Hi Everyone,
I am encountering a strange problem in mouse lung cancer studies
I have 2 sets of mice:
1. flox/flox +KrasG12D with Cre (Homo Test)
2. flox/WT + KrasG12D with Cre (Hetero Ctrl)
I use Tamoxifen to induce the expression of Cre (Tamoxifen = 1.5mg/ 5 times) to 4-5 weeks old mice. The problem is after 5-6 weeks of injection my hetero control mice are becoming sick (Hunched back and less movement) and losing weight. BUT my homo test mice are all fine.
My homo test mice are getting more tumors in the lungs compared to hetero control (which was expected) but why the hetero mice display such a weird phenotype. The lungs of these sick mice are exceptionally large (almost 2-3 times bigger ) and look very different from homo test mouse.
Does anyone have any experience with Flox/WT mice + KrasG12D getting sick? Pls share your thoughts & papers if any. I would be really grateful for any advise.
FYI : Without Krasg12D, Just Flox/WT + cre & Flox/Flox + cre mice are all perfectly fine. Just the combination of hetero (flox/WT)+krasg12d is giving this problem.
Thanks,
Apoorva
Amended on 13 April 2019
I have searched for GTPase KRas/K-Ras 2/Ki-Ras/c-K-ras/c-Ki-ras in my protein database in vain (please see files; HepG2 Fucoidin/Fucoidan, JMBT Alopecia, and The Fascio effect).
Further, I have found that PD-1/Programmed cell death 1, EGFR and Estrogen receptor/ER are also not present in Humans. Androgen receptor/Nuclear receptor subfamily 3, group C, member 4, Glucocorticoid receptor/GR, and Nuclear receptor subfamily 4 group A member 2/Orphan nuclear receptor NURR1 are present in Humans. IgD is present in human breast milk; i.e., IgD is present in primates, dog, mouse and rat whereas it is undetectable in rabbit, guinea pig, swine, cattle, sheep and frog.
Therefore, Tamoxifen and Nivolumab/Opdivo and/or Pembrolizumab are not effective to humans at all, but effective to mouse.
Thus, Japanese edible Fucoidan and/or edible brown alga Kinu-Mozuku now become to be an unique safe anti-cancer drug and/or anti-cancer foodstuff without side effects.
This is due to famous Species differences and/or to non-reliable DNA technology.
Therefore, Mouse and Rat should not be used in the cancer research.
I have luckily prevented the rat liver cancer by Fucoidin/Fucoidan. This is due to the strong power of Fucoidin/Fucoidan to reduce virus and bacteria safely (please see file; Rat DEN Np-Fuco and again the file "HepG2 Fucoidin"). Human liver cancer is caused by co-infection of human specific HIV-1 and HCV. Thus, HCC patient has low immunity due to HIV. Interestingly, more additive co-infection of pig specific Hog cholera virus/Classical swine fever virus/CSFV and/or HGV/Hepatitis G virus/GB virus C/GBV-HGV/GBV-C to the liver cancer patients (with lowered immunity) causes sudden death. CSFV and/or HGV can strongly repress the Apolipoprotein B-100/Apo B-100 expression. HCV up-regulates this gene, but expression of Apo B-100 is completely repressed if the amount of CSFV and/or HGV is superior to the amount of HCV.
HCC tissue (named as No.6; who has survived) has SIV and HCV. SIV seems to be lower immuno supressive activity than HIV-1. This tissue has Genome polyprotein (HCV; up-regulating virus for Apo B-100) at 0.61, and Genome polyprotein (Hog cholera virus/Classical swine fever virus/CSFV; down-regulating virus for Apo B-100) at 0.74 μg/mg of tissue protein, respectively. Then, CSFV and HCV are competing in this tissue, and Apolipoprotein B-100/Apo B-100 is richily expressed at 33.4 μg/mg of tissue protein.
Hepatoma HepG2 (derived from cancer liver of Caucasian of USA, 15y male; who has deceased) has no Apo B-100, but has Vigilin/HDL-binding protein at 1.9 μg/mg of cell protein. This cell has Genome polyprotein (HCV) 7.8, Genome polyprotein (HGV/GB virus C/GBV-HGV/GBV-C) at 15.4, and proteins of HIV-1 at 15.8 μg/mg of cell protein, respectively.
