Inspire and deepen your practice!

Laser, laser needle acupuncture,light emitting diode and pulsed electromagnetic field therapies are the right tools for healing today’s complex patients and for your practice success.

4-24-17 PrePNG - Images for HLS WHITE

All devices pictured above (and more) will likely be available for you to train and practice with in this course.  Learn more about them in the links below.

Healing Light Seminars and David Rindge have been practicing, teaching and continually updating our treatment methods and equipment since 2002. Our goal, first and foremost, is to provide you with a foundation for success with energy-based therapies.  We will only offer devices we have found to be effective, well made and which we are continuing to use clinically.  Yet our goal is to ensure that you learn the parameters and methods for success whether or not you buy from us.  .

Day 1 focuses on theory, biological effects and essentials for clinical success.   You have the opportunity for hands-on practice with state-of-the-art laser, laser needle, led and pemf systems for the treatment of pain, head to toe.

In Day 2, you will learn how to apply laser, laser needles, led and pulsed electromagnetic field therapies for aesthetics / dermatology / facial rejuvenation, cardiovascular disease, digestive, ear and eye disorders, gynecology, for hair regrowth, neuropathy, osteoporosis, respiratory disorders, sports medicine and more.

You will receive Laser Therapy: A Clinical Manual as part of the course.

Laser Therapy - A Clinical Manual This popular training manual by Blahnik and Rindge presents the theory and clinical application of laser therapy in clearly understandable terms with treatment protocols for more than 40 conditions.  Laser Therapy: A Clinical Manual is an important important resource in the course and a $79.00 value.  You will also receive treatment protocols for other conditions, updates and much, much more relevant material in this course.

Gain a solid understanding of energy-based therapies.    NCCAOM 322-5, seven hours each day, Saturday and Sunday.    Learn More.

Course Dates / Location

November 4-5, 2017.  SpringHill Suites Orlando Airport.  5828 Hazeltine National DriveOrlando, FL 32822. (407) 816-5533.

LEARN MORE AND REGISTER HERE

Or call 321-751-7001.

Healing Light Seminars

Training in Energy-based Therapies since 2002

14 PDAs – NCCAOM 322-5

14 CEUs Florida Acupuncturists

Celluma Cover large

Celluma LED Systems

Celluma’s unique flexible design allow it to mold closely to the body, and its extra large light panel and patented programs to blend red, near-infrared and blue light energy are FDA-cleared to treat:

  1. Acne Vulgaris
  2. Arthritis
  3. Muscle & Joint Stiffness
  4. Muscle Tissue Tension
  5. Muscle & Joint Pain
  6. Muscle Spasm
  7. Diminished Local Blood Circulation
  8. Wrinkles

Healing Light Seminars and David Rindge are delighted to make Celluma PRO, LITE and ELITE systems available to health professionals and to those seeking cost-effective home therapy.  Learn full details about this exciting new, affordable healing technology HERE.

Raising the Bar in the Clinic

Flash PEMF with coilHealing Light Seminars will only offer devices which we have found effective, well made and to deliver good value and which we ourselves are continuing to use in the clinic.

3-20-17 4-3-3 Images NEW FLASH-COMBO-CELLUMA

David Rindge and Healing Light Seminars have been practicing with and teaching energy-based therapies every year since 2002, continually updating our methods and equipment as new technology and information have become available.

Our goal over this seminar weekend is to provide you with everything you need to come from knowledge and strength with laser, light emitting diode and pulsed electromagnetic field therapies in your practice!

Day 1 focuses on theory, biological effects and essentials for treatment success.   You will have the opportunity for hands-on practice with state-of-the-art laser, laser needle acupuncture, light emitting diode and pulsed electromagnetic field therapy systems for the treatment of pain, head to toe.

In Day 2, you will learn how lasers, light emitting diodes and pulsed electromagnetic field therapy devices may be applied successfully in aesthetics / dermatology, cardiovascular disease, digestive, ear and eye disorders, gynecology, for hair regrowth, neuropathy, osteoporosis, respiratory disorders, sports medicine and much more.

Gain a solid understanding of the principles, technology and parameters of laser, laser needle, light emitting diode and pulsed electromagnetic therapies and the skills to apply them successfully in your practice!  NCCAOM 322-5, seven hours each day, Saturday and Sunday.  Learn More and Register Here

Course Date / Location

November 4-5, 2017.  SpringHill Suites Orlando Airport.  5828 Hazeltine National DriveOrlando, FL 32822. (407) 816-5533.

LEARN MORE AND REGISTER HERE

Or call 321-751-7001.

Healing Light Seminars

Training in Energy-based Therapies since 2002

14 PDAs – NCCAOM 322-5

14 CEUs Florida Acupuncturists

NCCAOM emblem

To be prepared is half the victory!

3-20-17 4-3-3 Images NEW FLASH-COMBO-CELLUMA

All equipment pictured above and more will likely be available for you to train and practice with in this course.  Healing Light Seminars will only offer a device if we ourselves are continuing to use it clinically and have found it effective, well made and to deliver value.

David Rindge and Healing Light Seminars have been practicing with and teaching energy-based therapies every year since 2002, continually updating treatment methods and equipment as new technology and information have become available.

Our goal over this seminar weekend is to provide you with everything you need to come from knowledge and strength with laser, light emitting diode and pulsed electromagnetic field therapies in your practice!

Day 1 focuses on theory, biological effects and essentials for treatment success.   You will have the opportunity for hands-on practice with state-of-the-art laser, laser needle acupuncture, light emitting diode and pulsed electromagnetic field therapy systems for the treatment of pain, head to toe.

In Day 2, you will learn how lasers, light emitting diodes and pulsed electromagnetic field therapy devices may be applied successfully in aesthetics / dermatology, cardiovascular disease, digestive, ear and eye disorders, gynecology, for hair regrowth, neuropathy, osteoporosis, respiratory disorders, sports medicine and much more.

Gain a solid understanding of the principles, technology and parameters of laser, laser needle, light emitting diode and pulsed electromagnetic therapies and the skills to apply them successfully in your practice!  NCCAOM 322-5, seven hours each day, Saturday and Sunday.  Learn More and Register Here

Course Date / Location

November 4-5, 2017.  SpringHill Suites Orlando Airport.  5828 Hazeltine National DriveOrlando, FL 32822. (407) 816-5533.

LEARN MORE AND REGISTER HERE

Or call 321-751-7001.

Healing Light Seminars

Training in Energy-based Therapies since 2002

14 PDAs – NCCAOM 322-5

14 CEUs Florida Acupuncturists

NCCAOM emblem

Celluma Testimonials

Acne

”Every acne patient we have treated has seen results with the first Celluma acne treatment and signed up for a package, or bought the Celluma to use at home. I have seen other blue light treatments, but nothing has given results like this with the first treatment. Here is what one patient with chronic cystic acne for years emailed, “I loved the light! I love how my skin feels/looks. The redness has subsided a bit and my skin (where it’s clear) feels so smooth.” Dietary changes certainly help but take time and it is sometimes hard to get patient compliance, especially with teenagers. The Celluma offers a way for the patient to see real results immediately, and these patients refer others.” – Dr. Anne Dunev, Burbank, CA.

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“My name is Jordan Watkins and I am a 17 year old student currently attending Laguna Beach High School. I play volleyball for the school and have practice every day during the week and sometimes even on the weekends. Although icing my joints and knees helps after practices, there is nothing better then what Celluma does. Celluma helps rid any pains I get in my knees or anywhere else after practices, games, tournaments, etc. Not only do I use Celluma for my joints, but also for my face. As a 17 year old boy who is constantly sweating from practice, I do get acne. Once I began to use Celluma every night on my face, I could see immediate results the next morning. The product has changed not only my appearance, but also my life.” – Jordan W, Laguna Beach, CA.

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”Adult acne haunted me for three years; I tried every product on the market. Often I had temporary success with expensive topical treatments, but nothing lasted. Using the Celluma daily healed my skin. After two weeks my cystic acne that spread across my face had diminished dramatically, eliminating deep painful blemishes. After six weeks I did not have inflamed acne blemishes. I have had clear skin for a year now; Celluma gave me my life back!” – Carley – New York, NY.

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“I had the chance to do a trial with the Celluma, and it worked so well for us, I am buying two– one for home, and one for my daughter with severe acne who goes to school out of state (she was home during our trial period, so we tried it on her). My husband used it on a sore knee and insists it feels better; he also used it on some scars on his arm along with CherlyLee MD TrueLipids Cream (chronic ones that just recently began healing up, not old ones he had had since he was little), and the scars have gotten much better. Not sure if it was the lights or the TrueLipids, but the scars do look better. My mom also tried the Celluma on her hands and shoulders for very bad arthritis and she feels like it really made a difference. My daughter has been on oral medication for severe, scarring acne for a good ten years, and finally decided she didn’t want to keep putting that in to her body. She was only able to try the Celluma a couple of times, but when she did, her face was noticeably better the next day. I really think that if she uses it regularly, it will make a huge difference for her, and it will be easier than getting her to the derm every other week for treatment. I am excited to get these and start using them and see what they can do”. – Mickey J. UT.

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“I use the Celluma for my face to clear acne. It sure is convenient to spend thirty minutes under a light instead of spending thirty minutes having your face poked at with a needle and then drenched in chemicals.” – Willie, Orange, CA.

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“Hi, I wanted to let you know that my husband and I are personally OBSESSED with the Celluma, it has helped our pain and my acne so much that we cannot believe it!!!!!” – Tari Dominy Sicairos de Vomaske. Owner, Allure Skincare & Lash, Denver, CO.

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Anti-Aging

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“I couldn’t be more pleased with the results from my Celluma, personally and professionally. It’s an amazing enhancement for all of our facial protocols from anti-aging to acne prevention.

Additionally, your tech support in assisting with questions as they arise has been an incredible asset. Though I felt I was well trained and well versed on LED previously; owning a Celluma and having the benefit of Biophotas staff to call upon, as needed, has been like a Masters Class in LED technology. I’m so grateful that every time I have a question, you and your staff are always so prompt with a reply. I’m honored and grateful for you and your time, knowledge and support. Your hard work and honest, straightforward approach is part of the beauty of what I love so much about your staff and company. It is how I approach my own life and business!

Celluma exceeds my expectations significantly. Lastly, I would like to provide some feedback on the packaging; this was one of the best examples I have ever seen in careful, mindful, strategic and safe shipping. I could not be more pleased.” – Nicholle Bertino, L.E. Benessere Skin Care, Santa Monica, CA

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“My aesthetic practice has found the Celluma panel very effective for anti-aging. We have incorporated the light therapy as part of our multi-modality care as pre and post treatment for facial rejuvenation surgery and in conjunction with our overall skin care management.” – Samuel Shatkin Jr., MD FACS Member of the American Society of Plastic Surgeons and American Society of Aesthetic Plastic Surgeons. Aesthetic Associate Centre Plastic Surgery & Advanced Medical Skincare. New York.

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“I have a clinical aesthetics practice, “Pampered Skin Studio”, in Tucson, AZ, within a physician’s office. The Celluma has been a great addition to my aesthetics repertoire and is the star ingredient of my “Anti-Aging Signature Facial”. I also encourage a series of six LED treatments for those clients who really want to see the long term benefits of LED. My acne clients are also seeing excellent results”.  –  Suzanne Pear, RN PhD CIC LE COE (registered nurse-  aesthetician specializing in corrective skin care).

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“I was a bit hesitant at investing in a Celluma, but I shouldn’t have hesitated; I couldn’t be happier. The results are fast and remarkable. My clients love it. I love it. On another note, the customer service is beyond amazing. They are quick to respond to questions and inquiries and beyond friendly! Thanks for transforming my business!” – Jenny Zarate Licensed Esthetician, Montara, CA.

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“I love my Celluma! I ordered my LED therapy panel after a severe injury left me bed-ridden for months. I’ve noticed an increase in my progress and pain management since using it. I’ve been using it on my face as well. It always puts me in the deepest, calmest trance”. – Jessie Ennis, Actor (Veep) & Director, Los Angeles, California.

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“I’ve been utilizing LED for years but the Celluma panel has made the treatment oh so much easier. You do need to have LED very close to tissue which is why the Celluma is a lifesaver. Love, love, love the ability to wash, scrub, extract, LED, treat, mask, etc, etc, and be done. The results are fantastic!” – Trecy Marr LE. Trinity Esthetics.

