Project

exercise and cancer metastasis

Goal: Physical-based treatments that impact connective tissue have the potential to influence tumor growth, spreading and metastasis through mechanisms explored in the emerging role of connective tissue in cancer biology. Recent advances in understanding the effect of mechanical forces on tissues provide clues that may now be useful to understand the biology of physical-based therapies in relation to cancer and perhaps eventually develop physical treatments that may enhance natural healing responses. the possibility that mechanical forces produced within tissues during exercise could directly impact tumor growth or recurrence has received little attention. While the safety of applying direct mechanical forces in the vicinity of tumors is a prime concern, active or passive mechanical forces applied away from the tumor itself may promote a healthy connective tissue environment throughout the body that is inhospitable to cancer and enhances natural immunity.

Thomas DeLorme is known for the progressive resistance exercise (PRE) protocol. However, many have overlooked or forgotten the fact that although DeLorme exercised patients through the full range of motion, he did so in a way that the muscle was maximally loaded when at its shortened length. My latest research explores short muscle length loading programs, with outcome measures such as range of motion, muscle length, soft tissue pliability and long-term function changes.

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Thomas W Findley
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3969 FASEB EXPERIMENTAL BIOLOGY APRIL 21-24, SAN DIEGO CA
A Role for Resistance Exercise in Cancer: Destruction of Circulating Tumor Cells in Contracting Muscle
Thomas W Findley1,2, Ellen Z Anderson3, Todd Stitik1, Rishi Singhal4, Jared Burch3, Cynthia Diaz3, Vivan Shah1, Zadok Ruben5, Sunil Dhar6, Hans Chaudhry7. 1Physical Medicine, Rutgers New Jersey Medical School, Newark, NJ, 2Cancer Institute of New Jersey, Rutgers, New Brunswick, NJ, 3Physical Therapy, School of Health Professions, Rutgers, The State University of New Jersey, Newark, NJ, 4College of New Jersey, Ewing Township, NJ, 5Patoximed Consultants, Westfield, NJ, 6Mathematical Sciences, 7Vetha Center for Transdisciplinary Studies, New Jersey Institute of Technology, Newark, NJ
OBJECTIVE At the Roswell Park Cancer Institute, Leonard Weiss explored why muscle tissue gets few cancer metastases, despite its large blood flow. (Weiss, L., 1992. Biomechanical interactions of cancer cells with the microvasculature Cancer Metastasis Rev, 11(3), pp.227-235). He found that injected tumor cells were destroyed in quadriceps muscles contracting to their shortest length. They were also destroyed in the lung capillaries during maximal but not normal inspiration. He further showed that as cancer cells squeeze through the much smaller capillaries, they elongate to the maximum extension of the cell membrane and hypothesized that additional forces on the cancer cell wall caused cell rupture. We developed mathematical models to analyze Weiss’ published lung data during a maximal inspiration, and found this induces radial stress of 8.7 KpA on a 4.6 mm diameter lung capillary. In our study,
Preliminary Data 12 healthy males age 20-30 were asked to flex the right elbow from 5° to 90°, with no load, and then with a 10 pound weight, in supine and standing. Longitudinal 2D B-mode ultrasound was performed of the long head of the biceps brachii muscle at specific measured locations based upon its proximal portion at the intertubercular groove and distal region at the anterior elbow joint line. Muscle length and maximum diameter was recorded and the truncated cone of the muscle image was converted to a cylinder of the same maximum diameter and shorter length (to keep constant volume). Odegard’s strain energy function for small and large deformations associated with the active and passive response of transversely isotropic skeletal muscle was used to determine longitudinal and radial strain and stress, Young’s modulus, and stiffness. Our mathematical models were applied to ultrasound generated architectural data of the contracting biceps muscle, to determine radial stress under different exercise conditions. We found the radial stress during biceps contraction to be: 1) 46 +26 KpA with the elbow unloaded at 90°; 2) 42 +17 KpA with participant in supine, the elbow at 90° and a 10 pound load on the biceps; and 3) 48+24 KpA with the participant standing and the biceps loaded with 10 pounds. With the elbow in 5° flexion, the radial stress is much lower, (15 +- 22 KpA), at both loads and in both supine and standing. This is highly significant p<.00001 2 tailed t test for all 90 degree tests compared to all 5 degree tests.
.CONCLUSIONS. Shortening of biceps muscle results in radial stress well above the level calculated to rupture circulating tumor cells in the lungs. Muscle capillaries have stiffening of their wall, so the high radial stress of a short length contraction may be necessary for tumor cell destruction in muscle tissue. Large muscle metastases are found in very few persons with common cancers – lung (2%), colon (1%), breast and prostate (<.5%). In contrast, extraocular muscles rarely contract to their shortest, and metastases are found here in 6% of persons with locally advanced or metastatic breast cancer, and in 12% of all persons dying of cancer. Normal resting cardiac output (CO) is 5 l/min, with a pulse of 80 and a blood volume of 5 liters. Resistance exercise sufficient to raise pulse rate 50% to 120 will raise CO similarly 50% to 7.5 liters/min, with 1/3 the cardiac output now going through the exercising muscle. Every minute of exercise thus leaves 2/3 blood volume unfiltered. After a short 7 minutes of this level of exercise, all but .677 or 0.02% of the blood volume will have passed through the exercising muscle. We suggest design of exercise for persons with cancer based on aspects of muscle and capillary architectur .
 
