Exercise & Radiosensitivity.

[pjoshea13]

New study below [1].

It appears in the journal "Sports Medicine - Open", where authors pay to be published, although the papers are peer reviewed.

But "Sports Medicine"? Isn't that akin to paying someone to bury your PCa paper in the middle of the Sahara?

Perhaps not, if you are still reading.

Some background: When a tumor outgrows its blood supply, hypoxia occurs in cells. Contrary to many internet sites, cancer does not "hate" oxygen. Cells respond to hypoxia via Hypoxia Inducible Factor 1alpha [HIF-1a]. One of the things that HIF-1a does is to cause the production of vascular endothelial growth factor (VEGF), which stimulates the formation of blood vessels.

But HIF-1a causes the production of over 200 other proteins that have a role in cell survival. {This is good if you fly from sea level to Colorago Springs (>1 mile high) with the intention of running up Pike's Peak (>14,000'). But PCa can induce HIF-1a even if there is no hypoxia, and the cell survival proteins offer a formidable barrier to all treatment drugs - & radiation.

It should be noted that some about to begin radiation treatment already have a HIF-1a issue, due to prior therapy.

Note also that castration 'therapy' reduces the red blood cell count (stay clear of Pike's Peak), making HIF-1a more likely.

The authors believe that exercise might help:

"Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity"

I just had my annual medical (RBC: 3.49; Hemoglobin: 11.9 g/dL; Hematocrit: 36.1% - all low) & I'm a bit dubious.

I am sporting a nitroglycerine patch, however. I'm doing my best to inhibit/reverse HIF-1a by improving the oxygen flow.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/353...

Sports Med Open

. 2022 Apr 8;8(1):48. doi: 10.1186/s40798-022-00436-9.

Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity

Malcolm Brown 1 , Amélie Rébillard 2 , Nicolas H Hart 3 4 5 , Dominic O'Connor 6 , Gillian Prue 7 , Joe M O'Sullivan 8 , Suneil Jain 8

Affiliations collapse

Affiliations

1 School of Nursing and Midwifery, Queen's University Belfast, Northern Ireland, Belfast, UK. [e-mail].

2 Movement, Sport and Health Sciences Laboratory, Université Rennes 2, ENS Rennes, Bruz, France.

3 College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia.

4 School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.

5 Institute for Health Research, University of Notre Dame Australia, Perth, WA, Australia.

6 School of Health Sciences, University of Nottingham, Nottingham, England, UK.

7 School of Nursing and Midwifery, Queen's University Belfast, Northern Ireland, Belfast, UK.

8 The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK.

PMID: 35394236 DOI: 10.1186/s40798-022-00436-9

Abstract

Prostate cancer is a complex disease affecting millions of men globally. Radiotherapy (RT) is a common treatment modality although treatment efficacy is dependent upon several features within the tumour microenvironment (TME), especially hypoxia. A hypoxic TME heightens radioresistance and thus disease recurrence and treatment failure continues to pose important challenges. However, the TME evolves under the influence of factors in systemic circulation and cellular crosstalk, underscoring its potential to be acutely and therapeutically modified. Early preclinical evidence suggests exercise may affect tumour growth and some of the benefits drawn, could act to radiosensitise tumours to treatment. Intracellular perturbations in skeletal muscle reactive oxygen species (ROS) stimulate the production of numerous factors that can exert autocrine, paracrine, and endocrine effects on the prostate. However, findings supporting this notion are limited and the associated mechanisms are poorly understood. In light of this preclinical evidence, we propose systemic changes in redox signalling with exercise activate redox-sensitive factors within the TME and improve tumour hypoxia and treatment outcomes, when combined with RT. To this end, we suggest a connection between exercise, ROS and tumour growth kinetics, highlighting the potential of exercise to sensitise tumour cells to RT, and improve treatment efficacy.

Keywords: Exercise; Hypoxia; Prostate cancer; Radiotherapy; Reactive oxygen species; Skeletal muscle.

© 2022. The Author(s).

. 2022 Apr 8;8(1):48. doi: 10.1186/s40798-022-00436-9.

Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity

Malcolm Brown 1 , Amélie Rébillard 2 , Nicolas H Hart 3 4 5 , Dominic O'Connor 6 , Gillian Prue 7 , Joe M O'Sullivan 8 , Suneil Jain 8

Affiliations collapse

Affiliations

1 School of Nursing and Midwifery, Queen's University Belfast, Northern Ireland, Belfast, UK. [e-mail].

2 Movement, Sport and Health Sciences Laboratory, Université Rennes 2, ENS Rennes, Bruz, France.

3 College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia.

4 School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.

5 Institute for Health Research, University of Notre Dame Australia, Perth, WA, Australia.

6 School of Health Sciences, University of Nottingham, Nottingham, England, UK.

7 School of Nursing and Midwifery, Queen's University Belfast, Northern Ireland, Belfast, UK.

8 The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, Northern Ireland, UK.

PMID: 35394236 DOI: 10.1186/s40798-022-00436-9

Abstract

Prostate cancer is a complex disease affecting millions of men globally. Radiotherapy (RT) is a common treatment modality although treatment efficacy is dependent upon several features within the tumour microenvironment (TME), especially hypoxia. A hypoxic TME heightens radioresistance and thus disease recurrence and treatment failure continues to pose important challenges. However, the TME evolves under the influence of factors in systemic circulation and cellular crosstalk, underscoring its potential to be acutely and therapeutically modified. Early preclinical evidence suggests exercise may affect tumour growth and some of the benefits drawn, could act to radiosensitise tumours to treatment. Intracellular perturbations in skeletal muscle reactive oxygen species (ROS) stimulate the production of numerous factors that can exert autocrine, paracrine, and endocrine effects on the prostate. However, findings supporting this notion are limited and the associated mechanisms are poorly understood. In light of this preclinical evidence, we propose systemic changes in redox signalling with exercise activate redox-sensitive factors within the TME and improve tumour hypoxia and treatment outcomes, when combined with RT. To this end, we suggest a connection between exercise, ROS and tumour growth kinetics, highlighting the potential of exercise to sensitise tumour cells to RT, and improve treatment efficacy.

Keywords: Exercise; Hypoxia; Prostate cancer; Radiotherapy; Reactive oxygen species; Skeletal muscle.

© 2022. The Author(s).

[LearnAll]

Exercise in many ways improve outcome in prostate cancer..such as keeping body fit, keeping vessels dilated for better oxygen delivery, reducing blood pressure . reducing obesity and decrease in blood sugar and of couse controlling HIF. Yogis recommend many breathing tecniques (active meditations) to increase oxygen supply to tissues. One such tecniques is called "Pranayam". Basically all these tecniques emphasize deep, strong inhalation and exhalation..in turn increasing oxygen blood level.

For last 2 years my Hemoglobin was hovering between 13 and 13.5. I started eating 100 grams of Dried Munakka Grapes daily with 2 average size Oranges/Tangerines including peel. In 8 weeks, rechecked hemoglobin...and it increased from 13.5 to 14.4. Increase in Hb can inhibit hypoxia inducing factor which in turn can slow new blood vessel formation (neoangiogenesis) Walking/running/streching/dancing and lifting some weights should be part of every PCa treatment protocol.

[treedown]

This is why I rode my bike 5 miles to each RT treatment (missed the 1st 3 due to icy roads) and up to 20 miles after, rain or shine. I also arrived early to get bladder ready and meditate and do deep breathing prior to getting on the machine. I hoped it would help and seeing the theory in writing makes me glad I did it. I also rode my bike the same 5 miles to and after each Lupron injection.

[depotdoug in reply to treedown]

Biked to RT’sWow! That’s amazing, how far was the ride!

[depotdoug in reply to treedown]

Ooops should have read the fine print.Five(5) miles and 20!

