to use this finding to design better drug delivery models to more effectively treat prostate cancer patients, and those with other types of cancer as well.”

The findings were presented in a poster session at the American Association for Cancer Research annual meeting on April 13 in San Diego, Calif. The study was funded by the United States Department of Defense, the Prostate Cancer Foundation and the American Urological Association Foundation, Rising Star in Urology Award, given to Stephen Freedland, one of the study’s investigators.

The researchers implanted prostate tumors subcutaneously in the flanks of 50 mice and then put half of the mice in cages with exercise wheels and half in cages with no wheels. All mice were fed the same diet. On average, the exercising mice ran more than half a mile each day.

“We found that among the mice that had the opportunity to voluntarily exercise, tumors grew approximately twice as fast as they did among the mice that did not have the opportunity to exercise,” Jones said.

Researchers and clinicians know that a challenge in delivering chemotherapy and radiation to tumors can be their poor blood flow, so these findings may hint at a way in which to improve blood flow to tumors, perhaps then allowing for better distribution of medicine, he said.

“We’re wondering, can we combine exercise with treatments such as chemotherapy, hormone therapy or radiation, to maximize the results we achieve in prostate cancer patients,” Jones said. “That question will be the subject of subsequent studies.”

The researchers are currently conducting a validation study, in mice, in which tumors are injected directly into the prostate, thereby better simulating human prostate cancer, Jones said.

“Down the line, we will test this hypothesis in humans undergoing medical treatment for prostate cancer,” he said.

The researchers want to caution men against interpreting these findings as an endorsement for not exercising for fear of getting or exacerbating cancer.

“These mice were not receiving treatment and we were allowing aggressive tumors to grow unchecked for the sake of the experiment,” said study investigator Freedland, a urologist at Duke. “Patients would not find themselves in the same situation.”

Concerns should also be overridden by the well-established benefits of exercise, including its positive effects on cardiovascular health, Type II diabetes, obesity, and many other chronic conditions, he said.

“This study gives us insight into which cellular pathways are affected by exercise, and starts to give us clues about how to harness the beneficial effects,” said Michael Potter, a medical student at Duke and lead investigator on the study. “Ultimately, we hope that this knowledge will help us use exercise to both deliver medicines more effectively and protect the body from the harmful side effects of treatment, as we already know it can.”

This is one of the first studies to look at the physiological effects of exercise on the tumor itself, rather than examining the quality-of-life or symptom-control effects of exercise in cancer patients, Jones said.

“The findings were a bit surprising, but provide a very important and exciting foundation upon which to build,” he said.

###

Other researchers involved in this study include Susan Poulton and Mark Dewhirst.

Source: Lauren Shaftel Williams

Duke University Medical Center

SuperGen Inc.
(Nasdaq: SUPG), a pharmaceutical company dedicated to the discovery, rapid
development and commercialization of therapies for solid tumors and
hematological malignancies, announced as part of a series of
presentations at the 2008 AACR Annual Meeting that MP-470 effectively
sensitizes prostate and breast cancer cells to erlotinib (Abstract No.
671).

Entitled, “Inhibition of erlotinib resistance on HER-family tyrosine
kinases by combination with MP-470, a multi-targeted TK inhibitor in
prostate and breast cancer,” the poster highlights data indicating that the
combination of MP-470 and erlotinib inhibits the binding of the p85 subunit
of PI3K, and has a greater impact than either agent alone in reducing
phosphorylation of Akt, ERK1/2, EGFR/HER1, HER2/Neu, and HER3.

“These data build upon previous results showing that MP-470 exhibits
anti-tumor activity in breast and prostate cancer cells,” said Dr. David
Bearss, SuperGen’s Vice President and Chief Scientist. “The fact that
MP-470 in combination with erlotinib effectively suppressed the HER pathway
suggests that concurrent administration of both compounds could represent a
new treatment for prostate and breast cancers. We will continue to explore
this synergy as we develop further MP-470.”

Copies of the 2008 AACR Annual Meeting poster presentations will be
available in the pipeline section of SuperGen’s Web site supergen.

About SuperGen

Based in Dublin, Calif., SuperGen, Inc. is a pharmaceutical company
dedicated to the discovery, rapid development and commercialization of
therapies for solid tumors and hematological malignancies. SuperGen is
developing a number of therapeutic anticancer products focused on kinase
and cell signaling inhibitors and DNA methyltransferase inhibitors. For
more information about SuperGen, please visit supergen.

Forward-Looking Statements

This news release contains certain “forward-looking” statements within
the meaning of the Private Securities Litigation Reform Act of 1995. These
statements are typically preceded by words such as “believes,” “expects,”
“anticipates,” “intends,” “will,” “may,” “should,” or similar expressions.
These forward-looking statements are not guarantees of future performance
and involve a number of risks and uncertainties that may cause actual
results to differ materially from the results discussed in these
statements. Factors that might cause the company’s results to differ
materially from those expressed or implied by such forward-looking
statements include, but are not limited to, the ability to discover,
develop and move target compounds into clinical development and other risks
and uncertainties detailed from time to time in the company’s filings with
the Securities and Exchange Commission including its most recently filed
Form 10-Q and 10-K. SuperGen, Inc. undertakes no duty to update any of
these forward-looking statements to conform them to actual results.