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“As an aesthetician for over twenty years, I’m always on the lookout for new technologies and new devices to use in my work. I purchased Celluma about two years ago and it has proved to be one of the best investments I’ve made in my business. My initial use of Celluma was for stubborn acne, but I have found that the blue LED is also extremely calming for skin after waxing. The device helps to create a relaxing spa atmosphere for clients and has proved helpful at home for aches, arthritis and overtaxed muscles. On top of all of that, the equipment is light and portable, so it is never cumbersome to use. I couldn’t be more pleased with my

purchase.”  – Urszula, Alexksandra’s European Skin Care – Commack, NY.

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“Your light, hands down, is the best esthetics product I have ever purchased!” – Sherri Lynn, L.E. Bartlesville – OK.

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“Shout out to Celluma! I have to try everything on myself to be a believer and before marketing it to my clients. I have not had a sustained luminous glow since winter in NJ started. Even with products, treatments etc. This happens to me every winter because of the cold outdoors and forced hot air indoors. I used my new Celluma panel twice this week and looking in the mirror…there it was – that healthy glow! :), and my moisture/oil balance seemed to be consistent for 24 hrs post use. Looking forward to the long term effects”. – Joy Papaioannou, RN/NCEA cert./Esthetician. Owner of Choose Joy Skin, Matawan of Monmouth County NJ.

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“My clients love the Celluma! And so do I! The results I have seen in my acne clients is

 amazing!” – Teresa, Owner – Natural Faces ~ Organic Skincare Treatments, Huntington, NY.

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“I had the chance to do a trial with the Celluma, and it worked so well for us, I am buying two– one for home, and one for my daughter with severe acne who goes to school out of state (she was home during our trial period, so we tried it on her). My husband used it on a sore knee and insists it feels better; he also used it on some scars on his arm along with Cheryl Lee M.D. TrueLipids Cream (chronic ones that just recently began healing up, not old ones he had had since he was little), and the scars have gotten much better. Not sure if it was the lights or the TrueLipids, but the scars do look better. My mom also tried the Celluma on her hands and shoulders for very bad arthritis and she feels like it really made a difference. My daughter has been on oral medication for severe, scarring acne for a good ten years, and finally decided she didn’t want to keep putting that in to her body. She was only able to try the Celluma a couple of times, but when she did, her face was noticeably better the next day. I really think that if she uses it regularly, it will make a huge difference for her, and it will be easier than getting her to the derm every other week for treatment. I am excited to get these and start using them and see what they can do”. – Mickey J. UT.

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“I purchased Celluma for a number of reasons. First, the affordability, then the versatility. I love how all the light spectrums run in the background on all the applications. I plan on using it mainly for my skin care practice that is largely directed toward oncology clients. I knew I wanted Celluma before I attended the Ft. Lauderdale IECSC show. The bonus that I got, was a company that is super supportive and truly values the relationship and success of the professionals with whom they associate. A company like yours, who is so willing to help make their partners successful and the clients who benefit from the treatments, is hard to come by. In an environment where corporations are acquiring multiple skin care companies, and big business has compromised relationships, it is refreshing to know that BioPhotas is committed to the success of the aesthetic professional. I know Celluma is going to be a huge part of my practice!” – Bea Erdman, Remedies Clinical Skin Care Mgmt LLC, Tampa, FL.

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“This is the best beauty and therapy product I have ever experienced. My Celluma is 3 years old and I use it four times a week for beauty, aches, back problems and pain relief” – Sally P. – NY, NY.

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“I love my Celluma! It paid for itself in a week! At my spa, we charge $2 per minute under the light with a minimum of 10 minutes. We also sell packages that are discounted the more they buy. With our spa specializing in acne treatments, the Celluma was the perfect addition to our menu. We are able to achieve quicker results and amazing healing benefits. Client always ask “when can we do the light again” because they love it so much!” – Miranda Jeremiah Alder. Owner/Aesthetician at Bliss Spa and Beauty Lounge, Clovis, New Mexico.

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“I LOVE my Celluma! Such amazing and quick results when I use it during my facials!” – Andrea Minor, L.E. Henderson, NV.

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“Since incorporating Celluma into my cosmetic surgery practice, my patients have enjoyed significant reduction in inflammation and bruising as a result of using the Celluma post operatively. Personally, I use it regularly, and swear by it, for pain relief for an old back injury”.

–      Dr. Jesse Mitchell, M.D., Board Certified Dermatologist, Diplomate, American Board of Cosmetic Surgery.

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“Would love to share something super nice!!! I have a friend who was my teacher in aesthetic beauty school. This past February she had surgery on the back of her right heel and the stitches were not done correctly and flush to the heel…looked bumpy and uneven and even after showing her surgeon how bad it had looked – and she was in constant pain – and the color of the area was blue and purple, his response was everything has been done as your last surgery and I don’t understand why you are still in pain!! Well fast forward, this month (July), I got her to come twice a week and put her heel under Celluma Aches & Pains setting. After her 3rd visit her co-workers mentioned she was walking normal and the color of her skin had evened out and the scar tissue was getting a much smoothened appearance and the swelling was much diminished and pain was also much lessened. When she used to get home from work, she would always have to elevate her legs and ice and take pain killers…..NOT ANY MORE!! Could not wait to report this exciting news! Celluma has saved me also in the last 2 weeks when I had a pinched nerve in my neck and a pulled muscle in my right front rib!! LONG LIVE CELLUMA!!!”

–   Sunita Aggarwal, Owner & Licensed Esthetician, Threading By Sunita, Hyannis, MA.

 

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“I think the selling point for a business owner is once you buy it (Celluma), there are no further costs to you! No products necessary, nothing. 100% profit, every single dollar. That’s way more profitable than any product or machine that uses product. Technology is a game-changer that way. Plus visible, palpable results, which drives sales.” – Lindsey Flint, LE & Owner – Sweet Cheeks Skincare of San Francisco.

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“Hi, I wanted to let you know that my husband and I are personally OBSESSED with the Celluma, it has helped our pain and my acne so much that we cannot believe it!!!!!” – Tari Dominy Sicairos de Vomaske. Owner, Allure Skincare & Lash, Denver, CO.

 

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“I received my CELLUMA yesterday!!! It’s nothing short of a miracle!! I was my own first “guinea pig” and today I gave a complimentary service for my long standing good client after I did derma planning also for the first time for her…and, DRUM ROLL PLEASEEEEE…it blew her socks off…to see a 62 year-old fairly good skin look bouncy like a baby’s bum…if I may expand…she had red spots that went away, dark circles looked diminished. I used it on absolutely bare skin after cleaning and DermPlanning. HER SKIN WAS RADIANT like she was in the spot light!! Thanks is an understatement!” – Sunita, Board Certified Aesthetician, Beauty Pros Day Spa, Hyannis, MA.

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“I freakin’ love my Celluma and so do my clients. I just introduced it and it’s paid for already! I sent out a newsletter on Thurs last week to introduce it and offered an introductory special of a single treatment for $65 (reg. $75) and a series of 6 for $330 (reg. $65) only good for the month of February. Sold 4 pkg’s, a single treatment and an add-on for $35 so far” – Kellie Spiak Campbell Bacchus LE – Advanced Skin Treatments, Skin Care & Acne Clinic, NY.

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“I specialize in the treatment of acne and I ALWAYS end each treatment with 15 minutes under the Celluma panel. It helps speed healing as well as helping to reduce inflammation after extractions. It has also been indispensable in the clearing of post in-inflammatory hyperpigmentation on the face and body”. – Cyndi Jarvis, LE/Owner at Saving Faces, Concord, NH.

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“I have used my Celluma twice each day since it arrived. I love using it on my feet as they are always a little sore. I am sure it is arthritis. In addition, it is great on my face. The texture is improving already”. – Sally, OC, CA.

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“I love my Celluma – Bella Forza NYC has been so busy since I started using it! It paid itself off in such a short time and my clients come in just for this service!  Thanks!!” – Bella Forza NYC, 1036 Park Ave Suite 1B, New York, New York.

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“I’ve had chronic neck pain for 15 years since someone, carrying me over their shoulder, slipped on ice and dropped me on my head. The result was 3 bulging discs. I used to use pain patches every night. Then, I got my Celluma and after only two treatments the patches were gone!” – Shari Oberst L.E. Skin & Body Works, Racine WI.

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“I LOVE Celluma! One of my favorite necessities to my treatment room! I have been a licensed Esthetician for 9 years and have no idea how I lived without this before! I have clients with acne and Celluma helped rid and smooth out the texture. Clients with aging skin, their skin starts looking firmer & tighter. Many clients call this my “magic light,” because to them it really is magic! I could go on and on about the stories and positive results with this device, but that would be too much to read. Lastly, you can have a good product, but the customer service and

 

support is on par as well (which can be hard to find), every time I call in to ask a question, everyone is so helpful & friendly. I would highly recommend trying a treatment with Celluma or buying the device”. – Elyse Helene L.E. Love Skin Nashville, Nashville, TN.

Pain

“In the eight months that I’ve been using the Celluma my life has become more enjoyable. My combat injuries, pain, discomforts and surgeries that I’ve been dealing with over the years have become more manageable. I’ve also been able to postpone additional surgeries, because along with other treatments, the Celluma has stimulated a comfortable healing process that has assisted me to live a more painless life. Thank you again for introducing me to the Celluma Pad. Strength and Honor.”  – S. Sgt. Jim Gularte, Vietnam Sniper, USMC (retired).

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“I love my Celluma! I ordered my LED therapy panel after a severe injury left me bed-ridden for months. I’ve noticed an increase in my progress and pain management since using it. I’ve been using it on my face as well. It always puts me in the deepest, calmest trance”. – Jessie Ennis, Actor (Veep) & Director, Los Angeles, California.

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“I had the chance to do a trial with the Celluma, and it worked so well for us, I am buying two– one for home, and one for my daughter with severe acne who goes to school out of state (she was home during our trial period, so we tried it on her). My husband used it on a sore knee and insists it feels better; he also used it on some scars on his arm along with CherlyLee MD TrueLipids Cream (chronic ones that just recently began healing up, not old ones he had had since he was little), and the scars have gotten much better. Not sure if it was the lights or the TrueLipids, but the scars do look better. My mom also tried the Celluma on her hands and shoulders for very bad arthritis and she feels like it really made a difference. My daughter has been on oral medication for severe, scarring acne for a good ten years, and finally decided she didn’t want to keep putting that in to her body. She was only able to try the Celluma a couple of times, but when she did, her face was noticeably better the next day. I really think that if she uses it regularly, it will make a huge difference for her, and it will be easier than getting her to the derm every other week for treatment. I am excited to get these and start using them and see what they can do”. – Mickey J. UT

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“I love the Cellumas! They work so amazing! “ – Dr. Jennifer Meng, D.C. Grafton, OH Case History 1  (Dr. Meng)

A 48 year old female had hip dysplasia at birth. Her shoulders were also slightly malformed. At 48 she experienced the right shoulder freezing up with almost no motion. This was the second time she experienced this with the right shoulder. She saw multiple caregivers, MDs, DCs, PTs, Massotherapists, etc without any relief. She was totally restricted in ADLs and the pain was so severe that her sleep was disrupted several times a night.  After using the Celluma for one

week, her PT said that he was able to get increased ROM for the first time. After 2 weeks, the pain was greatly diminished and no longer interrupted her sleep. She continued to improve and it has now been almost 5 months and she has almost full ROM and no pain. She uses the Celluma on it now only occasionally.

Case History 2 (Dr. Meng)

A 19 Year old female was injured in a farming accident. A disc pulled by a tractor ran over her foot while she was on an ATV. She had Crocs on her feet. The bottom of her foot was torn up by the saw toothed edge of the foot rests. There was also a deep cut on the top. X-Rays were negative for a fracture. The foot was dressed with Lavender essential oil and a Spenco burn dressing. 1-2 times a day the Celluma was used.  After only 5 days the young woman could walk barefoot on the foot and the second picture shows it 2 weeks after the injury. The cut on the top of the foot was deep. There was so much swelling initially that she could not bend the ankle or the foot. There was also a lot of bruising on the top of the foot. The bruising all cleared up within 48 hours using the Celluma. The edema also diminished significantly, although it was a little slower as she was up and using the foot so soon. – Dr. Jennifer Meng,

D.C. Grafton, OH.

