Tumor budding at the invasive tumor front of colorectal cancer is recognized as an independent prognostic factor significantly related to both lymph node and distant metastasis. Several lines of evidence seem to suggest that tumor buds may, to some extent, represent malignant colorectal cancer stem cells because of their potential for migration and re-differentiation locally and at sites of metastasis. However, phenotypic characterization of cancer stem cells in general is still debated although at least 8 putative stem cell markers have been suggested including CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. Little is known about the potential of these proteins to act as prognostic biomarkers in patients with colorectal cancer and most of these proteins have never before been explored within tumor buds themselves.

A research article published in the World Journal of Gastroenterology addressed this problem. Considering the apparent stem cell-like properties of tumor buds and association of budding with adverse clinical outcomes, the research team led by Dr. Alessandro Lugli performed immunohistochemical staining of 8 putative cancer stem cell markers, namely CD166, CD44s, EpCAM, ALDH1, CD133, CD24, CD90, and ABCG5. The expression within tumor buds was evaluated, their frequency of occurrence and their potential prognostic significance in patients with colorectal cancer were determined.

Their findings showed that expression of EpCAM and particularly of ABCG5 within the tumor buds of colorectal cancer are frequent events. Moreover, expression of EpCAM or ABCG5 within tumor buds themselves has the potential to stratify patients with colorectal cancer into prognostic subgroups. This was particularly pronounced for patients with node-negative disease.

The results of this study could have important implications for patients with lymph node-negative colorectal cancer. Stratification of this group of patients could help to identify those likely to have a particularly poor outcome who could perhaps be considered for adjuvant therapy.

The study is characterized technically by an excellent application of immunohistochemistry and provides interesting evidence to aid the understanding of the correlation between cancer stem cell markers at the invasive front of colorectal cancer and prognosis. The findings suggest that EpCAM and ABCG5 in tumor buds may be useful biomarkers of poor outcome in this subgroup of patients. However, further studies are necessary to address the important issue of whether EpCAM- or ABCG5-positive tumor buds indeed represent migrating colorectal cancer stem cells.

Mango. If you know little about this fruit, understand this: It’s been found to prevent or stop certain colon and breast cancer cells in the lab.

That’s according to a new study by Texas AgriLife Research food scientists, who examined the five varieties most common in the U.S.: Kent, Francine, Ataulfo, Tommy/Atkins and Haden.

Though the mango is an ancient fruit heavily consumed in many parts of the world, little has been known about its health aspects. The National Mango Board commissioned a variety of studies with several U.S. researchers to help determine its nutritional value.

“If you look at what people currently perceive as a superfood, people think of high antioxidant capacity, and mango is not quite there,” said Dr. Susanne Talcott, who with her husband, Dr. Steve Talcott, conducted the study on cancer cells. “In comparison with antioxidants in blueberry, acai and pomegranate, it’s not even close.”

But the team checked mango against cancer cells anyway, and found it prevented or stopped cancer growth in certain breast and colon cell lines, Susanne Talcott noted.

“It has about four to five times less antioxidant capacity than an average wine grape, and it still holds up fairly well in anticancer activity. If you look at it from the physiological and nutritional standpoint, taking everything together, it would be a high-ranking super food,” she said. “It would be good to include mangoes as part of the regular diet.”

The Talcotts tested mango polyphenol extracts in vitro on colon, breast, lung, leukemia and prostate cancers. Polyphenols are natural substances in plants and are associated with a variety of compounds known to promote good health.

Mango showed some impact on lung, leukemia and prostate cancers but was most effective on the most common breast and colon cancers.

“What we found is that not all cell lines are sensitive to the same extent to an anticancer agent,” she said. “But the breast and colon cancer lines underwent apotosis, or programmed cell death. Additionally, we found that when we tested normal colon cells side by side with the colon cancer cells, that the mango polyphenolics did not harm the normal cells.”