Healed normal hepatocyte HepG2 (cultured with Japanese edible fucoidan at 0.102 mg/mL for 3 days) has Apolipoprotein B-100/Apo B-100 at 29.7, and Vigilin/HDL-binding protein at 5.0 μg/mg of cell protein, respectively. This normal cell has Genome polyprotein (HCV) at 1.9 μg/mg of cell protein. HIV-1 and Pig virus of HGV/GB virus C/GBV-HGV/GBV-C are not present.
Therefore, presence of Apo B-100 and/or presence of cholesterol homeostasis is very important for HCC patients to alive.
I am now estimating that liver cancer of SD rat, which is induced by a stress-inducing chemical carcinogen of DEN/Diethylnitrosamine, has been caused by co-infection of retrovirus of rat in the past (Rat sarcoma virus or Murine leukemia virus) and Murine hepatitis virus/MHV.
By the way, it is said that iPS cell has been established by using these genes of mouse; i.e., Oct3/4 protein/POU domain, class 5, transcription factor 1, Nanog/Homeobox protein NANOG, Leucine rich repeat protein, contains F-box/FBX1, Sox2/SRY-box containing gene 2, Klf4/Krueppel-like factor 4/Epithelial zinc finger protein EZF/Gut-enriched krueppel-like factor, and c-Myc/Myc proto-oncogene protein/Class E basic helix-loop-helix protein 39/Proto-oncogene c-Myc/Transcription factor p64. But, these proteins are not present in humans as determined by the new proteomics PDMD method (our unpublished observation). This may be due to Species differences between Humans and Mouse.
As a reference, Human fetal hepatocyte expresses following genes; i.e.,
Zinc finger protein 880/Zinc finger protein LOC400713 at 5.5, Transcription factor Sp5 at 7.3, SEN1 homolog/Probable helicase senataxin at 4.3, Nuclear protein ZAP3/YLP motif-containing protein 1 at 5.7, Modulator recognition factor 2/AT-rich interactive domain-containing protein 5B at 8.6, Jumonji domain-containing protein 2B at 9.4, Histone deacetylase 4/HDAC4 at 15.0, and Coiled-coil and C2 domain-containing protein 1B/Freud-2 at 2.9 μg/mg of cell protein, respectively (please see file; HepG2 Fucoidin).
Since Hepatocellular carcinoma/HCC is occurring by the co-infection of HIV-1 and HCV. HCV is infecting to cells rich in Nutritions or cells rich in D-biotin; i.e., I have surprized to see that serum of 3y4mo girl (with biotin deficiency, alopecia, and GSD-1b) before biotin therapy has no HCV, but serum after long oral biotin therapy at 10 mg/mL for 8mo (alopecia is healed) surely be infected only by the HCV (other virus is not present) (our unpublished observation, and see the file again; JMBT alopecia). Thus, iPS cells may be infected during rich culture period. Then, iPS cells seem to become surely the cancer cells, but ES cells (without added retrovirus) seem to become non-cancer cells in lower frequency.
Other serum of biotin therapy patient for 13w (4y1mo girl, alopecia has been cured) has been infected by HIV-1 and Koala retrovirus.
Another serum of biotin therapy patient for 44w (1y11mo girl, alopecia has been cured) has been infected by HCV, HCoV, AKV Murine leukemia virus.
Adult serum with biotin deficiency and with Gait disorder (32y female; after the biotin therapy by dried Yeast (Ebios) and Lactobacillus casei, shirota (Yakult); Gait disorder has partially healed) has been infected by HCV and CCoV.
By the way, I am now estimating that human breast cancer is caused by the co-infection of HIV-1 and Dengue virus/DENV (Flavivirus) or Sindbis virus/SINV (Togavirus).
Human lung cancer semms to be caused by the co-infection of HIV-1 and ACoV, CCoV, or bacteriophage (+ssRNA, enveloped) of Mycoplasma pneumoniae (our unpublished estimation).
Furthermore, sad Morphological disease of Harelip is present. This disease is showing famous Species differences; i.e., biotin deficiency in Mother causes Harelip in the Mouse, but does not induce it in the Rat. Morphological Disease of Harelip or Cleft lip may be occurred similar mechanism to Alopecia (please see again; JMBT Alopecia). As has also been recently reported in this ResearchGate that Transcription factors of Homeobox proteins have been up-regulated by some inducing virus (HAV, VSIV, LIV, hPIV-5, MuV), and repressed by Flu virus.
