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Pathway found for treatment-resistant lung cancer
A big way chemotherapy works is by prompting cancer cells to commit suicide, and scientists have found a pathway the most common lung cancer walks to avoid death.
Scientists at the Medical College of Georgia and Georgia Cancer Center at Augusta University have found a first step appears to be lung cancer cells expressing high levels of the molecule TIMP-1, classically considered a tumor inhibitor but at high levels already associated with a poor prognosis for patients.
TIMP-1 then turns up expression of the immune system modulator IL-6, which is already associated with resistance to cancer chemotherapy.
Levels of both increase even further in the face of chemotherapy treatment, a mainstay for treatment of the common, non-small cell lung cancer they studied.
Chemotherapy resistance is a big problem in this lung cancer type, particularly when the cancer recurs at which point it’s also more aggressive, says Dr. Mumtaz Rojiani, cancer biologist.
To see just how TIMP-1 contributes, Rojiani and her colleagues first explored whether TIMP-1 enabled cancer cells’ uncanny ability to essentially spit out a chemotherapy drug. While they didn’t see evidence of that phenomenon in their studies in human lung cancer cells, they did see an increased level of IL-6.
IL-6 is a sugar-coated protein that can turn inflammation both up and down and actually has been shown to regulate TIMP-1 — rather than vice versa — in some cancers.
But in lung cancer, at least, the scientists saw TIMP-1 take the lead in avoiding cell suicide, a natural process that should happen when cells become dysfunctional.
“At least in lung cancer, we are showing that it is TIMP-1 that is controlling IL-6,” says Mumtaz Rojiani, corresponding author of the study in the journal Cancers.
“We have shown for the first time that if TIMP-1 goes up, IL-6 goes up and if TIMP-1 goes down, IL-6 decreases … and we have shown it in multiple different ways,” says Dr. Amyn Rojiani, chair of the MCG Department of Pathology and a study coauthor.
Their work indicates levels of this destructive duo may be an even more valuable indicator of a patient’s prognosis as well as an important new target for improving it.
In their studies, they looked at both human non-small cell lung cancer cells and the same cells with TIMP-1 knocked out, then used two frontline chemotherapeutic agents, gemcitabine and cisplatin, and found IL-6 production went down and cell death went up in response to the drugs in the cells with TIMP-1 missing, says Mumtaz Rojiani.
“We gave the two chemotherapy drugs and when we looked at the effect of those drugs we found that TIMP-1 was affecting apoptosis in cell lines and when we knocked it down, we found more apoptosis even in the presence of these drugs,” says Mumtaz Rojiani. “So we know TIMP-1 is affecting apoptosis.”
When they added TIMP-1, they saw IL-6 go back up and cell survival increase, she says. In fact, when they gave more IL-6, cell death also was reduced, however just adding TIMP-1 also increased IL-6 and using antibodies to neutralize just TIMP-1 also reduced levels of IL-6.
When they looked again at cancer cells that survived, they were even more treatment-resistant than the cells they came from and had higher levels of TIMP-1 and IL-6, Mumtaz Rojiani says.
“You develop chemo-resistant clones that have higher levels than the original cancer cells,” says Amyn Rojiani.
To ensure the IL-6 was functional at this higher level, they looked downstream at the IL-6 signaling pathway, which includes STAT3, a regulator of gene activity. STAT3 is known to be involved in controlling cell growth and division, movement and apoptosis, all of which cancer uses. With high levels of IL-6, they watched STAT3 move into the cell nucleus, which means it was also activated.
To see if this tumor-promoting synergy they identified in human lung cancer cell lines also occurred in patients, they turned to the Cancer Genome Atlas database, compiled by the National Cancer Institute, which includes samples and full genome sequencing from patients with a huge variety of outcomes, including chemotherapy resistance and death, says Dr. Wei Xiao, MCG postdoctoral fellow and the study’s first author.