Jann Arends
  • 39.23
  • University of Freiburg
This is a fascinating concept. Has this been published in the 2018 Exp Biol Proceedings?
 
Michael Oberlin
  • 2.75
  • Földiklinik GmbH & Co. KG
Sounds very interesting - important for physical therapy in lymphedema and cancer patienrts.
 
Thomas W Findley
added an update
Anti Metastasis Exercise
People usually die from cancer metastases, not from the primary cancer. These exercises are directed toward the circulating tumor cells, which carry the tumor to other locations, and carry drug resistance developed by a few cells during treatment from one metastasis to another. Leonard Weiss showed in animal studies in the 1980s that circulating tumor cells could be completely eliminated from the blood of animals by muscle contraction, as well as by deep lung inspiration. The rounded circulating tumor cells are much larger than the red and white blood cells, and to go through capillaries they must squeeze themselves into an elongated oblong shape. Additional pressure, either from deep inspiration stretching the capillary or muscle contraction squeezing it, stretches the cell membrane even more so that it breaks and the cell dies.
Existing studies in humans show that at rest, red blood cells travel through lung in one second and muscle in two minutes. During exercise, this is reduced to ½ second in lung and 30 seconds in muscle. In my recent human research I use direct ultrasound measurements to calculate the outside pressure on the capillaries, comparing two different types of resistance exercise. This information has been used to design exercises specifically directed at reducing or eliminating circulating tumor cells.
Breathing exercise at rest Inhale as deeply as possible and hold for 4-5 seconds. Exhale and inhale again (1/2 second each) and hold again for 4-5 seconds. Continue for two minutes for 20-24 repetitions. If you have a Continuous Positive Airway Pressure Machine (CPAP), you can put a finger over the exhalation port during inspiration to create additional expansion of your lungs.
Breathing exercise during aerobic exercise At the end of each inspiration, breathe in as much additional air as possible. Exhale normally. Continue for 20 minutes of exercise.
Muscle resistance exercise using weights Circuit progressive resistance training of 6-8 major muscle groups 3 times a week. 3 sets will take about 45-60 minutes. You can exercise quadriceps, hamstrings, hip extensors, biceps, triceps, latissimus and other muscles in most gyms, but you need to use a different technique which provides the greatest load to the muscle when it is the shortest. That means no squats or presses. Based on the heaviest weight you can lift 10 times, in the first circuit you lift 50% of that weight 10 times for each muscle. Then you perform another set of 10 repetitions using 75% of that weight. Your final round uses 100% of the weight, and you lift as many as you can. If you can lift 15 times, the next exercise day you add some weight.
Weiss, L., 1992. Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis. Cancer and Metastasis Reviews, 11(3), pp.227-235.
 
