The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author. Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.
BONE MARROW STEM CELLS & LIVER FAILURE
The liver is an extraordinarily complex organ, and is responsible for, literally, hundreds of critical metabolic processes in the body. While the liver is the only organ that is capable of regeneration in adults, this regenerative capability has its limits, making progressive liver failure a very serious health condition. When advanced liver failure occurs (most commonly from chronic hepatitis and cirrhosis), a liver transplant is generally the only hope for long-term survival. Unfortunately, there are far too few donor livers available to go around, and most patients with advanced liver failure will die before a liver transplant becomes available to them (liver failure is currently the 12th most common cause of death in the United States).
As in other areas of medicine, the emerging field of stem cell therapy has caught the attention of physicians who manage patients with liver failure. Due to the ongoing ethical debate over the use of embryonic stem cells, which are removed from aborted fetuses, a great deal of research has been done on harvesting a patient’s own stem cells from the bone marrow, and using these cells to repair or replace failing organs. In what has been widely hailed as a breakthrough in stem cell research, scientists at several different institutions have recently shown that specialized cells for many different organs can be produced from bone marrow stem cells, including the liver. While bone marrow stem cell research is still in its infancy, the fervent hope of researchers in this field is that failing organs, like the liver, might someday be revived by growing bone marrow stem cells under laboratory conditions that induce them to grow into the cells and, ultimately, the tissues specific to those failing organs. A new laboratory research study in the journal Gastroenterology, from researchers in Taiwan, and at Emory University, in Atlanta, has now demonstrated that, at least in mice, failing livers can indeed be rejuvenated and rescued with replacement liver cells grown from bone marrow stem cells.
In this innovative study, laboratory mice were treated to induce complete liver failure, which is a uniformly lethal condition. The researchers then injected liver cells derived from bone marrow stem cells into the mice, as well as bone marrow stem cells themselves (i.e., without first transforming them into liver cells). These cells were injected into the blood of some of the mice, while other mice received injections of these specialized cells directly into the spleen. Amazingly, both the stem cells that had been transformed into liver cells and the non-transformed stem cells were subsequently found to be growing in the livers of these mice when they were euthanized at the end of the research experiment, and both types of cells were found to have developed into functional, mature liver cells within the animals’ previously damaged livers. Even more amazing was the finding that these bone marrow stem cells, whether transformed into liver cells outside of the recipient animals or not, were able to induce liver regeneration and function in mice who had suffered otherwise lethal damage to their livers. In particular, the mice that had received stem cell injections directly into a vein had more impressive liver regeneration, and return of liver function, than the animals that had received their stem cell injections into the spleen.
In this striking experiment, mice with mortally damaged livers were, effectively, rescued by injecting them with bone marrow stem cells. These stem cells, including stem cells that were not deliberately transformed into liver cells in the laboratory, then made their way to the animals’ damaged livers, and began to grow and function as normal liver cells, regenerating the animals’ severely damaged livers in the process. Currently, there are a handful of human clinical trials underway that are working to replicate the dramatic results obtained in this mouse study. If stem cell therapy, using stem cells taken from a patient’s own bone marrow, can be shown to repopulate failing livers with healthy, functional new liver cells, this would represent an enormous step forward in the management of end-stage liver failure and might, someday, eliminate the need for liver transplants in the majority of liver failure cases. Similarly, the successful use of stem cells and genetic engineering to, someday, recreate other failing organs (like the heart, kidneys and pancreas, for example) would transform the field of regenerative medicine from something resembling the pages of science fiction books and futuristic movies into a mature technology suited for routine clinical use. Studies such as this are laying the essential groundwork for a coming revolution in the management of critical organ failure in humans.
VITAMIN D & COLORECTAL CANCER SURVIVAL
Colorectal cancer is the third most common cancer in the US, and the third most common cause of death due to cancer. I have previously reviewed other studies that have suggested that high levels of Vitamin D in the blood may reduce the risk of developing colorectal cancer (please see my recent Archives for my reviews of several such studies). Although not all studies have confirmed a protective effect of Vitamin D on the risk of developing colorectal cancer, many studies suggest a modest but significant reduction in the incidence of this disease among patients with higher levels of this important vitamin in their blood. A logical question to ask, then, is whether or not higher levels of Vitamin D in the blood might also be beneficial to patients who have already been diagnosed with colorectal cancer. A newly reported study, in the Journal of Clinical Oncology, from researchers at Harvard University and the University of South Carolina, may provide an answer to this important question.
In this study, 304 adults participating in the very large Nurses’ Health Study and the Health Professionals Follow-Up Study were diagnosed with colorectal cancer between 1991 and 2002. As with other participants in these two large public health studies, the patients who were diagnosed with colorectal cancer while participating in the study underwent extensive testing upon entering into the study, including the measurement of blood levels of Vitamin D. When the researchers compared patient outcomes (i.e., long-term survival versus death), they found that the patients with the highest Vitamin D levels were only half as likely to die, of any cause, during the course of these studies when compared to patients who had the lowest Vitamin D levels. When comparing the incidence of death specifically due to colorectal cancer according to Vitamin D levels in the blood, this study revealed a trend towards improved survival with higher blood levels of Vitamin D, although this trend did not quite reach statistical significance.