They found that patients with non-small cell lung cancer who had both low TIMP-1 and IL-6 had higher survival rates and these two genes were commonly elevated together, Xiao says. Also, just IL-6 being elevated did not affect survival as much as just TIMP-1 being elevated. But they found patient survival was much worse when both were elevated rather than TIMP-1 alone. “The two-gene signature became very important,” says Mumtaz Rojiani.
Next steps include examining exactly how STAT3 is helping reduce apoptosis in this scenario. They already are wondering if there is some sort of feedforward mechanism that also means another thing active STAT3 does is activate even more TIMP-1.
They also want to look at other cancers to see if the same chain of events also is set in motion, particularly in those where others have reported it’s IL-6 driving TIMP-1. The order definitely matters because it helps define the function of downstream molecules, they say.
Theirs is the first report of this relationship where TIMP-1 affects IL-6, which activates STAT3 in this most common lung cancer type.
Multiple studies have reported that TIMP-1 is significantly elevated in lung cancer cells versus healthy lung cells. Theirs defines a role for elevated TIMP-1 in cancer cells developing resistance to chemotherapy, the scientists say.
Cancer makes heavy-handed use of both MMPs, or matrix metalloproteinases, and their natural inhibitor TIMP-1. MMPs get secreted following injury to degrade adjacent tissue like collagen so a myriad of cells and factors can move in for repair. Particularly near the end of the repair process, levels of TIMP-1 increase to help keep the process from getting out of hand and healthy tissue from also getting destroyed, says Amyn Rojiani. Cancer takes advantage of MMPs to ensure it can grow at its main site and spread to others.
If we don’t have an injury — or cancer — we likely have very low levels of TIMP-1, the scientists say.
Lung cancer is the leading cause of cancer death in both men and women, and the non-small cell type accounts for 80-85 percent of lung cancers, according to the American Cancer Society.
The Georgia Cancer Coalition helped fund the research.
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Health24.com | Will feeding your pets raw food make you sick?
Pet food-related infections in people are rare in households that feed their pets raw food, according to a large international survey.
There is ongoing controversy about whether feeding raw pet food such as uncooked meat, internal organs, bones and cartilage puts people at risk.
Common pathogens
Researchers at the University of Helsinki in Finland surveyed more than 16 000 households in 81 countries that feed their pets raw food. Only 39 households (0.24%) reported pet food-related infections in people in which the infection-causing pathogens were identified.
The most common pathogens were Campylobacter and Salmonella. There were also cases of E.coli, Clostridium, Toxoplasma and one Yersinia infection.
Another 24 (0.15%) of the households reported pet food-related infections in which pathogens weren’t identified.
Households had been feeding raw food to their pets on average for 5.5 years. Reported infections spanned the entire time that raw pet food was used in the household.
The findings surprised researcher Johanna Anturaniemi of the faculty of veterinary medicine.
Pet food may not be the source
“It was surprising to find that statistical analyses identified fewer infections in the households with more than 50% of the pet diet consisting of raw food. Furthermore, feeding pets raw salmon or turkey was associated with a smaller number of infections,” she said in a university news release.
The median age of sickened people was about 40; half were older, half younger. In the 39 households where infections occurred and the pathogen was identified, four of the infected people were kids between two and six years of age. In two households, the infected people had weakened immune systems due to cancer and Crohn’s disease.
A quarter of the 39 households had children between two and six years of age, and 15% had people with weakened immune systems.
“This raises the question of whether the pathogens could have been transmitted by children from outdoors, daycare centres or other public spaces, even if pet food had been assumed to be the source of infection,” Anturaniemi said.
Image credit: iStock
Health24.com | “I lost 27 kilos and I did it all from the comfort of my own home”
When mother of two, Marlaine Witbooi realised that her eating was out of control, she did a total 360 and changed her life around for the better — without going to the gym. Armed with various exercise plans and the determination to get healthier, Marlaine lost 27 kilos and counting.
