Insulin and Insulin- like growth factor seem to be risk factors for cancer.

Yes I understand. But would you think or claim or know if training which makes cells more insulin sensitive and increases growth hormon, or combination of training and high carb ingestion (insulin peak) would lead to a situation in which cancer cells CAN grow.

I ask this because I would think maybe some people would advocate that strength training might be dangerous for people with high cancer genetics. I focus more on sport so I was wondering for this idea. Of course training also has many benefits to health and cancer prevention.

Some clean bodybuilders ingest so much carbs and protein that maybe this might increase mTOR also in cancer cells, without taking steroids, growth hormons and/or injecting insulin.

Further amended on 12 May 2018

I have surprized that mTOR (mechanistic target of rapamycin) or Serine/threonine-protein kinase mTOR/FK506-binding protein 12-rapamycin complex-associated protein 1/FKBP12-rapamycin complex-associated protein/Mammalian target of rapamycin/mTOR/Mechanistic target of rapamycin/Rapamycin and FKBP12 target 1/Rapamycin target protein 1 protein (Protein serine/threonine kinase; Mr 290,000) is not present in my Human protein database (our unpublished observation).

Hepatocyte HepG2 (cultured with edible Japanese Fucoidan at 0.102 mg/mL for three days) has similar protein of Regulatory-associated protein of mTOR/Raptor/p150 target of rapamycin (TOR)-scaffold protein/RPTOR/KIAA1303, RAPTOR (Regurator of Protein serine/threonine kinase; Mr 150,000) at 5.2 μg/mg of cell protein (please see file; HepG2 fucoidan). Therefore, this Raptor seems to be working an important unknown role in the normal skeletal muscle cells.

mTOR has been firstly found in the yeast (Saccharomyces cerevisiae), but seems to be absent in humans. Notorious Autophagy is also not present in Humans (our recent unpublished observation).

I am now thinking that Insulin-like growth factor 1(IGF-1), Growth hormone (GH), and Prolactin (PRL) are dangerous. Thus, I have found that as follows; i.e.,

HCC tissue (with PBC, Japanese female; who has died) has Growth hormone receptor/GH receptor at 12.4, Insulin-like growth factor-binding protein 5/IGFBP-5/IBP-5 at 3.0, and Insulin-like growth factor binding-protein 3/IGFBP-3/IBP-3 at 0.7, and Interferon alpha/beta receptor 1/IFN-alpha/beta receptor 1 at 9.5 μg/mg of tissue protein, respectively. (Total 25.6 μg/mg of tissue protein)

Hepatoma HepG2 (cultured without fucoidan, male Caucasoid, who has died) has Insulin receptor substrate 2/IRS-2 at 15.0, Down syndrome cell adhesion molecule/DSCAM at 6.8, and Transforming growth factor beta receptor type 3/TGF-beta receptor type III/Betaglycan at 2.7 μg/mg of cell protein, respectively. (Total 24.5 μg/mg of cell protein)

HCC tissue (named as No.6, male Japanes, who has survived) has Prolactin receptor type 2 at 6.4, Fibroblast growth factor receptor 1/BFGF-R at 1.0, Fibroblast growth factor receptor 2 at 1.0, Interferon-alpha receptor/IFN-alpha-Rec at 0.41, Interleukin-7 receptor alpha chain/IL-7RA at 0.29, and Transforming growth factor beta receptor type 3/TGF-beta receptor type III/TGFR-3/Betaglycan at 5.0 μg/mg of tissue protein, respectively. (Total 14.1 μg/mg of tissue protein)

Therefore, I must explain why such phenomena of gene expression has been occurred.

IGF-1, GH, and PRL receptors use JAK-STAT pathway, but EGF and Insulin receptors use MAPK pathway. Both JAK-STAT and MAPK are protein tyrosine kinases (PYK). JAK protein is seldom found; i.e., only HCC tissue (with PBC) has Interferon alpha/beta receptor 1/IFN-alpha/beta receptor 1 at 9.5 μg/mg of tissue protein. STAT protein (Signal transducer and activator of transcription 1-alpha/beta / Transcription factor ISGF-3 components p91/p84) is not present in my protein database.