Harelip-linked Homeobox protein MSX-1/Hox-7 seems to be up-regulated by Hepatitis A virus (HAV). HAV infection to pregnant mother may be occurred by biotin deficient state, which induces lowered innate immunity. HAV seems to infect preferably to female, and Flu seems to virulently infect to male (harelip seems to be higher in male persons; my unpublished observation). As shown in Alopecia case, Morphological change is also co-induced by biotin deficiency, which leads to instable membrane structures. Since fucoidan (sulphated poly-L-fucose) can reduce virus and bacteria without any side effect (very safe even to pregnant womem), taking edible fucoidan or edible brown algae (except inedible fucoidan from Ireland) may rescue the miserable morphological changes in the birth of humans.
About the grief Down syndrome.
It seems to be mainly due to infection by Human adenovirus/HAdV (linear dsDNA). Only three specimens have the Down syndrome cell adhesion molecule/DSCAM (a membrane glycoprotein).
Serum of 1y girl (with biotin deficiency and alopecia) has Down syndrome cell adhesion molecule/DSCAM at 9.8 μg/mg of serum protein. This serum has Maturation protein (Human adenovirus type 6/HAdV-6) at 7.7 μg/mg of serum protein.
Healed normal hepatocyte HepG2 (cultured with fucoidan) has Down syndrome cell adhesion molecule/DSCAM at 5.6 μg/mg of cell protein. This normal cell has DNA polymerase (Human adenovirus type 40/HAdV-40) at 0.9, and Fiber protein/Protein IV (Human adenovirus type 12/HAdV-12) at 0.4 μg/mg of cell protein, respectively.
Hepatoma HepG2 (cultured without fucoidan) has Down syndrome cell adhesion molecule/DSCAM at 6.8 μg/mg of cell protein. This cancer cell has Packaging protein 3 (Human adenovirus type 2/HAdV-2) at 0.2 μg/mg of cell protein.
Added on 14 April 2019
Since transcription factors (TFs) seem to be important in the cancer research, I have further studied.
Normal fetal hepatocyte Hc (similar to ES cell) has Zinc finger protein 880/Zinc finger protein LOC400713 at 5.5, Transcription factor Sp5 at 7.3, SEN1 homolog/Probable helicase senataxin at 4.3, Nuclear protein ZAP3/YLP motif-containing protein 1 at 5.7, Modulator recognition factor 2/AT-rich interactive domain-containing protein 5B at 8.6, Jumonji domain-containing protein 2B at 9.4, Histone deacetylase 4/HDAC4 at 15.0, and Coiled-coil and C2 domain-containing protein 1B/Freud-2 at 2.9 μg/mg of cell protein, respectively. Total TFs become to be 58.7 μg/mg of cell protein or 5.9% among cell proteins.
Normal healed hepatocyte HepG2 (cultured with Japanese edible fucoidan) has Zinc finger SWIM domain-containing protein 5/KIAA1511 at 1.6, Zinc finger MYM-type protein 1 at 4.1, Zinc finger protein 445 at 0.82, Zinc finger protein 460 at 0.72, Zinc finger protein 518 at 6.3, Zinc finger and SCAN domain-containing protein 2 at 0.27, Teashirt homolog 1 at 0.13, T-cell leukemia homeobox protein 2 at 0.04, Signal transducer and activator of transcription 4 at 5.5, Regulatory-associated protein of mTOR/Raptor at 5.2, Protein KIBRA/Kidney and brain protein/HBeAg-binding protein 3/WW domain-containing protein 1 at 0.49, Probable JmjC domain-containing histone demethylation protein 2C at 2.3, SEN1 homolog/Probable helicase senataxin at 1.2, Leucine-zipper-like transcriptional regulator 1at 8.4, Hypoxia-inducible factor 1 alpha at 0.63, HIV-EP2/Transcription factor HIVEP2/Human immunodeficiency virus type I enhancer-binding protein 2 at 1.4, Homeobox protein HMX3/Transcription factor HMX3 at 0.034, Homeodomain-interacting protein kinase 2 at 5.5, Histone H3-K9 methyltransferase 4/Histone-lysine N-methyltransferase, H3 lysine-9 specific SUVH4 at 0.67, Histone deacetylase 7a/HD7a/Histone deacetylase 7 at 0.09, Chromobox protein homolog 2 at 2.0, Cancer-amplified transcriptional coactivator ASC-2/Nuclear receptor coactivator 6/Activating signal cointegrator 2 at 5.3, and BRG1-associated factor 170/SWI/SNF complex subunit SMARCC2 at 4.7 μg/mg of cell protein, respectively. Total TFs become to be 57.39 μg/mg of cell protein or 5.7% among cell proteins.
