UroToday – Our study investigates the performance of the Partin Nomogram using a cohort of patients identified in the National Cancer Institute, Surveillance Epidemiology, and End Results (SEER) database for the years 2004-2005. The Partin tables [1] attempt to predict the pathologic extent of disease found at radical prostatectomy by categorizing patients into mutually exclusive categories of positive lymph nodes, positive seminal vesicles, extracapsular disease, and organ confined disease. The Partin tables rely on pre-surgical PSA, biopsy Gleason score, and clinical T stage in assigning risk. We investigated the overall discriminatory and predictive performance of the Partin Tables, and also investigated the association of race and age with the Partin Table’s performance.

An interesting limitation of our analysis is that we could not use the pre-surgical biopsy Gleason score, but rather used the Gleason score found in the radical prostatectomy specimen. This is a limitation of the SEER database, as the Gleason score is reported from the largest pathological specimen. In the case of radical prostatectomy, it is the pathology specimen, not the pre-surgical biopsy. In essence, our study presumed perfect concordance between the biopsy assigned Gleason score, and the radical prostatectomy specimen assigned Gleason score. Though “over grading” is a well known phenomenon, there are signs that this is improving in the most recent contemporary studies. [2][3] Therefore, we feel that this limitation does not invalidate our analysis.

We found that race does not predict for more advanced pathology, when matched by PSA, Gleason score, and clinical T-stage. This was consistent with another large study investigating the association between Race and the performance of the Partin Tables.[4] Interestingly, we found that younger age predicted for more advanced pathology compared to older age, and that the Partin Tables performed the best for young men under 61 years of age. This could be due to a multitude of factors, including the relative youth of the Johns Hopkins Medical Institute cohort (the group of patients used to “build” the Partin Tables), and the greater incidence of benign prostatic hypertrophy – attributable PSA in older men, perhaps increasing the perceived (but not actual) risk of advanced disease in these men. There could also be yet-undefined differences in cancer biology between younger and older men with prostate cancer, not taken into account by Gleason score, PSA, and clinical T-stage.

In conclusion, we showed excellent discrimination of the Partin tables for seminal vesicle invasion and positive lymph nodes. However, we found an interesting difference in the performance of the Partin tables between younger and older men.

[1] Makarov DV, Trock BJ, Humphreys EB et al. Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin Tables) based on cases from 2000 to 2005. Urology 2007;69:1095-1101.

[2] Fine SW, Epstein JI. A contemporary study correlating prostate needle biopsy and radical prostatectomy Gleason score. J Urol. 2008;179:1335-8.

[3] Rajnikanth A, Manoharan M, Soloway CT, et al: Trends in Gleason score: concordance between biopsy and prostatectomy over 15 years. Urology. 2009;72:177-82.

[4] Heath EI, Kattan MW, Powell IJ, et al. The effect of race/ethnicity on the accuracy of the 2001 Partin Tables for predicting pathologic stage of localized prostate cancer. Urology 2008;71:151-155.

Written by James B. Yu, MD as part of Beyond the Abstract on UroToday. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

UroToday – the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice. To access the latest urology news releases from UroToday, go to:
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Copyright © 2010 – UroToday Continue reading →

A person who opts for healthy lifestyle choices can have an 80% lower risk of first time stroke compared to individuals who do not, scientists have revealed in an article in the medical journal Stroke. Of the 795,000 strokes that occur in the USA, over 77% are first events, the authors explain. After heart disease and cancer, stroke is the biggest cause of premature death in America. It is a major cause of disability.

New stroke prevention guidelines, which had previously been updated in 2006, are being issued.

The researchers say two factors can significantly reduce the incidence of first time strokes:

Health lifestyle choices
Emergency room interventions

Larry B. Goldstein, M.D., director of the Duke Stroke Center in Durham, N.C., said:
“Between 1999 and 2006, there’s been over a 30 percent reduction in stroke death rates in the United States and we think the majority of the reduction is coming from better prevention.”
Up to 1999 stroke incidence had been on the rise. There had been a 39% increase in hospitalizations due to stroke from 1988 through 1997.

The authors say the stroke rate in America will rise because people are living longer.

This time the stroke prevention guidelines address the condition as a broad continuum of related events, including ischemic stroke, non-ischemic-stroke and TIA (transient ischemic attack).

A stroke is a condition in which a blood clot or ruptured blood vessel interrupts the flow of blood to a specific area of the brain. Lack of glucose and oxygen flowing to the brain results in the death of brain cells and subsequent brain damage. The patient may have problems with speech, memory and movement. There are two main types of stroke:
Ischemic stroke – represent about 87% of all strokes. A thrombus (blood clot) forms, blocking blood flow to a part of the brain. Sometimes the clot can form in another part of the body, becomes dislodged and free-floating (an embolus). The embolus can make its way through the bloodstream to the brain where it can cause an ischemic stroke.
Hemorrhagic stroke (non-ischemic stroke) – a blood vessel ruptures. The leaking blood fills the space between the brain and skull (subarachnoid hemorrhage). Can also occur if a defective artery in the brain bursts and fills the surrounding tissue with blood (cerebral hemorrhage). In both cases there is poor bloodflow to the brain, plus the accumulation of leaking blood places excessive pressure on the brain.