By the way, major protein of skeletal muscle is connectin (firstly discovered by famous Dr. Koscak Maruyama (The Tokyo University, Komaba-cho, Shibuya-ku, Tokyo, Japan); please see file, Connectin Maruyama JB), and connectin has pseudokinase domain of JAK pathway. Therefore, IGF-1, GH, and PRL seem to be very dangerous to healthy adult-human skeletal muscle.

By the way, enzyme (lipoamidase) has wide range of substrate specificities (please see file; Multiple hydrolase LIP). Then, kinases and phosphatases also may have wide range of substrate specificities.

Therefore, kinases - phosphatses are investigated.

HCC tissue (with PBC; who has sadly died) has kinases at 46.3 μg/mg of tissue protein. Phosphatase is not present. The diffrence is 46.3 μg/mg of tissue protein.

Hepatoma HepG2 (cultured without edible fucoidan; male Caucasoid, who has sadly died) has kinases at 225.4 μg/mg of cell protein. Phosphatase is present at 6.1 μg/mg of cell protein. The difference is 219.3 μg/mg of cell protein.

HCC tissue (named as No.6; who has survived) has kinases at 12.8 μg/mg of tissue protein. Phosphatases are present at 17.2 μg/mg of tissue protein. The difference is minus 4.4 μg/mg of tissue protein, or phosphatases are present in higher amount than kinases. This high expression of phosphatases may be the reason why he has survived.

Insulin may also be dangerous if phosphatase is present in low amount or absent.

Exasperated phosphorylation of proteins may reduce the membrane compartment of cancer cells (decreased membrane compartment is the main characteristics of cancer cells; please see file again, HepG2 fucoidan).

Thank you again to Dr. Peter Griepink to leading me to these important results.

no specialist. But much sport science is about mTOR activation so would it not be in skeletal muscle also?

The JAK-STAT I looked upon (quick and again no expert) but I saw it can both involve the mTOR pathway (Akt) and the AMPK, which inhibits mTOR. So for sport science this is interesting. AMPK is involved if the cell energy is low in amp/atp, so how would that relate to JAK-STAT.

Many thanks

Further amended on 7 May 2018

I have searched AMPK (5'-AMP-activated protein kinase catalytic subunit alpha-1/AMPK subunit alpha-1) in my human protein database in vain.

LC tissue (named as No.6 with pseudo liver cancer; normal tissue; male) has cAMP-dependent protein kinase type I-beta regulatory chain/Tissue-specific extinguisher 1 at 2.4 μg/mg of tissue protein.

Therefore, humans may not use ATP as a major energy source.

By the way, I would like to say about the abuse of growth hormones.

Growth hormone/Somatotrophin and Insulin, which have no glycochain, may be uptaken without digestion, and may give physiological and patho-physiological effects. Over dose of nutrition and hormone gives to induce many diseases (please see file; Feed by Measure). Insulin-like growth factor I/IGF-I/Somatomedin-C and Prolactin/PRL are glycoproteins and seems to be not uptaken in the gut (only human breast milk has N-Glycanase). But, uptaken Growth hormone can induce the liver to produce IGF-I, and dangerous.

Recombinant Insulin-like growth factor I/IGF-I/Somatomedin-C and Recombinant Prolactin/PRL, which have no glycochain, also are uptaken without digestion. Therefore, these two recombinant hormones seem to induce allergy (since glycochain is absent; recombinant hormone is structurary different from natural hormone with respect to glycochain structure) and to induce cancer (via up-regulating dangerous membrane proteins IGF-I receptor and PRL receptor).

If rBST（recombinant Bovine Somatotrophin）or rBGH （recombinant Bovine Growth Hormone） are fed with feeds, physiological effect seems to appear, but the meat and bovine milk of these hormone-fed cows may contain rBST or rBGH. Therefore, if humans eat these meat and bovine milk of these hormone-fed cows, the injested persons may become to allergy and cancers.