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“In 2006, I was combat wounded with over 100 pieces of shrapnel all over my body.  Today I deal with soft tissue, bone, and neurological related pain and discomfort all of the time. As a Navy Corpsman I understand, and have seen the results of, long-term medical drug use and I personally go out of my way to avoid taking any myself. I have used the Celluma now for about 8 months, and I Iike that it can be used as needed, with results that are equal to, or better, than taking a pain management drug. The Celluma also manages breakouts similar to acne, which develop on the back of my neck. With one use, it is often 50-90% better by the next day. The Celluma puts my mind at ease (with regard to pain management and acne breakouts) that I am not going to have to take a pill or use ointments for the rest of my life”. – Aaron Q Seibert HMC(FMF/AW) USN (ret). (Purple Heart 2006) Wounded Warrior Liaison.

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“I’d like to tell you about this product that I have been testing out, it’s called Celluma, from BioPhotas, Inc. I am not a Doctor and this is not a sales ad, just my experience and others who have told me about their experience with this device.

Parker Jones (member of the Jones motocross racing family) while working with an end mill – tore his tendon and had nerve damage, Parker used this Celluma pad on his hand and reported “it’s crazy, but that it works!” It definitely worked and helped him recover.

Dave Carlson (5 times world Mini Champion) had his palm ripped to the bone while using a grinder, in 4 weeks he was able to use his hand again while using Celluma pad every day for a ½ hour. His daughter had a C section while giving birth, she used the Celluma on her scar, she now has no scar.

As for myself; my back has been killing me, I have been using the Celluma every night. Now I can get out of bed without pain in the morning and am able to get work done again. I also had some knee tissue damage, and since using the Celluma it’s now almost completely gone. Again this is my own experience and others that have shared their experiences with me, the best part is; it is 100% made in the USA. I LIKE IT. If the rate card has 10 score as the best, then I give it a 10!!” – Marty Tripes, San Diego, California. Mr. Tripes was a leading AMA motocross and Supercross rider of the 1970s and early 1980s. He is remembered for winning the Super Bowl of Motocross at the Los Angeles Coliseum in July 1972, just a few weeks after turning 16. That race was considered the first true stadium Supercross race in America. Tripes also won the first FIM 250cc United States Motocross Grand Prix at Unadilla, New York in 1978. He was described as one of the most naturally talented motocross riders in history. His win at the Super Bowl of Motocross against some of the best riders in the world when he was only 16 years old launched his career. He won a total of 11 National Championship races during his career. Tripes was inducted into the AMA Motorcycle Hall of Fame in 2001.

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“I have been in the Marine Corps, Military Police for 15 years, most of that time on the SWAT team or deployed. I have had chronic lower back pain that started from when I attended Jump School in 2001. Throughout my career Navy Medicine was tried to help me with pain but nothing has helped, until about a month ago, when Steven Lubich started letting me use the Celluma device that he owns. I have only used it for about a month and the results are amazing. After the first 30-minute session my lower back felt like it hasn’t in years. I noticed I wasn’t experiencing the tightness nor pain I always feel after exercising or performing my duties on my job. I highly recommend that Navy Medicine uses this device and especially with the wounded warriors. I will still continue to use the Celluma on a day to day basis”. – SSgt Corral, Nicholas S.

2/3rd Plt Sgt

Law Enforcement Liaison Alpha Company

Wounded Warrior Battalion West

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“My husband has used the Celluma for three days in a row on multiple body parts and he is happy to report that the unrelenting heel pain is decreasing. Happy Day!!! The left wrist gets used and abused quite a bit, but he has more hope now that his guitar playing days won’t be over and he will be able to continue to make art with his hands. Update: when my husband got out of bed this morning, his heel pain wasn’t there…for the first time in, well, we can’t remember how long…. with only 8 consecutive days of using the Celluma!! Thank you so very much!” – Dr Beth Kiser, Family Wellness Chiropractic Center, 1875 North Ridge Road, Suite A, Lorain Ohio 44055.

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“In the winter of 2008, I was in a horrible MRAP accident in Iraq, that is when my life started spiraling down a long painful road. I didn’t know it at the time, but came to find out that I had herniated my L4 and L5 discs, which caused me to have nerve damage in my spine. My knees are shot from the constant running I used to do, and all the training I had done and been through. At one point, I was slated to go to Marine Special Operations Battalion and do what I do best. But due to tearing my labrum in my shoulder during training for that position, I had to give it up. But with every door that closes a new one opens… I earned a job working with General Mills as a Personal Security Officer in Afghanistan for 13 months so I pushed out on that but was in pain day-in and day-out. But it wasn’t going to stop me from doing what I loved. When I returned in the beginning of 2011 my body was done. I tried to take time to get my body back but was sent off on Recruiting Duty. I did as I was told, and while on Recruiting Duty I tried to get my body back in-shape but just couldn’t make it happen. After four years of unsuccessful treatment, I was sent to the Wounded Warrior Battalion to heal up and hopefully get back in the fight. Unfortunately, after numerous procedures and operations I was unable to get back to fighting mode and was retired from the Corps on Jan 30, 2014. On Jan 10, I was afforded the opportunity to use the Celluma device and have never looked back! I can honestly say that due to that AWESOME piece of gear I have made a tremendous turn around in my life. Since using the device 30 mins-a-day every day, I have been able to go to work full-time selling cars and being on my feet for 12 hours a day. I could only honestly stand for about 45 minutes to an hour before I got the Celluma device. I have been able to play with my two year old son non-stop with no pain and be the dad I should be. I have started going back to the gym and have lost 12 pounds since being on the Celluma device. On top of all that, I have done the one thing that I haven’t been able to do in years – which is RUN. I am up to a mile and a half without stopping and it is all because of the Celluma device. I wish that the corps and navy medicine would have adopted this when it first came out so I could still be a Marines Marine. But things are for the better now and I am HAPPY.

I hope that this gives an understanding as to how the Celluma has helped change my life. I will never give up on anything and the Celluma has given me the chance to do anything!!! THANK YOU BioPhotas, I am forever in your debt and if you ever need anything from me I will be there for you as you were for me”. –  Sgt. Steven Lubich,  Semper Fidelis, San Diego, CA.

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“I used the Celluma during my recovery from a total shoulder replacement. After one year, I have recovered a greater than expected range of motion, AND, the surgery scar has virtually disappeared where the Celluma was directly applied”. – Jeff R. Huntington Beach, CA.

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“My name is Jordan Watkins and I am a 17 year old student currently attending Laguna Beach High School. I play volleyball for the school and have practice every day during the week and sometimes even on the weekends. Although icing my joints and knees helps after practices, there is nothing better then what Celluma does. Celluma helps rid any pains I get in my knees or anywhere else after practices, games, tournaments, etc. Not only do I use Celluma for my joints, but also for my face. As a 17 year old boy who is constantly sweating from practice, I do get acne. Once I began to use Celluma every night on my face, I could see immediate results the next morning. The product has changed not only my appearance, but also my life.” – Jordan W, Laguna Beach, CA.

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“I am so impressed with the results from just two times I used Celluma. I used it the same day for 30mins each time back to back! I had been experiencing mild low back left side pain for weeks as a result of 2-4 hours of daily driving I do, but I am happy to say that it’s now been 5 days and the pain is gone! I tried other devices such as PEMF and Ionic Therapy the week prior to trying Celluma and the pain went away for a couple hours after the use of each device only to return later the same day… I am looking forward to continue to explore the benefits Celluma on my body. Thank you Celluma!” – Alfredo M, Dana Point, CA.

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“I badly sprained by right ankle on Wednesday. I stepped off a step wrong and hit the step below with the outside of my right foot and as I started to fall I heard a loud pop at my ankle. I did not hit the ground but my ankle sure did hurt. I could hardly bear weight on it. I sat on the step for a few minutes then went in the house. I used the Celluma on it about a 30 minutes later. Then I used it again right away. I slept for about 30 minutes, then used it again for another two cycles–2 hours total. The next morning I had no swelling or bruising. By the end of the day I could bear full weight on it. Yesterday and today are gradually improving and tomorrow I plan to pack up Christmas in a 17 foot U-Haul and take it all to storage with my 2 boys. Unbelievable!” – M. Allen DC, NMD, Orange County, CA.

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“I have been involved in Masters Weight Lifting and have found the Celluma most helpful to shorten my recovery times between weight lifting sessions. During my work out 2 months ago, I blew my rotator cuff in the right shoulder, requiring a surgical repair. I continued my Celluma usage both before and after the surgery. I was instructed not to exercise for several weeks after the surgery and then start physical therapy. The results I experienced were truly amazing. You could tell by the doctor’s facial expression that he did not understand what was going on. Not usually what you want to see from your surgeon! It was the same with the physical therapist…I kept asking for more exercise and resistance – and they kept looking at me with a bewildered stare. While I am not back to my original strength levels yet, I am months ahead of what they thought was possible. After only six weeks I have full range of motion with no pain, and my strength is building daily. I am thrilled with the results and credit much of my accelerated recovery rate to my Celluma”. Mike – Newport Beach, CA.

 

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“Here’s how the Celluma helped out “Brownie”, a female pit bull. “Brownie” has had 3 separate surgeries on her hind knees for torn muscles. After the third surgery, “Brownie” was healing much slower than the previous two surgeries and she had a lot of pain and stiffness in her knees. We started using the Celluma on her knees on all 3 settings every week. Even after just one treatment, we noticed a huge improvement in her mobility and she was not in as much pain. Her wounds and scars healed much quicker after using the Celluma using the “Anti-Aging” setting. She also had an infection in one of the surgery sites and when we used the Celluma on the “Acne” setting it helped to clear up the infection much quicker. Brownie was not as stiff after using the Celluma on the “Aches and Pains” setting. Using the Celluma on “Brownie” has made a dramatic improvement in her recovery after having multiple knee surgeries.” – Debra Olson-Warford, DC, Certified Animal Chiropractor, Lancaster, CA.

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The Celluma has been a valuable addition to my practice. It’s simplicity of use requires minimal attention from my assistants and my patients can be in complete control of the process. We have all been impressed with how a variety of conditions respond favorably to treatment with the Celluma. Several people have used it for pain control. Their first experience is the comfortable warmth that seems to penetrate to the core of their pain.  A few other people have experienced benefit with their complexion. One 19 year old girl said she felt an immediate toning of her skin that was refreshing. And a 17 year old boy used it on his legs for a follicular dermatitis issue and it cleared up after a short time.Dr. Michael Allen, Functional Neurologist & Chiropractor, Health Builders, Laguna Hills, CA.

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“Since incorporating Celluma into my cosmetic surgery practice, my patients have enjoyed significant reduction in inflammation and bruising as a result of using the Celluma post operatively. Personally, I use it regularly, and swear by it, for pain relief for an old back injury”.

– Dr. Jesse Mitchell, M.D., Board Certified Dermatologist, Diplomate, American Board of Cosmetic Surgery.

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I fell on my right knee a year ago and it was BAD! I used the Celluma on it for 2 days and it was like new after that. My father was here and could NOT believe the difference in my knee, Celluma literally made the knee look 100% in 2 days and fully functioning in a week.

Over the course of the next 4 months, I fell two more times on the same knee.  In the meantime, I gave my Celluma to my daughter to use on her acne.  My knee was so bad that I was forced to stop hiking (one of my falls was during a hike), playing golf, and working out. My hip was being thrown out because of my knee, and I couldn’t wear heels. I got my new Celluma in September and went right to work on my skin and my hand (Arthritis), but for some reason, didn’t think to put it on my knee. I was complaining to my Dad and he made a comment about the Celluma not working this time…then I realized wasn’t using it on my knee and I should be!

So, I used the Celluma every day for 3 straight weeks on my knee and I am amazed at the healing that has occurred. I am back with my personal trainer, I am hiking AND, can now wear heels again!  All that in 3 weeks!  I thought I was doomed to wear flats forever!

 

As a recipient of it’s wonderful healing, thank you for all you do to promote the Celluma! – Shelley, Anaheim, CA.

