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8 New Bright Ideas Take Flight Thanks to Donor Giving

PANCREATIC CANCER

Pancreatic cancer is one of the most lethal cancers because there are few treatments that are effective against it. With the help of this grant award, a new study will explore how a poorly understood protein called HNF1A promotes this cancer’s resistance to drugs targeting the protein KRAS, which is believed to drive more than 90% of all pancreatic cancers. It will also determine whether drugs called BET- inhibitors could improve the effectiveness of current treatments and save more lives from this deadly disease.

“Understanding and Overcoming HNF1A- Driven Drug Resistance in Pancreatic Cancer,” led by Ethan Abel, PhD,"

led by Ethan Abel, PhD, Department of Molecular and Cellular Biology

METASTATIC BREAST AND PANCREATIC CANCERS

Metastatic breast and pancreatic cancers are among the leading causes of cancer death in the United States. This study will investigate the effectiveness of a two-drug combination that has never been tested before. It will selectively target breast and pancreatic cancers that have a genetic alteration in a tumor suppressor called p53. With the data generated, researchers can launch a phase 1 clinical trial to test this new regimen, with the goal of improving patient outcomes and saving more lives from these devastating diseases.

“Selective Synthetic Lethality Strategy for p53-Deficient Breast and Pancreatic Cancers,”

led by Andrei Bakin, PhD, Department of Cancer Genetics and Genomics

TRIPLE NEGATIVE BREAST CANCER

Triple negative breast cancer (TNBC) is an aggressive type of cancer, with high incidence of metastatic progression. Understanding how tumors escape the primary cancer site to form distant lesions will help begin to prevent this spread. Roswell Park researchers have discovered a fundamental connection between the metabolism of GTP — a building block of our nucleic acids — and the metastatic process. This grant will allow for close investigation aimed at understanding how a rate-limiting enzyme for GTP production supports invasion, with the ultimate goal of developing novel ways to prevent deadly metastasis.

“Novel Interactions at the Cell Membrane of the GTP Biosynthetic Enzyme Inositol Monophosphate Dehydrogenase 2 (IMPDH2) Control Tumor Invasiveness,”

led by Anna Bianchi-Smiraglia, PhD, Department of Cell Stress Biology

Unfortunately, there are currently no targeted therapies for TNBC patients, and the majority patients become resistant to chemotherapy. Researchers have detected a cancer-specific energy-generating enzyme that is very active in aggressive TNBC. When this enzyme activity is elevated, TNBC patients experience the worst outcomes of recurrence and metastasis. If we find strategies to inhibit this powerful metabolic enzyme, we can potentially discover new ways to combat TNBC recurrence or metastasis.

“Targeting Metabolic Enzyme PFKFB4 in Triple Negative Breast Cancer,”

led by Subhamoy Dasgupta, PhD, Department of Cell Stress Biology

We know that TNBC patients who have no remaining signs of cancer after their first treatment regimen (known as pCR, or pathologic complete response) have improved survival rates overall. But they only comprise 25%-35% of TNBC patients. Through a phase 1 clinical trial, we will test a new combination of medications that we believe will produce an increased rate of pCR, better prognoses and decreased need for more intensive chemotherapy. The results will enable us to pursue national grant funding that will allow us to conduct further clinical trials of this drug combination.

“Mobilizing the Immune System to Reduce the Need for Chemotherapy and Improve Outcomes in Triple Negative Breast Cancer,”

led by Shipra Gandhi, MD, Department of Medicine

One of the factors determining how tumors grow is a protein known as the cellular gatekeeper: p53 tumor suppressor. But it also is frequently mutated and either is inactivated or becomes a tumor promoter in cancer, including 65%-85% of TNBCs. Researchers seek to shed light on how another protein, known as PEPD, could be used to trigger mutated p53’s tumor-suppressing actions. This research could revolutionize understanding of the biology and regulation of p53 mutants, identify a novel therapeutic strategy in cancers and generate data important for obtaining national funding for further research to develop PEPD-based therapeutic strategies in cancer.

“Reactivating p53 Mutants for Cancer Treatment by Targeting PEPD,”

led by Yuesheng Zhang, MD, PhD, Department of Pharmacology and Therapeutics

The Roswell Park Alliance Foundation has awarded over 500 grants to promising research studies thanks to donors like you.

BREAST CANCER IN AFRICAN-AMERICAN WOMEN

Black women who develop breast cancer have poorer prognoses than white women with the disease and are more likely to develop estrogen-receptor negative (ER-) breast cancer, which is harder to treat. This may be partly due to having multiple children and a lower rate of breastfeeding, which could result in abnormal cells accumulating in breast tissue. The hypothesis is that when these cells become cancerous, they will develop into ER- breast cancer. The results will reinforce education initiatives and hopefully lead to new preventative measures for women who don’t breastfeed.