The duo did further tests on the colon cancer lines because a mango contains both small molecules that are readily absorbed and larger molecules that would not be absorbed and thus remain present in a colon.

“We found the normal cells weren’t killed, so mango is not expected to be damaging in the body,” she said. “That is a general observation for any natural agent, that they target cancer cells and leave the healthy cells alone, in reasonable concentrations at least.”

The Talcotts evaluated polyphenolics, and more specifically gallotannins as being the class of bioactive compounds (responsible for preventing or stopping cancer cells). Tannins are polyphenols that are often bitter or drying and found in such common foods as grape seed, wine and tea.

The study found that the cell cycle, which is the division cells go through, was interrupted. This is crucial information, Suzanne Talcott said, because it indicates a possible mechanism for how the cancer cells are prevented or stopped.

“For cells that may be on the verge of mutating or being damaged, mango polyphenolics prevent this kind of damage,” she said.

The Talcotts hope to do a small clinical trial with individuals who have increased inflamation in their intestines with a higher risk for cancer.

“From there, if there is any proven efficacy, then we would do a larger trial to see if there is any clinical relevance,” she said.

Long-chain omega-3 fatty acids, primarily found in fish and seafood, may have a role in colorectal cancer prevention, according to results presented at the American Association for Cancer Research Frontiers in Cancer Prevention Research Conference, held Dec. 6 – 9, 2009, in Houston.

“Experimental data have shown benefits of long-chain omega-3 fatty acids in colorectal carcinogenesis, ranging from reduced tumor growth, suppression of angiogenesis and inhibition of metastasis,” said Sangmi Kim, Ph.D., a postdoctoral fellow at the National Institute of Environmental Health Sciences, Research Triangle Park, N.C. “Our finding of inverse association between dietary intakes of long-chain omega-3 fatty acids and distal large bowel cancer in white participants adds additional support to the hypothesis.”

Although experimental and clinical data suggest that long-chain omega-3 fatty acids possess anti-neoplastic properties in the colon, epidemiologic data to date has been inconclusive.

Kim and colleagues studied the link between polyunsaturated fatty acid intake and distal large bowel cancer using data from a population-based control study. They recruited 1,509 white participants (716 cancer cases and 787 controls) and 369 black participants (213 cancer cases and 156 controls) using the State Cancer Registry and Division of Motor Vehicles records.

Nineteen polyunsaturated fatty acids were assessed using a validated food frequency questionnaire, which included 124 questions on food items. The researchers used the questionnaire to collect information on the frequency and amount of foods typically consumed in the past 12 months.

Patients who consumed more long-chain omega-3 fatty acids had a reduced risk of distal large bowel cancer. Compared to the lowest quartile, fat intake in the highest quartile was linked with a 39 percent reduced risk of cancer.

The researchers detected these associations in white participants, but not in black participants.

“We were surprised that the association was not also observed among blacks,” Kim said. “We considered several possible explanations but were not able to account for this difference with the data we had. This finding warrants future study, but we should be careful about drawing conclusions about potential racial differences in the benefit from long-chain omega-3 fatty acids from this study.”

“An increase in dietary intake of long-chain omega-3 fatty acids, which mainly come from fish and seafood, may be beneficial in the prevention of distal large bowel cancer,” Kim said.

New study results strengthen the evidence that people who smoke cigarettes over a long period of time have an increased risk for developing colorectal cancer, even after adjusting for other risk factors.

“This provides one more reason not to smoke, or to quit as soon as possible,” said senior author Michael J. Thun, M.D., M.S., vice president emeritus, epidemiology and surveillance research at the American Cancer Society. “Colorectal cancer should be added to the list of cancers caused by smoking.”

Findings are published in the December issue of Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research, as part of a special focus on tobacco.

Thun and colleagues tested the association between long-term cigarette smoking and colorectal cancer after adjusting for multiple other factors that are generally associated with risk, including screening. From 1992 through 2005 the researchers followed almost 185,000 participants aged 50 to 74 years old; participants described their behaviors and medical conditions.