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“Turns out I had an upper thorasic release, last week, that had a dramatic affect and I am 90% improved. The Celluma helped me win sleep time when nothing else would touch my exhausting shoulder and back pain from the inflammation in my spine and limb joints”. – David, Tustin, CA.

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“I have used my Celluma twice each day since it arrived. I love using it on my feet as they are always a little sore. I am sure it is arthritis. In addition, it is great on my face. The texture is improving already”. – Sally, Orange County, CA.

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“I have been using the Celluma for three weeks on a regular basis, on both upper arms and shoulders. The results have been amazing. I compete in weight lifting, where I am constantly stressing the joints, tendons and muscles. I have been accepting the pain and soreness as just something I would have to accept. No more, since using the device the discomfort is much more manageable and shorter in duration. It seems that my recovery times have decreased at the same time. Thank you, I really appreciate your recommendation regarding Celluma.” – Mike, Newport Beach, CA.

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“I had major shoulder surgery in April and was not allowed any mobility for six weeks. I did however use the Celluma on a regular basis. I was allowed to start limited PT in early June (it has become my second home). I was finally allowed more aggressive PT in August. I had 8 session in Steamboat and when we left (August 25) my range of motion was 40 degrees. We took a two week driving trip when I did not have PT but used the Celluma almost daily. Upon returning to PT here in OC, my range of motion was 57 degrees! I did my exercises but I was doing them all along.  The therapist here was truly impressed and the only thing I can really

 

credit the extended range of motion during my PT hiatus is the light therapy! You better believe I am using it as often as possible! Thrilled beyond words! Thank you!!” Heidi, NY.

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“My wife reports that her knee is “so happy” while sitting under the Celluma. She was able to do “Pigeon Pose” in Yoga for the first time in months following 2 weeks of using the Celluma and I was able to sleep better last night after using it. We are loving our Celluma!” – Jeff, Orange County, CA.

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“I have recently begun to use Celluma on my knee which has given me problems on and off for years. I immediately noticed a marked difference in my comfort level doing everyday things and working out. I believe the use of Celluma has begun a healing process and has delivered remarkable pain reduction, increased range of motion and ability to perform weight bearing exercise”.  – Patti, OC, California.

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“I am an 89 year-old woman and suffer from chronic arthritis. I had the opportunity to try the Celluma by BioPhotas, and I was astounded by the relief I received! After one 30-minute session on my shoulder, I had full and pain-fee range of motion. I then tried a session on my very arthritic and painful hands. I awakened the next morning with full range of motion of all ten fingers, which was a first-time experience in many years.” – Meredith, Long Beach, CA.

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“I used the device last night on my knee that’s been bothering me for a couple of weeks and it really worked extremely well. Took down the swelling and pain and my knee felt fine this morning—-after only one use!” – Mike, Cowan Heights, CA.

 

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“I have been using my Celluma every day since I picked it up. I love it! It’s Perfect! I find the best way to use it on my lower Thoracic area is lying face down in my face cradle on my massage table. Today I used it on my lower back sitting in my chair working on the

computer.  Works great! My back is doing so much better”.   – Sharon, Costa Mesa, CA.

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“I am having so good results with my Celluma. I have 3 gals using it every day and they are all seeing results for different issues. I am happy with the results for myself as well and even tho it is not FDA approved for cellulite, at least in my case, I am seeing fairly dramatic results. I use it 4-5 times a week and in 4 weeks time I can visually see a big difference.  This is speaking volumes to all the ladies that have been watching me.” – Shelley, Anaheim, CA.

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“Following bi-lateral facial surgery, I decided to use the Celluma on one side of my face only. My plastic surgeon suggested the right side as it was visibly more swollen and angry.  Ten weeks post surgery, my right ear has healed much faster and is now completely healed. My left ear, without the use of Celluma, is still very bruised and swollen”. – P. E, Laguna Beach, CA.

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While playing rugby for 25 years I experienced several injuries and developed painful herniations between C5, C6 and C7.  In an effort to get comfortable, I routinely slept on the same side every night. As a result, I also developed bursitis in one shoulder. To relieve the depilating neck pain and 90% loss of strength in one arm I recently underwent discectomy and spinal fusion surgery.  It was around this time I was introduced to the Celluma and began using it to relieve the pain and inflammation caused by the bursitis. It worked well, and I experienced considerable relief after using it for about 10 days . I also used it following my neck surgery to assist with tissue repair. At my 2 week post-surgery follow-up, the nurse who was removing the 20 stapled sutures exclaimed “This thing is completely healed! I’ve never seen this before!”

–     Kevin, Senior Medical Device Executive, OC, CA.

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The Celluma was a huge help when I really needed one. I recently had my wrist fused following 35+ years of chronic pain and I was not prepared for the amount of trauma involved in the procedure. I began using the Celluma and began feeling relief the next day. My doctor commented on how nicely the fusion was coming along and said that I must have exceptional blood supply to my wrist. While observing my x-ray during subsequent visits, he mentioned several times that this was the result they strive to achieve with this procedure. How much can is attributable to the Celluma use and how much to my doing absolutely nothing is hard to say, but I highly recommend the Celluma and am a big fan.

I can also state that the five inch scar on my right wrist has healed nicer than any surgery I’ve ever had…and I’ve had a few. – Steve Bauer,  Motor Sports Journalist.

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“I am very impressed with the Celluma. A few weeks ago I drove from California to Rochester, NY to take a car to my daughter. By the time I finished, my right knee was in great pain and I could hardly walk. Unfortunately, I did not come straight back, and I lived on Advil and a heating pad for a few days, which did not do much. When I got back to LA, I tried the Celluma on my knee. After one treatment, it felt 80% better. I waited two days and then did another treatment and the pain is basically gone!” – Jim, Los Angeles, CA.

 

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”I was struggling with a lot of major pain in both my neck and down my back. I had a back massage earlier, but after 24 hours it still hurt. I had no relief. I could not move or turn. My friend mentioned she had a similar problem and used her Celluma continuously 3 times in a row and it was solved. She said, you should try it tonight when you get home. I used it twice wrapping it around the back of my shoulder and neck. It was perfect, I had not one pain no matter how I turned. You have one great product there, I am so grateful. Thank you for my Celluma!” – Sally, New York.

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“After taking multiple amounts of Advil for my shoulder pain, my son asked me why I wasn’t using Celluma. Duh….needless to say, I used it the entire weekend and I can now sit down and type without the pain I felt last week. I had used it only for my face until last Saturday. It really worked well. This morning I’m able to get total mobility back in my right arm and shoulder.

Hooray!” – Emily, Laguna Beach, CA.

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“I woke up this morning with excruciating lower back pain. The last couple of days, my back has been hurting, I wasn’t at home and didn’t have my Celluma with me, so when I got home late last night, I got in my massage chair to try to get it adjusted. It worked I guess, but overnight while I was sleeping, my back got really stiff and hurt to the point where I couldn’t hardly walk this morning. At lunch, I laid on my stomach with the Celluma in Aches & Pains mode across my lower back. After that, it loosened up quite a bit. Then I did it again while I was sitting upright in a chair, and my back is back to 90% of normal. Amazing results with the Aches & Pains program!”  – Mike Abbey, Spa Owner. Broken Arrow, OK.

 

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“I am a Doctor of Chiropractic who has lots of physical pain; fibromyalgia, severe arthritis in my hands and a degenerated right hip. I also cannot take NSAIDs due to a history of a bleeding ulcer. So many nights my leg pain makes it impossible to sleep. When I use the Celluma on my hip and right leg, it lessens the pain and allows me to fall asleep. Without the Celluma I wouldn’t be able to get the rest I need and perform I work I do”. – N. Rowan Richards. D.C. Monrovia, CA.

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“This is the best beauty and therapy product I have ever experienced. My Celluma is 3 years old and I use it four times a week for beauty, aches, back problems and pain relief” – Sally P. – NY, NY.

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Breast Cancer

Lasers Med Sci. 2016 Dec;31(9):1775-1782. Epub 2016 Aug 12.

The effects of low-level laser irradiation on breast tumor in mice and the expression of Let-7a, miR-155, miR-21, miR125, and miR376b.

Khori V1, Alizadeh AM2, Gheisary Z3, Farsinejad S3, Najafi F4, Khalighfard S3, Ghafari F3, Hadji M3, Khodayari H3.

Author information

  • 1Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
  • 2Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran, Zip Code: 1419733141. aalizadeh@sina.tums.ac.ir.
  • 3Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran, Zip Code: 1419733141.
  • 4Medical Engineering, Faculty of Biomedical Engineering, Amir Kabir University, Tehran, Iran.

Abstract

Low-level laser therapy (LLLT) is a form of photon therapy which can be a non-invasive therapeutic procedure in cancer therapy using low-intensity light in the range of 450-800 nm. One of the main functional features of laser therapy is the photobiostimulation effects of low-level lasers on various biological systems including altering DNA synthesis and modifying gene expression, and stopping cellular proliferation. This study investigated the effects of LLLT on mice mammary tumor and the expression of Let-7a, miR155, miR21, miR125, and miR376b in the plasma and tumor samples. Sixteen mice were equally divided into four groups including control, and blue, green, and red lasers at wavelengths of 405, 532, and 632 nm, respectively. Weber Medical Applied Laser irradiation was carried out with a low power of 1-3 mW and a series of 10 treatments at three times a week after tumor establishment. Tumor volume was weekly measured by a digital vernier caliper, and qRT-PCR assays were performed to accomplish the study. Depending on the number of groups and the p value of the Kolmogorov-Smirnov test of normality, a t test, a one-way ANOVA, or a non-parametric test was used for data analyses, and p?<?0.05 was considered to be statistically significant. The average tumor volume was significantly less in the treated blue group than the control group on at days 21, 28, and 35 after cancerous cell injection. Our data also showed an increase of Let-7a and miR125a expression and a decrease of miR155, miR21, and miR376b expression after LLLT with the blue laser both the plasma and tumor samples compared to other groups. It seems that the non-invasive nature of laser bio-stimulation can make LLLT an attractive alternative therapeutic tool.

Lasers Med Sci. 2016 Aug 19. [Epub ahead of print]

The use of low-level light therapy in supportive care for patients with breast cancer: review of the literature.

Robijns J1,2, Censabella S3, Bulens P4,3, Maes A4,3, Mebis J5,4,3.

Author information

  • 1Faculty of Medicine & Life Sciences, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium. jolien.robijns@uhasselt.be.
  • 2Limburg Oncology Center, Stadsomvaart 11, 3500 Hasselt, Belgium. jolien.robijns@uhasselt.be.
  • 3Division of Medical Oncology, Jessa Hospital, Campus Virga Jesse, Stadsomvaart 11, 3500 Hasselt, Belgium.
  • 4Limburg Oncology Center, Stadsomvaart 11, 3500 Hasselt, Belgium.
  • 5Faculty of Medicine & Life Sciences, Hasselt University, Martelarenlaan 42, 3500, Hasselt, Belgium.

Abstract

Breast cancer is the most common cancer in women worldwide, with an incidence of 1.7 million in 2012. Breast cancer and its treatments can bring along serious side effects such as fatigue, skin toxicity, lymphedema, pain, nausea, etc. These can substantially affect the patients’ quality of life. Therefore, supportive care for breast cancer patients is an essential mainstay in the treatment. Low-level light therapy (LLLT) also named photobiomodulation therapy (PBMT) has proven its efficiency in general medicine for already more than 40 years. It is a noninvasive treatment option used to stimulate wound healing and reduce inflammation, edema, and pain. LLLT is used in different medical settings ranging from dermatology, physiotherapy, and neurology to dentistry. Since the last twenty years, LLLT is becoming a new treatment modality in supportive care for breast cancer. For this review, all existing literature concerning the use of LLLT for breast cancer was used to provide evidence in the following domains: oral mucositis (OM), radiodermatitis (RD), lymphedema, chemotherapy-induced peripheral neuropathy (CIPN), and osteonecrosis of the jaw (ONJ). The findings of this review suggest that LLLT is a promising option for the management of breast cancer treatment-related side effects. However, it still remains important to define appropriate treatment and irradiation parameters for each condition in order to ensure the effectiveness of LLLT.

