Pancan - Cancer--> Resveratrol, Genistein and Baicalein-- Atad5 & Psors2 --> Anti-ROS Works!... do YOU?

[randall]

hi



OK so the below ATAD5 gene and anti-ROS via (Resveratrol, Genistein
and Baicalein) came in the mail while i was doing this one:

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Should have said: black cohosh and death to PANCAN in MAN?

pancan being pancreatic cancer... which is what steve APPLE jobs died
of.

btw.... :(

http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/d82b60b035650c6f
Mon, Mar 19 2012 3:19 pm
Subject: Killing CANCER: Black Cohosh--Actaea racemosa (γ-secretase &
ILL-e-fects?), Ferulic acid (Rhizoma of Cimicifuga), Figwort
(Scrophulariaceae), Sulfonylureas, EDHF, polyphenols, kaempferol
(flavonoid), Gamma-oryzanol ->rice bran oil --> LPS - +++
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/msg/d82b60b035650c6f


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http://www.bloomberg.com/news/2012-03-19/antioxidants-may-improve-cancer-drugs-nih-study-suggests.html
Resveratrol Kills Drug-Resistant Cancer Cells, Less Toxic Than
Chemotherapy

Antioxidants May Improve Cancer Drugs, NIH Study Suggests

By Nicole Ostrow on March 19, 2012 Bloomberg News

Antioxidants found in fruits, vegetables and red wine killed cancer
cells, including those that are resistant to treatment, in a study
that scientists said may lead to more effective tumor fighters.

Researchers from the U.S. National Institutes of Health identified 22
antioxidants that eradicated dividing cells, including two types that
showed promise against drug-resistant cancer cells. The study is
published online today in the Proceedings of the National Academy of
Sciences.

Antioxidants, widely used in dietary supplements, are thought to
protect cells against a damaging chemical reaction. The study found
that antioxidants resveratrol, which is found in red wine, and
genistein, found in certain plants, killed rapidly dividing cells and
selectively eliminated cancer cells that were resistant to multiple
drugs. Antioxidants “are potentially better chemotherapeutic agents
than ones currently used,” the researchers said in the paper.

“It’s a much safer chemotherapy agent if it can be developed,” said
study author Kyungjae Myung, a senior investigator in the Genetics and
Molecular Biology Branch of the National Human Genome Research
Institute in Bethesda, Maryland, part of the NIH, in a March 15
telephone interview. “Currently what we’re trying to see is if
antioxidants can selectively kill specific cancer cells.”

Three Antioxidants

Resveratrol, genistein and baicalein are currently used or being
studied to treat conditions like heart disease and diabetes, as well
as anti-aging. Resveratrol, also found in red grapes, blueberries and
cranberries, switches on a class of proteins called sirtuins that may
prevent gene mutations and repair DNA damage. London-based
GlaxoSmithKline Plc (GSK) stopped developing a drug, designed to mimic
the health benefits of red wine, in 2010 after the compound didn’t
work well enough in cancer patients and may have worsened kidney
damage.

[Note added: Longevinex exhibits no toxicity at high dose and has been
shown in animal and human studies to produce no kidney toxicity.]

<<randall note: i use www.longevinex.com as it's the BEST product out
there>>

More studies are needed before antioxidants can be used to fight
cancer in people, Myung said. Antioxidants in high amounts can damage
DNA and kill cells, he said.

“The dose that we used for this treatment in a laboratory setting was
way higher than you can get from wine or all those antioxidant tablets
or you can consume by eating,” said Myung,

Myung said his group is studying to see if antioxidants can kill
specific types of cancer cells, including those of the breast and
ovary, and if the antioxidants harm just diseased cells or healthy
cells too.

Proceedings National Academy of Sciences March 19, 2012

High-throughput genotoxicity assay identifies antioxidants as inducers
of DNA damage response and cell death

Abstract
Human ATAD5 is a biomarker for identifying genotoxic compounds because
ATAD5 protein levels increase posttranscriptionally in response to DNA
damage. We screened over 4,000 compounds with a cell-based
quantitative high-throughput ATAD5-luciferase assay detecting
genotoxic compounds. We identified 22 antioxidants, including
resveratrol, genistein, and baicalein, that are currently used or
investigated for the treatment of cardiovascular disease, type 2
diabetes, osteopenia, osteoporosis, and chronic hepatitis, as well as
for antiaging. Treatment of dividing cells with these compounds
induced DNA damage and resulted in cell death. Despite their genotoxic
effects, resveratrol, genistein, and baicalein did not cause
mutagenesis, which is a major side effect of conventional anticancer
drugs. Furthermore, resveratrol and genistein killed multidrug-
resistant cancer cells. We therefore propose that resveratrol,
genistein, and baicalein are attractive candidates for improved
chemotherapeutic agents.

