User:Areisdematos/sandbox

Article Evaluation

The article that is under evaluation seems to have everything relevant to the topic, Insulin signal transduction pathways. The one thing that stood out was that some of the sections in the article does not have much information. The sections that go over the secretion mechanism and the receptor signaling is missing more information. The atricle looks to have a neutral position in writing about this topic. All of the links go directly to the pdf files that were cited. The talk page seems to have alot of people letting the writer know that some of the things written are wrong.

Possible Article

The article that I am interesed in using for the WIKI project is about Diabetes mellitus. The aritcle's content is all relative to the topic. It has various sections going into depth to what this disease is, what causes it, how to manage it, and etc. The article is written neutrally and looks to have a citation for every statement.

Hormonal Therapy (oncology): SERMS section editing

Selective estrogen receptor modulators/degradation

Selective estrogen receptor modulators (SERMs) are an important class of hormonal therapy agents which act as antagonists of the estrogen receptor and are used primarily for the treatment and chemoprevention of breast cancer. Estrogen receptors are steriod receptors that manage the reproduction of cells. Estrogen receptors have two different isoforms, ERα and ERβ. SERMS act as competitive antagonist; they block the binding site of the receptor by acting like the agonist but in the end when they bind the receptor is not not activated. The Helix 12 in SERMs undergoes changes based on if it's stimulated by an agonist or an antagonist.Some modulator members of this family, such as tamoxifen, are actually partial agonists, which can actually increase estrogen receptor signalling in some tissues, such as the endometrium. NCOA1 is a protein that influences Tamoxifen to act as an agonist to promote gene transcription for the endometrial cells. Tamoxifen is currently first-line treatment for nearly all pre-menopausal women with hormone receptor-positive breast cancer. Tamoxifen's side chain blocks the helix 12 from capping the ligand binding domain and this action leads to the inhibition of the ERα signaling pathway in breast cancer cells(MCF7 cells). A study was done by Gottardist et. al. where mice were injected with both, breast cancer cells and an endometrial cell line. After being treated with Tamoxifen the count for endometrial cell line increased and the breast cancer cells decreased. Raloxifene, also known as Ketoxifene, is another partial agonist SERM which does not seem to promote endometrial cancer, and is used primarily for chemoprevention of breast cancer in high-risk individuals, as well as to prevent osteoporosis. Raloxifene's anatagonist abilities can be inhibited by changing the Nitrogen on it's side chain to a Carbon. This SERM can be used to inhibit Tamoxifen from having an effect on the endometrial cells, which can lead to possibly uterine cancer. Toremifene and fulvestrant are SERMs with little or no agonist activity, and are used for treatment of metastatic breast cancer.

Antiandrogens[edit]

Antiandrogens are a class of drugs which bind and inhibit the androgen receptor, which are steroid receptors,  blocking the growth- and survival-promoting effects of testosterone on certain prostate cancers.  Flutamide and bicalutamide are antiandrogens which are frequently used in the treatment of prostate cancer, either as long-term monotherapy, or in the initial few weeks of GnRH analog therapy.^[1] (See also Androgen deprivation therapy)

High levels of androgens also increases risks for postmenopausal women diagnosed with breast cancer. Concentrations of androgens can vary in pre-  and postmenopausal women. High testosterone in premenopausal leads to higher risks of BC. One of the reasons why it is believed that androgens play a part in breast cancer is because androgen receptors and ERalpha share the same coactivator. The coactivator for androgen receptors, ARA70, increases gene expression of ERalpa, which is the estrogen receptor subtype that is involved in BC. The antiandrogen, Casodex, prevents the resistance of Tamoxifen when in the presence of androgen receptors.

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