“Investigating the Role of Breastfeeding in Preventing Aggressive Breast Cancer,”

led by Michael Higgins, PhD, Department of Molecular and Cellular Biology

Black women who develop breast cancer have poorer prognoses than white women with the disease and are more likely to develop estrogen-receptor negative (ER-) breast cancer, which is harder to treat. This may be partly due to having multiple children and a lower rate of breastfeeding, which could result in abnormal cells accumulating in breast tissue. The hypothesis is that when these cells become cancerous, they will develop into ER- breast cancer. The results will reinforce education initiatives and hopefully lead to new preventative measures for women who don’t breastfeed.

“Investigating the Role of Breastfeeding in Preventing Aggressive Breast Cancer,”

led by Michael Higgins, PhD, Department of Molecular and Cellular Biology

“I am excited that this project was selected for funding by the Roswell Park Alliance Foundation and wish to thank the donors for their generous support. Previous funding by the Foundation made it possible for me to successfully compete for funding from the National Cancer Institute and has allowed me to pursue promising research leads.”

- Dr.Zhang

Nutrition Tips for Cyclists

Hello again ESR riders.

Our world as we know it has changed since I wrote the last blog. There’s so much uncertainty in what will develop in the next couple of months and the challenges we will be faced with. But in the midst of it all is the certainty of our commitment to the ESR’s mission, our health and well-being. So, let’s move forward and not let what is out of our control interfere with all the things we can control. As of today, ESR is happening and we continue to prepare our mind and body for the challenge.

Nutrition and the Empire State Ride 22 Week Training Plan

The focus of this blog is nutrition but first I want to briefly go over the next training block of the ESR 22 Week Training Plan.

Nutrition for Endurance Training

Now let’s get into nutrition … fuel for your machine.

The primary goal of the training diet is to provide nutritional support to allow the athlete to stay healthy and injury-free while maximizing the functional and metabolic adaptations to a periodized exercise program that prepares him or her to better achieve the performance demands of their event.

Athletes need to consume energy that is adequate in amount and timing of intake during periods of high-intensity and/or long duration training to maintain health and maximize training outcomes. Low energy availability can result in unwanted loss of muscle mass; menstrual dysfunction and hormonal disturbances; sub-optimal bone density; an increased risk of fatigue, injury, and illness; impaired adaptation and a prolonged recovery process.

The following charts will help guide you to consume the right amount of daily carbohydrates, carbohydrates during exercise and daily protein to maximize the training adaptations of the ESR 22 Week Training Plan.

Moving into the Tempo Interval Training Block

The next 3-week block of training begins Monday, March 23 after the recovery week you’re in now. The goal of this block is to begin increasing your aerobic capacity with interval training. With this kind of work, we begin to train your Glycolytic Energy System. ‘Tempo Intervals’, as described in the Table 7.2 Summary of the Six Key Cycling Workouts, are the first level of intensity you will do in this plan. This level of intensity should result in labored breathing from about the middle to the end of the prescribed interval time. Please refer to Table 7.1 Workouts, RPE, and Breathing Rate to guide you to the right intensities.

The rest of your workouts will be in that nice and easy conversation pace Endurance Miles zone and continuing to develop good pedaling mechanics with some Fast Pedaling (FP) intervals.

Daily Carbohydrate Needs for Fuel and Recovery

Carbohydrates – During Exercise

Carbohydrate ingestion during exercise can improve exercise performance even during shorter duration, higher intensity exercise (for example, approximately 1 h at 75 % of maximal oxygen uptake; VO2max).” (1. Jakendrup)

Now that we begin the level of intensity that requires glycolytic energy metabolism, we need to make sure we replenish the fuel in our muscles during training. For this type of work, carbohydrates will be your primary source of energy. To estimate the amount of carbohydrates we need for the work we have to take into account the duration (and intensity) of exercise. The table below is a guideline to help make sure you have enough fuel for the workouts.

Please note that these recommendations are for well-trained athletes. Aspiring athletes may need to adjust these recommendations downwards.

Carbohydrates – During Exercise

Current data suggest that dietary protein intake necessary to support metabolic adaptation, repair, remodeling, and for protein turnover generally ranges from 1.2 to 2.0 g/kg/d. Daily protein intake goals should be met with a meal plan providing a regular spread of moderate amounts of high-quality protein across the day.

At 1.5 g/kg/d, the middle of the range, this is what you would need to consume daily based on body weights of 125-200lbs:

Daily Protein Needs for Adaption and Recovery

Recommendations are currently to consume 20-25g of protein per meal. This is the maximum amount of protein your body can use for protein synthesis at one time. Amounts greater than this will just be stored as energy in your body, a.k.a. fat.

So, the key to maximizing protein benefits is to consume 20-25g, 4-6 times per day with at least 3 hours in between each consumption.

Nutrition itself does not make you fitter on the bike. What it does however is provide significant contributions to the adaptations we are trying to achieve from training.

Train right, eat well and be well!

CTS Coach Charlie Livermore

References:

  1. Asker Jeukendrup, A step Towards Personalized Sports Nutrition: Carbohydrate Intake During Exercise, Sports Med (2014) 44 (Suppl 1): S25-S-33
  2. MEDICINE & SCIENCE IN SPORTS & EXERCISE 0195-9131/16/4803-0543/0

Stretching to Optimize Cycling Performance

Seated

Sitting on the edge of a chair, place your heel on the floor in front of you with your leg straight. With your chest up, lean forward until a stretch is felt in the back of your leg. Hold this for 30 seconds.

