Cancers In The News: Can Chemicals Found In Vegetables Prevent Colon Cancer?

Chemicals produced by vegetables such as kale, cabbage and broccoli could help to maintain a healthy gut and prevent colon cancer, says a new study from the Francis Crick Institute. The research, published inImmunity, shows that mice fed on a diet rich in indole-3-carbinol referred to as I3C, produced when we digest vegetables from the Brassica genus, were protected from gut inflammation and colon cancer. This study offers the first concrete evidence of how I3C in the diet can prevent colon inflammation and cancer by activating a protein called the aryl hydrocarbon receptor referred to as AhR.

"Seeing the profound effect of diet on gut inflammation and colon cancer was very striking," says senior author Dr. Gitta Stockinger, group leader at the Francis Crick Institute. "We often think of colon cancer as a disease promoted by a Western diet rich in fat and poor in vegetable content, and our results suggest a mechanism behind this observation. Many vegetables produce chemicals that keep AhR stimulated in the gut. We found that AhR-promoting chemicals in the diet can correct defects caused by insufficient AhR stimulation. This can restore epithelial cell differentiation, offering resistance to intestinal infections and preventing colon cancer. These findings are a cause for optimism; while we can't change the genetic factors that increase our risk of cancer, we can probably mitigate these risks by adopting an appropriate diet with plenty of vegetables."

AhR acts as an environmental sensor, passing signals to immune cells and epithelial cells in the gut lining to protect from inflammatory responses to the trillions of bacteria that live in the gut. "We studied genetically-modified mice that cannot produce or activate AhR in their guts, and found that they readily developed gut inflammation which progressed to colon cancer," added first author Dr. Amina Metidji from the Francis Crick Institute. "However, when we fed them a diet enriched with I3C, they did not develop inflammation or cancer. Interestingly, when mice whose cancer was already developing were switched to the I3C-enriched diet, they ended up with significantly fewer tumors which were also more benign."

While the health benefits of vegetables are well-established, many of the mechanisms behind them remain unknown. By studying both mice and mouse gut organoids mini guts made from stem cells - the researchers found that AhR is vital for repairing damaged epithelial cells. Without AhR, intestinal stem cells fail to differentiate into specialized epithelial cells that absorb nutrients or generate protective mucus. Instead, they divide uncontrollably which can ultimately lead to colon cancer. As well as correcting altered AhR dependent gene expression, dietary I3C also had a surprising effect on unmodified mice with normal AhR expression. While normal mice fed on standard or I3C-enriched food did not develop tumors during the study, those fed on a purified control diet did.

Purified Control Diets

Laboratory mice are usually fed a standard grain-based chow which contains a mix of ingredients and nutrients. For dietary studies, they are given a purified control diet so that researchers know exactly what is in the food. These are designed to precisely fulfil the animal's nutritional needs while being free of allergens, pathogens or variable ingredients found in standard chow.

Purified control diets contain exact mixtures of carbohydrates, proteins, fats and fibers enriched with vitamins and minerals. However, the latest study suggests that these diets have fewer AhR-promoting chemicals than the standard chow or the I3C-enriched diet. "Normal mice on the purified control diet developed colon tumors within 10 weeks, whereas mice on the standard chow didn't develop any," says co-corresponding author Dr. Chris Schiering. "This suggests that even without genetic risk factors, a diet devoid of vegetable matter can lead to colon cancer."

The team is now hoping to do further experiments in organoids made from human gut biopsies and eventually human trials. "A number of epidemiological studies suggested that vegetables may be protective against cancer," Stockinger added. "However, there is very little literature on which vegetables are the most beneficial or why. Now that we've demonstrated the mechanistic basis for this in mice, we're going to investigate these effects in human cells and people. In the meantime, there's certainly no harm in eating more vegetables!"