A transient ischemic attack (TIA), also known as a mini-stroke, is a temporary interruption of blood flow to a part of the brain. TIA symptoms may be similar to a stroke, however they last for a shorter time and do not leave noticeable permanent damage. TIAs are considered major risk factors for a later, larger stroke.

Goldstein said there is little difference along the stroke spectrum for effective prevention.

Highlighted below are some major updates in the new stroke prevention guidelines:

Healthy lifestyle choices – don’t smoke, follow a healthy low fat diet with plenty of fruits and vegetables, if you consume alcohol do so in moderation, keep your body weight within normal limits, and exercise regularly. People who adopt ALL these lifestyle choices can have an 80% lower risk of developing a stroke.
Emergency room doctors – attempts should be made to spot those who are at high risk for stroke. The doctors should consider screening, referrals, or even starting preventive treatment.
Genetic screening – not recommended for the general population. However, in some cases, depending on family history and some other factors, screening might be appropriate.
Stenting vs. endarterectomy – this is still uncertain. Doctors need to view each case individually, and take into account advances in standard medical therapies, including hypertension treatment, administering antiplatelet and cholesterol lowering medications, and encouraging healthy lifestyle choices.
Carotid artery narrowing screening – no recommended for the general population.
Aspirin – for low risk individuals, patients with diabetes, and those with asymptomatic peripheral artery disease aspirin does not help prevent a first stroke. Aspirin is recommended for patients whose stroke risk is higher than bleeding risk (which aspirin can cause).

“Guidelines for the primary prevention of stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association”
Goldstein LB, Cheryl D. Bushnell, M.D., M.H.S.; Robert J. Adams, M.S., M.D.; Lawrence J. Appel, M.D., M.P.H.; Lynne T. Braun, Ph.D., C.N.P.; Seemant Chaturvedi, M.D.; Mark A. Creager, M.D.; Antonio Culebras, M.D.; Robert H. Eckel, M.D.; Robert G. Hart, M.D.; Judith A. Hinchey, M.D., M.S.; Virginia J. Howard, Ph.D.; Edward C. Jauch, M.D., M.S.; Steven R. Levine, M.D.; James F. Meschia, M.D.; Wesley S. Moore, M.D.; J.V. (Ian) Nixon, M.D.; and Thomas A. Pearson, M.D.
Stroke Journal 2010; DOI:10.1161/STR.0b013e3181fcb238

Continue reading →

ADVENTRX Pharmaceuticals,
Inc. (Amex: ANX) today announced the initiation of a Phase II clinical
trial using CoFactor(R) in the treatment of refractory metastatic breast
cancer. CoFactor (ANX-510) is a folate-based biomodulator drug designed to
enhance the activity and reduce associated toxicity of the widely used
cancer chemotherapeutic agent 5-fluorouracil (5-FU).

This study builds on the results of earlier studies and will more fully
investigate the efficacy and safety of CoFactor for patients with
previously treated, advanced breast cancer.

“The initiation of this Phase II clinical trial for CoFactor represents
an important milestone in the global registration strategy for our lead
product development program,” said Evan M. Levine, chief executive officer
of ADVENTRX. “We are enthusiastic about CoFactor’s potential to enhance the
efficacy and safety of 5-FU chemotherapy in the treatment of refractory
breast cancer.”

“We are pleased to have launched this study of CoFactor in combination
with 5-FU in advanced breast cancer,” added James A. Merritt, MD, president
and chief medical officer of ADVENTRX. “The CoFactor and 5-FU regimen has
demonstrated activity in multiple tumor types, including breast in a Phase
I clinical trial, and we have safety data from other CoFactor studies in
metastatic colorectal cancer that suggest CoFactor is well-tolerated. We
believe a CoFactor plus 5-FU regimen could offer a worthwhile alternative
in the overall management of breast cancer.”

This Phase II clinical trial is a single arm, multicenter study to
evaluate the safety and efficacy of treatment with CoFactor plus 5-FU in
advanced breast cancer patients who have failed anthracycline and taxane
chemotherapies. Patients will be treated with CoFactor followed by 5-FU
administered by IV bolus weekly for 6 weeks, with tumor and safety
assessments every 8 weeks. The primary endpoint for the study is objective
response rate (RECIST criteria), and secondary endpoints are duration of
response, progression free survival, overall survival and incidence and
severity of adverse events (AEs), as defined by the NCI Common Terminology
Criteria. A total of 31 patients are expected to be enrolled at 6 clinical
sites.

According to the American Cancer Society, breast cancer is the most
frequently diagnosed cancer in American women and the second leading cause
of cancer-related deaths in women after lung cancer. Over 214,000 new cases
of breast cancer and over 41,000 deaths from breast cancer are expected in
the US in 2006. Despite advances made in treatment options that have led to
a significant increase in survival and quality of life, metastatic disease
is still incurable. Five-year survival rates decrease with advancing
disease stage: from 98% in localized disease to 80% with regional spreading
to only 26% with metastatic disease.