Free full text: http://www.pnas.org/content/early/2012/03/12/1114278109.full.pdf+html

Their ABSTRACT:

http://www.ncbi.nlm.nih.gov/pubmed/21901109
PLoS Genet. 2011 Aug;7(8):e1002245. Epub 2011 Aug 25.
Predisposition to cancer caused by genetic and functional defects of
mammalian Atad5.

Bell DW, Sikdar N, Lee KY, Price JC, Chatterjee R, Park HD, Fox J,
Ishiai M, Rudd ML, Pollock LM, Fogoros SK, Mohamed H, Hanigan CL; NISC
Comparative Sequencing Program,
Zhang S, Cruz P, Renaud G, Hansen NF, Cherukuri PF, Borate B, McManus
KJ, Stoepel J, Sipahimalani P, Godwin AK, Sgroi DC, Merino MJ, Elliot
G, Elkahloun A, Vinson C, Takata M, Mullikin JC, Wolfsberg TG, Hieter
P, Lim DS, Myung K.

Source
Cancer Genetics Branch, National Human Genome Research Institute,
National Institutes of Health, Bethesda, Maryland, United States of
America. belld...@mail.nih.gov

Abstract
ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA
deubiquitination. Since PCNA modification is important to regulate DNA
damage bypass, ATAD5 may be important for suppression of genomic
instability in mammals in vivo. To test this hypothesis, we generated
heterozygous (Atad5(+/m)) mice that were haploinsuffficient for Atad5.
Atad5(+/m) mice displayed high levels of genomic instability in vivo,
and Atad5(+/m) mouse embryonic fibroblasts (MEFs) exhibited molecular
defects in PCNA deubiquitination in response to DNA damage, as well as
DNA damage hypersensitivity and high levels of genomic instability,
apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient
Atad5(+/m) mice developed tumors, including sarcomas, carcinomas, and
adenocarcinomas, between 11 and 20 months of age. High levels of
genomic alterations were evident in tumors that arose in the Atad5(+/
m) mice. Consistent with a role for Atad5 in suppressing
tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6%
of sporadic human endometrial tumors, including two nonsense mutations
that resulted in loss of proper ATAD5 function. Taken together, our
findings indicate that loss-of-function mutations in mammalian Atad5
are sufficient to cause genomic instability and tumorigenesis.

PMID: 21901109
Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21901109/?tool=pubmed


myung time?

Oh! --> k..

69 hits ::: "Myung K"[Author]
http://www.ncbi.nlm.nih.gov/pubmed?term=%22Myung%20K%22%5BAuthor%5D

#1 of sixty nine has my interest... non prurient... ok

I like bioTRANSFORMATIONs if you didn't know....

http://www.ncbi.nlm.nih.gov/pubmed/22342630
Bioorg Med Chem Lett. 2012 Mar 15;22(6):2279-82. Epub 2012 Jan 30.
Biotransformations of 6',7'-dihydroxybergamottin and 6',7'-
epoxybergamottin by the citrus-pathogenic fungi diminish cytochrome
P450 3A4 inhibitory activity.

Myung K, Manthey JA, Narciso JA.

Source
U.S. Horticultural Research Laboratory, Agricultural Research Service,
U.S. Department of Agriculture, 2001 S. Rock Road, Fort Pierce, FL
34945, USA.