Marlaine Witbooi
Occupation: Sales Administrator for an I.T Company
Age: 35 years
City: Cape Town
Weight before: 95kg
Weight after: 68kg
Height: 169cm
Time required to reach current weight: Oct 2016 — now
Secret weapon to your weight loss: Dedication and Commitment
The Gain
“If I must be honest, I have had two weight loss journeys,” admits Marlaine. She says that she gained weight when she became comfortable in her relationship and then piled on more kilos after the birth of her first child.
In 2013 she lost 13 kilos but when she stopped smoking, she gained back 7 of those kilos. Her weight stabilised for the next few years until she had her second child.
“I had a plan to eat healthily and to exercise throughout my pregnancy, but my first trimester hit me really hard. I felt sick ALL the time and had no energy so I rested a lot and did no exercise.
“I then started craving all the things like potato chips and rolls and so on. I gained 15 kilos in my pregnancy and became so lazy,” she explains.
After the birth of her second daughter, Marlaine picked up another 5-6 kilos which put her at her heaviest of 95kg.
“I binged on a lot of takeaways and I was crazy-obsessed with hot chips (with salt and vinegar). I would sometimes snack late at night [on hot chips] or other things even after dinner, just because I was ‘lis’ for something”.
Adding to her love of carbs, Marlaine loved biscuits, chocolate and fizzy drinks.
“I must admit that I developed this snacking problem after I stopped smoking in 2013. I kind of battled with it for some time because I felt the need to have something sweet in my mouth. I guess I replaced one crutch with another,” she adds.
READ MORE: “I Lost 38 Kilos When I Discovered My Passion For Running”
The Change
“I noticed it [her weight] the first time when I looked at my honeymoon photos and it was a picture of me from behind. I left me wanting to crawl into a hole and die. It was seeing this side of me that made me realise how much weight I had gained. I was shocked!” says Marlaine.
Marlaine says that she couldn’t accept that she let herself ‘go’. “I needed to love me and I knew that I couldn’t love this person I was. I felt pathetic in these moments and it pained me that my girls saw this too, so I needed to make that change, not only for me but for them and for my husband because this affected them too,” says Marlaine.
She also found inspiration in her friend, Natasha, who was doing well in her own weight loss journey.
“She spoke to me and told me that I was pushing myself too hard and she was right. I was working so hard by doing crazy cardio training, my nutrition was definitely off-key and I wasn’t getting any rest which can be hard when you have a little one (plus I was still breastfeeding).
“So, I took a break over December 2017 and started on January 1st, 2018. For me, this was my real turning point in my journey. I found an eating plan that I decided to follow which helped a lot. I started incorporating much more weight training into my workouts and slowly but surely got into a proper routine”.
READ MORE: Your Weight Loss Struggles Might Be Genetic, According To Experts
The Lifestyle
Marlaine’s proper routine included following a 21-day meal plan that had her cutting out sugar and fizzy drinks.
“I started to drink more water and upped my intake to 3 litres a day. Some days I get in between 2-3 litres, but never less. Meal prep became — and still is — a priority in my life and helped me stay on track. I have tried different diets or meal plans as I believe we need to find what works for us,” she explains.
The different diets and meals plans included a colour portion container system, macro counting, timed nutrition and working with a coach.
Marlaine says that all of these methods contributed to her weight loss and getting a better handle on her eating, with some doing better than others.
She’s now in the process of trying intermittent fasting and keto to help with her gut issues and drop the last few kilos.
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With her first weight loss journey, Marlaine focused on cardio but this time around she made 80% of her workouts resistance training. She started training three days a week then slowly worked her way to six 30-60 minute sessions a week.
“I usually have 1-2 days a week that are cardio-based and 4 days where weights, bands, loops and sliders are involved. I LOVE home workouts. It works for me because I haven’t got time to run around to gym. Getting up at 3:55 am each morning, getting dressed and starting my workout at 4:30 am is what works for me,” she says.
