Celecoxib May Help Prevent Colorectal Cancer In High Risk Patients, Studies Confirm

During the past year, the study of the potential use of COX-2 (cyclooxygenase-2) inhibitors to prevent colorectal and breast cancer has come under intense scrutiny. Recent research questioned the safety of these medicines as pain relievers, which was the initial indication, as well as for chemoprevention of cancer. Now, the latest data show that COX-2 inhibitors are highly effective in preventing pre-malignant tumors of the colon, and therefore may be useful in preventing colorectal cancer among high-risk patients.


According to two studies presented today at the 97th Annual Meeting of the American Association for Cancer Research, the over-expression of the COX-2 enzyme is related to the growth and spread of colorectal tumors. COX-2 inhibitors may reduce the occurrence of the precursor,colorectal adenomas(benign tumors) in patients with a family history of the disease, as well as the development of sporadic colorectal tumors.


Celecoxib reduces sporadic colorectal adenomas: Results from the Adenoma Prevention with Celecoxib (APC) trial.: Abstract No. CP-3
Investigators from the Adenoma Prevention with Celecoxib Study (APC)
enrolled 2,035 patients to a randomized, double-blind trial of the COX-2 inhibitor, celecoxib (Celebrex®), to prevent colorectal adenomas. Results of the study revealed that celecoxib significantly reduced the formation of large intestinal adenomas during a 3-year period after removal of polyps in patients at high risk of developing colorectal cancer.


Of the participants, 679 patients received a placebo, 685 patients received 200 mg of celecoxib and 671 patients received 400 mg of celecoxib, administered twice daily. The randomization of this trial took into consideration the use of low dose aspirin in 31 percent of participants. A follow-up colonoscopy was conducted in 89 percent of participants after one year and 76 percent received a follow-up colonoscopy at three years.


The incidence of one or more benign tumors during colonoscopy was 61
percent in those taking placebo; in patients taking celecoxib this percentage was reduced by 45 percent (p







"This work shows that drugs that inhibit COX-2 activity are important tools in developing effective preventive therapies for colorectal cancer," she said.


Chemoprevention of Colorectal Adenomas With Celecoxib in an International Randomized, Placebo-Controlled, Double-Blind Trial: Abstract No. CP-3


A prior study has shown that administration of the COX-2 inhibitor, celecoxib, is associated with a reduction in colorectal adenoma size and number in familial adenomatous polyposis (FAP). Therefore, researchers in the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) with Celecoxib Trial tested the effectiveness of celecoxib in reducing the incidence of sporadic colorectal adenomas.


The PreSAP study was a randomized, double-blind, placebo-controlled study enrolling 1,561 patients at 107 sites in 32 countries. PreSAP researchers hoped to determine the effectiveness of taking 400 mg celecoxib once daily to reduce the number of patients with new adenomas and the grade, size and number of new adenomas.


The trial started in March 2001 with patients who had undergone removal of all colorectal polyps, known as a polypectomy. Patients were excluded if they had FAP, hereditary nonpolyposis colorectal cancer (with an absence of polyps) or a history of inflammatory bowel disease. During the trial, patients did not take nonsteroidal anti-inflammatory drugs (NSAIDs) except cardioprotective doses of aspirin.


"Results of our study showed that celecoxib holds great promise for the prevention of cancer," said Nadir Arber, M.D., M.Sc., Head, Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Israel. "For patients at high-risk of developing colorectal cancer, celecoxib may be considered while weighing the risk of potential cardiovascular events."


Patients were split into a 3:2 ratio of celecoxib and placebo and divided by baseline aspirin use (17 percent, placebo; 16.6 percent celecoxib) or non-use(83 percent placebo; 83.4 percent celecoxib); 933 patients received celecoxib and 628 received placebo. Of the total patients, 88.7 percent underwent a colonoscopy with or without removal of polyps at one year and 79.2 percent at year three.


The administration of celecoxib was stopped after the Adenoma Prevention with Celecoxib (APC) study found at 33 months a two-to-three-fold increase in serious adverse cardiovascular events. PreSAP data at the time of the APC announcement indicated a hazard ratio of 1.2 for those taking celecoxib compared with placebo for death from cardiovascular events and nonfatal heart attack or stroke.


The incidence of adenomas at year three was 49.3 percent in the placebo group, but significantly lower in the group taking celecoxib (p

Hope For Crohn's Patients With Fistulas Found In HUMIRA/Adalimumab

At the recent European Crohn's and Colitis Organization (ECCO) annual
meeting in Lyon, France, Abbott Laboratories announced that HUMIRA
(Adalimumab) is successful in the treatment of fistulas in susceptible
Crohn's patients.



