This gene could be the link between iron and prostate cancer

Hasil gambar untuk This gene could be the link between iron and prostate cancerNew research may explain the link between a high level of iron in the body and prostate cancer.

The researchers uncovered the role of the iron storage gene FTH1 and its pseudogenes in regulating iron levels in cells and slowing down prostate cancer growth. The new findings could pave the way for future developments in prostate cancer diagnostics and therapeutics.

Targeting or restoring proper iron storage could also be a potential avenue for therapeutic development.

 

Prostate cancer is the most common cancer and the second leading cause of cancer death in men worldwide. The survival rate for prostate cancer is high with early diagnosis but it falls significantly at advanced stages. Currently, there is no available drug to treat aggressive or late-stage prostate cancer, and the accuracy of current screening techniques remain relatively low at 20 to 30 percent.

With global prostate cancer incidence rising rapidly, accounting for 9.6 percent of all newly diagnosed cancer cases in 2017, there is a need to attain better understanding of the underlying biological mechanisms leading to the disease in order to build more robust diagnostic tools and efficacious therapies against it.

In a paper in Nucleic Acids Research, researchers from Cancer Science Institute Singapore at the National University of Singapore focused their investigation on the iron storage gene, FTH1, noting the link between iron level in cells and the development of prostate cancer. They found that the function of FTH1 is highly influenced by its pseudogenes, a set of genes originating from their parental gene, which were previously thought to be non-functional and were classified as “genomic junk.” FTH1 and its pseudogenes are often suppressed in prostate cancer, and expression of both FTH1 and its pseudogenes are required to reduce iron levels in cells and slow down prostate cancer growth.

Can cinnamon compound prevent cancer?

Hasil gambar untuk Can cinnamon compound prevent cancer?The compound that gives cinnamon its distinctive flavor and smell is a potent inhibitor of colorectal cancer, a study with mice shows.

When researchers added the compound cinnamaldehyde to the diet of mice they were protected against colorectal cancer. In response to cinnamaldehyde, the animals’ cells had acquired the ability to protect themselves against exposure to a carcinogen through detoxification and repair.

“This is a significant finding,” says Donna Zhang, professor of pharmacology and toxicology at University of Arizona. “Because colorectal cancer is aggressive and associated with poor prognoses, there is an urgent need to develop more effective strategies against this disease.”

“Given cinnamon’s important status as the third most consumed spice in the world, there’s relatively little research on its potential health benefits,” says Georg Wondrak, professor of pharmacology and toxicology. “If we can ascertain the positive effects of cinnamon, we would like to leverage this opportunity to potentially improve the health of people around the globe.”

Cell protection

The two major types of cinnamon in the world are known as cassia cinnamon and true (or “Ceylon”) cinnamon. Cinnamaldehyde can be derived from both types.

Wondrak researches molecular interventions that target skin and other epithelial cancers. Zhang studies the Nrf2 molecular pathway, which is involved in strengthening cells against stressors such as carcinogen exposure. The common denominator between their labs is the identification of molecules that might protect cells from environmental damage and cancer.

“We look for compounds that can activate the Nrf2 pathway,” Wondrak says, “—synthetic ones, or preferably things we already eat, because we know they are not toxic. I’m the person who brings in the molecules, the molecular agents that might modulate this pathway.”

The two scientists started off doing structure-activity relationship studies to find molecular dietary factors that induce the Nrf2 pathway. Their investigation led to the identification of cinnamaldehyde as an Nrf2 inducer.

Other kinds of cancer, too

After that discovery, they began studying the effects of the compound on the Nrf2 pathway and on cancer outcomes. Because the Nrf2 pathway is so important in cellular protection, the new study, published online in Cancer Prevention Research, suggests that cinnamaldehyde may also protect cells from other kinds of chemical carcinogens, UV-induced cancers, and more.

“We are not preaching at this point, ‘You have to eat a lot of cinnamon,’” says Wondrak. “We are just saying that cinnamaldehyde has interesting properties that are consistent with protecting cells through activation of the Nrf2 pathway.”

The next step in the research is to test whether cinnamon, as opposed to cinnamaldehyde, prevents cancer using this same cancer model. Because cinnamon is a common food additive already considered safe—it’s not a synthetic, novel drug—a study in humans may not be too far off.