About CoFactor

CoFactor (ANX-510) is a folate-based biomodulator drug designed to
replace leucovorin to enhance the activity and reduce associated toxicity
of the widely used cancer chemotherapy 5-fluorouracil (5-FU). In comparison
to leucovorin, CoFactor creates more stable binding of the active form of
5-FU to the target enzyme, thymidylate synthase (TS). CoFactor bypasses the
chemical pathway required by leucovorin to deliver the active form of
folate, allowing 5-FU to work more effectively. In addition to the Phase II
breast cancer trial, CoFactor is being studied in first-line treatment of
metastatic colorectal cancer in a Phase IIb and pivotal Phase III clinical
trial.

About ADVENTRX Pharmaceuticals

ADVENTRX Pharmaceuticals is a biopharmaceutical research and
development company focused on commercializing low development risk
pharmaceuticals for cancer and infectious disease that enhance the efficacy
and/or safety of existing therapies. More information can be found on
ADVENTRX’s web site at adventrx.

Forward Looking Statement

ADVENTRX cautions you that statements included in this press release
that are not a description of historical facts are forward-looking
statements that involve risks, uncertainties, assumptions and other factors
that, if they do not materialize or prove to be accurate, could cause
ADVENTRX’s results to differ materially from historical results or those
expressed or implied by such forward-looking statements. Such
forward-looking statements are made based on management’s current
expectations and beliefs and should not be regarded as a statement or
representation by ADVENTRX that any of its plans, including its anticipated
milestones, will be achieved on time or at all. The potential risks and
uncertainties that could cause actual results to differ materially include,
but are not limited to: the risk that ADVENTRX will be unable to raise
sufficient capital to fund the projects necessary to meet its anticipated
or stated goals and milestones; the potential to attract a strategic
partner and the terms of any related transaction; the ability to timely
enroll subjects in ADVENTRX’s current and anticipated clinical trials; the
results of pending clinical trials for CoFactor(R) or ADVENTRX’s other
product candidates; the potential for CoFactor(R) and ADVENTRX’s other
product candidates to receive regulatory approval for one or more
indications on a timely basis or at all, and the uncertain process of
seeking regulatory approval; other difficulties or delays in developing,
testing, manufacturing and marketing of and obtaining regulatory approval
for CoFactor(R) or ADVENTRX’s other product candidates; the market
potential for fluoropyrimidine biomodulators and other target markets, and
ADVENTRX’s ability to compete in those markets; unexpected adverse side
effects or inadequate therapeutic efficacy of CoFactor(R) or ADVENTRX’s
other products that could delay or prevent regulatory approval or
commercialization, or that could result in recalls or product liability
claims; the risk that preclinical and clinical results are not indicative
of the success of subsequent clinical trials and that products will not
perform as preclinical and clinical data suggests or as otherwise
anticipated; the potential for regulatory authorities to require additional
preclinical work or other clinical requirements to support regulatory
filings; the scope and validity of patent protection for CoFactor(R) and
Adventrx’ other product candidates; and other risks and uncertainties more
fully described in ADVENTRX’s press releases and periodic filings with the
Securities and Exchange Commission. ADVENTRX’s public filings with the
Securities and Exchange Commission are available at sec.

You are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date when made. All forward-looking
statements are qualified in their entirety by this cautionary statement and
ADVENTRX assumes no obligation to revise or update any forward-looking
statement, including as set forth in this press release, to reflect events
or circumstances arising after the date on which it was made.

ADVENTRX Pharmaceuticals, Inc.
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Newly released data from the United Network of Organ Sharing (UNOS) shows that in 2008 Northwestern Memorial Hospital’s heart transplant program achieved the largest volumes and top-rated outcomes in Illinois – a ranking that places the program among the top 20 heart transplant programs nationally.

“We are very proud of the collaborations and diligent focus of our multi-disciplinary transplant team,” said Patrick McCarthy, MD, the hospital’s chief of cardiothoracic surgery, who is co-director of its Bluhm Cardiovascular Institute and the Heller-Sacks Professor of Surgery at the Feinberg School of Medicine of Northwestern University.

Many patients transfer to the Bluhm Cardiovascular Institute from outside institutions for heart transplantation surgery. “The partnership that we have forged with outstanding community programs has been largely responsible for our growth,” commented Edwin McGee, MD, cardiac surgeon and the surgical director of Heart Transplantation and Mechanical Assistance at the Bluhm Cardiovascular Institute. “We recognize the integral role that cardiologists and nurses from outside institutions play in coordinating a safe and seamless transfer of care for their patients to our center.”

“The collective expertise of Northwestern Memorial’s established transplant program helps the heart transplant team thrive. Because we are able to leverage an established infrastructure and system for organ transplantation, our expert heart surgeons and cardiologists are positioned to be equally successful,” commented William Cotts, MD, medical director of the Advanced Heart Failure Program at the Bluhm Cardiovascular Institute.

Northwestern Memorial’s Center for Heart Failure has a 97 percent one year survival rate for heart transplantation. This ranks among the highest in the state of Illinois and the surrounding region.

Heart transplantation is an option for patients who are experiencing end-stage heart failure that can no longer be controlled by medications and other therapies. Each year only about 2,000 donor hearts become available which means that transplantation is not an option for a majority of patients. Experts at the Bluhm Cardiovascular Institute are committed to finding alternative life-extending therapies for patients, and many patients awaiting a transplant may benefit from heart assist devices. These devices help the heart to pump blood to the body’s organs and serve as bridge to transplantation while significantly improving the patient’s quality of life.