Antioxid Redox Signal. 2015 Sep 28. [Epub ahead of print]

Phototherapy-induced antitumor immunity: long-term tumor supression effects via photoinactivation of respiratory chain oxidase-triggered superoxide anion burst.

Lu C1,2, Zhou F3, Wu S4,5,6, Liu L7, Xing D8.
Author information
1Guangzhou, China.
2MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; lucx@scnu.edu.cn.
3MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; zhouff@scnu.edu.cn.
4South China Normal UniversityGuang Zhou, China , 510631.
5China.
6MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; wushn@scnu.edu.cn.
7MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; liulei@scnu.edu.cn.
8South China Normal University , No. 55 Zhongshan west road, Tianhe district , guangzhou, China , 510631 ; xingda@scnu.edu.cn.

Abstract
AIMS:
Our previous studies have demonstrated that as a mitochondria-targeting cancer phototherapy, high-fluence low-power laser irradiation (HF-LPLI) results in oxidative damage that induces tumor cell apoptosis. In this study, we focused on the immunological effects of HF-LPLI phototherapy and explored its antitumor immune regulatory mechanism.
RESULTS:
We found not only that HF-LPLI treatment induced tumor cell apoptosis but also that HF-LPLI-treated apoptotic tumor cells activated macrophages. Due to mitochondrial superoxide anion burst after HF-LPLI treatment, tumor cells displayed a high level of phosphatidylserine oxidation, which mediated the recognition and uptake by macrophages with the subsequent secretion of cytokines and generation of cytotoxic T lymphocytes. In addition, in vivo results showed that HF-LPLI treatment caused leukocyte infiltration into the tumor and efficaciously inhibited tumor growth in an EMT6 tumor model. These phenomena were absent in the respiration-deficient EMT6 tumor model, implying that the HF-LPLI-elicited immunological effects were dependent on the mitochondrial superoxide anion burst.
INNOVATION:
Here, for the first time, we show that HF-LPLI mediates tumor-killing effects via targeting photoinactivation respiratory chain oxidase to trigger a superoxide anion burst, leading to a high level of oxidatively modified moieties, which contributes to the phenotypic changes in macrophages and mediates the antitumor immune response.
CONCLUSION:
Our results suggest that HF-LPLI may be an effective cancer treatment modality that both eradicates the treated primary tumors and induces an antitumor immune response via photoinactivation of respiratory chain oxidase to trigger superoxide anion burst.
Discov Med. 2015 Apr;19(105):293-301.

Advances in strategies and methodologies in cancer immunotherapy.

Lam SS1, Zhou F2, Hode T1, Nordquist RE1, Alleruzzo L1, Raker J1, Chen WR3.

Author information

  • 1Immunophotonics Inc., 4320 Forest Park Ave. #303, St. Louis, MO 63108, USA.
  • 2Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, University of Central Oklahoma, Edmond, OK 73034, USA.
  • 3Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, University of Central Oklahoma, Edmond, OK 73034, USA and Immunophotonics Inc., 4320 Forest Park Ave. #303, St. Louis, MO 63108, USA.

Abstract

Since the invention of Coley’s toxin by William Coley in early 1900s, the path for cancer immunotherapy has been a convoluted one. Although still not considered standard of care, with the FDA approval of trastuzumab, Provenge and ipilimumab, the medical and scientific community has started to embrace the possibility that immunotherapy could be a new hope for cancer patients with otherwise untreatable metastatic diseases. This review aims to summarize the development of some major strategies in cancer immunotherapy, from the earliest peptide vaccine and transfer of tumor specific antibodies/T cells to the more recent dendritic cell (DC) vaccines, whole cell tumor vaccines, and checkpoint blockade therapy. Discussion of some major milestones and obstacles in the shaping of the field and the future perspectives is included. Photoimmunotherapy is also reviewed as an example of emerging new therapies combining phototherapy and immunotherapy.

 J Biomed Opt.  2012 Oct;17(10):101516. doi: 10.1117/1.JBO.17.10.101516.

Low-level laser therapy on MCF-7 cells: a micro-Fourier transform infrared spectroscopy study.

Magrini TD, dos Santos NV, Milazzotto MP, Cerchiaro G, da Silva Martinho H.

Source

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia 166, Bangu, Santo André, SP 09210-170, Brazil.

Abstract

Low-level laser therapy (LLLT) is an emerging therapeutic approach for several clinical conditions. The clinical effects induced by LLLT presumably scale from photobiostimulation/photobioinhibition at the cellular level to the molecular level. The detailed mechanism underlying this effect remains unknown. This study quantifies some relevant aspects of LLLT related to molecular and cellular variations. Malignant breast cells (MCF-7) were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences of 5, 28.8, and 1000 mJ/cm². The cell viability was evaluated by optical microscopy using the Trypan Blue viability test. The micro-Fourier transform infrared technique was employed to obtain the vibrational spectra of each experimental group (control and irradiated) and identify the relevant biochemical alterations that occurred due to the process. It was observed that the red light influenced the RNA, phosphate, and serine/threonine/tyrosine bands. We found that light can influence cell metabolism depending on the laser fluence. For 5 mJ/cm², MCF-7 cells suffer bioinhibition with decreased metabolic rates. In contrast, for the 1 J/cm² laser fluence, cells present biostimulation accompanied by a metabolic rate elevation. Surprisingly, at the intermediate fluence, 28.8 mJ/cm², the metabolic rate is increased despite the absence of proliferative results. The data were interpreted within the retrograde signaling pathway mechanism activated with light irradiation.

Photomed Laser Surg.  2012 Sep;30(9):551-8. doi: 10.1089/pho.2011.3186. Epub 2012 Aug 1.

A preliminary study of the safety of red light phototherapy of tissues harboring cancer.

Myakishev-Rempel M, Stadler I, Brondon P, Axe DR, Friedman M, Nardia FB, Lanzafame R.

Source

Department of Dermatology, University of Rochester, Rochester, New York, USA. max.rempel@gmail.com

Abstract

OBJECTIVE:

Red light phototherapy is known to stimulate cell proliferation in wound healing. This study investigated whether low-level light therapy (LLLT) would promote tumor growth when pre-existing malignancy is present.

BACKGROUND DATA:

LLLT has been increasingly used for numerous conditions, but its use in cancer patients, including the treatment of lymphedema or various unrelated comorbidities, has been withheld by practitioners because of the fear that LLLT might result in initiation or promotion of metastatic lesions or new primary tumors. There has been little scientific study of oncologic outcomes after use of LLLT in cancer patients.

METHODS:

A standard SKH mouse nonmelanoma UV-induced skin cancer model was used after visible squamous cell carcinomas were present, to study the effects of LLLT on tumor growth. The red light group (n=8) received automated full body 670 nm LLLT delivered twice a day at 5 J/cm(2) using an LED source. The control group (n=8) was handled similarly, but did not receive LLLT. Measurements on 330 tumors were conducted for 37 consecutive days, while the animals received daily LLLT.

RESULTS:

Daily tumor measurements demonstrated no measurable effect of LLLT on tumor growth.

CONCLUSIONS:

This experiment suggests that LLLT at these parameters may be safe even when malignant lesions are present. Further studies on the effects of photoirradiation on neoplasms are warranted.

J Biomed Opt. 2012 Oct 25;17(10):101516-1. doi: 10.1117/1.JBO.17.10.101516.

Low-level laser therapy on MCF-7 cells: a micro-Fourier transform infrared spectroscopy study.

Magrini TD, Dos Santos NV, Milazzotto MP, Cerchiaro G, da Silva Martinho H.

Abstract

ABSTRACT. Low-level laser therapy (LLLT) is an emerging therapeutic approach for several clinical conditions. The clinical effects induced by LLLT presumably scale from photobiostimulation/photobioinhibition at the cellular level to the molecular level. The detailed mechanism underlying this effect remains unknown. This study quantifies some relevant aspects of LLLT related to molecular and cellular variations. Malignant breast cells (MCF-7) were exposed to spatially filtered light from a He-Ne laser (633 nm) with fluences of 5, 28.8, and 1000 mJ/cm2. The cell viability was evaluated by optical microscopy using the Trypan Blue viability test. The micro-Fourier transform infrared technique was employed to obtain the vibrational spectra of each experimental group (control and irradiated) and identify the relevant biochemical alterations that occurred due to the process. It was observed that the red light influenced the RNA, phosphate, and serine/threonine/tyrosine bands. We found that light can influence cell metabolism depending on the laser fluence. For 5 mJ/cm2, MCF-7 cells suffer bioinhibition with decreased metabolic rates. In contrast, for the 1 J/cm2 laser fluence, cells present biostimulation accompanied by a metabolic rate elevation. Surprisingly, at the intermediate fluence, 28.8 mJ/cm2, the metabolic rate is increased despite the absence of proliferative results. The data were interpreted within the retrograde signaling pathway mechanism activated with light irradiation.

Photomed Laser Surg.  2012 Aug 1. [Epub ahead of print]

A Preliminary Study of the Safety of Red Light Phototherapy of Tissues Harboring Cancer.

Myakishev-Rempel M, Stadler I, Brondon P, Axe DR, Friedman M, Nardia FB, Lanzafame R.

Source

1 Department of Dermatology, University of Rochester , Rochester, New York.

Abstract

Abstract Objective: Red light phototherapy is known to stimulate cell proliferation in wound healing. This study investigated whether low-level light therapy (LLLT) would promote tumor growth when pre-existing malignancy is present.

Background data: LLLT has been increasingly used for numerous conditions, but its use in cancer patients, including the treatment of lymphedema or various unrelated comorbidities, has been withheld by practitioners because of the fear that LLLT might result in initiation or promotion of metastatic lesions or new primary tumors. There has been little scientific study of oncologic outcomes after use of LLLT in cancer patients.

Methods: A standard SKH mouse nonmelanoma UV-induced skin cancer model was used after visible squamous cell carcinomas were present, to study the effects of LLLT on tumor growth. The red light group (n=8) received automated full body 670 nm LLLT delivered twice a day at 5 J/cm(2) using an LED source. The control group (n=8) was handled similarly, but did not receive LLLT.

Measurements on 330 tumors were conducted for 37 consecutive days, while the animals received daily LLLT. Results: Daily tumor measurements demonstrated no measurable effect of LLLT on tumor growth.

Conclusions: This experiment suggests that LLLT at these parameters may be safe even when malignant lesions are present. Further studies on the effects of photoirradiation on neoplasms are warranted.

Vopr Kurortol Fizioter Lech Fiz Kult.  2012 Jul-Aug;(4):23-32.

The efficacy of polychromatic visible and infrared radiation used for the postoperative immunological rehabilitation of patients with breast cancer.

[Article in Russian]
[No authors listed]

Abstract

The immunological rehabilitation of the patients with oncological problems after the completion of standard anti-tumour therapy remains a topical problem in modern medicine. The up-to-date phototherapeutic methods find the increasingly wider application for the treatment of such patients including the use of monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers and photodiodes. The objective of the present study was to substantiate the expediency of postoperative immune rehabilitation of the patients with breast cancer (BC) by means of irradiation of the body surface with polychromatic visible (pVIS) in combination with polychromatic infrared (pIR) light similar to the natural solar radiation without its minor UV component. The study included 19 patients with stage I–II BC at the mean age of 54.0 +/- 4.28 years having the infiltrative-ductal form of the tumour who had undergone mastectomy. These patients were randomly allocated to two groups, one given the standard course of postoperative rehabilitation (control), the other (study group) additionally treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1 to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter of 15 cm). The modern standard immunological methods were employed. It was found that mastectomy induced changes of many characteristics of cellular and humoral immunity; many of them in different patients were oppositely directed. These changes were apparent within the first 7 days postoperatively. The course of phototherapy (PT) was shown to prevent the postoperative decrease in the counts of monocytes and natural killer (NK) cells, the total amount of CD3+ -T-lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells) and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted bacteria. Moreover PT promoted faster normalization of postoperative leukocytosis and activation of cytotoxic CD8+ -T-LPC, reduced the elevated concentration of immune complexes in blood. Among the six tested cytokines, viz. IL-1beta, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma, only the latter two underwent significant elevation of their blood concentrations (IL-6 within 1 day) and IFN-gamma (within 7 days after mastectomy). The course of PT resulted in the decrease of their levels to the initial values. The follow-up of the treated patients during 4 years revealed neither recurrence of the disease nor the appearance of metastases.