This study adds to prior studies that have suggested a potentially beneficial role for Vitamin D in reducing both the incidence and mortality of colorectal cancer. Whether these benefits, if they truly exist, result directly from the effects of Vitamin D itself, or whether a high level of Vitamin D in the blood is simply a marker of other factors that are providing these benefits, is unknown at this time. (For this reason, taking significant doses of Vitamin D supplements cannot be recommended for colorectal cancer prevention or treatment at this time.)
Vitamin D supplementation is beginning to find its way into clinical research trials looking at colorectal polyp and colorectal cancer formation, but it will probably be at least 5 to 10 years before definitive, prospective clinical research data becomes available regarding Vitamin D’s true role, if any, in preventing or treating colorectal cancer. For now, I can only recommend that readers ensure a sufficient intake of Vitamin D, including modest sun exposure (5 to 10 minutes at a time, 2 to 3 times per week, although dark-skinned people may require longer and more frequent sun exposure in order to generate adequate levels of Vitamin D); and moderate intake of foods rich in Vitamin D, including fish (and salmon, in particular), Vitamin D-fortified dairy products and, if you are an aficionado of organ meats, an occasional slice of liver. At the same time, remember that taking large amounts of Vitamin D supplements may cause very high levels of Vitamin D to accumulate in the blood, which can be toxic and harmful to your health.
GREEN TEA & COLORECTAL CANCER
The antioxidant effects of the active compounds in green tea are the focus of tremendous clinical research in the areas of cardiovascular disease and cancer prevention (please see my Archives for my reviews of several important recent studies in this area). Numerous studies of the “catechins” derived from green tea have suggested that, at least in laboratory animals, green tea catechin supplementation appears to reduce the risk of some types of cancer, including precancerous polyps and cancers of the colon and rectum. An interesting new study from Columbia University, Cornell University, and Gifu University in Japan, and just now published in the journal Carcinogenesis, extends our understanding of at least one possible mechanism whereby green tea catechins might reduce the risk of developing colorectal cancers, and might even potentially improve survival once colorectal cancer has been diagnosed.
One important mechanism whereby colorectal cancer cells grow and divide is through a molecule found on the surface of such cells, the epidermal growth factor receptor (EGFR). When EGFR encounters certain other circulating proteins, including the epithelial growth factor (EGF), the receptor and its growth factor bind together and set off a chemical chain reaction that, ultimately, results in increased tumor cell growth and reproduction. Indeed, newer “molecularly-targeted” drugs have recently been developed that interrupt EGFR binding to its stimulatory proteins (also known as ligands).
Recent research has shown that the predominant catechin in green tea, epigallocatechin gallate, appears to inhibit EGF binding to the EGFR in Petri dish cultures of human colon cancer cells. Researchers in this study, therefore, sought to better understand the effects of epigallocatechin gallate on EGFR function, as the EGFR-EGF pathway is an important mechanism whereby cancers of the colon and rectum, and other cancers as well, reproduce themselves and grow.
In this study, researchers treated cultures of human colon cancer cells with epigallocatechin gallate. They found that even tiny concentrations of this green tea extract resulted in markedly reduced numbers of EGFR on the surface of colon cancer cells, and with as little as 30 minutes of treatment time. However, this presumably beneficial reduction in EGFR levels on the surface of the cancer cells only lasted 1-2 hours, following 30 minutes of treatment with the green tea extract, before the cells were able to begin restoring the prior number of surface EGFR molecules.
This study is an important advance in our understanding of how green tea might exert its possible anti-cancer effects at the cellular and molecular levels. While other potential anti-cancer mechanisms have also been described for green tea and its active components, this particular study focuses on the EGFR-EGF pathway, which is known to be very important for many cancer cells, including colorectal cancer cells, in terms of their survival and progression. Other studies have also suggested, as this study does, that the effects of individual doses of green tea extracts only persists for a couple of hours, implying that frequent doses of green tea, or its active components, may be required for sustained effect around the clock (alternatively, longer-acting synthetic analogues of these active green tea compounds will have to be synthesized).
While this particular study offers no proof that green tea might be clinically useful in patients with colorectal cancer, it does very elegantly reveal at least one potential mechanism whereby green tea catechins might be able to exert significant alterations in cancer cell physiology that, in turn, might result in clinically significant benefits for patients diagnosed with colorectal cancer.
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:
http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html
Send your feedback to Dr. Wascher at: rwascher@doctorwascher.net
Copyright 2008. Robert A. Wascher, MD, FACS.
All rights reserved.
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