"This study in mice suggests that it's not just the fiber contained in vegetables like broccoli and cabbage that help reduce the risk of bowel cancer, but also molecules found in these vegetables too, added Professor Tim Key, Cancer Research UK's expert on diet and cancer. This adds to the evidence that a healthy diet, rich in vegetables, is important. Further studies will help find out whether the molecules in these vegetables have the same effect in people, but in the meantime there are already plenty of good reasons to eat more vegetables."

Lung Cancer Development Insight

Lung cancer, the leading cause of preventable cancer death, is a disease of complex origin usually considered to result from effects of smoking and multiple genetic variants. One of these genetic components, a chromosome named 15q25.1, has been previously identified as a leading influencer of susceptibility to lung cancer, smoking behavior, and nicotine addiction. However, no previous study had investigated the mechanisms of this lead agent, or documented the susceptibility pathways that allow this chromosome to modify development of disease.

A research team led by Xuemie Ji, MD, Ph.D., Research Associate in the Department of Biomedical Data Science at Dartmouth's Geisel School of Medicine, helped solve this central problem. The team identified two main pathways involving the mechanism by which the chromosome 15q25.1 locus influences lung cancer risk. The first pathway is an interaction pathway in the nervous system that is implicated in nicotine dependence. The other pathway can control key components in many biological processes, such as transport of nutrients and ions, and the human immune system. The results were published inNature Communications.

"Our findings in pathways uncover insights into the mechanism of lung cancer etiology and development, which will potentially shorten the interval between increasing biological knowledge and translation to patient care," says Ji. "Blocking genes downstream or in parallel pathways might provide a strategy to treat such cancer." The study used two independent cohorts of 42,901 individuals with a genome-wide set of genetic variants, as well as an expression dataset with lung tissue from 409 lung cancer patients to validate findings. Two different methods were used to analyze data, and confirm that the findings are reliable and can be repeated with different methods.

"To our knowledge, this is the first study to explore the pathogenic pathways related to the mechanisms of chromosome 15q25.1 and the first to use a novel analysis approach to analyze data and to validate the findings," says Ji. "The ability to block the damaging genetic variants downstream or in parallel pathways might improve lung cancer prognosis and survival, and therefore provide alternative strategies to treat such cancer." The team is working to identify more mechanisms contributing to the increased risk of lung cancer. They aim to provide more explanation for the large, unexplainable division of lung cancer occurrences.

Skin Cancer Facts And Types

Skin cancer is the most common type of cancer in the United States, according to the Centers for Disease Control and Prevention Skin cancer, like all types of cancer, is capable of destroying healthy tissue and spreading to distant body sites, says C. Blake Phillips, M.D., a fellow in theUniversity of Alabama at BirminghamDepartment of Dermatology. If undetected or untreated, skin cancers lead to loss of vital functions or death. It is important to keep an eye on your skin and watch for changes that could be a sign of skin cancer.

There are many types of skin cancer with varied causes, most commonly ultraviolet radiation directly damaging skin DNA. The three most common types of skin cancer are basal cell carcinoma, squamous cell carcinoma and melanoma. Basal cell carcinoma is the most common type of skin cancer, and the least prone to spread from the primary tumor site. It is a locally destructive cancer, and if untreated can become a bleeding sore that eventually destroys the structures it overlies. When skin cells are exposed to ultraviolet rays, the DNA can become damaged over time, leading to the potential for basal cell carcinoma growth. People with a history of sunburn are more susceptible to this type of skin cancer.

The second most common skin cancer is squamous cell carcinoma, which is most commonly due to chronic sun exposure. It is both locally destructive and prone to spreading to lymph nodes and other organs. Melanoma is highly capable of spreading and can be rapidly deadly if not treated. Acral lentiginous melanoma is often seen on the palms, soles and under the toenails of patients with darker skin. Over a lifetime, its quite common for high-risk patients to develop multiple skin cancers on different body sites, Phillips added. That said, most skin cancers have an excellent cure rate if detected and treated early.I encourage learning the signs of skin cancer and self-exams between clinic visits. Patient awareness is extremely helpful in early diagnosis.