SuperGen Inc.
supergen

Tapping into a growing body of knowledge about the origins and progression of cancer, researchers are now developing and testing new preventive therapies to stop it in its tracks. At the 2008 Annual Meeting of the American Association for Cancer Research, April 12-16, researchers present data on the preventive effects of celecoxib and atorvastatin and vitamin D in colorectal, prostate and breast cancer, respectively, and the relationship between diet, metabolism and the development of pancreatic cancer.

The Adenoma Prevention with Celecoxib (APC) trial: Five-year efficacy and safety results: Abstract LB-141

Colon adenoma prevention with celecoxib, a non-steroidal anti-inflammatory drug (NSAID), is effective and can be safe for patients without underlying cardiovascular risk factors, according to five-year data of a randomized phase III trial.

“There has been a significant amount of negative press about Cox-2 inhibitors including celecoxib, and clearly these drugs are risky for some patients. However, our study also shows that for patients without major cardiovascular risk factors, celecoxib at low doses protects against high-risk lesions that can lead to colon cancer,” said Monica Bertagnolli, M.D., associate professor of surgery at the Brigham and Women’s Hospital.

Bertagnolli was the lead researcher on the Adenoma Prevention with Celecoxib (APC) trial, which enrolled 2,035 patients and randomly assigned them to 200 mg twice-daily (400 mg) of celecoxib, 400 mg twice-daily (800 mg) of celecoxib or a placebo group.

At three years, patients taking celecoxib at 400 mg had a 29 percent reduction in adenomas, a precursor to colon cancer, while those taking 800 mg had a 38 percent reduction. Advanced adenomas, which are lesions with a high-risk for cancer development, were reduced by 55 percent with 400 mg and 63 percent with 800 mg.

After three years, patients stopped taking celecoxib and were followed for another two years to assess safety and effectiveness. Even after two years off medication, the five-year rate of advanced adenoma was reduced by 41 percent among patients taking the lower dose and 26 percent among patients taking the higher dose.

Cardiovascular events were more common in patients taking celecoxib, with a rate of 3.8 percent among those patients taking placebo to 6 percent among the low dose group and 7.5 percent among the high dose group. However, when researchers looked at factors that might predict cardiovascular complications, they found a much different story.

For patients with no cardiovascular risk factors before using celecoxib, the rate of cardiovascular adverse events was 0.9 percent in the placebo group, 3.9 percent in the 400 mg group and 1.9 percent in the high dose group. Cardiovascular risk factors included smoking, high cholesterol, high blood pressure, diabetes, presence of atherosclerosis and age over 65.

If a patient had one risk factor, the risk was 2.2 percent in the placebo group, 3.7 percent in the 400 mg dose group and 4.9 percent in the high dose group.

The greater cardiovascular risk was observed among patients who had at least two cardiovascular risk factors at the time they entered the study, where the placebo group had a 5.9 percent risk, the 400 mg group had an 8.2 percent risk and the 800 mg group had an 11.2 percent risk.

“This new data allows us to carefully select patients who can benefit from this drug,” Bertagnolli said. “Although it should be used with caution, those patients with a high risk for colon cancer and a low risk for cardiovascular disease are going to receive significant benefit.”

Inhibition of androgen-independent growth of LNCaP xenograft tumors in immunodeficient mice by a combination of atorvastatin (Lipitor) and celecoxib (Celebrex): Abstract 2100

Suggesting a new role for the prevention of advanced prostate cancer by two commonly prescribed drugs, researchers found that a combination of atorvastatin and celecoxib potently inhibited the androgen-independent growth of prostate tumors in a laboratory model.

“This represents a viable prevention strategy to stop the progression of prostate cancer from androgen-dependent to androgen-independent, which is much more aggressive and has limited therapeutic options,” said Xi Zheng, Ph.D., M.D., assistant research professor at Rutgers University in New Jersey.

Previous epidemiology research has shown that statins like atorvastatin and non-steroidal anti-inflammatory drugs (NSAIDs) like celecoxib may reduce the risk of prostate cancer. Zheng and colleagues assessed the effects of atorvastatin and celecoxib alone or in combination on androgen-independent growth of human prostate cancer cells cultured in vitro or grown as tumors in mice.

In the animal study, mice with an androgen-dependent tumor were deprived of androgen and randomly assigned to four groups: those receiving either 10 micrograms/gram body weight per day of atorvastatin or the same dose of celecoxib; those receiving a combination of each drug at 5 micrograms/gram body weight per day; or a control group receiving no drugs.

All mice had temporary tumor regression in the absence of androgen, but then the untreated mice experienced substantial tumor regrowth as the tumor become androgen-independent. Mice treated with a single drug had some reduction of androgen-independent tumor growth, while administration of atorvastatin and celecoxib in combination resulted in a more potent inhibition of androgen-independent growth than either drug alone. “The agents appear to work by inhibiting a signal transduction pathway that is important for the growth of these cancer cells,” Zheng said.

