Long Term Survival Indicated for Advanced Stage Colorectal Cancer Patients who Survive at Least Two Years

Improvements in chemotherapy and liver surgery have resulted in increased overall survival in patients with advanced stage colorectal cancer in recent decades. In order to better predict outcomes for these patients, researchers at Rutgers Cancer Institute of New Jersey conducted a retrospective analysis and found that stage IV colorectal cancer patients who survived at least two years have a better prognosis than originally thought. Results of the work will be presented as part of a poster presentation at the American Society of Clinical Oncology Annual Meeting being held in Chicago early next month.

“With patients in this population living longer, it is imperative we refine prognostic information to more accurately predict survival.  This data will assist multi-disciplinary cancer management teams in making treatment decisions that ultimately will impact a patient’s quality of life,” notes Darren Carpizo, MD, PhD, surgical oncologist and director of the Hepatobiliary Program at Rutgers Cancer Institute and senior investigator of the work (pictured).

Investigators examined data on more than a thousand stage IV colorectal cancer patients seen at Rutgers Cancer Institute between 2005 and 2015. This included patients who had their cancer removed through surgery and were treated with follow-up therapies, as well as those patients who were not eligible for surgery. Complete data was available for 125 patients who survived for more than two years (75 had surgical removal of their cancer; 50 did not).  Median overall survival of patients who underwent surgery was not reached, while median overall survival for those who were not eligible for surgery was six years and three months.

“For those patients not eligible for initial surgery who survive two years, these findings indicate they may benefit from future surgery, if feasible, to treat remaining disease. For those patients who initially had surgery, this information may be helpful to identify patients who might benefit from repeat surgery to resect any recurrent metastatic disease,” adds Dr. Carpizo, who is also an associate professor of surgery and pharmacology at Rutgers Robert Wood Johnson Medical School.

Rutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, Rutgers Cancer Institute is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention both at its flagship New Brunswick location and at its Newark campus at Rutgers Cancer Institute of New Jersey at University Hospital. Physician-scientists across Rutgers Cancer Institute also engage in translational research, transforming their laboratory discoveries into clinical practice that supports patients on both campuses.

Study Finds Association Between Specific Gut Bacteria and Colorectal Cancer

Researchers identify less invasive method to detect colorectal cancer

Specific strains of bacteria in the gut are significantly associated with colorectal cancer, according to a new study by researchers at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health. The study, which also identified a less invasive and less expensive way to screen for colorectal cancer, was recently published in the journal Gut.

Colorectal cancer is the second leading cause of cancer-associated death in the U.S., according to the American Cancer Society. Previous studies have found associations between gut bacteria and colorectal cancer, but this is the first to link several studies to identify specific strains and species that are associated with the disease: Parvimonas micra ATCC 33270, Streptococcus anginosus and multiple members of the phylum proteobacteria.

First author Manasi Shah, Ph.D., examined the raw data from nine previous studies of colorectal cancer and the gut. The study cohorts were ethnically diverse, recruited between 2012 and 2016 and the scientists conducting each study used non-uniform laboratory methods. Despite these challenges, Shah established that across the cohorts, specific bacteria were frequently and significantly found in stool samples from patients with colorectal cancer.

“Although previous studies have found associations between the gut microbiome and colorectal cancer, there was little agreement between the results. To our knowledge, our study is the first attempt to gather existing microbial marker gene data and reprocess it uniformly.  Despite differences in cohort demographics, laboratory protocols and downstream analysis, which are known to influence microbiome outcomes, it is encouraging that we found bacterial signals that are consistently and significantly associated with colorectal cancer,” said Shah, who completed the research while she was a doctoral student at UTHealth School of Public Health.

Identifying the bacteria that could serve as biomarkers for the disease is a new method that could be used to screen for colorectal cancer using stool samples, Shah said. This new approach could be less invasive and less expensive than a colonoscopy, which is the most commonly used screening method.

“Microbiome studies offer tremendous potential for advancing diagnostics and therapeutics. For some diseases and conditions, identifying microbiome-based associations has been relatively simple. For the majority, however, the research community is still sifting through a lot of data and a lot of noise as we seek to understand how the microbiome contributes to disease onset, progression and our ability to provide rapid, accurate diagnoses,” said Emily Hollister, Ph.D., senior author and assistant professor of pathology and immunology at Baylor College of Medicine. “The identification of consistent patterns across studies of the colorectal cancer-associated microbiome represents a big step forward in these efforts.”

Microbial markers by themselves could accurately detect colorectal cancer 80 percent of the time. For a subset of the data, when combined with a home-based diagnostic fecal occult to test for blood in the stool, as well as a patient’s age and gender, the new biomarker method could accurately detect colorectal cancer 91 percent of the time.

“In order to discover improved biomarkers and therapeutics based on the microbiome, you must have a strain-focused computational platform able to detect changes in abundance as a disease progresses,” said Todd DeSantis, co-author and vice president of informatics at Second Genome. “This study demonstrated that our platform was unique in that it enabled the identification of important microbiome-based biomarkers.”