“Can cinnamon do it, now that we know pure cinnamaldehyde can?,” Wondrak says. “And can we use cinnamaldehyde or cinnamon as a weapon to go after other major diseases, such as inflammatory dysregulation and diabetes? These are big questions to which we might be able to provide encouraging answers using a very common spice.”

Colonoscopies lead to way more infections than experts thought

Hasil gambar untuk Colonoscopies lead to way more infections than experts thoughtColonoscopies and upper-GI endoscopies performed at outpatient specialty centers in the United States result in far more infections than previously believed, according to a new study.

An analysis of data from 2014 shows that patients who had one of the common procedures at facilities known as ambulatory surgery centers were at greater-than-expected risk of bacterial infections, including E. coli and Klebsiella.

“Though patients are routinely told that common endoscopic procedures are safe, we found that post-endoscopic infections are more common than we thought, and that they vary widely from one ASC facility to another,” says lead researcher Susan Hutfless of Johns Hopkins University.

Colonoscopy is one of six options suggested by the American Cancer Society for colon cancer screening. The traditional recommendation is that patients be regularly screened starting at 50, but the ACS recently reduced its recommended age to 45.

Upper-GI endoscopies, known as EGDs, can be used to diagnose a number of problems in the upper digestive tract, including heartburn, swallowing issues, and abdominal pain.

Each year in the United States, there are more than 15 million colonoscopies and 7 million EGDs. Both procedures are performed with an endoscope, a reusable optical instrument that gives doctors a view of a patient’s gastrointestinal tract. Besides screening and diagnosis, they can be used for procedures such as removing polyps without invasive surgery.

Researchers examined data from six states—California, Florida, Georgia, Nebraska, New York, and Vermont—to track infection-related emergency room visits and unplanned inpatient admissions within seven and 30 days after a colonoscopy or EGD.

Post-endoscopic infection rates were previously believed to be in the neighborhood of one in a million, Hutfless says. The new study found a rate of infection seven or fewer days after a procedure was slightly higher than one in 1,000 for screening colonoscopies and about 1.6 per 1,000 for non-screening colonoscopies. Rates for EGDs within that time were more than three per 1,000.

Patients who had been hospitalized before undergoing one of the procedures were at even greater risk of infection.

Though the nation’s first ASC was established more than 40 years ago, the facilities gained popularity over the past 20 years as more convenient, less expensive alternatives for outpatient surgeries and other procedures.

The team found evidence that, among the ASC post-procedure infections, the rates were slightly higher for diagnostic procedures than for screening procedures.

ASCs with the highest volume of procedures had the lowest rates of post-endoscopic infection.

According to the Ambulatory Surgery Center Association, in 2017, 64 percent of ASCs were owned by physicians; 28 percent were affiliated with hospitals or health systems. Since many ASCs lack an electronic medical record system connected to hospital emergency departments, those ASCs are unlikely to learn of their patients’ infections, Hutfless says.

“If they don’t know their patients are developing these serious infections, they’re not motivated to improve their infection control.”

While the overwhelming majority of ASCs follow strict infection-control guidelines, says Hutfless, she and her team found infection rates at some ASCs more than 100 times higher than expected.

Other authors of the study, which appears in Gut, are from Johns Hopkins and McKinsey & Co. The Agency for Healthcare Research and Quality funded the work.

Colon cancer patients who eat nuts have lower death risk

Hasil gambar untuk Colon cancer patients who eat nuts have lower death riskPeople with stage III colon cancer who regularly eat nuts are at significantly lower risk of cancer recurrence and mortality than those who don’t, according to a new study.

The study followed 826 participants in a clinical trial for a median of 6.5 years after they received treatment with surgery and chemotherapy. Those who regularly ate at least two, one-ounce servings of nuts each week demonstrated a 42 percent improvement in disease-free survival and a 57 percent improvement in overall survival.

“If you like coffee or nuts, enjoy them, and if you don’t, there are many other helpful steps you can take.”

“Further analysis of this cohort revealed that disease-free survival increased by 46 percent among the subgroup of nut consumers who ate tree nuts rather than peanuts,” says Charles S. Fuchs, director of the Yale University Cancer Center and senior author of the study. Tree nuts include almonds, walnuts, hazelnuts, cashews, and pecans, among others. In contrast, peanuts are actually in the legume family of foods.