Crohn's
Disease (CD) is a gastrointestinal disorder which is indicated by
chronic
inflammation of the wall of the digestive tract. The disease involves
constant cycles of flare-ups and
remission throughout the life of the patient, and without proper
treatment, must be addressed surgically. It is considered an
inflammatory bowel disease (IBD), similar to ulcerative colitis. Up to
43% of Crohn's disease patients develop painful and embarrassing
fistulas, which are tunnels that connect affected organs to surrounding
tissues such as the bladder, vagina, or skin. These are difficult to
treat, can cause fecal discharge in abnormal locations, and can thus
lead to incontinence, infections, and complications that will
necessitate surgery.



HUMIRA, or Adalimumab works by binding Tumor Necrosis Factor ?± (TNF-?±),
an important part of the immune response pathway -- in this way it is
related to infliximab and other TNF-?± blockers. It has been
approved in several countries for treatment of many autoimmune diseases
including CD, psoriasis, and certain types of arthritis. Abbott Labs is
also studying HUMIRA in pediatric CD.



The fistula study was based on data taken in the CHARM study. In a
subanalysis, it was shown that fistula healing was improved with
treatment with HUMIRA:


60% of patients experienced fistula healing at one year of
treatment
76% of patients who experienced healing at one year
sustained the healing through two years
71% of patients demonstrated a 50% reduction in the number
of draining fistulas after two years of treatment

Over a two year term, fistula patients had a higher quality of life
because the CD was in remission, defined as scoring greater than 170
points on the Inflammatory Bowel Disease Questionnaire (IBDQ):
after 1 year, 54% of patients and after 2 years, 60% of patients
achieved this score.


Sustainability of Adalimumab in Improving the Quality of Life
of Patients With Fistulizing Crohn's Disease: 2-Year Data From CHARM

E. V. Loftus, Jr., J. F. Colombel, R. Panaccione, B. G. Feagan, M. A.
Kamm, P. F. Pollack, J. Chao, P. Mulani

For More Information, see humira/



Anna Sophia McKenney



View drug information on Humira.

University Of Kentucky Gill Heart Researchers Study Abdominal Aortic Aneurysms

As the baby boomer generation races toward Medicare eligibility, a new screening procedure could mean that many men in the United States may soon learn that they have a killer condition they can do little or nothing about.



Anticipating a surge in diagnosed cases of abdominal aortic aneurysm, a condition for which Medicare just approved a one-time free screening for men, University of Kentucky researchers are working with $8.5 million in NIH funding to understand the condition and how it can be treated.



"In collaborative studies with Lisa Cassis, professor and director of the UK Graduate Center for Nutritional Sciences, we serendipitously developed an animal model of abdominal aneurysms that is not used in many laboratories, This model has provided us with way of defining the mechanisms that initiate and propagate this devastating disease," said Alan Daugherty, Director, UK Cardiovascular Research Center.
the United States there are currently 78.8 million baby boomers - people born between 1946 and 1964. More than half of baby boomers will be age 50 or older by next May, and this January will mark the 60th birthdays of the oldest boomers, according to an analysis of U.S. Census data by American Demographics.



Abdominal aneurysm currently ranks as the 10th leading killer in the United States; although scientists suspect that the incidence may be even higher as the disease is only detected upon autopsy, and autopsies are not always performed in the deaths of older people. The condition primarily affects men over age 55, so the Medicare-covered screening will only be for men. Currently, if a screening detects an abdominal aneurysm, patients face an expensive and unsure course of surgical of treatment. The aneurysm must be monitored, and physicians must use their best judgment to decide when and if surgery is warranted. Open surgery is a long term fix for this disease, but is associated with risks and long recovery times. More recently, endovascular approaches have been developed in which patients recover quickly. However, this intervention is not without significant risk, and is expensive. There is a dire need for development of a drug that will favorably impact this disease. At present, there is no non-surgical therapy for abdominal aortic aneurysm that has proven of benefit.



The expected hit to the Medicare system from the influx of aging baby boomers means that surgical treatment for every case of abdominal aneurysm expected to be diagnosed in coming years would be prohibitive.



Aside from costs, the number of surgeons, support staff and facilities equipped to deal with the surgery will be outstripped by the need to treat the huge numbers of men who may learn they have an aneurysm threatening their lives.



The research team at UK HealthCare's Jack and Linda Gill Heart Institute, led by Daugherty, will spend the next five years working with an animal model of abdominal aneurysm. The goal is to form a sufficient understanding of the condition to move into clinical trials, and eventually into the implementation of a pharmacological treatment for abdominal aneurysm.
















Cassis and Nancy R. Webb, associate professor of internal medicine, along with Daugherty will direct their research toward understanding three separate facets of abdominal aneurysm. Cassis will lead a group focusing on gender effects, asking why the condition is much more prevalent in men. Webb's team will look at the role inflammation processes play in the disease, while Daugherty will investigate why abdominal aneurysm is always located in a specific location of the abdominal aorta.



