our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer. Indeed our results are more suggestive of an increase in risk, rather than a decrease, with higher levels of 2-OHE1
8More
shared by Nathan Goodyear on 07 Oct 15
- No Cached
Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of en... - 0 views
www.ncbi.nlm.nih.gov/...PMC3241553
estrogen metabolism 2-hydroxyestrone 4-hydroxyestrone estrogen metabolites cancer uterine cancer endometrial cancer hormones 2:16alpha-OHE1 2:16
![](/images/link.gif)
-
women with a higher 2-OHE1 : 16α-OHE1 ratio did not have a decreased risk of endometrial cancer as compared with women with a lower ratio
-
The findings from this first prospective epidemiological study of oestrogen metabolites and endometrial cancer are in line with results from prospective studies on breast cancer, another oestrogen-related cancer. None of the seven studies on breast cancer reported significant associations overall
- ...4 more annotations...
-
On the whole, prospective epidemiological data do not support the hypothesis that the 2-hydroxyestrogen pathway is protective, and the 16α-hydroxyestrogen pathway harmful, in hormone-dependent cancers
-
Both 2- and 4-hydroxyestrogens are catecholestrogens, and it has been suggested that catecholestrogens increase risk of oestrogen-mediated cancers through direct genotoxic effects, rather than through stimulation of cell proliferation via binding to oestrogen receptors
-
a significant increase in risk of breast cancer with levels of 2-OHE1 has also been reported previously, although it was limited to hormone receptor-negative tumours
1More
shared by Nathan Goodyear on 25 Feb 14
- No Cached
Sugar-Sweetened Beverage Intake and the Risk of Type I and Type II Endometrial Cancer a... - 0 views
cebp.aacrjournals.org/...2384
sugar soda coke uterine endometrial cancer postmenopausal women nutrition diet
![](/images/link.gif)
1More
Long-term effects of the rhaponti... [J Steroid Biochem Mol Biol. 2012] - PubMed - NCBI - 0 views
1More
shared by Nathan Goodyear on 07 Nov 18
- No Cached
Dichloroacetate induces apoptosis in endometrial cancer cells - 0 views
Dichloroacetate induces apoptosis in endometrial cancer cells
DCA dichloracetic acid dichloroacetate cancer
![](/images/link.gif)
1More
New use of microsatellite instability analysis in endometrial cancer - 0 views
1More
shared by Nathan Goodyear on 26 Nov 12
- No Cached
Relative Expression of Progesterone Receptors A and B in Endometrioid Cancers of the En... - 0 views
cancerres.aacrjournals.org/...4576.long
progesterone receptor progesterone receptors A B PR-A PR-B endometrial cancer uterine progesterone receptor receptors
![](/images/link.gif)
1More
shared by Nathan Goodyear on 07 Oct 14
- No Cached
Estradiol-17β Upregulates Pyruvate Kinase M2 Expression to Coactivate Estroge... - 0 views
press.endocrine.org/...jc.2013-2639
Estradiol ER alpha ER-alpha women female hormone hormones aerobic glycolysis Warburg effect estrogen
![](/images/link.gif)
-
This is an important study. Study found that Estradiol increased the transcription of pyruvate kinase M (PKM2)production in endometrial stromal cells. This increase in PKM2 shifted metabolism to a aerobic glycolysis pattern similar to the Warburg effect described in cancer. Additionally, increased PKM2 via Estradiol increased ER alpha transcription and functioned as a ER alpha coactivator.
1More
shared by Nathan Goodyear on 30 Jul 14
- No Cached
The role of androst-5-ene-3β,17β-diol (androstenedi... [Steroids. 2014] - Pub... - 0 views
www.ncbi.nlm.nih.gov/...25065586
DHT metabolite 3-beta androstanediol 3-beta-diol 3 beta androstanediol PCOS endometrial proliferation cancer women hormone hormones Testosterone
![](/images/link.gif)
1More
Subtype-specific activation of estrogen recept... [Phytomedicine. 2007] - PubMed - NCBI - 0 views
40More
Intravenous Ascorbate as a Tumor Cytotoxic Chemotherapeutic Agent - 0 views
-
Ascorbic acid and its salts (AA) are preferentially toxic to tumor cells in vitro (6 — 13) and in vivo
- ...36 more annotations...