Hepatoma HepG2 (who has deceased; cultured without fucoidan) has Zinc finger protein 16/Zinc finger protein KOX9 at 1.4, Zinc finger protein 366/Dendritic cell-specific transcript protein at 2.3, Zinc finger protein 614 at 3.1, Zinc finger protein 694/Zinc finger protein with KRAB and SCAN domains 2 at 1.7, Zinc finger protein 710 at 2.0, Zinc finger protein 84/Zinc finger protein HPF2 at 4.7, Unconventional prefoldin RPB5 interactor 1/RNA polymerase II subunit 5-mediating protein/Protein phosphatase 1 regulatory subunit 19 at 1.7, Transcription factor Dp-1 at 0.22, Transcription elongation factor SPT5 at 2.6, TATA-binding protein-associated factor 172/ATP-dependent helicase BTAF1 at 11.8, SWI/SNF complex subunit SMARCC1/SWI/SNF complex 155 kDa subunit at 3.1, SET and MYND domain-containing protein 3 /Histone-lysine N-methyltransferase SMYD3 at 0.4, REST corepressor 3 at 2.6, Pinin at 0.76, Nuclear receptor coactivator 1/Renal carcinoma antigen NY-REN-52 at 4.8, Neurogenin 2 at 3.0, Myb-related protein B at 5.3, mTERF domain-containing protein 2/Transcription termination factor 4, mitochondrial at 0.54, Methyltransferase-like protein 6/Protein arginine methyltransferase 6 at 0.83, Jumonji domain-containing protein 1B/Jmj C domain-containing histone demethylation protein 2B/Lysine-specific demethylase 3B at 8.6, Hypoxia-inducible factor 1alpha at 1.4, Transcription factor HIVEP2/HIV-EP2/Human immunodeficiency virus type I enhancer-binding protein 2/HIV-1-EP2 at 5.4, HIV Tat-specific factor 1 at 1.6, Histone-lysine N-methyltransferase SUV39H1/Histone H3-K9 methyltransferase 1 at 9.7, Histone-binding protein RBBP7/Retinoblastoma-binding protein 7 at 0.4, DNA-directed RNA polymerase III subunit RPC7/DNA-directed RNA polymerase III subunit G at 0.58, CREB-binding protein at 1.8, Bromodomain and WD repeat domain-containing protein 1 at 8.0, Breast tumor novel factor 1/Chordin-like protein 2 at 0.97, ATP-dependent helicase 1/SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 at 1.4, ATPase family AAA domain-containing protein 2/AAA nuclear coregulator cancer-associated protein at 23.8, 5'-3' Exoribonuclease 2 at 2.7, and Splicing factor, proline- and glutamine-rich/100 kDa DNA-pairing protein/SEPQ at 2.1 μg/mg of cell protein, respectively. Total TFs become to be 12.34 μg/mg of cell protein or 12.1% among cell proteins.