Standing

Stand with one leg in front of you, farther out than the other. Place your heel on the ground and hands on your hips. Lean forward until a stretch is felt in the back of your leg. It is important to keep your chest up to properly position the hips and low back during this stretch.

Quad Stretch 1

Your quadriceps muscle group is made up of 4 muscles.These muscles help to straighten the knee and bend the hip. You can lean backwards to increase the stretch.

Quad Stretch 2

If you feel off balance completing this, you can achieve the same stretch on a bed or the floor.

Abuduction

Stretching the muscles in the side of the hip that are responsible for both moving your leg away from you (abduction) or rotating your hip inward (internal rotation) can be stretched by crossing your legs while seated and pressing downward on your knee.

External Rotation

To stretch the muscles that turn your hip outwards (external rotation), you can bring one knee towards your chest and pull across your body. You can either pull further across your body or closer to your chest to increase the stretch felt.

Abuduction

To stretch the muscles of the hip that pull your legs together (adduction), a warmup of squeezing something between your legs 30 times will work well. To stretch these muscles, place your leg on the ground and lean away from it. This stretch is commonly taught through sports or general stretching, so you are probably familiar with it. This stretch can also be completed by lying on your back with your knees bent and allowing the knees to stretch out to the side.

Tips for Stretching at Work

You can still complete a warm up without having to break a sweat. It’s all about targeting the desired area. In the case of the hamstrings, you can complete 30 standing hamstring curls or squats for warm up and then stretch your legs at your desk. You can complete the stretch sitting as described above or to enhance the stretch, place a small wastebasket upside down and place your foot on top. Make sure you empty it before you turn it upside down!

The same pattern can be used for your quadriceps muscles. To warm up this muscle group, perform 30 kicks in a seated position. Squats can also help to target these muscles and warm them up. Bending your knee can stretch these muscles. You can stretch on the floor like the image above, you can modify this movement to be completed in a chair, or you can do it in standing. The images in this blog can serve as a reference for each of these.

I hope this helped to provide some insight on how and why we should stretch. The muscles that we use on a daily basis are often not evenly moved and, consequently, run the risk of becoming tight or imbalanced. Remember that stretches are not a “no pain, no gain” mentality. Once you feel a gentle pull in the muscle, hold that position for a static stretch. You can stretch in a static fashion, which has been described throughout this article and is recommended in place of dynamic stretching, or a brief and repetitive on/off stretch. When stretching dynamically, you are still accomplishing elongation of your muscles, but it has been shown to be less effective. If anyone has any further questions or would like me to elaborate more, please feel free to reach out to me directly.

Your on the road PT,

Easton Osborn

Roles Reversed: Meet The Osts

When you spend a few minutes with Darwin and Mary Ost, it doesn’t take long to see their marriage is still as exciting today as it was 25 years ago. Darwin and Mary are best friends who spend most of their time laughing together and raising a beautiful family.

In 2019 Darwin participated in his first Empire State Ride. With Mary as his cheerleader, Darwin absolutely crushed his first year, raising over $6,000 for cancer research at Roswell Park. Shortly after returning from the ESR, it was Darwin’s turn to be the cheerleader for Mary as she received the words that no one ever wants to hear.

Her journey began in May 2019, when she started experiencing back pain. As the pain progressed, Mary sought help from doctors, but initially no one was able to find anything. Eventually her family practitioner sent her to a general surgeon for a lipoma on her back, thinking that could be the source of the pain. The general surgeon did not agree and sent Mary for an MRI. Two days later she had the test, and within hours she received a call instructing her to go directly to the emergency room at Buffalo General Medical Center. The doctors came in and informed her that she had a destructive mass on her spine, and she would be admitted. After biopsies were completed, Mary was released to go home on bed rest. One week after being admitted to the hospital, Mary was informed she had large B cell lymphoma.

After her diagnosis, Mary called Roswell Park right away. Within a few hours of that phone call, she was informed that she had several appointments scheduled for the following week. “Monday, we met with Dr. Suchitra Sundaram in the lymphoma clinic, then a whirlwind week where a PET scan, CT scan, port installation and the first cycle of chemo were performed,” Mary said. “They informed me that I would be on R-CHOP for treatment and that there were six cycles, each three weeks apart. After the sixth treatment there was an additional three weeks when we waited for a third PET scan and then the results.”

When we asked how she got through her diagnosis, Mary described herself as a jokester. “When my husband had just brought me home from that initial stay at Buffalo General, I started cracking jokes about ‘having the cancers.’” Throughout her entire cancer journey, Mary’s positivity held strong. “I just set my mind that it was no big deal; so what, I am sick; they know what they are doing, and I will be fixed.

“I was told I was in remission and rang the bell on February 13.”

Mary will be welcoming our riders home as they cross the finish line this year. She does not have the words to express how grateful she is for the 250+ cyclists who will be riding across the state and raising money for patients like her. For now, Mary leaves us with her mantra: “Have fun and be awesome.”