Great story in your life. Treedown

[treedown in reply to depotdoug]

Correct 5 miles to the CC and after would ride an additional 6-20 some days, but a minimum of 5 to get back to where I parked. In addition for some odd reason I decided to break in a new Brooks leather saddle at the time. If your familiar with them you know it wasn't my brightest move as they are very hard. I had assembled a bike just for parking at the hospital that I would not have been upset had it gotten stolen. My avatar is a pic of the bike in front of the CC. In total I estimate I rode approx 742 miles during the 9 weeks of RT to and after the treatments. I also did rides on the weekend I did not count in that #. Really glad I did it reading things like this as it made me feel empowered at the time. Bike riding still means a lot to me and helps keep me sane.

[Nusch in reply to treedown]

Same for me. Running instead of riding the bike but also coming early to RT daily and meditate during each session. I’m now 10 days after VMAT (25 fractions) and looks like everything is back to normal.

[treedown in reply to Nusch]

That's great. Glad it worked out for you as well. I know not all of us are physically able to do this but for those young enough and fit at the time of dx it seems like a good idea. I was asymptomatic when my random and first PSA came back 156. It may have been different if like many the dx came from pain or worse.

[cesces]

So that's why Myers had me on low dosage Viagra.

[KocoPr in reply to cesces]

Can you elaborate on why LD viagra? I couldn’t find any articles on it for people with prostate cancer other than ED after RP

[cesces in reply to KocoPr]

To keep the cancer cells well oxygenated so they don't grow blood supply networks on their own.

Not fully logical to me. But then complex biological systems seldom are.

[Hidden]

Nice find. Thanks. I added this to my RT reference list.

Full article: Modulating Tumour Hypoxia in Prostate Cancer Through Exercise: The Impact of Redox Signalling on Radiosensitivity | Sports Medicine - Open | Full Text

sportsmedicine-open.springe...

Exercise is the best thing I've found to reduce blood sugar spikes. I did a few dozen experiments, eating a certain meal, adding supplements or drugs, not much change over baseline for most of them. Metformin did have a measurable effect. Berberine did absolutely nothing. I tested it over and over. Perhaps it does something long-term that I didn't pick up. But exercise was the biggest by far and could actually take the 2-hour area under the curve to a negative value! That means that you could eat and then exercise and not only would you not get a blood sugar spike you would see a blood sugar drop. I was the only test subject so I have no idea how others would fare. For exercise I did moderate 100-120 bpm stationary biking for 15-30 minutes and also tried heavy weightlifting. Cardio seemed better but both were better than anything else I tested.

If anyone is interested, some exercise references

1. Association of Muscle Mass with Survival after Radical Prostatectomy in Patients with Prostate Cancer pubmed.ncbi.nlm.nih.gov/309...

2. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review: Robert James Thomas, Stacey A Kenfield, Alfonso Jimenez bjsm.bmj.com/content/bjspor...

3. A prospective study of physical activity and incident and fatal prostate cancer: Edward L Giovannucci, Yan Liu, Michael F Leitzman, Meir J Stamfer, Walter C Willett pubmed.ncbi.nlm.nih.gov/158...

4. Recreational Physical Activity in Relation to Prostate Cancer-specific Mortality Among Men with Nonmetastatic Prostate Cancer: Ying Wang, Eric J Jacobs, Susan M Gapstur, Maret L Maliniak, Ted Gansler, Marjorie L McCullough, Victoria L Stevens , Alpa V Patel pubmed.ncbi.nlm.nih.gov/287...

5. MET-hour equivalents of various physical activities health.harvard.edu/staying-...

6. Muscle Mass Index as a Predictor of Longevity in Older-Adults Preethi Srikanthan, M.D., M.S. and Arun S. Karlamangla, M.D., Ph.D ncbi.nlm.nih.gov/pmc/articl...

7. Why Exercise Is Important When You Have Prostate Cancer, and the Best Workouts to Do: Maria C Masters livestrong.com/article/1372...

8. Muscle–Organ Crosstalk: The Emerging Roles of Myokines: Mai Charlotte Krogh Severinsen, Bente Klarlund Pedersen academic.oup.com/edrv/artic...

9. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review: Robert James Thomas, Stacey A Kenfield, Alfonso Jimenez bjsm.bmj.com/content/51/8/640

10. Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells – PubMed (Myostatin inhibition leads to non-androgenic muscle hypertrophy) pubmed.ncbi.nlm.nih.gov/230...