Marlaine follows along with Beachbody on Demand, a network that hosts various workout programmes. Added to her daily workouts, Marlaine goes a host of physical activities with her family and is a regular at Women’s Health events.
READ MORE: 7 Types of Hunger That Can Sabotage Your Weight-Loss Goals
The Rewards
The first few months of her journey were frustrating as she wasn’t seeing results but she kept pushing and a few months later, the kilos started dropping.
Within 2 and half years, she’s dropped 27 kilos, went from a size 18 to a size 10, and gained some serious muscle and confidence in the process.
“I am more confident and so much happier, which is great because I feel that I can be a great example for my girls. I now feel like ‘me’ and that is what counts the most. I do things and eat things that feel good to me,” she explains.
READ MORE: 3 Practical Habit Changes That’ll Help You Lose Weight
Marlaine’s Tips
- Figure out your ‘why’: “There will be times where you fall off track and it’s this ‘why’ that would get you back into it. I know because it’s what helped me”.
- Go at your own pace: “It doesn’t help to try to be like the person next to you because we are all different. If you are trying to be like that person, you are only setting yourself up for failure because you will constantly be hard on yourself and you won’t notice what you have accomplished”.
- Take photos of your journey: “I stress on this because if it weren’t for my photos or videos, I would completely forget where I started. We get so caught up in the now that we forget and when we stop seeing results for a few weeks because maybe we have plateaued, these pictures and videos will remind you and keep you wanting to go for Gold”.
- Keep a journal: I believe in journaling, tracking my weights, how many calories I burnt, what I ate (even if its roughly documented) but also how I felt each day. Get yourself a really cute journal and maybe some gel pens to make it fun and colourful. It helps and its fun to read back on things. I wish I started my journal from day one.
This article was originally published on www.womenshealth.co.za
Image credit: iStock
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Health24.com | Does a plant-based diet actually increase metabolism or not?
Health and wellness expert Vanessa Ascencao – a nutritional consultant – answers your critical questions about whether a plant-based diet really does increase your metabolism and help you lose weight…
So, let’s be honest: does a plant-based diet actually increase metabolism?
Plant-based diets are loaded with phytonutrients, minerals, vitamins and other phytochemicals that provide the body with nourishment and, yes, help improve metabolism.
At a cellular level, it increases the function of the mitochondria, known as the powerhouses of the cell.
It’s important to focus on your nutrient intake, not on calories. When you eat a natural plant-based diet with the removal of processed foods you automatically feed your cells optimum nutrients and your body will self-regulate and reach optimal weight.
Eating a plethora of plant-based foods means you eat less of the bad stuff and body fat will naturally decrease.
READ MORE: 10 Ways To Make Your Switch To Veganism A Whole Lot Easier
How does increased fibre rev metabolism?
Increased fibre-rich foods in the diet such as beans, legumes, flax seeds, asparagus, Brussels sprouts and oats can help boost metabolism, improve gut health, reduce the risk of heart disease and lower inflammation – the root cause of most chronic disease today.
Since the body can’t easily digest fibre, it works extra hard to try to break it down, which leads to (you guessed it) weight loss.
READ MORE: How Meal-Time Planning Can Improve Appetite And Aid Fat Burn, According To A Study
To see lasting results, in addition to increasing fibre-rich produce, you need to live a healthy lifestyle that includes exercise and nutritious food.
I also advocate supplementing with green tea extract, which helps to fight disease, or the plant compound berberine, which supports gut health, helps to reduce inflammation and assists in regulating metabolism.
Is plant-based protein as effective as meat protein in firing up metabolism?
Foods derived from both plants and animals can provide protein. If you like the idea of following a plant-based diet, focus on including plenty of nutrient-dense vegetables, good quality fats and less refined foods.
Try to limit “meat alternatives” as many varieties are loaded with sugar, oil and excess salt, which can contribute to water retention. The less processed your diet, the better.
READ MORE: 8 Dietician-Approved Snacks That Don’t Taste Like Cardboard
What are some of the best sources of plant-based protein and fibre?
