User:Ginseng777/sandbox

Jess Uzonyi
 * Heart and Stroke Foundation of Canada - added the section 'Allocation of donations'. Includes a citation.
 * Green tea - spelling correction, changed 'geen' to 'green'.
 * Fish oil - added the EFSA's opinion on maximum intake. Includes a citation.

WIkipedia Project Please note the first paragraph would be inserted into the top of the EGCG page, while below it would in the cancer subsection of that page.

Camellia sinensis is the plant from which leaves are picked to make tea. Green tea is made from unoxidized, unfermented plant matter that has been steamed and dried in order to denature the enzyme polyphenol oxidase, in order to halt the transformation of polyphenols from their natural state. About one third of tea leaf dry weight is catechins, with epigallocatechin-3-gallate (EGCG) being the most abundant, two thirds of all catechin content.

Breast cancer and epigenetics

Breast cancers can be classified into three major groups based on the presence or absence of certain cellular receptors: - Estrogen receptor positive (ER+) contain the estrogen receptor (ER) and will grow in response to estrogen/oestrogen. - Estrogen receptor negative (ER–) lack the ER, and therefore will not respond to estrogen. - Triple negative designation means the additional absence of human epidermal growth factor 2 receptors (HER2), and progesterone receptors (PR).

Classification is an important determinant for which treatment strategy will be used. Traditional drugs affect estrogen levels, it’s binding, or ER quantity. Aromatase-inhibitors (e.g. letrozole and anastrozole) inhibit the enzyme aromatase located in the endoplasmic reticulum within various tissues such as ovaries or testicles, brain, breast, and uterus. Aromatase is responsible for converting androgens to estrogens, so blocking it decreases estrogen levels. SERMs (selective estrogen receptor modulators) (e.g. Tamoxifen) compete with estrogen for its binding site on the ER, lessening downstream effects. SERDs (selective ER down-regulator) (e.g. fulvestrant) bind to the ER and destabilize it, leading to its removal from the cellular membrane, thus reducing binding and signalling ability.

Epigenetics are heritable changes in gene expression excluding change in the DNA nucleotide sequence. Epidrugs (epigenetic drugs) modify the epigenome. Four major ways this can happen is by:
 * Cytosine methylation
 * Histone modification
 * microRNA sequestration of target mRNA
 * DNase hypersensitive sites

Epigenetically altered genes in breast cancer: Hyper-methylation of promoters of tumour-suppressor genes (causing decreased expression) and overexpression of DNA methyltransferases (DNMTs) has been associated with breast cancer. EGCG is a potential chemotherapeutic epidrug that works by inhibiting the DNMT family of proteins, of which some can silence gene expression through two different mechanisms. Additionally, EGCG lowers levels of SAM, while increasing S-adenosyl homocysteine (SAH) and homocysteine.
 * Underexpressed: HOXA5; RASSF1A; TWIST1; BRCA1; P16INK4a; APC; GSTP1; CDH1; CDH13.
 * Overexpressed: SNCG.
 * DNMT uses methyl donor S-adenosyl-methionine (SAM) to methylate cytosines in the CpG-rich promoters.
 * DNMT forms a repressive complex at the replication fork involving HDACs, MDBs, and DMAP1.

In vitro studies have shown EGCG to reduce methylation in the RARβ promoter in MCF-7 and MDA-MB-23199b cells. Furthermore, in the same cell lines it lowered levels of acetyl-H3, acetyl-H3K9, and acetyl-H4 in the hTERT promoter.