Abstract
Penicillium digitatum, as well as five other citrus pathogenic
species, (Penicillium ulaiense Link, Geotrichum citri Link, Botrytis
cinerea P. Micheli ex Pers., Lasiodiplodia theobromae (Pat.) Griffon &
Maubl., and Phomopsis citri (teleomorph Diaporthe citri)) were
observed to convert 6',7'-epoxybergamottin (1) into 6',7'-
dihydroxybergamottin (2), bergaptol (3), and an opened lactone ring
metabolite 6,7-furano-5-(6',7'-dihydroxy geranyloxy)-2-hydroxy-
hydrocoumaric acid (4). Metabolism of 2 by these fungi also proceeded
to 4. The structure of 4 was established by high resolution mass
spectrometry and (1)H and (13)C NMR techniques. The inhibitory
activity of 4 towards human intestinal cytochrome P450 3A4 (CYP3A4)
was greatly decreased (IC(50) >172.0μM) compared to 2 (IC(50)=0.81μM).

PMID: 22342630

CYP3A4-- 33 hits - p ng
http://groups.google.com/groups/search?q=CYP3A4+randall+psoriasis&sitesearch=groups.google.com&scoring=d

OK but...if i take me out of that equation i see
41 results for CYP3A4 - p ng:
http://groups.google.com/group/alt.support.skin-diseases.psoriasis/search?q=CYP3A4&start=0&

Ok back to ATAD5

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7 hits : ATAD5 - pubmed
http://www.ncbi.nlm.nih.gov/pubmed?term=atad5

13 articles available
http://www.ncbi.nlm.nih.gov/sites/gquery?term=%20atad5

oMIM has this:

And psors2 is on 17q iirc... i'll check it after doing this:

http://omim.org/entry/609534
*609534
CHROMOSOME 17 OPEN READING FRAME 41; C17ORF41

Alternative titles; symbols
FRAG1
FLJ12735

HGNC Approved Gene Symbol: ATAD5

Cytogenetic location: 17q11.2 Genomic coordinates (GRCh37):
17:29,159,019 - 29,222,294 (from NCBI)

TEXT
Cloning
By searching for sequences similar to mouse Frag1, Ishii et al. (2005)
identified human FRAG1. The deduced mouse and human proteins contain
1,820 and 1,844 amino acids, respectively. FRAG1 contains N-terminal
nuclear localization signals, followed by a central region similar to
the large subunit of replication factor C (RFC1; 102579) in budding
yeast, an AAA family (see 601681) motif, and a C-terminal RB1 (614041)-
binding motif. It also has 2 ATR (601215) phosphorylation sites.
Northern blot analysis detected Frag1 expression in all murine cell
lines examined.

Gene Function
Ishii et al. (2005) found that expression of Frag1 was reduced in
mouse embryonic fibroblasts following exposure to DNA replication-
inhibiting agents. Reduction of Frag1 with small interfering RNA
increased sensitivity to replication stress and gamma irradiation.
Cells showed caspase-7 (601761) activation and increased Bax (600040)
protein expression, which was independent of p53 (191170) activation.
Immunoprecipitation analysis and in vitro pull-down assays indicated
that Frag1 interacted with Rad9 (see 603761), and mutation analysis
indicated that the RFC-like domain of Frag1 mediated the interaction.
Inhibition of ATR inhibited downregulation of Frag1 in response to DNA
damage and reduced the association of Rad9 with Frag1. Ishii et al.
(2005) concluded that the FRAG1 signaling pathway links replication
stress surveillance with apoptosis induction, and thus determines
whether DNA damage is compatible with cell survival or whether it
requires cell elimination by apoptosis.
<<<<snip snap i was taking a 17 q bath... LOL>>>>>

And now for psors2

And it is.... 17Q25 which means it's not on top of atad5. I'll pubmed
just to see.


http://omim.org/entry/602723?search=602723&highlight=602723
602723
PSORIASIS SUSCEPTIBILITY 2; PSORS2

HGNC Approved Gene Symbol: PSORS2

Cytogenetic location: 17q25 Genomic coordinates (GRCh37):
17:70,900,000 - 81,195,210
<snip>

Or look at this one
http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&position=chr17:70900000-81195210&dgv=pack&knownGene=pack&omimGene=pack

and look at atad5
http://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&position=chr17:29159019-29222294&dgv=pack&knownGene=pack&omimGene=pack

It feels like looking in to the MAD mind of GAWD? LoL

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And wiki gene:
http://www.wikigenes.org/e/gene/e/237877.html



randall... i'm excited...i'm poPPing a longevinex.com pill in 5
seconds...
LOL--> ATAD5 re-adjustment count down... 4, 3, 2,
1...oh what a relief it is