Photomed Laser Surg. 2010 Feb;28(1):115-23.

The effect of laser irradiation on proliferation of human breast carcinoma, melanoma, and immortalized mammary epithelial cells.

Powell K, Low P, McDonnell PA, Laakso EL, Ralph SJ.

School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.

Abstract

OBJECTIVE: This study compared the effects of different doses (J/cm(2)) of laser phototherapy at wavelengths of either 780, 830, or 904 nm on human breast carcinoma, melanoma, and immortalized human mammary epithelial cell lines in vitro. In addition, we examined whether laser irradiation would malignantly transform the murine fibroblast NIH3T3 cell line.

BACKGROUND: Laser phototherapy is used in the clinical treatment of breast cancer-related lymphoedema, despite limited safety information. This study contributes to systematically developing guidelines for the safe use of laser in breast cancer-related lymphoedema. METHODS: Human breast adenocarcinoma (MCF-7), human breast ductal carcinoma with melanomic genotypic traits (MDA-MB-435S), and immortalized human mammary epithelial (SVCT and Bre80hTERT) cell lines were irradiated with a single exposure of laser. MCF-7 cells were further irradiated with two and three exposures of each laser wavelength. Cell proliferation was assessed 24 h after irradiation.

RESULTS: Although certain doses of laser increased MCF-7 cell proliferation, multiple exposures had either no effect or showed negative dose response relationships. No sign of malignant transformation of cells by laser phototherapy was detected under the conditions applied here.

CONCLUSION: Before a definitive conclusion can be made regarding the safety of laser for breast cancer-related lymphoedema, further in vivo research is required.

Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Nov-Dec;(6):49-52.

Application of low-power visible and near infrared radiation in clinical oncology.

[Article in Russian]

Zimin AA, Zhevago NA, Buniakova AI, Samoilova KA.

Although low-power visible (VIS) and near infrared (nIR) radiation emitted from lasers, photodiodes, and other sources does not cause neoplastic transformation of the tissue, these phototherapeutic techniques are looked at with a great deal of caution for fear of their stimulatory effect on tumour growth. This apprehension arises in the first place from the reports on the possibility that the proliferative activity of tumour cells may increase after their in vitro exposure to light. Much less is known that these phototherapeutic modalities have been successfully used for the prevention and management of complications developing after surgery, chemo- and radiotherapy. The objective of the present review is to summarize the results of applications of low-power visible and near infrared radiation for the treatment of patients with oncological diseases during the last 20-25 years. It should be emphasized that 2-4 year-long follow-up observations have not revealed any increase in the frequency of tumour recurrence and metastasis.

Photomed Laser Surg. 2009 Oct;27(5):763-9.

Managing postmastectomy lymphedema with low-level laser therapy.

Lau RW, Cheing GL.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China.

OBJECTIVE: We aimed to investigate the effects of low-level laser therapy (LLLT) in managing postmastectomy lymphedema. BACKGROUND DATA: Postmastectomy lymphedema (PML) is a common complication of breast cancer treatment that causes various symptoms, functional impairment, or even psychosocial morbidity. A prospective, single-blinded, controlled clinical trial was conducted to examine the effectiveness of LLLT on managing PML.

METHODS: Twenty-one women suffering from unilateral PML were randomly allocated to receive either 12 sessions of LLLT in 4 wk (the laser group) or no laser irradiation (the control group). Volumetry and tonometry were used to monitor arm volume and tissue resistance; the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire was used for measuring subjective symptoms. Outcome measures were assessed before and after the treatment period and at the 4 wk follow-up.

RESULTS: Reduction in arm volume and increase in tissue softening was found in the laser group only. At the follow-up session, significant between-group differences (all p < 0.05) were found in arm volume and tissue resistance at the anterior torso and forearm region. The laser group had a 16% reduction in the arm volume at the end of the treatment period, that dropped to 28% in the follow-up. Moreover, the laser group demonstrated a cumulative increase from 15% to 33% in the tonometry readings over the forearm and anterior torso. The DASH score of the laser group showed progressive improvement over time.

CONCLUSION: LLLT was effective in the management of PML, and the effects were maintained to the 4 wk follow-up.

Clin Rehabil. 2009 Feb;23(2):117-24

Efficacy of pneumatic compression and low-level laser therapy in the treatment of postmastectomy lymphoedema: a randomized controlled trial.

Kozanoglu E, Basaran S, Paydas S, Sarpel T.

Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Cukurova University, Adana, Turkey.

Objective: To compare the long-term efficacy of pneumatic compression and low-level laser therapies in the management of postmastectomy lymphoedema.

Design: Randomized controlled trial.Setting: Department of Physical Medicine and Rehabilitation of Cukurova University, Turkey.

Subjects: Forty-seven patients with postmastectomy lymphoedema were enrolled in the study.Interventions: Patients were randomly allocated to pneumatic compression (group I, n=24) and low-level laser (group II, n=23) groups. Group I received 2 hours of compression therapy and group II received 20 minutes of laser therapy for four weeks. All patients were advised to perform daily limb exercises.Main measures: Demographic features, difference between sum of the circumferences of affected and unaffected limbs (triangle upC), pain with visual analogue scale and grip strength were recorded.

Results: Mean age of the patients was 48.3 (10.4) years. triangle upC decreased significantly at one, three and six months within both groups, and the decrease was still significant at month 12 only in group II (P = 0.004). Improvement of group II was greater than that of group I post treatment (P = 0.04) and at month 12 after 12 months (P = 0.02). Pain was significantly reduced in group I only at posttreatment evaluation, whereas in group II it was significant post treatment and at follow-up visits. No significant difference was detected in pain scores between the two groups. Grip strength was improved in both groups, but the differences between groups were not significant.

Conclusions: Patients in both groups improved after the interventions. Group II had better long-term results than group I. Low-level laser might be a useful modality in the treatment of postmastectomy lymphoedema.

Photomed Laser Surg. 2008 Aug;26(4):393-400.

Low-level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients.

Abramoff MM, Lopes NN, Lopes LA, Dib LL, Guilherme A, Caran EM, Barreto AD, Lee ML, Petrilli AS.

Private practice, São Paulo, Brazil.

Abstract Objective: A pilot clinical study was conducted to evaluate the efficacy and feasibility of low-level laser therapy (LLLT) in the prevention and treatment of chemotherapy (CT)-induced oral mucositis (OM) in young patients. Background Data: Besides compromising the patient’s nutrition and well-being, oral mucositis represents a portal of entry into the body for microorganisms present in the mouth, which may lead to sepsis if there is hematological involvement. Oncologic treatment tolerance decreases and systemic complications may arise that interfere with the success of cancer treatment. LLLT appears to be an interesting alternative to other approaches to treating OM, due to its trophic, anti-inflammatory, and analgesic properties. Materials and Methods: Patients undergoing chemotherapy (22 cycles) without mucositis were randomized into a group receiving prophylactic laser-irradiation (group 1), and a group receiving placebo light treatment (group 2). Patients who had already presented with mucositis were placed in a group receiving irradiation for therapeutic purposes (group 3, with 10 cycles of CT). Serum granulocyte levels were taken and compared to the progression of mucositis. Results: In group 1, most patients (73%) presented with mucositis of grade 0 (p = 0.03 when compared with the placebo group), and 18% presented with grade 1. In group 2, 27% had no OM and did not require therapy. In group 3, the patients had marked pain relief (as assessed by a visual analogue scale), and a decrease in the severity of OM, even when they had severe granulocytopenia. Conclusion: The ease of use of LLLT, high patient acceptance, and the positive results achieved, make this therapy feasible for the prevention and treatment of OM in young patients.

Ann Oncol. 2007 Apr;18(4):639-46. Epub 2006 Oct 3

A systematic review of common conservative therapies for arm lymphoedema secondary to breast cancer treatment.

Moseley AL, Carati CJ, Piller NB.

School of Nursing & Midwifery, University of South Australia, Adelaide, Australia. amanda.moseley@yahoo.com.au

Secondary arm lymphoedema is a chronic and distressing condition which affects a significant number of women who undergo breast cancer treatment. A number of health professional and patient instigated conservative therapies have been developed to help with this condition, but their comparative benefits are not clearly known. This systematic review undertook a broad investigation of commonly instigated conservative therapies for secondary arm lymphoedema including; complex physical therapy, manual lymphatic drainage, pneumatic pumps, oral pharmaceuticals, low level laser therapy, compression bandaging and garments, limb exercises and limb elevation. It was found that the more intensive and health professional based therapies, such as complex physical therapy, manual lymphatic drainage, pneumatic pump and laser therapy generally yielded the greater volume reductions, whilst self instigated therapies such as compression garment wear, exercises and limb elevation yielded smaller reductions. All conservative therapies produced improvements in subjective arm symptoms and quality of life issues, where these were measured. Despite the identified benefits, there is still the need for large scale, high level clinical trials in this area.

Lasers Med Sci. 2006 Jul;21(2):90-4. Epub 2006 May 4.

Low-level laser therapy in management of postmastectomy lymphedema.

Kaviani A, Fateh M, Yousefi Nooraie R, Alinagi-zadeh MR, Ataie-Fashtami L.

Tehran University of Medical Sciences and Iranian Center for Medical Laser Research, Tehran, Iran. akaviani@sina.tims.ac.ir

The aim of this paper was to study the effects of low-level laser therapy (LLLT) in the treatment of postmastectomy lymphedema. Eleven women with unilateral postmastectomy lymphedema were enrolled in a double-blind controlled trial. Patients were randomly assigned to laser and sham groups and received laser or placebo irradiation (Ga-As laser device with a wavelength of 890 nm and fluence of 1.5 J/cm2) over the arm and axillary areas. Changes in patients’ limb circumference, pain score, range of motion, heaviness of the affected limb, and desire to continue the treatment were measured before the treatment and at follow-up sessions (weeks 3, 9, 12, 18, and 22) and were compared to pretreatment values. Results showed that of the 11 enrolled patients, eight completed the treatment sessions. Reduction in limb circumference was detected in both groups, although it was more pronounced in the laser group up to the end of 22nd week. Desire to continue treatment at each session and baseline score in the laser group was greater than in the sham group in all sessions. Pain reduction in the laser group was more than in the sham group except for the weeks 3 and 9. No substantial differences were seen in other two parameters between the two treatment groups. In conclusion, despite our encouraging results, further studies of the effects of LLLT in management of postmastectomy lymphedema should be undertaken to determine the optimal physiological and physical parameters to obtain the most effective clinical response.

J Photochem Photobiol B. 2000 Dec;59(1-3):1-8.

Magnetic resonance imaging (MRI) controlled outcome of side effects caused by ionizing radiation, treated with 780 nm-diode laser –preliminary results.

Schaffer M, Bonel H, Sroka R, Schaffer PM, Busch M, Sittek H, Reiser M, Duhmke E.
Department of Radiation Therapy, University of Munich, Germany.

sroka@life.med.uni-muenchen.de

BACKGROUND and OBJECTIVE: Ionizing radiation therapy by way of various beams such as electron, photon and neutron is an established method in tumor treatment. The side effects caused by this treatment such as ulcer, painful mastitis and delay of wound healing are well known, too. Biomodulation by low level laser therapy (LLLT) has become popular as a therapeutic modality for the acceleration of wound healing and the treatment of inflammation. Evidence for this kind of application, however, is not fully understood yet. This study intends to demonstrate the response of biomodulative laser treatment on the side effects caused by ionizing radiation by means of magnetic resonance imaging (MRI). STUDY

DESIGN/PATIENTS and METHODS: Six female patients suffering from painful mastitis after breast ionizing irradiation and one man suffering from radiogenic ulcer were treated with lambda=780 nm diode laser irradiation at a fluence rate of 5 J/cm2. LLLT was performed for a period of 4-6 weeks (mean sessions: 25 per patient, range 19-35). The tissue response was determined by means of MRI after laser treatment in comparison to MRI prior to the beginning of the LLLT.

RESULTS: All patients showed complete clinical remission. The time-dependent contrast enhancement curve obtained by the evaluation of MR images demonstrated a significant decrease of enhancement features typical for inflammation in the affected area.