During the past three years there has been a steady increase in the volume of assist devices that are implanted at the Bluhm Cardiovascular Institute, which is a trend that is being seen nationally as well. The Bluhm Cardiovascular Institute offers the latest clinical trials for devices and drugs that help to ensure that patients receive the best possible care for heart failure and heart transplantation.

To learn more about Northwestern’s heart transplant program, visit nmh/heart

Continue reading →

UroToday – The androgen receptor (AR) is currently the major target for prostate cancer (PCa) prevention and treatment. Nevertheless, there are multiple lines of evidence to suggest that oestrogens and their receptors are also involved in PCa development and tumor progression.

Oestrogens can affect normal and abnormal growth in the human prostate through at least two mechanisms:

– Systemic (endocrine) effects by acting via the pituitary gland to indirectly lower serum androgen levels

– Local effects that directly target the prostate by specific oestrogen receptors (ER), which may be present in epithelial (autocrine action) and stromal compartments (paracrine action) of prostate and PCa tissue.

The human prostate is equipped with a dual system of oestrogen receptors (ERa, ERb) that undergo profound remodeling during PCa development and tumor progression. The current data obtained from human tissue and animal models implicate the ERa as an oncogene, which is upregulated during PCa development (HGPIN) and tumor progression. Interestingly, the major ligand of the ERa derives from testosterone. The conversion of testosterone to estradiol is mediated by the P450 aromatase enzyme (CYP19 gene), which is active in adipose tissue, adrenal glands, testicules, and even the prostate. Therefore, aromatase may be a key regulator of the ratio of androgen to oestrogen in the prostate gland. The ERa antagonist toremifene prevents PCa and slow tumor progression in the TRAMP mouse model, and has been proven effective in reducing PCa detection in a phase 2 clinical trail enrolling 514 patients with diagnosed HGPIN.

In apparent contrast to ERa, the ERb, by binding phytoestrogens with high affinity, is considered a functional tumor suppressor, which is partially lost during PCa development (HGPIN) and castration resistant disease. The anticancer properties of phytoestrogens have been documented in vitro and in vivo, including inhibition of cell proliferation and angiogenesis, decrease of 5?±- reductase activity and androgen receptor expression (AR silencing). Importantly, both oestrogen receptors (ERa, ERb) have been reported to regulate a potentially aggressive molecular subtype of prostate cancer, i.e. the TMPRSS2- ERG fusion.

Nevertheless, the translation of the current information into potential therapeutic applications remains highly challenging. A major problem is still agonist (= oestrogenic) effects of ERa antagonists. With the selective ER modulators (SERMs) currently available, it is perhaps unrealistic to expect objective clinical response in patients with end- stage hormone refractory disease. The usefulness of SERMs in hormone na??ve prostate cancer in preventing disease progression has not yet been addressed by clinical studies. Little is known about the expression and function of ERb splice variants, ERa and ERb isoforms, ligand- dependent and ligand-independent activities, the role of genomic versus non-genomic signaling and the role of ER coactivators in regulating antagonist/ agonist response. Answers to these questions will further our understanding of ER signaling pathways and will open new avenues for drugs designed to antagonize ERa activity and function as ER?? agonists. This approach may provide new preventive and therapeutic strategies for prostate cancer.

Written by Helmut Bonkhoff, MD as part of Beyond the Abstract on UroToday

UroToday – the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to:
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Copyright © 2008 – UroToday

View drug information on Estradiol. Continue reading →

CuraGen Corporation
(Nasdaq: CRGN) and TopoTarget A/S (Copenhagen Stock Exchange: TOPO)
announced today the initiation of patient dosing in a Phase II clinical
trial evaluating the antitumor activity of intravenous PXD101, a small
molecule histone deacetylase (HDAC) inhibitor, for the treatment of ovarian
cancer. This trial is being sponsored by the National Cancer Institute
(NCI) under a Clinical Trials Agreement with CuraGen for PXD101.

The Phase II trial is an open-label study being led by Dr. Amit Oza at
Princess Margaret Hospital in Toronto, Canada. Patients with either
advanced platinum resistant ovarian tumors or micropapillary/borderline low
malignant potential (LMP) ovarian carcinoma may be enrolled for treatment
with PXD101. Patients may have received no more than three prior lines of
therapy. Upon enrollment, patients will receive intravenous PXD101 daily
for five days in three week cycles until disease progression. The primary
endpoint for the study is the determination of objective disease response,
as evaluated by the RECIST criteria. Secondary endpoints include evaluation
of safety and tolerability of PXD101, stable disease rates, duration of
response, progression-free survival, as well as median and overall
survival. Up to 62 patients at sites across Canada and the United States
will be enrolled into the study.

“Hypoacetylation appears to play an important role in silencing the
expression of genes, including tumor supressors that regulate cell
survival, proliferation, and differentiation,” commented Dr. Oza. “The
ability to reactivate tumor suppressor gene(s), together with the new
published preclinical data, provides an excellent rationale to evaluate the
role of the histone deacetylase inhibitor, PXD101 in treating two different
populations of patients with ovarian cancer, those with advanced refractory
tumors and those patients with micropapillary and borderline, or low
malignant potential, tumors.”