Risk Factors
Most skin cancers are the result of exposure to radiation from the sun or other sources. UV radiation from the sun directly damages the skin DNA of susceptible people. Over time, this damage can build up, leading to the formation of cancerous cells, which grow into tumors. Sources of artificial UV rays, such as tanning beds and manicure UV lamps, also contribute. Genetics plays a large role in underlying risk for sun-induced cancers and seems to be more important in melanoma.

Global location matters sincethe suns UV radiation is most intensenear the equator.This means thatlivinginthe Southeast increases therisk for skin cancer when compared tothe northern United States orCanada.Anyone with skin is at risk for developing skin cancers, though the common types and locations vary by ethnicity, Phillips said. While less common, even those with heavily pigmented skin can develop skin cancer.

The strongest risk factors includefair skin with a tendency to sunburn, red hair or light hair, light eyes, growing up insouthern latitudes, history of numerous sunburns - especially peeling or blistering burns - outdoor jobs or hobbies, routine and longstanding sun exposure, family history of skin cancers, age, prior radiation treatments,chronic lymphomaor leukemia, and immune system-altering medicines.

Skin Cancer Signs And Symptoms
Signs of non-melanoma skin cancers include new red lesions that steadily grow, non-healing sores or crusted areas on the skin, bumps with a pearly or translucent surface, and any tender growths on the skins surface.

Melanomas are darkly pigmented, discolored areas or bumps with an asymmetrical shape, irregular borders, or dark black or multicolored surface. While the majority of melanomas do not arise from moles, new or changing moles in adulthood should be examined. You should see a doctor if you are concerned that a lesion is changing, is newly symptomatic, or is non-healing, Phillips said. If you have a first-degreerelative withmelanoma or you havemany darkmoles, its a good idea to have a baseline skin exam by a dermatologist. A doctor should examine those with prior skin pre-cancers or skin cancers at least annually, with some people requiring more frequent visits.

Protecting Your Skin
The most important aspect of protecting your skin is to avoid UV radiation exposure from the sun.I recommend sunscreen with an SPF value of 30 or higher every day to exposed areas, Phillips said. Look for products that dont feel greasy and block bothUVA and UVB. Many regular moisturizers now contain sunscreens,makingselection of a comfortable sunscreen quite easy and inexpensive.

Wear protective clothing and wide-brimmed hats withsunglasses when out in the sun. Avoid peak sun hours of the day from 10 a.m. to 5 p.m., choosing to do outdoor activities in morning or evening hours. Avoid indoor tanning, and choosepigmented lotion,spray tan or no tan instead, Phillips said.

Is Skin Cancer On The Rise?

Recent diagnoses for two types of skin cancer have increased in recent years, according to a Mayo Clinic-led team of researchers. Theirpaper, published inMayo Clinic Proceedings, uses medical records from theRochester Epidemiology Projectto compare diagnoses of basal cell carcinoma and squamous cell carcinoma - bothnonmelanoma skin cancers - between 2000 and 2010 to diagnoses in prior years. The Rochester Epidemiology project is a medical records linkage system and research collaborative in Minnesota and Wisconsin.

The researchers report that, between 2000 and 2010, squamous cell carcinoma diagnoses increased 263 percent, and basal cell carcinomas increased 145 percent. They compared the 2000-2010 period to two other segments of time: 1976 to 1984 and 1985 to 1992.Women 30 to 49 experienced the greatest increase in basal cell carcinoma diagnoses; whereas, women 40 to 59 and 70 to 79 experienced the greatest increase in squamous cell carcinomas. Men had an increase in squamous cell carcinomas between the first and second time period studied 1976 to 1984 and 1985 to 1992 - but experienced a slight decline in the 2000 to 2010 period. However, for basal cell carcinomas, men over 29 showed similar increases in diagnoses in the 2000 to 2010 period then the two earlier periods.