CONCLUSION: Biomodulation by LLLT seems to be a promising treatment modality for side effects induced by ionizing radiation.

Inspire and Deepen Your Practice!

Laser, laser needle acupuncture, led and pulsed electromagnetic field therapies are the right tools for healing today’s complex patients and for your practice success.

10-6-15 3 rows of 4 productsl

All devices pictured above (and more) will likely be available for you to train and practice with in this course.  Learn more about them in the links below.

Healing Light Seminars and David Rindge have been practicing, teaching and continually updating our treatment methods and equipment since 2002. Our goal first and foremost is to provide you with an understanding of the parameters and methods for success so that you come from the knowledge to make the best relevant clinical and business decisions for your practice.  We will only offer devices we have found to be effective, well made and which we are continuing to use clinically.  Yet whether or not you buy from us, you should learn what device parameters will achieve the best results for your purposes.

Day 1 focuses on theory, biological effects and essentials for clinical success.   You have the opportunity for hands-on practice with state-of-the-art laser, laser needle, led and pemf systems for the treatment of pain, head to toe.

In Day 2, you will learn how to apply laser, laser needles, led and pulsed electromagnetic field therapies for aesthetics / dermatology / facial rejuvenation, cardiovascular disease, digestive, ear and eye disorders, gynecology, for hair regrowth, neuropathy, osteoporosis, respiratory disorders, sports medicine and more.

You will receive Laser Therapy: A Clinical Manual as part of the course.

Laser Therapy - A Clinical Manual This popular training manual by Blahnik and Rindge presents the theory and clinical application of laser therapy in clearly understandable terms with treatment protocols for more than 40 conditions.  Laser Therapy: A Clinical Manual is an important important resource in the course and a $79.00 value.  You will also receive treatment protocols for other conditions, updates and much, much more relevant material in this course.

Gain a solid understanding of energy-based therapies.    NCCAOM 322-5, seven hours each day, Saturday and Sunday.    Learn More.

Course Dates / Location

November 5-6, 2016.  SpringHill Suites Orlando Airport.  5828 Hazeltine National DriveOrlando, FL 32822. (407) 816-5533.

LEARN MORE AND REGISTER HERE

Or call 321-751-7001.

Healing Light Seminars

Training in Energy-based Therapies since 2002

14 PDAs – NCCAOM 322-5

14 CEUs Florida Acupuncturists

New Software

If you are already own a 2000PC system, by upgrading the software you gain the option to add the new, Combination High Power PEMF-LED Probe.

Software on laptop plus controller

The new software increases the maximum intensity of the PEMF which can be generated by your 2000 PC system by 50%, from 100 milliTeslas to 150 milliTeslas, and allows  simultaneous therapy with 2 Watts of  640 nanometer led light with your Combo Probe.

The new software  is easy to install and user-friendly.  It operates presets for almost 100 conditions and allows you to create custom protocols with intensity, pulse rate (1-50 Hz) and treatment times fully programmable.

  • All treatment parameters are under direct control of the PC program running under Windows 7, 8.1 & 10 or Mac OS X Yosemite 10.10 & EI Capitan
  • User-friendly database for patient data and follow up.
  • Preset treatment protocols ready-to-use for almost 100 conditions.
  • Therapy parameters can be set manually, saved in the Custom Disorders database and then run automatically.
  • Full PEMF report printing, including treatment history data, treatment time and accumulated treatment time.
  • Automatic USB communication port detection for very easy installation without basic computer knowledge.

You will save 50% on the price of the new software ($337.50 vs $675) when you purchase it bundled with the Combination High Power PEMF-LED Probe and a second cable.

Software Screenshot 1

Software Screenshot 2

Software Screenshot 3

Software Screenshot 4

Inspire and deepen your practice!

Laser, laser needle acupuncture, led and pulsed electromagnetic field therapies are the right tools for healing today’s complex patients and for your practice success!

10-6-15 3 rows of 4 productsl

All devices pictured above (and more) will likely be available for you to train and practice with in this course.  Learn more about them in the links below.

Our primary goal in this course is to provide you with an understanding of laser, led and pulsed electromagnetic field therapy parameters and methods for your success, so that you come from the knowledge and are able to make the best clinical and business decisions for your practice.  That said, to our knowledge these are the best available laser, PEMF and led devices in the US.  It is our policy only to offer equipment which we have found effective, well made and which we ourselves are continuing to use extensively in the clinic.  These products may be available to seminar attendees at a discount otherwise unobtainable and one which will easily pay for the course and more.

Healing Light Seminars and David Rindge have been practicing, teaching and continually updating our treatment methods and equipment since 2002.   That you gain the theoretical and clinical foundation so that you can confidently make the correct decisions for your practice and achieve best outcomes for your patients remains our #1 goal.

Day 1 focuses on theory, biological effects and essentials for treatment success.   You have the opportunity for hands-on practice with state-of-the-art laser, laser needle, led and pemf systems for the treatment of pain, head to toe.

In Day 2, you will learn how to apply laser, laser needle, led and pulsed electromagnetic field therapies for aesthetics / dermatology / facial rejuvenation, cardiovascular disease, digestive, ear and eye disorders, gynecology, for hair regrowth, neuropathy, osteoporosis, respiratory disorders, sports medicine and much more.

You will receive Laser Therapy: A Clinical Manual as part of the course.

Laser Therapy - A Clinical Manual This popular training manual by Blahnik and Rindge presents the theory and clinical application of laser therapy in clearly understandable terms with treatment protocols for more than 40 conditions.  Laser Therapy: A Clinical Manual is an important important resource in the course and a $79.00 value.  You will also receive treatment protocols for other conditions, updates and much, much more relevant material in this course.

Gain a solid understanding of energy-based therapies.    NCCAOM 322-5, seven hours each day, Saturday and Sunday.    Learn More.

Course Dates / Location

November 5-6, 2016.  SpringHill Suites Orlando Airport.  5828 Hazeltine National DriveOrlando, FL 32822. (407) 816-5533.

LEARN MORE AND REGISTER HERE

Or call 321-751-7001.

Healing Light Seminars

Training in Energy-based Therapies since 2002

14 PDAs – NCCAOM 322-5

14 CEUs Florida Acupuncturists

Osteosarcoma

J Orthop Surg Res. 2015; 10: 104.
Published online 2015 Jul 7. doi:  10.1186/s13018-015-0247-z
PMCID: PMC4496869

Nanosecond pulsed electric field inhibits proliferation and induces apoptosis in human osteosarcoma

Xudong Miao,# Shengyong Yin,# Zhou Shao, Yi Zhang, and Xinhua Chencorresponding author
The Department of Orthopedics, the Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang Province 310003 China
The Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University, Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, 79 Qinchun Road, Hangzhou, Zhejiang Province 310003 China
The Department of Gynecology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province 310000 China
Xinhua Chen, Phone: +86-571-87236570, nc.ude.ujz@nehc_auhnix.
corresponding authorCorresponding author.
#Contributed equally.
Author information ? Article notes ? Copyright and License information ?
Received 2015 Jun 11; Accepted 2015 Jun 29.

Abstract

Objective

Recent studies suggest that nanosecond pulsed electric field (nsPEF) is a novel minimal invasive and non-thermal ablation method that can induce apoptosis in different solid tumors. But the efficacy of nsPEF on bone-related tumors or bone metastasis is kept unknown. The current study investigates antitumor effect of nsPEF on osteosarcoma MG-63 cells in vitro.

Method

MG-63 cells were treated with nsPEF with different electric field strengths (0, 10, 20, 30, 40, and 50 kV/cm) and different pulse numbers (0, 6, 12, 18, 24, and 30 pulses). The inhibitory effect of nsPEF on the growth of MG-63 cells was measured by Cell Counting Kit-8 (CCK-8) assay at different time points (0, 3, 12, 24, and 48 h post nsPEF treatment). The apoptosis was analyzed by Hoechst stain, in situ terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), and flow cytometric analysis. The expression of osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and tumor necrosis factor a (TNF-a) was examined by reverse-transcription polymerase chain reaction (RT-PCR) and western blot.

Results

The CCK-8 assay showed that nsPEF induced a distinct electric field strength- and pulse number-dependent reduction of cell proliferation. For treatment parameter optimizing, the condition 40 kV/cm and 30 pulses at 24 h post nsPEF achieved the most significant apoptotic induction rate. Hoechst, TUNEL, and flow cytometric analysis showed that the cell apoptosis was induced and cells were arrested in the G0/G1 phase. PCR and western blot analysis demonstrated that nsPEF up-regulated OPG expression had no effect on RANKL, increased OPG/RANKL ratio.

Conclusion

NsPEF inhibits osteosarcoma growth, induces apoptosis, and affects bone metabolism by up-regulating OPG, indicating nsPEF-induced apoptosis in osteosarcoma MG-63 cells. NsPEF has potential to treat osteosarcoma or bone metastasis. When nsPEF is applied on metastatic bone tumors, it might be beneficial by inducing osteoblastic differentiation without cancer proliferation. In the future, nsPEF might be one of the treatments of metastatic bone tumor.

Keywords: Osteosarcoma, MG-63 cells, Nanosecond pulsed electric field, Apoptosis

Introduction

Osteosarcoma is a malignant bone tumor with high occurrence in children and young adolescents. Retrospective review showed that in the past 30 years, osteosarcoma had a poor prognosis and there was no significant improvement of disease-free survival and the stagnated situation has not improved even with the aggressive use of neoadjuvant chemotherapy and radiation therapy [1]. Patients did not benefit from overtreatment, and as a result, a high rate of lung metastasis, recurrence, and pathological fracture frequently occur, keeping osteosarcoma still one of the lowest survival rates in pediatric cancers [2]. Thus, new therapeutic strategy needs to be developed.

Nanosecond pulsed electric field (nsPEF) is an innovative electric ablation method based on high-voltage power technology, which came into medical application in the last decade [3]. NsPEF accumulates the electric field energy slowly and releases it into the tumor in ultra-short nanosecond pulses, altering electrical conductivity and permeability of the cell membrane, causing both cell apoptosis and immune reaction [4].Quite different from any other traditional local ablation method, nsPEF accumulate less Joule heating and showed no hyperthermic effects [5], indicating unique advantage over other thermal therapies such as radiofrequency, cryoablation, microwave, and interstitial laser; nsPEF can be used alone and so avoid the side effect caused by chemotherapy or percutaneous ethanol injection [6].

We have used nsPEF to ablate tumor and showed the equal outcome as the radical resection with proper indication [7]. Clinical trials and pre-clinical studies from different groups proved that nsPEF has direct antitumor effects by inhibiting proliferation and causing apoptosis in human basal cell carcinoma [8, 9], cutaneous papilloma, squamous cell carcinoma [10], melanoma [11, 12], hepatocellular tumor [13], pancreatic tumor [14], colon tumor [15, 16], breast cancer [17, 18], salivary adenoid cystic carcinoma [19], oral squamous cell carcinoma [20], et al. Local ablation with nsPEF indicates the noticeable advantage of not only eliminating original tumors but also inducing an immune reaction, e.g., enhance macrophage [21] and T cell infiltration [22] and induce an immune-protective effect against recurrences of the same cancer [23]. The characteristic of electric field on bone metabolism [24] is extremely helpful for osteosarcoma patients with pathological fracture which leads to poor prognosis [25, 26].

Considering osteosarcoma is especially prevalent in children and young adults during quick osteoblastic differentiation [1, 2], unstable RB gene and p53 gene are commonly involved in this malignant transformation process [27]; we hypothesize that nsPEF affects osteosarcoma growth by targeting the Wnt/?-catenin signaling pathway, a key signaling cascade involved in osteosarcoma pathogenesis. Here, we investigate nsPEF-induced changes on human osteosarcoma MG-63 cells to determine (1) the dose-effect relationship and time-effect relationship of nsPEF on osteosarcoma cell growth and apoptosis induction and (2) the nsPEF effect on the osteosarcoma cell; osteoblast specific gene and protein expression (receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG)) were measured along with the production of the pro-inflammatory cytokine tumor necrosis factor a (TNF-a).