“These findings are in keeping with several other observational studies that indicate that a slew of healthy behaviors—including increased physical activity, keeping a healthy weight, and lower intake of sugar and sweetened beverages—improve colon cancer outcomes,” says Temidayo Fadelu, a postdoctoral fellow at Dana-Farber Cancer Institute and lead author of the paper. “The results highlight the importance of emphasizing dietary and lifestyle factors in colon cancer survivorship.”

Additionally, the researchers emphasize, the study highlighted connections between biological mechanisms that worsen disease not just in colon cancer but in certain chronic illnesses such as type 2 diabetes.

Many previous studies have reported that nuts, among other health benefits, may help to reduce insulin resistance, a condition in which the body has difficulty processing the insulin hormone. Insulin resistance leads to unhealthy levels of sugar in the blood and is often a predecessor to type 2 diabetes and related illnesses.

Earlier research among patients with colon cancer revealed that people had worse outcomes when they had lifestyle factors—such as obesity, lack of exercise, and a diet with high levels of carbohydrates—that heighten insulin resistance and quickly raise levels of blood sugar.

“These studies support the hypothesis that behaviors that make you less insulin-resistant, including eating nuts, seem to improve outcomes in colon cancer,” Fuchs says. “However, we don’t know yet what exactly about nuts is beneficial.”

Nuts also might play a positive role by satisfying hunger with less intake of carbohydrates or other foods associated with poor outcomes, Fuchs notes.

Patients may not be eating nuts due to concerns about the high fat content, says Fuchs. For example, a one-ounce serving of about 24 almonds holds about 200 calories, including 14 grams of fat.

“People ask me if increasing nut consumption will lead to obesity, which leads to worse outcomes,” he says. “But what’s really interesting is that in our studies, and across the scientific literature in general, regular consumers of nuts tend to be leaner.”

Dietary changes can make a difference. An earlier analysis of diets in the same patient cohort found a significant link between coffee consumption and reduced recurrence and mortality in colon cancer.

When Fuchs advises his patients about lifestyle choices, “first and foremost, I talk about avoiding obesity, exercising regularly, and staying away from a high-carbohydrate diet,” he says. “Then we talk about things like coffee and nuts. If you like coffee or nuts, enjoy them, and if you don’t, there are many other helpful steps you can take.”

“Overall, we are working to apply the same rigorous science to the understanding of diet and lifestyles in the colon cancer patient population that we apply to defining new drugs,” Fuchs says.

The researchers report their findings in the Journal of Clinical Oncology.

Jeffrey Meyerhardt of Dana-Farber, and Ying Bao of Brigham and Women’s Hospital are co-corresponding authors of the paper.

Funding for the research came from the National Cancer Institute. Support also came from private sponsors including Pfizer Oncology and the International Tree Nut Council Nutrition Research & Education Foundation. The private sponsors did not participate in the design, conduct, or analysis of the study, or in review or approval of the paper.

Purple potatoes slow colon cancer in mice

Gambar terkaitCompounds found in purple potatoes suppressed the growth of colon cancer tumors in petri dishes and in mice by targeting the cancer’s stem cells.

Attacking stem cells is an effective way to counter cancer, says Jairam K.P. Vanamala, associate professor of food sciences at Penn State.

“You might want to compare cancer stem cells to roots of the weeds. You may cut the weed, but as long as the roots are still there, the weeds will keep growing back and, likewise, if the cancer stem cells are still present, the cancer can still grow and spread.”

Vanamala and colleagues used a baked purple potato because potatoes are widely consumed and typically baked before they are consumed, especially in western countries. They wanted to make sure the vegetables maintained their anti-cancer properties even after cooking.

Findings from the initial laboratory study showed the baked potato extract suppressed the spread of colon cancer stem cells while increasing their deaths. Researchers then tested the effect of whole baked purple potatoes on mice with colon cancer and found similar results. They published the findings in the Journal of Nutritional Biochemistry.

The portion size for a human would be about the same as eating a medium size purple-fleshed potato for lunch and dinner, or one large purple-fleshed potato a day.

There may be several substances in purple potatoes that work simultaneously on multiple pathways to help kill the colon cancer stem cells, including anthocyanins and chlorogenic acid, and resistant starch, researchers say.