Tanning And UV Rays
We know that the sun and some artificial sunlight sources give offskin-damaging ultraviolet, or UV, rays, saysChristian Baum, M.D., a Mayo Clinic dermatologist and the studys senior author. This skin damage accumulates over timeand can often lead to skin cancer. Despite the fact that sunscreens and cautionary information have been widely available for more than 50 years, we saw the emergence of tanning beds in the 1980s, and tanning indoors or out was a common activity for many years. Baum notes that tanning has slowed, tanning beds still exist, and beaches will never be empty. But what people should remember is that the damage accumulates and eventually sunburns, reddened skin, and peeling shoulders can add up to one or more skin cancers.

Shifts in exposure to UV light may be the reason for a location shift in where the cancer tumors are found. In the earlier time periods, both basal cell and squamous cell carcinomas were diagnosed more often on the head and neck. In the most recent time period, the records showed that basal cell tumors on the torso increased, as did squamous cell carcinomas on the arms and legs.Baum says that the risk of cancer should provide the ultimate argument for using sunscreen every day, year-round on all exposed skin.Use sunscreen, says Dr. Baum. This includes on your left arm for those who do a lot of driving. UV rays can penetrate car windows and exposed skin even when the sun isnt shining. UV rays bounce around under the clouds, off the snow, buildings, and more, causing damage ? even on gray days.

Using theRochester Epidemiology Projectmedical records linkage system, the research team was able to identify nearly all of the Olmsted County, Minnesota, adult residents who received an initial diagnosis of the most common nonmelanoma skin cancers - basal or squamous cell carcinoma or both during the 2000 to 2010 period and the comparison years. There is no tumor registry for these types of cancer, Baum says. So it is difficult to have accurate estimates of the national or worldwide impact of these cancers. However, because the Rochester Epidemiology Project contains health care information for virtually all residents of Olmsted County since 1966, it provides a good proxy for information on many global population health concerns.

Study: Tomato Extract Fights Stomach Cancer

A recent studypublished in theJournal of Cellular Physiology shows that whole tomato extracts from two different Southern Italy cultivars inhibit gastric cancer cell growth and malignant features, paving the way for future studies aimed at implementing lifestyle habits not only for prevention, but potentially as a support to conventional therapies. Their antitumoral effect seem not related to specific components, such as lycopene, but rather suggest that tomatoes should be considered in their entirety, says Daniela Barone, researcher at the Oncology Research Center of Mercogliano (CROM), and one of the authors of the study.

The researchers analyzed whole tomato lipophilic extracts for their ability to tackle various neoplastic features of gastric cancer cell lines. Extracts of both theSan MarzanoandCorbarinotomato varieties were able to inhibit the growth and cloning behavior of malignant cells. Treatment with the whole tomato extracts affected key processes within the cells hindering their migration ability, arresting cell cycle through the modulation of retinoblastoma family proteins and specific cell cycle inhibitors, and ultimately inducing cancer cell death through apoptosis.

Our results prompt further assessment of the potential use of specific nutrients not only in the cancer prevention setting but also as a supportive strategy along with conventional therapies, says Professor Antonio Giordano, Director of the Sbarro Institute for Molecular Medicine, Temple University, Philadelphia, Pa.Distinct species may exert different effects, in different stages of a certain neoplasm, added Daniela Barone from the research group at the National Cancer Institute of Naples, Pascale Foundation, CROM.

Gastric cancer is the fourth most common type of cancer worldwide and has been associated with genetic causes,Helicobacter pyloriinfection, and eating habits, such as consumption of smoked and salted food. Tomatoes are consumed worldwide and are a staple of the Mediterranean diet, which is popularly thought to lower cancer risk. Various tomato components have also been analyzed for their ability to counteract tumor growth in experimental systems, although few studies have analyzed the effects of tomatoes in their entirety.

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