Thomas W Findley
added 2 research items
The upcoming Third International Fascia Research Congress will have much exciting information for the clinician, as well as for the clinical and basic science researcher. This paper provides a perspective from a clinician/scientist, including the fascial network of body-wide connections between and within individual cells, and sharing of loads between muscle and fascia. Basic studies of fibroblast cell shape show the impact of manual therapy, acupuncture, and yoga-like stretching at the cellular level. Advances in scientific equipment have made it possible to study a layer of hyaluronan fluid, which allows sliding between deep fascia and muscle. Collagen fibers within fascia affect both blood flow to muscles and lymphatic fluid flow.
Thomas W Findley
added an update
two abstracts just submitted to the society for integrative oncology
RESISTANCE EXERCISE AND METASTATIC INEFFICIENCY
BACKGROUND Weiss explored metastatic inefficiency to muscle with its large blood flow in the 1980s. Circulating tumor cells were destroyed in contracting cardiac tissue, electrically stimulated quadriceps, and in maximal lung inspiration, by radial stress breaking open elongated cancer cells as they squeeze through the capillaries. Exercise is recommended for patients at all stages of cancer diagnosis and treatment. We use mathematical models to calculate radial stress generated in resistance exercise.
METHODS 12 healthy males age 20-30 flexed the right elbow from 180 to 90 ‘, with no load or a 10 pound weight, in supine and standing. From 2D longitudinal Ultrasound recorded during contraction, we measured muscle length and maximum diameter. The truncated cone of the muscle image was converted to a cylinder of the same maximum diameter and shorter length (to keep constant volume). Odegard’s strain energy function for small and large deformations associated with the active and passive response of transversely isotropic skeletal muscle was used to determine longitudinal and radial strain and stress, Young’s modulus, and stiffness.
RESULTS Our analysis of published Weiss lung data during a maximal inspiration which is sufficient to rupture 100% of cancer cells, gives radial stress of 8.7 KpA for a 4.6 mm diameter capillary. We find biceps muscle at elbow of 90’, has radial stress of 46 +-26 supine unloaded, 42 +-17 supine with a10 pound load, and 48+-24 standing loaded 10 pounds. With elbow extended the radial stress is much lower, 15 KpA.
CONCLUSIONS Shortening of biceps muscle results in radial stress well above the level calculated to rupture circulating tumor cells caught in the lung capillaries. We plan to study other muscles and more joint angles to guide practical application to exercise programs for persons with cancer.
TITLE: RESISTANCE TRAINING INCREASES SERUM TESTOSTERONE IN CASTRATE RESISTANT PROSTATE CANCER ON ABIRATERONE
BACKGROUND: Androgen deprivation treatment (ADT) for prostate cancer reduces testosterone levels to 30 -50 ng/dL (normal 300-700 ng/dL) and causes loss of muscle mass. The anti-prostate cancer drug Abiraterone acetate (ABA) further reduces serum testosterone to almost undetectable levels (1-3 ng/dL). Resistance training is widely recommended to build muscle mass or maintain strength for men with prostate cancer. Muscles themselves in normal older men on resistance exercise synthesize testosterone and elevate serum levels, using a pathway from dehydroepiandrosterone (DHEA), which is reduced but not eliminated by ABA.
METHODS: A 66 year old man with prostate cancer had surgery in 2010 and then radiation and ADT for 6 months in 2011. Full time ADT began in 2013. In 2012 he began 1-1.5 hour circuit resistance training, 2-3 x/week for 5 upper, 6 lower and 3 trunk muscle groups, using 10 repetitions at 50% (Borg 6-8), then 10 at 75% (Borg 11-13) and 10 at 100% (Borg 16-18) of the 10 repetition maximum (DeLorme protocol).
RESULTS: Metastatic progression required starting ABA in May 2016. Serum testosterone measured less than 2.5 ng/dL on 8/11/16, a day with no exercise. Surprisingly, on 9/13/16, 5 hours after resistance training, testosterone increased to 26 ng/dL. On 9/29/16, another day of no resistance training, testosterone level was reduced back to <3 ng/dL. Finally, on 12/1/16, at 2.5 h after resistance training, testosterone rose to 16 ng/dL. Despite this rise in testosterone with exercise, there was 99.8% reduction in tumor volume and PSA levels.
CONCLUSIONS: An increase in serum testosterone was associated with resistance training while the patient was under ABA treatment, but the clinical effectiveness of ABA was not impaired. The increase is attributed to the production of testosterone by exercising muscle.
 