Normal liver (with pseudo liver cancer) has 14-3-3 Protein Eta/Protein AS1 at 1.73, AT-rich interactive domain-containing protein 1A/SWI/SNF complex protein P270/B120/ARID domain-containing protein 1A at 9.8, Bone morphogenetic protein 7/Osteogenic protein 1 at 21.3, DNA-templated cAMP-response element binding protein/CreB at 1.5, Cyclic AMP-dependent transcription factor ATF-1/Protein TREB36/Activating transcription factor 1 at 1.5, DNA-directed RNA polymerase II subunit RPB1/DNA-directed RNA polymeras II subunit 2 at 4.8, EMSY protein/GL002/BRCA2-interacting transcriptional repressor EMSY at 3.1, Homeobox protein Hox-B7/Homeobox protein Hox-2C at 1.3, Forkhead box protein N2/Human T-cell leukemia virus enhancer factor/HTLF at 1.3, Insulinoma-associated protein 1 /Zinc finger protein IA-1 at 0.44, Lupus KU autoantigen protein P86/X-ray repair cross-complementing protein 5 at 0.51, Lysine-specific demethylase 6A/Ubiquitously transcribed X chromosome tetratricopeptide repeat protein at 2.0, Mitogen-activated protein kinase kinase kinase 9/Mixed lineage kinase 1/MAP3K9 at 14.9, Ras GTP-activating protein nGAP/RAS protein activator like 1 at 6.8, Peroxisome proliferator-activated receptor delta/PPAR-beta; Nuclear hormone receptor 1 at 4.0, RNA-binding motif protein, X chromosome/Heterogeneous nuclear ribonucleoprotein G/Glycoprotein G43 at 1.2, Transcription factor AP-4/Class C basic helix-loop-helix protein 41 at 2.0, Ubiquitin carboxyl-terminal hydrolase 36/Ubiquitin thioesterase 36 at 7.4, Zinc finger E-box-binding homeobox 1NIL-2-A zinc finger protein at 1.6, and Zinc finger Y-chromosomal protein at 7.3 μg/mg of tissue protein, respectively. Total TFs become to be 94.48 μg/mg of tissue protein or 9.45% among tissue proteins.
LC tissue (with leprosy; who has deceased) has Acute myeloid leukemia 1 protein/CBF-alpha-2/Runt-related transcription factor 1/Oncogene AML-1 at 0.27, Beta-Catenin/Catenin beta-1 at 3.2, COUP transcription factor/COUP-TF at 2.4, Glycoprotein hormones alpha chain/Luteinizing hormone alpha chain at 0.88, GLIPR1-like protein 1 at 0.33, Heat shock protein HSP 90-beta/HSP 90 at 3.6, Homeobox protein OTX1 at 6.6, Homeobox/POU domain protein RDC-1/Brain-specific homeobox/POU domain protein 3A at 1.6, Mineralocorticoid receptor at 0.19, Ring3 protein/Really interesting new gene 3 protein/Bromodomain-containing protein 2 at 3.1, Transcription factor jun-D at 1.6, Transcription initiation factor IIF subunit alpha/General transcription factor IIF subunit 1/Transcrition factor IIF, alpha subunit at 6.5, Transcription initiation factor IIF subunit alpha /Transcrition factor IIF, alpha subunit at 3.4, Transducin-like enhancer protein 1/Enhancer of split groucho-like protein 1 at 5.0, Zinc finger protein HRX/Histone-lysine N-methyltransferase 2A at 72.5 μg/mg of tissue protein, respectively. Total TFs become to be 111.17 μg/mg of tissue protein or 11.1% among tissue proteins.
HCC tissue (with PBC; who has deceased) has Androgen receptor/Nuclear receptor subfamily 3, group C, member 4 at 7.1, CCAAT/enhancer-binding protein beta/Nuclear factor NF-IL6/C/EBP beta at 3.6, DNA-directed RNA polymerase II subunit RPB1at 33.5, DNA-templated Endothelial actin-binding protein/Filamin A at 20.6, Homeobox protein MSX-1/Hox-7 at 1.1, Mast/stem cell growth factor receptor Kit at 3.0, Tact Peptidyl-glycine alpha-amidating monooxygenase/PAM at 0.89, Phosvitin/Casein kinase II, beta chain at 1.0, Receptor tyrosine-protein kinase erbB-2/Proto-oncogene Neu/CD340 at 5.7, Ring3 protein/Really interesting new gene 3 protein/Bromodomain-containing protein 2 at 7.7, Steroid hormone receptor ERR2/Estrogen receptor-like 2 at 2.2, Transcriptional activator GLI3/Gli3 protein at 11.7, and Transcription initiation factor TFIID subunit 1/TAFII-250 at 20.3 μg/mg of tissue protein, respectively. Total TFs become to be 118.39 μg/mg of tissue protein or 11.8% among tissue proteins.