A pharmacological solution to abdominal aneurysm treatment would mean that instead of waiting and wondering about a diagnosed aneurysm, patients and their doctors could aggressively treat the problem through drug therapies.



Pharmacological treatment is projected to be less expensive and less risky for most patients. Given the amount of time it takes to research a drug and bring it to market, it is possible that today's crop of 50-something baby boomer men may have an answer to abdominal aneurysm treatment by the time they qualify for the Medicare-approved screening at age 65.



UK was chosen as the site for this research after a peer review process at the National Institutes of Health enthusiastically endorsed the proposed research program that has been developed by the team of UK investigators, Daugherty, Cassis, and Webb. The Cardiovascular Research Center currently has more than $20 million dollars in NIH and other funding, and is a leader in cutting-edge clinical and translational research.







In striving to become a Top 20 public research institution, the University of Kentucky is a catalyst for a new Commonwealth - a Kentucky that is healthier, better educated, and positioned to compete in a global and changing economy. For more information about UK's efforts to become a Top 20 university, please go to uky.edu/OPBPA/Top20.html



Contact: Allison Elliott



University of Kentucky

New Technique Reveals Pancreatic Stem Cells

Wanted: stems cells. Just like those absconders chased by police all over the world, everybody can tell about their good deeds but none really knows how to recognize them. Yet, thanks to a study published in the Proceedings of the National Accademy of Sciences (PNAS) and authored by Nobel Laureate for Medicine in 2007 Mario Capecchi and by the researcher from the Catholic University of Rome Eugenio Sangiorgi, we now know how to reveal the stem cells camouflaged in the pancreas.



A stem cell is a cell capable of generating all the other cells constituting the same tissue (sometimes also called "adult stem cell").



"Reading the newspapers sometimes one would doubt it," says Sangiorgi, "but we don't know many things about stem cells. It might look odd, but for instance we don't have a method to distinguish a priori between a stem cell and any other cell in the same tissue. We can only infer that a cell really is a stem cell by observing its behaviour."



In other words, when a researcher encounters a tissue, it's not immediately possible to identify with certainty and thus isolate a stem cell. In some case, like in the meadows, we now know where they are located and how to single them out - and hence we have been capable of successful life saving transplants for many years. But in the case of the pancreas, as in that of many other tissues, until some years ago we doubted that these special cells were even present there.



"Together with Professor Capecchi, we had already designed in the past a novel way to mark the stem cells in a tissue: a sort of little flag, capable of helping us to effectively label the cells we were looking for", explains Sangiorgi. In order to achieve this, Capecchi and Sangiorgi used a molecular switch, that is a piece of DNA, which activates itself once the mouse under scrutiny takes a special drug. When the switch is "on", a special fluorescent protein is produced (and, as a matter of fact, the study about this type of proteins won the Nobel Prize in Chemistry last October). The luminous cells are indeed the long-sought stem cells.



"In order to understand that these are really stem cells, we need only to wait", comments Sangiorgi. "A normal cell is sooner or later destined to die. A stem cell, instead, retains its capacity to renew itself and replicate. Thus, if we can still observe, many months later, that a cell is still alive, that means it is indeed a stem cell - or a cell derived directly from the division of a stem cell".



In the newly published article, Sangiorgi and Capecchi have shown with their technique that a particular subset of the pancreatic cells, the so-called acinar cells, are indeed stem cells. The truly interesting aspect of their results is that these cells also produce important digestive enzymes.



"So far, a stem cell was really looked upon as a sort of General, in charge of all the other cells, but really doing nothing: an undifferentiated cell, but with no specific task other than generating new tissue. Acinar cells, on the other hand, despite being proved stem cells, have a well defined task in the pancreas. They are like soldiers doing their job, but also capable - when necessary - of taking over the reins of the government", tells Sangiorgi with a metaphor.



The work of Capecchi and Sangiorgi paves the way to an extension of the definition of the stem cell, which will lead to a more detailed study on the proliferation mechanisms at the root of the success of these cells - and of their potential danger.



"Thanks to their extraordinary reproductive power - Sangiorgi, in fact, explains - these cells might even turn out to be carcinogenic. But if we are capable of constructing an effective instrument like ours in order to isolate and study them even in other organs, we can study their properties and give many answers about the way they work. One of the things we would like to understand is if also in vivo these types of cells - somehow eternal - are more tumour-sensitive - for instance because they tend to accumulate all the potential environmental risk factors throughout their very long life".



Eugenio Sangiorgi has been collaborating with Mario Capecchi for many years: "I already admired him a great deal before he won the Nobel Prize", he says. "The nicest thing about him is that - even at 72 - he keeps working in active research and continues being as enthusiastic as a child, always full of new ideas".



Source:
Eugenio Sangiorgi


Catholic University of Rome