Participants who smoked cigarettes for 40 or more years, or who did not quit before age 40, had a 30 percent to 50 percent increased risk of developing colon or rectal cancer during the follow-up, even in analyses that adjusted for 13 other potential risk factors, according to Thun. After 13 years of follow-up, the researchers identified 1,962 cases of invasive colorectal cancer.

While previous large studies conducted in long-term smokers showed similar results, Thun stated that this study is the first to control for screening and all of the suspected risk factors for colorectal cancer, such as alcohol consumption, physical inactivity and consumption of red or processed meat.

“These findings contributed to the evidence recently reviewed by the International Agency for Research on Cancer (IARC) in October of this year,” Thun said. “IARC upgraded the evidence that smoking causes colorectal cancer from ‘limited’ to ’sufficient’.”

This IARC reclassification brings the number of cancer organ sites causally related to cigarette use to 17, which includes cancers of the oral cavity, pharynx, nasopharynx, nasal cavity and paranasal sinuses, larynx, lung, esophagus (both squamous cell and adenocarcinoma), stomach, colorectum, liver, pancreas, kidney (both renal cell and transitional cell carcinoma), urinary bladder and lower urinary tract, uterine, cervix, and myeloid leukemia.

University of Florida researchers have found a way to use just a fraction of the normal dosage of a highly toxic, debilitating chemotherapy drug to achieve even better results against colon cancer cells.

More research is needed before the therapy can be tested in patients, but the discovery in human colon cancer cell lines and mice with established human tumors suggests that the addition of a small molecule to the cancer drug Temozolomide disrupts repair mechanisms in a type of tumor cells that is highly resistant to treatment.

The discovery will be featured on the cover of December’s Molecular Cancer Research, a journal of the American Association for Cancer Research.

“This is very important because aside from aggressive surgery with possibly chemotherapy, there are no specific treatments for colon cancer,” said Satya Narayan, a professor of anatomy and cell biology at the College of Medicine and a member of the UF Shands Cancer Center. “The recurrence rate for this type of cancer after surgery is very high, about 30 to 50 percent, and there is an urgent need to develop new approaches to manage this deadly disease.”

The National Cancer Institute estimates there will be about 106,000 new cases of colon cancer in the United States in 2009. It is the second most common cause of cancer-related death in both men and women in the Western hemisphere. The disease forms in the large intestine and survival rates vary according to how soon the cancer is diagnosed and the treatment is started.

Narayan’s research team evaluated more than 140,000 small molecules, finally arriving at a tiny molecule that precisely blocks the ability of cancer cells to recognize and repair the DNA damage inflicted by Temozolomide, or TMZ.

“Our idea was if you induce DNA damage (with TMZ), and at the same time block cell repair, you can synergize toxic effects to the cancer cells,” Narayan said. “We hope that with this combination treatment we can reduce the tumors drastically and expand the lifetime of patients much longer than is currently possible.”

TMZ is commonly used against certain types of brain cancer. It works by damaging the DNA of the cancer. However, the challenge of treating patients is that colon cancer is not a single disease but an array of disorders with distinct molecular mechanisms, with one type being quite proficient at repairing the DNA damage inflicted by the drug.

By combining TMZ with the small molecule, Narayan’s team was able to disable the colon cancer’s ability to manufacture repair enzymes.

The UF researchers effectively used an amount of TMZ that is about 10 times lower than recommended in its studies of mice with human colon cancer tumors.

If only about one-tenth as much TMZ is needed to kill cancer cells, Narayan said, it will be possible to use lower doses of a drug that creates a great deal of adverse side effects, a partial listing of which includes anxiety, back pain, breast pain, constipation, cough, diarrhea, dizziness, drowsiness, dry skin, hair loss, headache, joint pain, loss of appetite, mouth sores, muscle aches and nausea.