LC tissue (named as No.6; who has survived) has Gli3 protein/Transcriptional activator GLI3 at 30.2, Helix-loop-helix protein 2/HEN2 at 1.4, Hepatocyte nuclear factor 1-beta /HNF-1B at 1.2, High mobility group protein B1/HMG-1/High mobility group protein 1 at 0.21, HIV-EP2 at 13.8, Homeobox protein HOX-B7/Homeobox protein Hox-2C at 0.6, LINE-1 retrotransposable element ORF2 protein/Line-1 reverse transcriptase homolog at 1.3, Nuclear receptor subfamily 4 group A member 1/Early response protein NAK1/TR3 orphan receptor at 4.4, Polycomb group RING finger protein 2/DNA-binding protein MEL-18 at 0.7, Ras-like protein TC10/Rho-related GTP-binding protein RhoQ/Ras-like protein family member 7A at 0.23, SET protein/SET nuclear proto-oncogene at 2.6, Sterol regulatory element binding protein 1/Class D basic helix-loop-helix protein 1/SREBP-1 at 42.8, Wilms' tumor protein/WT33 at 1.8, and Zinc finger protein 90/Zinc finger protein HTF9 at 0.53 μg/mg of tissue protein, respectively. Total TFs become to be 102.13 μg/mg of tissue protein or 10.2% among tissue proteins.
HCC tissue (named as No.6; who has survived) has Aryl hydrocarbon receptor nuclear translocator at 0.66, B-cell lymphoma 3 protein/BCL-3 protein/Proto-oncogene BCL3 at 1.2, Blym-1 protein at 0.82, Bone morphogenetic protein 2 at 8.9, Breast cancer type 1 susceptibility protein/RING finger protein 53/RING-type E3 ubiquitin transferase BRCA1 at 7.4, Cellular tumor antigen p53/Tumor suppressor p53 at 0.22 , DNA-(Apurinic or apyrimidinic site) lyase at 0.21, E3 ubiquitin-protein ligase CBL/Proto-oncogene c-CBL at 0.055, Fibroblast growth factor receptor 1/Basic fibroblast growth factor receptor 1/BFGFR/Proto-oncogene c-Fgr/CD331 at 1.0, Fibroblast growth factor receptor 2/FGFR-2/Keratinocyte growth factor receptor/CD332 at 1.0, HIV-EP2 at 9.5, Merlin/Schwannomin at 0.29, Norrin/Norrie disease protein/X-linked exudative vitreoretinopathy 2 protein at 0.011, Possible global transcription activator SNF2L/ATP-dependent helicase SMARCA1 at 5.2, Ring3 protein/Really interesting new gene 3 protein at 5.2, Serine/threonine-protein kinase A-Raf/Proto oncogene Pks2 at 0.53, Serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha/Protein phosphatase PP2A, 130 KD regulatory subunit at 14.0, Tyrosine-protein phosphatase non-receptor type 2 /T-cell protein-tyrosine phosphatase/TCPTP at 0.53, Transforming growth factor beta receptor type 3/TGF-beta receptor type III/TGFR-3 at 5.0, Transcription factor-7/T-cell-specific transcription factor 1/TCF-1 at 3.2, Tyrosine-protein kinase ITK/TSK/Interleukin-2-inducible T-cell kinase/T-cell-specific kinase/Tyrosine protein kinase LYK at 10.6, Tyrosine protein kinase Lyn/Lck/Yes-related novel protein tyrosine kinase at 1.3, and Tyrosine-protein kinase BTK/Bruton tyrosine kinase at 0.35 μg/mg of tissue protein, respectively. Total TFs become to be 77.26 μg/mg of tissue protein or 7.73% among tissue proteins.
Amount of TFs is a good indicator of the human cancer destined to death. Therefore, the human iPS cell cannot replace the human ES cell. ES cell seems to become to be an important tool in the Regenerative medicine. The Ethics of Christianity may deny this truce, but Buddhism and Islamism may support in this conclusion.
Interestingly, amount of TFs and amount of HIV-1 plus HCV (cause of Hepatocellular carcinoma/HCC) is strongly correlated; i.e., p < 0.01 (Wilcoxon signed-rank test; two-sided test; n = 8). TFs seem to be up-regulated by Retrovirus and HCV. Therefore, Japanese edible fucoidan can reduce HIV-1 plus HCV, and it then can also reduce TFs.
Appearances of SEN1 homolog/Probable helicase senataxin and Histone deacetylase/HDAC seem to be the indications of normalization and/or healing/curing effect by Japanese edible fucoidan.
I am grateful to Dr. Apoorva Verma (Division of Molecular Genetics and Cell Biology, Nanyang Technological University, Singapore, Singapore) for leading me to these important findings.