Estradiol 17β, Progesterone, and Testosterone seem to not induce cancer at low dose but to induce morphology changes in humans. Excess of Steroid Hormones and Vitamin D in Cow's feeds may also induce cancer in humans.

Further, AquAdvantage salmon (genetically modified (GM) Atlantic salmon; A growth hormone-regulating gene from a Pacific Chinook salmon (King salmon) has been added to the Atlantic salmon's genes) and aquafarming cultivation of salmon using growth hormones seem also to be dangerous to injested humans.

Therefore, "Natural foods" and "Feed by measure and defy the physician" are strongly recommended in humans.

Furthermore added on 10 May 2018

Sports influence on the metabolism of kidney (please see file; Urinary alb deter in HPSEC). Cycling seems to be a good sport.

But if you have kidney cancer you would not promote strength training but only cardio?

Amended on 12 May 2018

I think that cardio exercise may induce hypoxy and/or hyperoxygenation stress, although cardio exercise may reduce lipids of the body (I do not know such a conclusive research paper). But, I like to say that ATP is not the major energy source in humans, and NADH or reduced-form lipoic acid (via electron transport system) may be the major energy souce since humans is aerobic. I must consider about the energy source of fucoidan transport (please see file; JCB Fucoidan transport). Since active transport of fucoidan seems to be occurred through plasma membrane, I am considering that plasma membrane may have the oxidation system for NADH and reduced-form lipoic acid/thioctic acid without relation to mitochondrial ATP.

I have found a research paper by Late Hon. Prof. Dr. Tsuneo Okuyama (Department of Chemistry, Faculty of Science Tokyo Metropolitan University, Tokyo, Japan, and my teacher of HPLC at the Tokyo Research Center, Shimadzu Co., Shibasaki-cchou, Chofu-city, Tokyo, Japan), who has described about the presence of plasma membrane NADH dhydrogenase (Erythrocyte has no mitochondria).

Biochim Biophys Acta. 1972 Jun 16;268(3):629-37. Study on the reduced pyridine nucleotide dehydrogenase of bovine erythrocytes. I. Crystallization and properties of the reduced pyridine nucleotide dehydrogenase of bovine erythrocytes. Adachi K, Okuyama T.

Abstract; Reduced pyridine nucleotide dehydrogenase (NADH: (acceptor) oxidoreductase, EC 1.6.99.3) of bovine erythrocytes was purified with DEAE-cellulose chromatography, ammonium sulfate fractionation (30–65%) and DEAE-Sephadex A-50 chromatography. One major and three minor active fractions were eluted with DEAE-Sephadex A-50 chromatography. The major active fraction was crystallized with ammonium sulfate. The sedimentation coefficient (s020,w) of this enzyme was 2.5 S and the molecular weight 2.9·104. Absorption spectra showed a maximal absorbance at 406 nm and a shoulder at 450 nm, but with repeated crystallization the absorbance at 406 nm decreased. The ratio of absorbance at 406 nm against 278 nm was 0.026, which was smaller than that obtained by other workers, and the absorption spectrum and fluorescence measurements showed that this enzyme contained neither flavin nor heme. The molar absorbance coefficient at 278 nm of this enzyme was calculated by amino acid analysis as 2.46·104. The relative activity for dehydrogenation of NADH and NADPH was approximately 2.9/1.0 at pH 7.5.

Stress is not good to cancer, and mental stress may be reduced by adequate smoking unexpectedly. When I have worked as an arbiter undergone a medical examination, strong mental stress given by a boss has induced tachycardia and high blood pressure to me, but after the smoking both tachycardia and high blood pressure have returned to normal levels (my unpublished experience at The University of Tokyo).

ATP is needed for a contraction of myosin and actin and creates movement. ATP is formed in the glycolysis, and krebs cyclus. Most ATP is formed in the ETS which uses NADH and FAD that are created through the cycle.

Cardio will create hypoxia and ROS mostly this will increase hif1/2a and redd 1.2 which will activate TSC1 and inhibit mTOR, so for cancer cell this might lead to no growth. For muscles no myofibrillar growth.