Although a high dose of celecoxib has been linked to a small increase in cardiovascular risk in prior human studies, Zheng said the dose used in this study was low and the benefits should outweigh the risks.

Dietary energy balance impacts spontaneous pancreatic lesions in the K5X-2 transgenic model of pancreatic cancer: Abstract 4188

Shedding light on the links between obesity and cancer, researchers at the University of Texas M. D. Anderson Cancer Center report that modulating energy balance by restricting calories can prevent pancreatic cancer in laboratory models.

“We are very excited that our research may lead to insights to prevent or control this deadly disease in the near future,” said lead researcher Laura M. Lashinger, Ph.D., a post-doctoral fellow at M. D. Anderson.

Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. Obesity, the overall rate of which has risen sharply over the past 40 years, has emerged in epidemiological studies as a key risk factor for pancreatic cancer.

Other studies have shown that calorie restriction, a dietary strategy for inducing negative energy balance and preventing or reversing obesity, has significant anticancer effects in several species, against a variety of tumor types. However, the exact mechanisms underlying the obesity-pancreatic cancer association are not clearly understood.

“It is likely that inflammation may be playing a role,” Lashinger said. “Fat tissue is more than simply weight; it produces an inflammatory property that leads to greater risk of cancer and other diseases.”

In the current study, Lashinger and colleagues hypothesized that spontaneous tumor development in the K5X-2 transgenic mouse model of pancreatitis-driven pancreatic cancer would be reduced in lean mice, when compared with overweight or diet-induced obese mice.

They placed 36 mice on one of three diets for 14 weeks: a lean diet with a 30 percent calorie restriction (n = 12), an overweight diet (n = 12), or a high calorie, high fat diet-induced obese regimen (n = 12).

The mice developed spontaneous pancreatic lesions as early as four weeks, with 100 percent approaching death within six to eight months, the researchers report. The calorie-restricted animals were significantly protected from spontaneous formation of pancreatic lesions: 7.5 percent of them developed lesions in stark contrast to 45 percent of the overweight group and 57.5 percent of the diet-induced obese group, the researchers report. Furthermore, calorie-restricted mice had smaller lesions than those in the overweight and diet-induced obese groups.

Gemini vitamin D analogs inhibit estrogen receptor positive and estrogen receptor negative mammary tumorigenesis without hypercalcemic toxicity: Abstract 2097

Researchers at Rutgers University have found that, in animal studies, a synthetic form of active vitamin D has a substantive preventive effect on the development of both estrogen receptor (ER)-positive and ER-negative breast cancers. Unlike many of the other synthetic vitamin D agents that have been tested in humans, this compound, known as Gemini 0097, shows no toxicity, they report.

The research team found that daily injections of Gemini 0097 cut growth of ER-positive cancer by 60 percent in rat studies, and reduced ER-negative breast cancer by half in mice.

“These are very promising findings, especially because no toxicity is observed,” said researcher Hong Jin Lee, a graduate student at Rutgers. Lee works in the laboratory of lead investigator Nanjoo Suh, Ph.D., an assistant professor at the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers, the State University of New Jersey. Suh said that Gemini 0097 likely did not cause the most common vitamin D toxicity, an overload of calcium in blood known as hypercalcemia, because the compound has an extra side chain of chemicals.

“It is quite different from the natural shape of active vitamin D,” she said. “Because the binding affinity of Gemini 0097 with vitamin D receptor is low that may contribute to the lower toxicity, but the efficacy stays the same or even better.”

Epidemiologic studies have shown that use of vitamin D is beneficial in preventing colon cancer, but studies in prostate and breast cancer have yielded mixed conclusions, Suh says.

Vitamin D is a pro-hormone that is produced in the skin after exposure to sunlight. Vitamin D dietary supplements are converted into an active, useful form by metabolism in the liver and kidneys. Although the active form of vitamin D has been tested as a cancer treatment, the higher doses needed for prevention or treatment have typically produced intolerable side effects in clinical trials, Suh says.

In this study, the researchers tested 60 novel Gemini vitamin compounds, with Gemini 0097 performing the best, Lee says.

In one set of studies, the researchers exposed rats to a mammary carcinogen, then injected groups of 15 animals with different doses of Gemini 0097. They found that the lowest dose had little effect but higher doses slowed the growth of resultant ER-positive tumors by 60 percent, compared with a group of control rats. Some treated rats developed small mammary tumors and some developed none at all, says Lee. “The data are very convincing,” he said.

In a second, similar experiment in a mouse model of ER-negative breast cancer, mice treated with Gemini vitamin D had 50 percent fewer tumors than did control mice.

The researchers analyzed tumor samples from both the rats and the mice and discovered that Gemini 0097 prevents tumorigenesis by increasing expression of the p21 protein, which arrests the cell cycle, and by inducing insulin-like growth factor binding protein-3 (IGFBP-3), which slows down cell proliferation.

“These data are from animal studies, and we need more data before these compounds can be tested in humans,” said Suh. “Still, we are hopeful that we have found a way of providing vitamin D without toxicity that has a significant effect on cancer prevention.”

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

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