“This NCI-sponsored trial evaluating PXD101 monotherapy complements our
ongoing Phase Ib/II clinical trial, which is studying intravenous PXD101 in
combination with paclitaxel and carboplatin for the treatment of advanced
ovarian cancer. Both of these trials will generate data that will allow us
to better understand the role of PXD101 in the treatment of this disease,
and provide results to enable a decision regarding registrational
development for ovarian cancer,” stated Dr. Timothy Shannon, Executive Vice
President of Research and Development and Chief Medical Officer at CuraGen
Corporation.

Correlative pharmacodynamic studies will also be conducted to evaluate
the potential inhibition of HDACs in ovarian tumor cells from patients
enrolled in this trial. Evaluation of the genes regulating proliferation
and apoptosis (programmed cell death), as well as acetylation of histone
and non-histone proteins, will be performed.

In an article published in the August 2006 issue of Molecular Cancer
Therapeutics, CuraGen and TopoTarget scientists also reported new
preclinical data for PXD101 that is relevant to ovarian cancer. Data in the
study demonstrates that PXD101 has growth-inhibitory activity as mono- or
combo therapy on multidrug resistant ovarian cancer lines, as well as on
primary clinical cancer specimens grown in culture. Furthermore, PXD101 was
found to have anti-tumor activity in animal models of ovarian cancer.

About Ovarian Cancer

Ovarian cancer causes a significant burden of disease accounting for 5%
of all cancer deaths and is the fifth leading cause of death in women in
Canada, the U.S., and Europe. Despite the efficacy of the combination of
platinum/paclitaxel chemotherapy in advanced ovarian carcinoma, more than
75% of patients with stage III/IV disease ultimately relapse and die from
their disease. Recurrent ovarian carcinoma is incurable and is treated with
platinum-based therapy when the treatment free interval following initial
therapy is longer than 6 months. Patients who have resistant ovarian
cancer, whose disease does not respond to first line carboplatin and
paclitaxel have a dire prognosis and the likelihood of response to further
chemotherapy is very low (approximately 10%). There is therefore a need to
develop new agents for the treatment of patients with this malignancy.

About PXD101

PXD101 is a promising small molecule HDAC inhibitor being investigated
for its role in the treatment of a wide range of solid and hematologic
malignancies either as a single-agent, or in combination with other active
anti-cancer agents, including 5-fluorouracil (5-FU), carboplatin,
paclitaxel, cis-retinoic acid, azacitidine and Velcade(R) (bortezomib) for
Injection. HDAC inhibitors represent a new mechanistic class of anti-cancer
therapeutics that target HDAC enzymes and have been shown to: arrest growth
of cancer cells (including drug resistant subtypes); induce apoptosis, or
programmed cell death; promote differentiation; inhibit angiogenesis; and
sensitize cancer cells to overcome drug resistance when used in combination
with other anti-cancer agents.

PXD101 is currently being evaluated in multiple clinical trials as a
potential treatment for multiple myeloma, T- and B-cell lymphomas, AML,
mesothelioma, liver, colorectal, ovarian cancers, either alone or in
combination with anti-cancer therapies. In August 2004, CuraGen signed a
Clinical Trials Agreement with the NCI under which the NCI is sponsoring
several clinical trials to investigate PXD101 for the treatment of various
cancers, both as a single-agent and in combination chemotherapy regimens.
In May 2005, TopoTarget announced the signing of a Cooperative Research and
Development Agreement (CRADA) with the NCI to conduct preclinical and
nonclinical studies on PXD101 in order to better understand its anti-tumor
activity and to provide supporting information for clinical trials.

About CuraGen

CuraGen Corporation (Nasdaq: CRGN) is a biopharmaceutical company
developing diverse approaches, including novel protein, antibody, and small
molecule therapeutics, that aim to offer hope for patients with cancer,
inflammatory diseases, and diabetes. CuraGen’s strategic alliances have
resulted in a deep pipeline of potential therapeutics that is being
developed by the Company’s experienced research and development teams. By
leveraging the drug development strengths cultivated over the years,
CuraGen expects to make a difference in the lives of patients by bringing
forward promising therapeutics that address unmet medical needs. To further
capitalize on CuraGen’s extensive research and development expertise,
CuraGen founded a majority-owned subsidiary, 454 Life Sciences, which has
developed and is commercializing advanced technologies for the sequencing
of DNA. CuraGen and 454 Life Sciences are headquartered in Branford,
Connecticut. For additional information on the companies please visit
curagen and 454lifesciences.

About TopoTarget

TopoTarget (CSE: TOPO) is a biopharmaceutical company, headquartered in
Denmark and with subsidiaries in the UK and Germany, dedicated to finding
“Answers for Cancer” and developing improved cancer therapies. TopoTarget
is founded and run by clinical cancer specialists and combines years of
hands-on clinical experience with in-depth understanding of the molecular
mechanisms of cancer. Focus lies on highly predictive cancer models and key
cancer enzyme regulators (mainly HDAC, mTOR, and topoisomerase II
inhibitors) and a strong development foundation has been built. TopoTarget
has a broad portfolio of small molecule preclinical drug candidates and
seven drugs are in clinical development, including both novel anti-cancer
therapeutics and new cancer indications for existing drugs. Savene(TM) is
TopoTarget’s first product on the market. In addition to organic growth,
TopoTarget consistently looks for opportunities to strengthen and expand
its activities through acquisitions and in-licensing. For more information,
please refer to topotarget.