Materials and methods

Cell lines and cell culture

MG-63 human osteosarcoma cells were purchased from the Cell Bank of Chinese Academy of Sciences (Shanghai, China), cultured in Dulbecco’s Modified Eagle’s medium (DMEM, Gibco Invitrogen, Carlsbad, CA, USA) supplemented with 10 % fetal bovine serum (FBS, SAFC Biosciences, Lenexa, KS, USA), 100 units/mL penicillin, and 100 mg/mL streptomycin (Sigma, Aldrich, St. Louis, MO, USA). Cells were kept in a humidified atmosphere of 5 % CO2 at 37 °C.

The nsPEF treatment and dose-effect exam

The nsPEF treatment system was made by Leibniz Institute for Plasma Science and Technology, Germany, and an nsPEF generator with duration of 100 ns was applied. Varied electric fields were released in a cell treatment system from 10 to 60 kV/cm. Waveforms were monitored with a digital phosphor oscilloscope (DPO4054, Tektronix, USA) equipped with a high voltage probe (P6015A, Tektronix, USA). MG-63 human osteosarcoma cells were harvested with trypsin and resuspended in fresh DMEM with 10 % FBS to a concentration of 5.0 × 106 cells/mL. Five hundred microliters of cell suspension were placed into a sterile electroporation cuvette (Bio-Rad, US, 0.1-cm gap). Cells were exposed to 100 pulses at 0, 10, 20, 30, 40, 50, and 60 kV/cm electric field strengths, respectively. Under the 50 kV/cm electric field strength, the different pulse numbers were applied (0, 6, 12, 18, 24, and 30 pulses). The experiments were repeated for three times. After incubation for 24 h, cells were calculated by Cell Counting Kit-8 (CCK-8) assay (Dojindo Laboratories, Kumamoto, Japan).

Measurement of apoptosis with TUNEL assay, Hoechst stain, and flow cytometry

At different hours after nsPEF treatment (40 kV/cm, 30 pulses), the treated cells were incubated for 0, 3, 12, 24, and 48 h to determine single-cell apoptosis using the assay of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) with In Situ Cell Death Detection Kit (Millipore, USA) and Hoechst stain kit (Beyotime, Shanghai, China) according to the manufacturer’s instruction, as previously described [14]. Under different electric field strengths and with different pulses, the treated cells were incubated for 24 h to detect cell apoptosis by Annexin V-FITC Apoptosis Detection Kit (BD Biosciences). The cell cycle was also analyzed as previously described [14].

Reverse-transcription polymerase chain reaction

Reverse-transcription polymerase chain reaction (RT-PCR) was performed for assessing the expression of OPG, RANKL, and TNF-a. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a house keeping gene, was used as the internal control to calculate the comparative expression. Total RNA was extracted using TRIzol reagent (Sangon, Shanghai, China). The first strand cDNA synthesis from 1 mg of RNA was performed using SuperScript II Reverse Transcriptase (Invitrogen) and Oligo dT primer (Promega, Madison, WI, USA) according to the manufacturer’s instructions. PCR was performed using the oligunucleotides listed as the following. The specific primers were made by Sangon, Shanghai, China, which were listed as the following: RANK: F: CAGGAGACCTAGCTACAGA, R: CAAGGTCAAGAGCATGGA, 95 °C, 1 min; 55 °C, 1 min; 72 °C, 1 min; OPG (264 bp): F: AGTGGGAGCAGAAGACAT, R: TGGA CCTGGTTACCTATC, 95 °C, 1 min; 57 °C, 1 min; 72 °C, 1 min; TNF-a: F: GTGGCAGTCTCAAACTGA, R: TATGGAAAGGGGCACTGA, 94 °C, 40 s; 55 °C, 40 s; 72 °C, 40 s; GAPDH: F: CAG CGACACCCACTCCTC, R: TGAGGTCCA CCACCCTGT, 94 °C, 1 min; 57 °C, 1 min; 72 °C, 1 min.

Western blotting analysis

MG-63 cells (5 × 105) were plated and treated with different doses of nsPEF. Cells were then lysed with a lysis buffer and then quantified. The equal amounts of protein were loaded, and electrophoresis was applied on a 12 % sodium dodecyl sulfate-polyacrylamide gel electrophoresis mini-gel. Proteins were transferred to a PVDF membrane and blocked with casein PBS and 0.05 % Tween-20 for 1 h at room temperature. Membranes were incubated with mouse monoclonal OPG, anti-OPG (1:500), RANKL (1:200), TNF-a (1:300), GAPDH (1:1000) antibodies which were purchased from Santa Cruz (Santa Cruz Biotechnology, Santa Cruz, CA, USA). Horseradish peroxidase-conjugated secondary antibody was purchased from Zhongshan (Zhongshan Golden Bridge, Beijing, China.). The protein expression was visualized with enhanced chemiluminescence reagent (ECL kit, Amersham, UK).

Statistical analysis

Statistical significance was determined using Student’s t test, using SPSS 13.0. P < 0.05 was considered to indicate a statistically significant result.

Results

NsPEF parameter optimizing by CCK-8 and flow cytometry

CCK-8 assay was used to calculate the IC50 values, and flow cytometry was used to detect apoptosis. There were significant growth inhibition and apoptosis induction in a dose-dependent manner following nsPEF treatment for 24 h. MG-63 cell growth was inhibited in an electric field strength- and pulse number-dependent manner. There was significant (P > 0.001) growth inhibition when electric field strength was 40–50 kV/cm (Fig. 1a) and when pulse number was 30 (Fig. 1d) vs control. Cells were treated by nsPEF and then incubated for 24 h. Apoptotic and dead cells were analyzed by flow cytometry using dual staining with propidium iodide (PI) and Annexin V-FITC. NsPEF induced viable apoptotic cells stained with Annexin. The apoptotic cell rate is significantly increased when electric field strength was 40–50 kV/cm (Fig. 1b, c) and when pulse number was 30 (Fig. 1e, f).

Fig. 1

NsPEF treatment parameter optimizing by CCK-8 and flow cytometry. After 24 h post nsPEF, CCK-8 assay was used to calculate the IC50 values under different electric field strengths (a) and different pulse numbers (d). The flow cytometry was used to detect

Apoptosis induction at different times post nsPEF treatment

To determine the effects of nsPEF on the induction of apoptosis in MG-63 cells, the Annexin V assay was performed. After 40 kV/cm and 30 pulses of nsPEF treatment, the control and treated cells were stained with Hoechst 33528 (Fig. 2a upper lane) and TUNEL (Fig. 2a lower lane). The statistical analysis of the positive apoptotic cells were counted and shown in Fig. 2b at different hours (0, 3, 12, 24, and 48 h). Apoptotic cells induced by nsPEF treatment were recognized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL), detecting DNA fragmentation by labeling the terminal end of nucleic acids. The number or percentages of apoptotic cells detected following nsPEF treatment was shown in Fig. 2b. The quantitative analysis showed the percentages of apoptotic cells detected following nsPEF treatment which were 2.6 % (0 h), 8.8 % (3 h), 21 % (12 h), 42 % (24 h), and 15 % (48 h) without nsPEF treatment. The apoptotic induction 12 and 24 h post nsPEF treatment showed significance (P = 0.01243, 0.00081, respectively, vs control). The cell cycle was analyzed by flow cytometry (Fig. 2c) and statistically analyzed in Fig. 2d, which indicates that nsPEF arrest cells in the G0/G1 phase (Fig. 2d).

Fig. 2

Apoptosis induction at different times post nsPEF treatment. After 40 kV/cm and 30 pulses of nsPEF treatment, the control and treated cells were stained with Hoechst 33528 (a upper lane) and TUNEL (a lower lane). The statistical analysis of the positive

The effect of nsPEF on OPG/RANKL, TNF-? gene, and protein expression

With 30 pulses, 24 h post treatment, PCR and western blot were used to determine the different electric field strengths on cell OPG/RANKL, TNF-? gene (Fig. 3a), and the corresponding protein expression (Fig. 3b). NsPEF significantly increased OPG transcription and protein expression at 20–50 kV/cm (Fig. 3a, c). RANKL was almost undetectable both in the control and nsPEF-treated MG-63 cells (Fig. 3a, c). NsPEF slightly down-regulated TNF-a (Fig. 3a, c). The OPG is important in the regulation of bone formation. PCR results showed that the nsPEF-treated cells demonstrated a significantly up-regulation of OPG transcription. Western blot analysis confirmed that nsPEF stimulated osteoprotegerin protein production in the MG-63 cells.

Fig. 3

The nsPEF effect on gene and protein expression. With 30 pulses, 24 h post treatment, PCR and western blot were used to determine the different electric field strengths on cell OPG/RANKL, TNF-a gene (a), and protein expression (b). NsPEF significantly

Discussion

The primary bone malignancy osteosarcoma is still a challenge for orthopedics. For patients who are not suitable for radical resection, the minimal invasive ablation techniques can be used as an alternative to surgery. NsPEF has been proved to be a novel non-thermal ablation method which can activate a protection immune response [2123]. According to the Clinical Practice Guidelines in Oncology of the National Comprehensive Cancer Network (NCCN), local ablation can be used for curative or palliative intent, either alone or in combination with immunotherapy or chemotherapy [11]. The effect of systemic chemotherapy may be enhanced by the physiological changes produced by ablation [11]. Furthermore, ablation can sometimes be used as a complement to surgery [13].

A number of studies have demonstrated that local ablation is effective in osteosarcoma [2830]. To our best knowledge, the application of nsPEF in osteosarcoma has never been reported. The bone-related tumor study is extremely important because many solid tumors tend to have metastasis in bones. The present study applies a new ablation methodology in osteosarcoma and identifies its molecular target. Our data suggest that nsPEF had direct effects on osteosarcoma cells, including the inhibition of tumor cell proliferation and induction of apoptosis. These results are consistent with previous reports. NsPEF inhibits cell proliferation and induces apoptosis in tumor cells [11, 16].

The development of osteoclasts is controlled by cytokine synthesized by osteoblasts like receptor activator of NF-?B ligand (RANKL), osteoprotegerin (OPG), and tumor necrosis factor ? (TNF-a) [31].The extension of the current study is the investigation of nsPEF’s effect on bone resorption when nsPEF is in its ablation dosage. OPG is a member of the tumor necrosis factor receptor family. It has multiple biological functions such as regulation of bone turnover. OPG can block the interaction between RANKL and the RANK receptor [31]. NsPEF increased OPG expression in MG-63 in in vitro assays. Our data indicate that nsPEF up-regulated the OPG expression. Bone remodeling can be assessed by the relative ratio of OPG to RANKL [32]. NsPEF had no effect on RANKL expression. Defined as a potent bone-resorbing factor, TNF-a is responsible for stimulating bone resorption. TNF-? exerts its osteoclastogenic effect by activating NF-?B with RANKL [33]. Our results show that in osteosarcoma MG-63, in addition to apoptosis induction, nsPEF can regulate bone metabolism through adjusting OPG/RANKL ratio.

TNF-a expression still needs further investigation due to the weak expression. But, it is the key cytokine that we assume which would change the local inflammatory microenvironment in the ablation zone.

The limit of the current study

In this in vitro study, the MG-63 osteosarcoma cell line is used as a model system. Therefore, results obtained from cultured cells only gave hints for the nsPEF treatment of osteosarcoma. The current results need to be tested in an in vivo osteosarcoma model, e.g., MG-63 cell xenografts.

Conclusion

NsPEF can be considered as a potential therapeutic intervention to suppress bone remodeling and osteoclast activity involved in osteosarcoma. Further in vivo studies are required to optimize the dosing regimen of nsPEF to fully study its antitumor potential in the bone microenvironment.

Acknowledgments

All authors acknowledge Dr.Karl H. Shoenbach, Dr. Stephen Beebe, and Mr. Frank Reidy from Old Dominion University for their kind support.

Financial support

This research is supported by National Natural Science Foundation of China (Nos. 81372425 and 81371658), National S & T Major Project (No. 2012ZX10002017), Zhejiang Natural Science Foundation (LY13H180003), and Xinjiang Cooperation Project (2014KL002).

Footnotes

Xudong Miao and Shengyong Yin contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

XM and SY carried out the molecular genetic studies and drafted the manuscript. ZS carried out the immunoassays. YZ participated in the design of the study and performed the statistical analysis. XC conceived of the study, participated in its design and coordination, and helped draft the manuscript. All authors read and approved the final manuscript.

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