“Our earlier work and other research studies suggest that potatoes, including purple potatoes, contain resistant starch, which serves as a food for the gut bacteria that the bacteria can covert to beneficial short-chain fatty acids such as butyric acid,” Vanamala says.

“The butyric acid regulates immune function in the gut, suppresses chronic inflammation and may also help to cause cancer cells to self-destruct.”

Eat from the rainbow

In addition to resistant starch, the same color compounds that give potatoes, as well as other fruits and vegetables, a rainbow of vibrant colors may be effective in suppressing cancer growth.

“When you eat from the rainbow, instead of one compound, you have thousands of compounds, working on different pathways to suppress the growth of cancer stem cells,” Vanamala says. “Because cancer is such a complex disease, a silver bullet approach is just not possible for most cancers.”

The next step would be to test the whole food approach using purple potatoes in humans for disease prevention and treatment strategies. The researchers also plan to test the purple potatoes on other forms of cancer.

Using evidenced-based foods as a proper cancer prevention strategy could complement current and future anti-cancer drug therapies. Foods could actually offer a healthier way to prevent cancer because they often have limited side effects compared to drug treatments.

“Indeed, we have seen that the animals that consumed purple potatoes are healthier compared to animals that received drug treatment,” Vanamala says.

 

Purple potatoes could be potentially used in both primary and secondary prevention strategies for cancer, Vanamala says. Primary prevention is aimed at stopping the initial attack of cancer, while secondary prevention refers to helping patients in remission remain cancer-free.

Most of the funding in cancer research currently goes to cancer cures but not to prevention. However, as cancer incidences are predicted to surge in the next two decades, an equal emphasis on both food-based cancer prevention and therapeutic drug approaches should be used to counter the growing epidemic of cancer in the US and around the world.

Other researchers from Penn State and from the University of Colorado are coauthors of the study. The United States Department of Agriculture supported the work.

DNA blood test helps predict colon cancer’s return

Hasil gambar untuk DNA blood test helps predict colon cancer returnA genetic blood test that spots bits of colon cancer-related DNA can help predict recurrence of the disease in some patients.

If the findings are confirmed by further research, the test could eventually help clinicians decide which patients need additional treatment after surgery for stage 2 cancer, researchers say.

Stage 2 tumors, in general, have invaded nearby tissues but have not yet spread to other organs and doctors don’t know for sure when chemotherapy after surgery is beneficial.

“Most patients with stage 2 colon cancers will be cured of the disease after surgery alone,” says Bert Vogelstein, professor of oncology at Johns Hopkins University School of Medicine.

“However, some of these cancers will recur, and we need to improve our diagnostic approaches to detect recurrence earlier than it can be found with current conventional methods.” Labs worldwide are working on DNA-based tests.

For the study, published in the journal Science Translational Medicine, scientists followed 230 stage-2 colon cancer patients in 13 hospitals in Australia for four years, taking more than 1,000 blood samples. They also identified at least one colon cancer-related gene mutation in the tumor taken from each patient.

Over the next two years, they tracked each patient’s cancer-related mutation in periodic blood samples. The tracking used highly sensitive genetic tests to locate and amplify DNA found in the blood. Patients also underwent a CT scan of their entire body every six months after surgery for two years.

Among the 230 patients, 20 had cancer-linked DNA fragments in their blood, including 14 who did not receive chemotherapy and six who did. Of the 14, 11 developed a recurrence, found on a CT scan, during the study. Of the six who received additional chemotherapy, three experienced a recurrence during the study period. An additional 14 patients experienced cancer recurrences, but their blood tests had shown no cancer- linked DNA.

Predicting risk

“Although this and other DNA-based blood tests are not perfect, this study shows that when we find tumor DNA circulating in the blood of cancer patients, recurrence is very likely,” says Nickolas Papadopoulos, professor of oncology.

Currently, 40 percent of patients with stage 2 colon cancers are considered at risk for recurrence, based on measurements of how far cancer has grown into the intestine’s wall, the number of lymph nodes examined during surgery, and whether the cancer has spread to blood or lymphatic vessels. Those at higher risk usually get chemotherapy after surgery, but efforts to demonstrate its benefit have been hampered by the lack of large-scale studies.