The world’s first patient to have a malignant rectal tumor removed through the anus, thus avoiding painful abdominal incisions, was a 76-year old woman who was able to leave the Barcelona hospital where she was treated 5 days later, with no complications, and is said to be making an excellent recovery.

The surgeons are optimistic that the method can now be developed to treat a range of colorectal diseases, including cancer and diverticulitis, offering patients the benefit of fewer postoperative complications and a speedier recovery.

According to a report from Barcelona issued at the end of November, a team of surgeons from the Hospital Clinic Barcelona, Spain, and Massachusetts General Hospital of Boston (Harvard University) in the US, used a procedure called NOTES (Natural Orifice Transluminal Endoscopy Surgery), an innovative surgical approach that allows surgical access using the body’s natural orifices.

NOTES is said to offer many benefits for the patient, including less time in hospital and speedier recovery. It also has the potential to achieve safe oncologic results better than laparoscopic surgery, because it leaves no surgical scars, whereas laparoscopic surgery requires four or five minimal incisions.

Another example of natural orifice surgery is the removal of the gallbladder through the mouth, where the surgeon inserts a tube down the esophagus, makes a small cut in the stomach or digestive tract to get into the abdominal cavity, and then removes the organ through the same route.

However, this type of minimally-invasive surgery is still at the research and development stage. And while surgery through the mouth and the vagina is relatively common, surgery through the anus is not.

The successful operation was the result of collaboration between two surgical teams from the Hospital Clinic of Barcelona and Massachusetts General Hospital. Both teams specialize in minimally-invasive surgical approaches to treat diseases of the colon and rectum.

Dr Antonio Mª de Lacy headed the Gastrointestinal Surgery team of the Hospital Clinic of Barcelona, and Dr Patricia Sylla, Instructor of Surgery at the Harvard Medical School, headed the Massachusetts General Hospital team.

Lacy has done much to widen the use of laparoscopic surgery, where small incisions are made in the abdomen, to treat colorectal cancer, and Sylla has been working since 2007 with Dr David Rattner, Professor of Surgery at the Massachusetts General Hospital and Harvard Medical School, to develop methods for use in colorectal surgery. Rattner is an expert on NOTES and co-founded the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR).

The surgery to remove the malignant rectal tumor was carried out on the 9th of November and the patient was discharged only five days later, on the 14th.

During the operation, nearly all the surgical instruments went in through the anus, thus avoiding painful incisions in the abomen.

One of the advantages of removing a tumor through the anus using this type of surgery is that the colon or rectum can be opened and closed under direct vision without having to rely on a camera. In this case the surgeons used techniques developed for Transanal Endoscopic Microsurgery (TEM), an approach that allows local treatment of rectal lesions.

With TEM, surgeons use rectal endoscopy to introduce a specially-designed proctoscope connected to a carbon dioxide insufflation system that dilates the rectum. This creates enough room for surgeons to insert instruments to section and dissect the mass. This route also allows them to dissect the rectum and surrounding tissue to reach the abdominal cavity, if necessary; a completely new approach.

Unlike other NOTES procedures where surgeons have to make incisions to access the tumor, the transanal method is the only route where the tissue they cut to gain access is part of what they are going to remove anyway (thus leaving no incision scars; the only scar to heal is the one where the tumor was attached to surrounding tissue).

The teams first tested the TEM method on pigs, then on human human cadavers.

They hope this method can also be developed to treat other diseases of the colon and rectum.

Lacy told the media that:

“We are convinced that this type of surgery will bring additional advantages to those already shown by laparoscopic surgery, reducing surgical invasiveness by eliminating abdominal incisions, and resulting in fewer postoperative complications and a speedier recovery.”

Sylla added that:

“Based on this first case, I am encouraged that in the near future we will be able to offer this type of procedure to more patients. This approach could have wide use for patients with colorectal cancer, diverticulitis, and other diseases of the colon and rectum.”