As far as protein goes, think fruit, veggies, legumes and nuts, almonds, quinoa, lentils, chickpeas and beans.
To fill up on fibre, go for fruits such as berries, apples, mangos, pears, melons and oranges; leafy green veg such as broccoli, kale and carrots; nuts, seeds, beans and legumes.
This article was originally published on www.womenshealthsa.co.za
Image credit: iStock
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Labour pledges free personal care for over-65s in England
Help with dressing, washing and meals will be paid for by the state in England, costing £6bn a year.
Health24.com | Just 2 weeks on the couch starts to damage your body
A new study proves that the old adage “use it or lose it” is definitely true when it comes to fitness.
After just two weeks of sedentary behaviour, formerly fit people had:
- A decline in heart and lung health
- Increased waist circumference
- Greater body fat and liver fat
- Higher levels of insulin resistance
“The study showed that two weeks of reduced physical activity – from approximately 10 000 steps per day down to 1 500 per day – caused changes in health markers that are associated with type 2 diabetes and cardiovascular disease,” said study author Kelly Bowden Davies.
She’s a lecturer at Newcastle University and the University of Liverpool in the United Kingdom.
Health changes reversed
But the good news from the study is that the body seems to quickly bounce back once you start moving again.
“It’s important to note that when people resumed their normal activity levels after this period, the negative health changes were reversed,” she said.
The researchers recruited 28 healthy, regularly active adults. Eighteen were women. The average age of the study volunteers was 32. Their average body mass index (BMI) – a rough measure of body fat based on height and weight measurements – was just over 24.
A BMI under 24.9 is considered normal weight.
The study volunteers had been quite active, normally clocking about 10 000 steps daily. Bowden Davies said most of this was just from daily activity, rather than structured exercise. She said they usually participate in no more than two hours of structured exercise weekly.
The researchers asked the volunteers to cut their activity drastically. They dropped an average of just over 100 minutes a day, the researchers said.
After two weeks of couch potato life, the study volunteers underwent a battery of testing. These results were compared to findings measured when the study started.
Findings validate advice
Bowden Davies said cardiorespiratory fitness levels dropped by 4% in just two weeks.
Waist circumference rose by nearly one-third of an inch. Liver fat increased by 0.2%. Total body fat went up by 0.5%. Insulin resistance increased and triglyceride (a type of blood fat) levels went up slightly.
Fourteen days after resuming activity, these measures all bounced back, the investigators found.
“Even subtle increases in activity can have a positive effect on health. Moving more and breaking up sedentary activity is encouraged,” Bowden Davies added.
Dr John Osborne, an American Heart Association spokesman, said this was a very interesting, and somewhat surprising, study. The findings validate advice he gives his patients.
“If you can be a shark or a turtle, be a shark – always moving. This study showed you can lose the benefits of exercise very quickly, but the good news is that when they became sharks again, all the benefits came right back.”
Another expert who reviewed the study, Dr Edmund Giegerich, chief of endocrinology and vice chairman of medicine at NewYork-Presbyterian Brooklyn Methodist Hospital in New York City, was also somewhat surprised by the magnitude of changes that happened in just two weeks.
Walking is fine
Giegerich said the study confirms how important it is to stay active.
“Going from being sedentary to more active can help a great deal in preventing the onset of type 2 diabetes. Just try to be more active. You’ll feel better, and if you’re trying to lose weight, it can help a little. You don’t have to run a marathon. Walking is fine. Just get up and get moving,” he advised.
Both experts pointed out that the study was small, and in a larger group, the findings might be different. The study was also only done for a short period of time.
Bowden Davies, Osborne and Giegerich all suspect that if people who are at a lower fitness level stop almost all of their activity that the results might even be worse.
The study was presented at the European Association for the Study of Diabetes meeting, in Barcelona. Findings presented at meetings are typically viewed as preliminary until they’re published in a peer-reviewed journal.
Image credit: iStock