AACR: Phase II Trial Shows Rice Bran Promotes Microbiome Diversity, Slows Growth of Colorectal Cancer Cells

Today at the American Association for Cancer Research (AACR) Annual Meeting 2017, University of Colorado Cancer Center researchers at Colorado State University present results of a phase II clinical trial of 29 people exploring the effects of adding rice bran or navy beans to the diets of colorectal cancer survivors. After the 4-week randomized-controlled trial during which people added rice bran, navy bean powder or neither, both the rice bran and navy bean groups showed increased dietary fiber, iron, zinc, thiamin, niacin, vitamin B6, folate, and alpha-tocopherol. The rice bran group also showed increased microbiome richness and diversity. When researchers treated colorectal cancer cells with stool extracts from these groups, they saw reduced cell growth from the groups that had increased rice bran and navy bean consumption.

Previous work shows the ability of these diets to decrease colorectal cancer risk in animal models. The current trial confirms that people can eat enough bean- and rice bran-enhanced foods to promote gut health at levels shown to prevent colorectal cancer in animals.

Guidelines from the American Institute for Cancer Research recommend reducing the risk of cancer by eating more vegetables, fruits, whole grains and legumes, such as beans. Ryan has established from these studies that eating a half-cup of beans and 30 grams of rice bran per day is enough to see changes in small molecules that can confer protection against colorectal cancer.

“The simple message is, ‘Food is medicine,’ and we are looking at how to simplify that and make it apply to our everyday lives,” says study co-author Regina Brown, MD, assistant professor at the CU School of Medicine and oncologist for CUHealth.

Brown is long-time collaborator of CU Cancer Center investigator and CSU assistant professor, Elizabeth Ryan, PhD. The Ryan Lab in the CSU College of Veterinary Medicine and Biomedical Sciences studies the potential power of navy beans and rice bran to promote digestive health and to prevent metabolic alterations in obesity, heart disease and certain cancers.

“The evidence is there in animals and we can now study this in people. The question is, what are we doing to achieve adequate levels of intake of these foods?” Ryan said. “It’s not enough to say ‘I eat them once in a while.’ That’s not going to work, particularly if you are at higher risk. You have to meet a dose, just like you need a dose of a certain drug, you need to reach intake levels and consume increased amounts of these foods, and that’s where people, including me, are challenged. Not everyone wants to open up a can of beans and eat them every day.”

The two met about 10 years ago, when Ryan was a researcher in CSU professor Henry Thompson’s Cancer Prevention Lab, and Brown was practicing medicine in Fort Collins and caring for her mother, who had uterine cancer.

“It was kind of a novel partnership and had we not dug in our heels it could have died, but I told Elizabeth, ‘Your work is so interesting and so valuable. We have to take this translational research from the benchtop to the clinic.’ I guarantee, nine out of 10 of my patients, the first thing they ask is about their diet,” Brown said.

The study’s lead author is Erica Borresen, Ryan’s research associate and study coordinator, who worked with colorectal cancer survivors to make sure they ate their beans and rice bran provided in meals and snacks, and that they filled out their food logs and gastrointestinal health questionnaires. It was sometimes intimate and awkward, but so is getting a colonoscopy and being treated for colorectal cancer.

“Our participants donated their time and effort, and I want to make sure they understand they are appreciated,” said Borresen, who earned her Master of Public Health at the Colorado School of Public Health, and plans to become a physician’s assistant. “I came to realize I love the patient interaction – that’s one of my favorite parts about coordinating our studies.”

The next phase of Ryan’s research examines effects of the cooked navy bean powder and rice bran on the colon tissue of people who have already had colorectal cancer and are at high risk for recurrence.

“I really feel that there’s hope in this being a practical solution to improve gut health and specifically colorectal cancer prevention,” says Ryan.

Study Tightens Connection Between Intestinal Microorganisms, Diet, and Colorectal Cancer

A new study provides some of the strongest evidence to date that microorganisms living in the large intestine can serve as a link between diet and certain types of colorectal cancer, the lead authors at Dana-Farber Cancer Institute and Massachusetts General Hospital report.

The paper, published online today by JAMA Oncology, focuses on Fusobacterium nucleatum, one of hundreds of types of bacteria that dwell in humans’ large intestines, and one that is thought to play a role in colorectal cancer. By tracking the diets of more than 137,000 people for decades and examining more than 1,000 colorectal tumor samples for F. nucleatum, the researchers determined that individuals with a “prudent” diet – rich in whole grains and fiber – had a lower risk of developing colorectal cancer containing the bacterium, but their risk for colorectal cancer that lacked the bacterium was essentially unchanged.

Prudent diets appear to protect against colorectal cancer. The new study suggests that healthy foods may achieve these benefits, in part, by altering the relative amounts of various microorganisms in the digestive tract, including F. nucleatum.