11. Greater stimulation of myofibrillar protein synthesis with ingestion of whey protein isolate v. micellar casein at rest and after resistance exercise in elderly men – PubMed pubmed.ncbi.nlm.nih.gov/222...

12. Myokine Signaling Blockade Prevents Androgen Deprivation Therapy Induced Sarcopenia and Suppresses Tumor Growth: Chunliu Pan Shalini Singh John Krolewski Kent Nastiuk faseb.onlinelibrary.wiley.c...

13. The effects of different exercise training mode on interleukin, 15_life0403_82_86.pdf lifesciencesite.com/lsj/lif...

[GreenStreet]

I exercised in a gym just prior to radiotherapy (SRT) didn’t help much because they were aiming in the wrong place as it turned out. Lol

[London441]

Thanks! Not surprising. The benefits of a combination of cardiovascular and strength training exercise are wide ranging, as has been noted.

I believe the true synergy of exercise with every one of the available treatment modalities, as well as its enhancement of our overall physical physiological, biological, mental and spiritual health as Pca patients is only beginning to be documented/proven.

Many fine phase 3 clinical trials with level 1 evidence report slight improvements in delayed disease progression and types of survival benefit from drugs, combinations etc.

However, it’s quite likely that the positive effects of these treatments alone are puny when compared to us assisting their efficacy through strong exercise and diet habits.

[pjoshea13]

Ferroptosis seems hot right now, with 36 (of 45) papers since last year.

However, I lost interest in 2018 when I read:

"Ferroptosis plays an important role in inhibiting some types of cancers, such as hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, and breast cancer. Conversely, the activation of ferroptosis accelerates neurodegeneration diseases, including PD and Alzheimer's disease."

I maintain a rather large family tree & took a DNA test to find matches on my father's side. I was offerred health risk factors (perhaps not wise to do so) & there was nothing to fear except a higher risk for Alzheimer's.

-Patrick

[Spyder54]

Patrick, thank you again for your many contributions. We are all looking for answers. I just went thru SEVERE HYPOXIA.

I pride myself on excercise. My URO/ONC here in St Pete says I am, by far, his most active patient. I took my Family to Breckenridge for my 68th Bday. We rented a nice home at 9,300’ above sea level. Sea level in St Pete to Denver right up to Breck same day. No energy to ski first half day. Started vomiting at 5pm. Stopped counting at 16! Made decision at 3am to head back to Denver (lower elev). On the drive back down to Denver my bone marrow and bones became so painful I was moaning and covered in sweat (like the Bends in diving from coming up too fast). Our daughter drove and said she was taking me to Denver ER. My bp was 219/160. Doc said I was in stroke territory. Couldn’t get bp below 200 until 7:30am. Morphine didn’t phase the pain. Added 2 more meds, and my daughter said I was snoring within 10 seconds. Wanted to check me in to hospital. Singed docs to go home to daughters home in Colorado Springs (like your example above-haha). Stayed for 2 days then went back up for 2 good days of skiing. No probs. I thought w common sense that Hypoxia may have done me some good by starving PCa cells of oxygen. The article above says opposite if I understand ? But the cardio from 20,000 vertical each day probably did some good. Playing 2-3 hrs of Pickleball 4 days per week since then with no issues. Kite surfing/foiling as this is the windy season. Walking the dogs at park. Some light weights. Seems good. First scans and bloodwork since SBRT RT in late Jan will be first week of May. Know that RT makes progress 18mos to 24 mos after procedure. Hoping for best,

Mike

St Pete, FL

[pjoshea13]

Hi Mike,

You say: "Made decision at 3am to head back to Denver (lower elev)." LOL - Denver, the "Mile High City” only 5280 feet above St. Pete.

When I viisited my daughter in Colorado Springs 30+ years ago, she warned me about needing to adjust before serious exertion. I didn't feel in good enough shape to drive up Pike's Peak. Supposedly, unwary teens with beer run into problems half way up. A half can can make one feel blind drunk if not adjusted.

Glad you returned safely.

-Patrick

[Spyder54 in reply to pjoshea13]

PJ,So am I right? The Hypoxia did not starve the PCa of oxygen? May have helped the PCa?