Safe Harbor

This press release contains forward-looking statements that are subject
to certain risks and uncertainties. These forward-looking statements
include statements regarding future expectations, beliefs, intentions,
goals, strategies, plans or prospects regarding the future, including
statements about the expected benefits of PXD101, and our ability to
generate data that will allow us to better understand the role of PXD101 in
the treatment of ovarian cancer. We caution investors that there can be no
assurance that actual results or business conditions will not differ
materially from those projected or suggested in such forward-looking
statements as a result of various factors, including, but not limited to,
the following: the risk that any one or more of the PXD101 or any other
CuraGen drug development program will not proceed as planned for technical,
scientific or commercial reasons or due to patient enrollment issues or
based on new information from nonclinical or clinical studies or from other
sources; the success of competing products and technologies; technological
uncertainty and product development risks; uncertainty of additional
funding; CuraGen’s history of incurring losses and the uncertainty of
achieving profitability; CuraGen’s stage of development as a
biopharmaceutical company; government regulation; patent infringement
claims against CuraGen’s products, processes and technologies; the ability
to protect CuraGen’s patents and proprietary rights; uncertainties relating
to commercialization rights; and product liability exposure. Please refer
to CuraGen’s Annual and Quarterly Reports on Forms 10-K and 10-Q for a
complete description of these risks. CuraGen disclaims any intention or
obligation to update or revise any forward-looking statements, whether as a
result of new information, future events, or otherwise, unless required by
law.

CuraGen Corporation
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The Transcendental Meditation technique may be an effective method to reduce blood pressure, anxiety, depression, and anger among at-risk college students, according to a new study to be published in the American Journal of Hypertension, December 2009.

“The Transcendental Meditation Program, a widely-used standardized program to reduce stress, showed significant decreases in blood pressure and improved mental health in young adults at risk for hypertension,” said David Haaga, PhD, co-author of the study and professor of psychology at American University in Washington, D.C.

This study was conducted at American University with 298 university students randomly allocated to either the Transcendental Meditation technique or wait-list control over a three-month intervention period. A subgroup of 159 subjects at risk for hypertension was analyzed separately. At baseline and after three months, blood pressure, psychological distress, and coping ability were assessed.

For the students at risk for developing hypertension, significant improvements were observed in blood pressure, psychological distress and coping. Compared to the control group, students practicing the Transcendental Meditation program showed reductions of 6.3 mm Hg in systolic blood pressure and 4.0 mm Hg in diastolic blood pressure. These reductions are associated with a 52% lower risk for development of hypertension in later years.

The findings are timely. Today, an estimated 18 million students are dealing with mental health issues on college campuses. Statistics from colleges nationwide indicate there has been a 50% increase in the diagnosis of depression, and more than twice as many students are on psychiatric medications as a decade ago. According to recent national surveys of campus therapists, more students than ever are seeking psychiatric help on college campuses all across the United States.

“This is the first randomized controlled study to show in young adults at risk for hypertension reductions in blood pressure that were associated with changes in psychological distress and coping,” said Sanford Nidich, EdD, lead author and senior researcher at the Institute for Natural Medicine and Prevention at Maharishi University of Management. “Previous research has shown that psychological distress such as anxiety, depression, and anger contribute to the development of hypertension in young adults,” said Dr. Nidich.

College students are particularly prone to psychological distress caused by interpersonal and social problems, pressures to succeed academically, financial strains, and uncertain futures. For the entire sample in this study, there was a significant improvement in students’ mental health.

“Hypertension is a common risk factor for cardiovascular disease in adulthood. Yet, decades of research show that high blood pressure begins in youth. This well-controlled clinical trial found that blood pressure can be effectively lowered in students with a stress-reducing intervention. This has major implications for the prevention of hypertension, heart attacks and strokes in adulthood,” said Robert Schneider MD, FACC, specialist in clinical hypertension, Director of the Institute for Natural Medicine and Prevention and study co-author.

This study was supported, in part, by a Specialized Center of Research Grant from the National Institutes of Health – National Center for Complementary and Alternative Medicine, and by the Abramson Family Foundation, David Lynch Foundation, and other private donors.

Facts on Stress and Young Adults:
Hypertension affects approximately one-third (33%) of the US adult population.

College-age individuals with blood pressure (BP) elevated beyond the optimal range are three times more likely to develop hypertension than normotensives.

Psychological distresses such as anxiety, depression, and anger/hostility have been found to contribute to the development of hypertension in young adults.

In 2007, around 15% of students reported having been diagnosed with depression at some point in their lives – up from 10% in 2000.

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A report in Circulation from the Framingham Heart Study, which compared acute myocardial infarction (AMI) incidence in 9824 men and women over four decades, has proposed an explanation for the apparent paradox of improved prevention, falling mortality rates but stable rates of hospitalisation.(1) The study found that over the past 40 years rates of AMI diagnosed by ECG decreased by 50%, whereas rates of AMI diagnosed exclusively by infarction biomarkers doubled. This “evolving” diagnosis of AMI, say the investigators, “offers an explanation for the apparently steady national AMI rates in the face of improvements in primary prevention”.