The ROS will form more mitochondria (at least in a healthy person) So more energie can be created and less chance of low adp/atp ratio. However AMPK will block mTOR so cardiovascular would be good in this case, but the adaptation will create that next time with cardio AMPK will be less involved. The only choice is to keep improving cardio, but that would be hard to do when someone is sick.

It might be that doing cardio with not eating much can lead to a situation of more inhibition of mTOR. So low CHO, low PRO, low insulin, low Growth hormone, low testosterone. Maybe fibers, slow CHO and fats might be okay.

Anyway it is complex and interesting.

Many thanks

Production of Energy-source in Humans is an important issue.

I have searched energy-source producing enzymes in Lactobacillus casei Shirota. This bacterium is facultative anaerobic and/or microaerophilic.

NADH producing enzymes of Proline dehydrogenase and Hydrogenase 2 are present at 50.0 μg/mg of cell protein. ATP producing enzyme of ATP synthase is present at 19.1 μg/mg of cell protein.

Humans with mitochondria is obligate aerobic like Bacillus subtilis and Pseudomonas K-62. Escherichia coli is a facultative anaerobic bacteria.

Therefore, Humans seems to obtain NADH as an energy source from mitochondria. Unexpectedly, ATP seems to be not working in aerobic Humans.

Further added on 15 June 2018

Carbohydrate metabolism is important in Sports Medicine.

I have searched Insulin-related and Glucose Transport Proteins in my protein database. Interstingly, Insulin receptor (IR) and Solute carrier family 2, facilitated glucose transporter member 4/GLUT4/Glucose transporter type 4, insulin-responsive/SLC2A4 are not present in my database.

Healed hepatocyte HepG2 (cultured with fucoidan for 3 days) has Solute carrier family 35 member G2/Transmembrane protein 22 at 0.6 μg/mg cell protein, and has protein of Human adenovirus type 40/HAdV-40 (dsDNA, no envelope) at 3.8 μg/mg cell protein.

Liver tissue with pseudo-liver cancer has Sodium-glucose cotransporter/Solute carrier family 5 member 1/SLC5A1 at 11.2 μg/mg tissue protein, and has protein of Human adenovirus-7/HAdV-7 at 2.0 μg/mg tissue protein.

LC(Liver Cirrhosis) tissue (complicated with leprosy) has Solute carrier family 2, facilitated glucose transporter member 1/GLUT1/ SLC2A1/HepG2 glucose transporter/Glucose transporter type 1, erythrocyte/brain at 4.9 μg/mg tissue protein, and has protein of Human adenovirus/HAdV at 2.9 μg/mg tissue protein.

LC tissue (named as No.6) has Glucose transporter type 1 erythrocyte/brain/GLUT1 at 2.1 μg/mg tissue protein, and has protein of Human adenovirus-2/HAdV-2 and Avian adenovirus 1/AAdV-1 at 2.6 μg/mg tissue protein.

HCC tissue (named as No.6) has Sodium/glucose cotransporter-like protein/SGLT2 at 1.2 μg/mg tissue protein, and has protein of Human adenovirus-12/HAdV-12 at 4.6 μg/mg tissue protein.

Therefore, Carbohydrate transporter genes seem to be up-regulated by Human adenovirus/HAdV.

LC tissue (named as No.6) has Insulin-degrading enzyme/Insulinase/IDE at 4.0 μg/mg tissue protein (present at membrane sub-fraction), and has Pol polyprotein (Simian Immunodeficiency virus/SIV; retrovirus) at 7.5 μg/mg tissue protein.

HCC tissue (named as No.6) has Insulin-degrading enzyme/Insulinase/IDE at 13.3 μg/mg tissue protein (present at soluble fraction), and has Gag polyprotein (SIV/Chimpanzee-IV) at 10.9 μg/mg tissue protein.

Therefore, Insulinase gene seems to be up-regulated by SIV.

Therefore, knowledges about infection-state by virus are very important to study about Sports Medicine.

Thank you so much!