Mike

[pjoshea13 in reply to Spyder54]

Mike,

Hypoxia can only be helpful if on a HIF-1a inhibitor.

-Patrick

[KocoPr]

From reading this post and the that nice article on hypoxia inducing HIF1 i am wondering if Hyperbaric Oxygen Therapy would be beneficial? I have read quite a bit about it and bought one to increase oxygen in the tumor micro environment via plasma oxygen to stop the fermentation process. I have used it quite a bit but my mHSPC is still growing. I have tried keto with it but still growing I will be doing a trial with LU177 PSMA soon so i don’t know if I should start back on the Hyperbaric. Any thoughts on this?

That trial i just mentioned didn’t pan out. Oh well I’ll keep looking.

[pjoshea13 in reply to KocoPr]

If we improve the blood supply to a tumor, it will have no need to induce HIF-1a, but it will continue to grow as before.

Many years ago, I thought that hypoxia would be a good thing. I didn't know that HIF-1a was the kiss of death for drugs & radiation. Massive treatment resistance.

Oxygen is the lesser of two evils. We have no PCa-hyperbaric studies, but daily use makes sense.

As I mentioned earlier, PCa can sometimes induce HIF under normoxic conditions. But if one does not have HIF-1a, and is about to begin a new treatment, it seems to make sense to improve the oxygen supply. Perhaps it will delay resistance.

On a different topic, there have been more studies on the prognostic value of subclinical inflammation markers. Men do better on a wide range of therapies if they don't have inflammation. (I wrote about this 6 years ago, when there was already an association between chronic, albeit low-level, inflammation & a poor response to new treatment.

-Patrick

[Spyder54 in reply to KocoPr]

There was a post here on HU where a wife urged her husband to use a hyperbaric oxygen chamber, and her husbands PCa accelerated with the lab tech telling the wife that he had seen acceleration before and had to wonder if it was somehow feeding the PCa. I’ll seach the forum history and see if I can find it. Mike

[pjoshea13 in reply to Spyder54]

Hi Mike,

Hyperbasic oxygen has been used safely to treat problems associated with PCa treatment - rather than PCa itself.

From a 2019 Japanese paper [1]:

:"Hyperbaric oxygen therapy is a promising medical technology that delivers oxygen to targeted tissues at high pressure to increase the amount of dissolved oxygen in the blood. Over the past three decades, hyperbaric oxygen has been used in a variety of conditions, including radiation-induced tissue injuries, non-healing states with ischemia and malignant neoplasms. In the field of urology, hyperbaric oxygen has also been applied to some pathological conditions (e.g. radiation-induced hemorrhagic cystitis, Fournier gangrene, interstitial cystitis, male infertility, acute kidney injury and urological cancers). In normal and injured tissues, hyperoxia from hyperbaric oxygen therapy contributes to anti-inflammation, angiogenesis through endothelial proliferation, enhanced fibroblastic activity, increased lymphocyte and macrophage activity, and bactericidal effects with the aim of wound repair.

"In cancerous tissues, the enhanced supply of oxygen into the hypoxic cancer cells can exert inhibitory effects on factors that contribute to their aggressiveness (e.g. cell survival, escape from apoptosis, epithelial-to-mesenchymal transition and tumor immunotolerance), and sensitize the tumor to radiation therapy and chemotherapy.

"However, further research, including multicenter clinical studies, is essential for determining the role of hyperbaric oxygen therapy in refractory urological diseases that are resistant to conventional therapies."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/310...

Review Int J Urol

. 2019 Sep;26(9):860-867. doi: 10.1111/iju.14015. Epub 2019 May 13.

Potential of hyperbaric oxygen in urological diseases

Tomoaki Tanaka 1 2 , Akinori Minami 2 , Junji Uchida 2 , Tatsuya Nakatani 2

Affiliations collapse

Affiliations

1 Department of Urology, Suita Municipal Hospital, Suita, Osaka, Japan.

2 Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan.