Thomas W Findley
added 2 research items
This article reviews fascia research from our laboratory and puts this in the context of recent progress in fascia research which has greatly expanded during the past seven or eight years. Some readers may not be familiar with the terminology used in fascia research articles and are referred to LeMoon (2008) • LeMoon K. Glossary of terms: terminology used in fascia research. Journal of Bodywork and Movement Therapies. 2008; 12/3 : 204-212 • Google Scholar for a glossary of terms used in fascia-related articles.
Thomas W Findley
added 2 research items
More than 100 years ago AT Still MD founded osteopathic medicine, and specifically described fascia as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and is highly innervated. Fascia is intimately involved with respiration and with nourishment of all cells of the body, including those of disease and cancer. This paper reviews information presented at the first three International Fascia Research Congresses in 2007, 2009 and 2012 from the perspective of Dr Still, that fascia is vital for organism's growth and support, and it is where disease is sown.
Thomas W Findley
added a research item
full lecture is online at https://www.youtube.com/watch?v=TPCuHQ9Vbw4&feature=youtu.be Increasing evidence indicates that the physical and mechanical environment can regulate cell behavior and tumor progression at a cellular level. It is likewise clear that many patients benefit from physical manipulation of connective tissue, but it is not clear what happens at the cellular and molecular level when these manipulations occur. Thus, a large disconnect exists between the cell and connective tissue biology and integrative medicine approaches. As such, considerations of physical sciences in oncology should be expanded to include the whole host and possible ways that integrative medicine might be deployed, to determine whether we can safely impact tumor progression and the underlying biology with active and passive physical manipulation. Dr.Findley explores the possibility that active or passive mechanical forces applied away from the tumor itself may promote a healthy connective tissue environment that is inhospitable to cancer.
Thomas W Findley
added an update
my lecture at the november 2015 harvard conference on fascia acupuncture and oncology describes my basic thoughts on this issue. The whole conference lectures are on line, http://oshercenter.org/joint-conference-2015-video-presentations/ but here is the link to my specific talk
Link between Manual Therapy, Movement, Fascia and Cancer
 
Thomas W Findley
added 7 research items
Is fascia an Organ? Regardless of whether one considers fascia an organ, an organ system, or merely structural parts of other organs, we must recognize that there is a collection of structures within this overarching concept. Any discussion of fascia as an organ must start with the observations on its function made by AT Still MD more than 100 years ago. Modern research sheds light on his astute observations on fascia as a covering, a continuous structure with discontinuous names, an organ of gliding, regulating fluid flow in the extracellular matrix, and highly innervated. There is a continuity of fibers from the extracellular matrix, through the integrin receptor and the cell membrane, to the nucleus. A broad range of physiological and biochemical factors need to be taken into account to understand the basis for the broad spectrum of clinical applications purporting to affect the "fascial organ." Some are specific to fascia. Others, such as work hardening, are general properties of hardening by plastic deformation which have been used with copper, steel and other metals for thousands of years. Fascia may graduate from being a connective tissue, a cellular and extracellar matrix filler between defined structures, to become regarded as a structural system with well-defined functions from the embryo to the adult.
Thomas W Findley
added a project goal
Physical-based treatments that impact connective tissue have the potential to influence tumor growth, spreading and metastasis through mechanisms explored in the emerging role of connective tissue in cancer biology. Recent advances in understanding the effect of mechanical forces on tissues provide clues that may now be useful to understand the biology of physical-based therapies in relation to cancer and perhaps eventually develop physical treatments that may enhance natural healing responses. the possibility that mechanical forces produced within tissues during exercise could directly impact tumor growth or recurrence has received little attention. While the safety of applying direct mechanical forces in the vicinity of tumors is a prime concern, active or passive mechanical forces applied away from the tumor itself may promote a healthy connective tissue environment throughout the body that is inhospitable to cancer and enhances natural immunity.
Thomas DeLorme is known for the progressive resistance exercise (PRE) protocol. However, many have overlooked or forgotten the fact that although DeLorme exercised patients through the full range of motion, he did so in a way that the muscle was maximally loaded when at its shortened length. My latest research explores short muscle length loading programs, with outcome measures such as range of motion, muscle length, soft tissue pliability and long-term function changes.