However, the investigators emphasise that this study like others before it highlights a “40-50%” reduction in heart disease mortality in the USA from 1968 to 2000 and a 50% decline in the incidence of AMI when diagnosed by ECG. This, they propose, “implies that primary prevention efforts have influenced the incidence of AMI”. That the incidence of hospitalised AMI has not similarly declined is explained by the greater sensitivity of diagnostic AMI biomarkers; they note, for example, that the detection rate of AMI by troponin was higher than in earlier decades.

Another explanation for the decline in AMI mortality rates may be found in a second report from the same Circulation issue.(2) A cohort study of more than 13,000 residents of Worcester, USA, hospitalised with AMI found that the incidence of cardiogenic shock, the most common complication of AMI associated with fatality, declined throughout the 30-year study period. “The results of our study suggest that patients hospitalized with AMI in the 2000s were less likely to develop cardiogenic shock than greater Worcester residents hospitalized with AMI during earlier study years,” the investigators report. Cardiogenic shock results from failure of the ventricles to provide adequate circulation of blood.

Commenting on behalf of the European Society of Cardiology, Professor Frans Van de Werf, Chairman of the Cardiology Department at the University Hospital, Leuven, Belgium, said: “These papers are indeed very helpful for understanding trends reported in recent epidemiological studies of AMI. The data underline the critical importance of the definition of an AMI. The increasing use of very sensitive and specific markers of myocardial necrosis (troponins) and the acceptance of a ‘universal definition’ of AMI have certainly influenced its detection and reporting. This also explains the increase in reporting of non-ST-elevations AMI.

“The decrease in hospital mortality in patients with cardiogenic shock in the last decade is most likely due to reperfusion therapy, in particular primary angioplasty. An aggressive approach to these patient is recommended in both the US and European guidelines.”

References

(1) Parikh NI, Gona P, Larson MG, et al. Long-term trends in myocardial infarction incidence and case fatality in the National Heart, Lung, and Blood Institute’s Framingham Heart Study. Circulation 2009; 119: 1203-1210.

(2) Goldberg RJ, Spencer FA, Gore JM, et al. Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction. A population-based perspective. Circulation 2009; 119: 1211-1219.

European Society of Cardiology (ESC)
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Chokeberry bushes have for centuries been residents of eastern deciduous forests where their bright red and dark purple fruits continue to be favorite snacks of local bird species. Native Americans have also traditionally eaten dried chokeberries and prepared teas from parts of the plant, and several domesticated varieties now grace contemporary lawns and gardens from coast to coast. However, the chokeberry (Aronia) is enjoying a new claim-to-fame as a potentially powerful antioxidant, and can now be found for sale in the dietary supplement and “health food” aisles of your local pharmacies and grocery stores.

What makes the humble chokeberry so healthful? Scientists think the answer lies in their unusually high levels of substances called anthocyanins (from the Greek anthos + kyanos meaning dark blue). There are many different anthocyanins in these colorful berries, but they all function as antioxidants – originally protecting the chokeberry seed from sunshine-induced oxidative stress. And when we eat them, they also appear to protect our bodies from a variety of damaging situations, including exposure to pollution and metabolically-derived free radicals. Indeed, a growing body of scientific literature has shown promising effects of chokeberry consumption on diseases ranging from cancer to obesity. These health-promoting effects may be due to the potent anti-inflammatory properties of anthocyanins, as uncontrolled inflammation is now universally recognized as a common thread in many of our most prevalent and deadly diseases. In addition, certain anthocyanins – including those found in chokeberry – have also been shown to improve blood sugar and the function of insulin.

To better understand how chokeberries influence health, Drs. Bolin Qin and Richard Anderson from the US Department of Agriculture in Beltsville, MD studied what happens when prediabetic rats are fed chokeberry extracts for an extended period of time. The results of their research will be presented on April 25 at the Experimental Biology 2010 meeting in Anaheim, CA. This presentation is part of the scientific program of the American Society for Nutrition, home of the world’s leading nutrition researchers.

The researchers first made 18 male rats “prediabetic” or insulin insensitive by feeding them a fructose-rich diet for 6 weeks. Then they randomized the animals to continue drinking either pure water or water spiked with low or high levels of chokeberry extract (CellBerry®, Integrity Nutraceuticals International). After drinking this water for 6 weeks, the groups were compared in terms of body weight, body fat, blood glucose regulation, and molecular markers for inflammation.

Qin and Anderson found that at the end of the study the rats consuming the chokeberry-spiked water weighed less than the controls; both levels of chokeberry had the same effect in this regard. Similar beneficial effects of chokeberry consumption were found for body fat (specifically, that of the lower abdominal region). They also discovered that animals that had been drinking chokeberry extract had lower blood glucose and reduced levels of plasma triglycerides, cholesterol, and low-density lipoprotein (LDL) cholesterol when compared to the control animals. These alterations would theoretically lead to lower risk for diabetes and cardiovascular disease in humans. And to add even more evidence for a healthful impact of this super-berry, the researchers documented numerous alterations in expression of genes that would likely lead to reduced chronic inflammation and perhaps even lower cancer risk. For instance, drinking chokeberry extract lowered expression of the gene coding for interleukin-6 (IL-6), a protein that normally triggers inflammation following trauma or infection. Chronic overproduction of IL-6 has been documented in many diseases such as diabetes, arthritis, and atherosclerosis and is thought to be a partial cause of these conditions.