PMID: 31083787 DOI: 10.1111/iju.14015

Abstract

Hyperbaric oxygen therapy is a promising medical technology that delivers oxygen to targeted tissues at high pressure to increase the amount of dissolved oxygen in the blood. Over the past three decades, hyperbaric oxygen has been used in a variety of conditions, including radiation-induced tissue injuries, non-healing states with ischemia and malignant neoplasms. In the field of urology, hyperbaric oxygen has also been applied to some pathological conditions (e.g. radiation-induced hemorrhagic cystitis, Fournier gangrene, interstitial cystitis, male infertility, acute kidney injury and urological cancers). In normal and injured tissues, hyperoxia from hyperbaric oxygen therapy contributes to anti-inflammation, angiogenesis through endothelial proliferation, enhanced fibroblastic activity, increased lymphocyte and macrophage activity, and bactericidal effects with the aim of wound repair. In cancerous tissues, the enhanced supply of oxygen into the hypoxic cancer cells can exert inhibitory effects on factors that contribute to their aggressiveness (e.g. cell survival, escape from apoptosis, epithelial-to-mesenchymal transition and tumor immunotolerance), and sensitize the tumor to radiation therapy and chemotherapy. However, further research, including multicenter clinical studies, is essential for determining the role of hyperbaric oxygen therapy in refractory urological diseases that are resistant to conventional therapies.

Keywords: Fournier's gangrene; hyperbaric oxygen; interstitial cystitis; prostate cancer; radiation-induced hemorrhagic cystitis.

© 2019 The Japanese Urological Association.

[KocoPr]

Thank you for the info. Question though? Is there a way to test if ones cancer is expressing HIF-1a ?

Also hyperbaric oxygen floods the plasma with high concentration of oxygen as it’s normal levels are 1.1% and HOT increases depending on the pressure you use. Cant find the % amount but the 2 articles i referenced below are good reading.

I wonder how angiogenesis is affected by enriched plasma oxygen since the red blood cells already have 99% O2. My thoughts are the tumors angiogenesis mechanism is only via red blood cells and could care less about the plasma levels of O2. My thinking and correct me if im wrong is the plasma levels of oxygen would directly effect the tumor micro environments ability to continue its fermentation process via anerobic and tactic acid environment.

I have a home chamber which the FDA only allows for 1.3 ata -atmospheres, equivalent to 11 ft under sea water. Breathing up to 97% oxygen.

Hospitals HBOTs are 3 ata and 99% oxygen brething. Much more restrictive because of the fire dangers of 99% O2.

Here is an interesting 2020 article on related pO2 levels.

pubmed.ncbi.nlm.nih.gov/326...

Abstract

In human blood, oxygen is mainly transported by red blood cells. Accordingly, the dissolved oxygen level in plasma is expected to be limited, although it has not been quantified yet. Here, by developing dedicated methods and tools, we determined that human plasma pO2 = 8.4 mmHg (1.1% O2). Oxygen solubility in plasma was believed to be similar to water. Here we reveal that plasma has an additional ascorbate-dependent oxygen-reduction activity. Plasma experimental oxygenation oxidizes ascorbate (49.5 μM in fresh plasma vs < 2 μM in oxidized plasma) and abolishes this capacity, which is restored by ascorbate supplementation. We confirmed these results in vivo, showing that the plasma pO2 is significantly higher in ascorbate-deficient guinea pigs (Ascorbateplasma < 2 μM), compared to control (Ascorbateplasma > 15 μM). Plasma low oxygen level preserves the integrity of oxidation-sensitive components such as ubiquinol. Circulating leucocytes are well adapted to these conditions, since the abundance of their mitochondrial network is limited. These results shed a new light on the importance of oxygen exposure on leucocyte biological study, in regards with the reducing conditions they encounter in vivo; but also, on the manipulation of blood products to improve their integrity and potentially improve transfusions' efficacy.

Here is another 2020 article on the physics of HBOT

ncbi.nlm.nih.gov/books/NBK4...

[pjoshea13 in reply to KocoPr]

Seemingly, there is a way to detect HIF-1a in blood, i.e. without needing a biopsy, but I doubt the test is available to us.

nature.com/articles/s41598-...

-Patrick