Vogelstein says better methods to predict risk for recurrence, such as the blood test, could identify a very-high-risk subset of patients who can form the basis of rigorous study of the benefit of additional treatment.

“There is mounting evidence that ctDNA is a viable approach for earlier detection of cancer recurrence, and more research is underway to refine the technology, improve its sensitivity and determine the best testing intervals,” says Kenneth Kinzler, co-director with Vogelstein of the Ludwig Center at the Johns Hopkins Kimmel Cancer Center.

There are no DNA-based blood tests for cancer now approved by the Food and Drug Administration, although several biotechnology companies are designing and studying them. Costs of the tests are estimated to range in the many hundreds to thousands of dollars, and it is unclear if health insurance companies would pay.

Kinzler, Papadopoulos, Vogelstein, and Luis Diaz, also of Johns Hopkins, are founders of PapGene Inc. and Personal Genome Diagnostics Inc., and members of the scientific advisory boards of Morphotek and Sysmex-Inostics. These companies and others have licensed patent applications on genetic technologies from Johns Hopkins, some of which result in royalty payments to Kinzler, Papadopoulos, Diaz, Vogelstein, and Isaac Kinde. The terms of these arrangements are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

Additional collaborators are from the University of Melbourne; Monash University; Eastern Health; Alfred Hospital; Warrnambool Hospital; the University of Adelaide; Ludwig Cancer Research; and Johns Hopkins.

Ludwig Cancer Research, the Conrad N. Hilton Foundation, the Sol Goldman Sequencing Facility at Johns Hopkins, the National Cancer Institute, and the Victorian Cancer Agency funded the work.

Stuff in broccoli helps drug kill colon cancer

Hasil gambar untuk Stuff in broccoli helps drug kill colon cancerEven small amounts of an ingredient found in broccoli can make a cancer drug work better, new research shows.

Colon cancer cells were more likely to die when they were pretreated with sulforaphane, an ingredient found in cruciferous vegetables, and then treated with a cancer drug currently in development.

The concentration used was equivalent to eating a typical serving of broccoli, and, importantly, at a dose that did not itself act in killing the cells.

This is one of only a few examples of a food ingredient that, in moderate amounts, has a positive influence on the efficacy of a cancer drug.

The researchers from ETH Zurich and the University of Zurich discovered that sulforaphane increases the concentration of a number of enzymes in the colon cancer cells, including those of an enzyme with the abbreviation AKR1C3. Interestingly, sulforaphane does not have this effect in all cases: In colon cancer cells that already exhibit a significantly elevated concentration of AKR1C3 as a result of the cancer, the broccoli substance caused a further increase in the concentration of the enzyme.

But sulforaphane had no influence in colon cancer cells with an initially very low concentration of AKR1C3. The same was found with intestinal cells unaffected by cancer.

Less drug, fewer side effects?

The enzyme AKR1C3 is a biochemical actor in several metabolic pathways in the human body. It is also central in the efficacy of a cancer drug that is currently still in development and clinical testing. This drug, called PR-104A, is administered in an inactive form and is converted into its active form inside the cancer cells by the AKR1C3 present there.

The researchers used cell culture to investigate whether the broccoli ingredient increased the efficacy of PR-104A. When the scientists pre-treated the colon cancer cells with sulforaphane, less than a third of the usual dose of PR-104A was enough to kill the cancer cells.

“Since cancer drugs generally have strong side effects, any approach that reduces the dose of medication while maintaining efficacy is always welcome,” says Shana Sturla, a professor in health sciences and technology at ETH Zurich.

“What’s interesting with sulforaphane is that it occurs naturally in our food and is nontoxic in the concentrations we used,” says Sturla. “In addition, the sulforaphane-enhancing effect was seen only in cancer cells and not cells from healthy tissue, which would be very important for avoiding unwanted side-effects from the combination”.

Future studies

Based on these results in cell cultures, the scientists aim to conduct biomarker-based clinical studies with cancer patients to investigate whether sulforaphane positively supports a treatment with PR-104A.

The researchers also want to find further food ingredients that positively influence the efficacy of medication, even in small amounts, as well as accompanying biomarkers that can help track personalized responses.

“We assume that there are other such combinations out there,” says Sturla.