Of course, human studies will be needed before scientists can declare whether we derive the same health benefits from the chokeberry, but Qin and Anderson believe that their study “provides evidence that the chokeberry extract inhibits weight gain in insulin-resistant animals and that it modulates multiple genes associated with adipose tissue growth, blood glucose regulation, and inflammatory pathways.” A final word to the wise: raw chokeberries are exceptionally bitter, so don’t be tempted to harvest the shrubs in your backyard. Instead, look for this unassuming berry in fruit juice blends, jellies, and sweetened syrups.

Drs. Qin and Anderson are federal researchers in the Diet, Genomics, and Immunology Laboratory at the Beltsville Human Nutrition Research Center, a component of the US Department of Agriculture. This study was supported, in part, by Integrity Nutraceuticals International (South Spring Hill, TN).

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Turnhout, 08 January 2008, Movetis NV, a European-based specialist pharmaceutical company, announced today that M0002, an orally-active selective V2 vasopressin antagonist for the treatment of ascites has successfully completed enrollment in a Phase IIa clinical trial, and that M0003, an innovative gastrokinetic compound for the treatment of paediatric reflux and gastroparesis has now begun a Phase IIa clinical trial in patients with gastroparesis.

M0002 is an aquaretic, electrolyte-sparing treatment that promotes the excretion of bodily water without extra loss of sodium. It is currently being studied for the treatment of ascites or accumulation of water in the abdomen of patients with liver cirrhosis as a result of hepatitis C or alcoholism. M0002 has the potential to reduce the number of invasive hospital procedures (paracenthesis) currently used to reduce the accumulation of water in the abdomen. Trial results for M0002 to date show that it is well tolerated and maintains aquaretic activity in healthy volunteers. Single dosing of M0002 in cirrhotic patients resulted in a significantly increased output of diluted urine. Results from the Phase IIa clinical trial are expected to be available at latest by the end of Q2 2008.

M0003 is a powerful, and specific, high affinity 5-HT4 agonist that stimulates upper GI motility and accelerates gastric emptying at low dose. It is currently being studied for the treatment of gastroparesis, a disorder in which the stomach takes too long to empty its contents, as well as paediatric reflux, or involuntary regurgitation of gastric contents into the oesophagus. Results from the Phase IIa clinical trial of M0003 in gastroparesis are expected in 2009.

In a further boost to its commitment to bring innovation back to GI, Movetis was granted 1.67 million Euros by the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) at the end of 2007 to support early and innovative development for M0002 and start discovery efforts with its library of 5-HT4 agonists.

‘We are encouraged to see that our compounds are successfully progressing through research on time and within budgets. Obviously we are honoured that the IWT institute feels our programme merits such a grant and we are committed to work with them to progress innovation and create jobs in our region.” commented Dirk Reyn, CEO of Movetis “Through these grants and the support of our distinguished investors, we can pursue our path to discover, develop and ultimately commercialise innovative treatments targeting selected GI conditions where patients do not get adequate relief from older drugs with less favourable benefit/risk profiles” .

About Movetis

Through a clear focus on GI, Movetis seeks to improve the lives of millions of patients – both adults and children – by discovering, developing and commercialising innovative treatments targeting GI conditions that have recently benefited less from innovation. Movetis NV – founded in Belgium in December 2006 – aims to become the leading European specialty pharmaceutical organisation focused on GI diseases. Movetis has a broad GI portfolio with four products in clinical development and four in preclinical, all aiming to address important areas of unmet medical need, including chronic constipation (CC), ascites, paediatric reflux, diabetic gastroparesis, specific subgroups of patients with severe forms of IBS or dyspepsia and secretory diarrhoea. In addition, Movetis has rights to a large library of qualified lead compounds with potential for development. The current portfolio has been licensed from Janssen Pharmaceutica NV, Belgium and Ortho-McNeil Pharmaceutical Inc., two Johnson & Johnson (J&J) companies.

The current clinical portfolio includes:

- RESOLOR (prucalopride), a compound for the treatment of CC currently in preregistration

- M0002, a compound for the treatment of ascites, which has completed recruitment of a Phase IIa trial, results are expected before the end of Q2 2008

- M0003, a gastrokinetic compound for the treatment of paediatric reflux and gastroparesis, which has recently entered Phase IIa clinical trials in gastroparesis

- M0004, another gastrokinetic compound for nocturnal heartburn and other motility complaints related to gastro-oesophageal reflux disease (GORD).

In 2006, Movetis secured 49 million Euros in a series ‘A’ financing from major European and US investors – one of the biggest series ‘A’ rounds in Europe. These funds are being used to complete the development and registration filing of RESOLOR, and to continue preclinical and clinical development of all other products. Investors include Sofinnova Partners, J&J, Life Sciences Partners, Sofinnova Ventures, KBC Private Equity and KBC Private Equity Fund Biotech, GIMV, Quest for Growth and BIP Investment Partners. Movetis is based in Turnhout, Belgium.

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