“Though our research dealt with only one type of bacteria, it points to a much broader phenomenon – that intestinal bacteria can act in concert with diet to reduce or increase the risk of certain types of colorectal cancer,” said Shuji Ogino, MD, PhD, of Dana-Farber, Harvard T.H. Chan School of Public Health, and Brigham and Women’s Hospital, the co-senior author of the study with Charles Fuchs, MD, MPH, director of the Gastrointestinal Cancer Center at Dana-Farber and Brigham and Women’s, and Andrew Chan, MD, MPH, of Massachusetts General Hospital, Brigham and Women’s, and the Broad Institute of MIT and Harvard.

“These data are among the first in humans that show a connection between long-term dietary intake and the bacteria in tumor tissue. This supports earlier studies that show some gut bacteria can directly cause the development of cancers in animals,” added Chan.

The research drew on dietary records of 137,217 participants in the Nurses’ Health Study and Health Professionals Follow-up Study – large-scale health-tracking studies – some of whom developed colon or rectal cancer over a period of decades. The researchers measured the levels of F. nucleatum in the patients’ tumor tissue and blended these data with information of diet and cancer incidence.

“Recent experiments have suggested that F. nucleatum may contribute to the development of colorectal cancer by interfering with the immune system and activating growth pathways in colon cells,” Ogino remarked. “One study showed that F. nucleatum in the stool increased markedly after participants switched from a prudent to a Western-style, low fiber diet. We theorized that the link between a prudent diet and reduced colorectal cancer risk would be more evident for tumors enriched with F. nucleatum than for those without it.”

That is precisely what the study results showed: Participants who followed a prudent diet had a sharply lower risk of developing colorectal cancer laden with F. nucleatum. But they received no extra protection against colorectal cancers that didn’t contain the bacteria.

“Our findings offer compelling evidence of the ability of diet to influence the risk of developing certain types of colorectal cancer by affecting the bacteria within the digestive tract,” Ogino commented.

“The results of this study underscore the need for additional studies that explore the complex interrelationship between what someone eats, the microorganisms in their gut, and the development of cancer,” said Chan.

Enzyme Could Protect Against Type of Colorectal Cancer By Suppressing Tumors, Study Finds

An enzyme that plays an active role in inflammation could be a natural way to suppress tumors and ulcers in the colon that are found in colitis associated cancer (CAC), a type of colorectal cancer that is driven by chronic inflammation, according to a new study.

Researchers at Georgia State University and Stony Brook University have identified the tumor suppressor role of matrix-metalloproteinase (MMP9), which belongs to a family of enzymes called proteinases and serves as an essential regulator of extracellular matrix components via a novel mechanistic pathway. The findings are reported in the journal Oncotarget.

“In the setting of chronic inflammation, MMP9 expression functions as a silver lining by suppressing the advancement of the tumor microenvironment in CAC,” said Dr. Pallavi Garg, assistant professor in the Institute for Biomedical Sciences at Georgia State.

Inflammation can be a beneficial response to tissue damage or pathogens, but if unregulated it can become chronic inflammation and induce malignant cells in tissue that lead to cancer. Inflammatory bowel disease, which includes ulcerative colitis and Crohn’s disease, involves inflammation of all or part of the digestive tract. Patients with chronically active ulcerative colitis have a significantly higher risk (up to 50 percent depending on the group of subjects) of developing CAC, a subtype of colorectal cancer. The risk of CAC increases with the duration of the disease and the severity of inflammation.

The protein expression and activity of MMP9 is undetectable in most healthy adult tissues, including the colon and intestine, but it is highly expressed in a variety of inflammatory states. Previous studies have shown that MMP9 derived from epithelial cells plays a protective role in the development of CAC. Epithelial cells represent the lining of the gastrointestinal tract along the lumen, which is the inside space of a tubular structure. Almost 80 percent of cancers have epithelial cell origin. This study aimed to determine whether epithelial-derived MMP9 has a defensive role of tumor suppressor in CAC and the underlying molecular mechanism.

Researchers used transgenic mice that expressed MMP9 in the colonic epithelium for in vivo experiments. In vitro experiments used human colon carcinoma cells with and without MMP9 and mouse embryonic fibroblasts, which are connective tissue cells that make the extracellular matrix and collagen and play an important role in tissue repair.

The researchers found mice that expressed MMP9 in the epithelium exhibited fewer tumors and increased apoptosis, or programmed cell death that gets rid of cells that are no longer needed or are a threat to the organism. Human colon carcinoma cells that overexpressed MMP9 showed decreased cell proliferation, less DNA damage and cell cycle arrest in the S-phase to prevent cell proliferation.

In addition, they found that epithelial-derived MMP9 suppresses tumors in CAC by activating the MMP9-Notch1-ARF-p53 axis pathway, which increases apoptosis, initiates cell cycle arrest and keeps a check on DNA damage.