-
Increases animal and human resistance to infectious agents by enhancing lymphocyte blastogenesis, enhancing cellular immunity, strengthening the extracellular matrix, and enhancing bactericidal activity of neutrophils and modulation of complement protein
-
Strengthens the structural integrity of the extracellular matrix which is responsible for stromal resistance to malignant invasiveness
-
In 1977, Bram et al reported preferential AA toxicity for several malignant melanoma cell lines, including four human-derived lines
-
Noto et al reported that AA plus vitamin K3 had growth inhibiting action against three human tumor cell lines at non-toxic levels
-
The AA begins to reduce cell proliferation in the tumor cell line at the lowest concentration, 1.76 mg/dl, and is completely cytotoxic to the cells at 7.04 mg/dl
-
preferential toxicity of AA for tumor cells. >95% toxicity to human endometrial adenocarcinoma and pancreatic tumor cells (ATCC AN3-CA and MIA PaCa-2) occurred at 20 and 30 mg/dl, respectively.
-
No toxicity or inhibition was demonstrated in the normal, human skin fibroblasts (ATCC CCD 25SK) even at the highest concentration of 50 mg/dl.
-
Cameron and Pauling have published extensive suggestive evidence for prolonged life in terminal cancer patients orally supplemented (with and without initial intravenous AA therapy) with 10 g/day of AA
-
the long-term, oral dosage used in those experiments (10 g/day), while substantial and capable of producing immunostimulatory and extracellular matrix modulation effects, was not high enough to achieve plasma concentrations that are generally cytotoxic to tumor cells in culture
-
5 — 40 mg/dl of AA is required in vitro to kill 100% of tumor cells within 3 days. The 100% kill levels of 30 mg/dl for the endometrial carcinoma cells and 40 mg/dl for the pancreatic carcinoma cells in Figure 2 are typical
-
1 h after beginning his first 8-h infusion of 115 g AA (Merit Pharmaceuticals, Los Angeles, CA), the plasma AA was 3.7 mg/dl and at 5 h was 19 mg/dl. During his fourth 8-h infusion, 8 days later, the 1 h plasma level was 158 mg/dl and 5 h was 185 mg/dl
-
plasma levels of over 100 mg/dl have been maintained in 3 patients for more than 5 h using continuous intravenous infusion
-
In rare instances of patients with widely disseminated and rapidly proliferating tumors, intravenous AA administration (10 — 45 g/day) precipitated widespread tumor hemorrhage and necrosis, resulting in death
-
Although the outcomes were disastrous in these cases, they are similar to the description of tumor-necrosis-factor-induced hemorrhage and necrosis in mice (52) and seem to demonstrate the ability of AA to kill tumor cells in vivo.
-
toxic effects of AA on one normal cell line were observed at 58.36 mg/dl and the lack of side effects in patients maintaining >100 mg/dl plasma levels
-
Although it is very rare, tumor necrosis, hemorrhage, and subsequent death should be the highest priority concern for the safety of intravenous AA for cancer patients.
-
Cathcart (55) who describes no ill effects with doses of up to 200 g/d in patients with various pathological conditions
-
following circumstances: renal insufficiency, chronic hemodialysis patients, unusual forms of iron overload, and oxalate stone formers
-
Screening for red cell glucose-6-phosphate dehydrogenase deficiency, which can give rise to hemolysis of red blood cells under oxidative stress (57), should also be performed
-
any cancer therapy should be started at a low dosage to ensure that tumor hemorrhage does not occur.
-
a scorbutic rebound effect can be avoided with oral supplementation. Because of the possibility of a rebound effect, measurement of plasma levels during the periods between infusions should be performed to ensure that no such effect takes place
-
Every effort should be made to monitor plasma AA levels when a patient discontinues intravenous AA therapy.
1More
Survival implications of time to surgical treatment of endometrial cancers - American J... - 0 views
Curcumin and endometrial carcinoma: an old spice as a novel agent - 0 views
Progesterone Inhibits Epithelial-to-Mesenchymal Transition in Endometrial Cancer - 0 views
journals.plos.org/...article
EMT progesterone endometrial cancer epithelial to mesenchymal transition
![](/images/link.gif)
CA 125: a useful marker in endometrial carcinoma - PubMed - 0 views
1More
shared by Nathan Goodyear on 02 Sep 22
- No Cached
Frontiers | Artesunate Suppresses the Proliferation and Development of Estrog... - 0 views
www.frontiersin.org/...full
ER alpha ER-alpha uterine cancer endometrial cancer cancer artesunate mTOR
![](/images/link.gif)
32More
shared by Nathan Goodyear on 15 Apr 12
- No Cached
Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunolog... - 0 views
edrv.endojournals.org/...44.full
natural killer cells pregnancy loss recurrent immune system miscarriage NK
![](/images/link.gif)
-
NK cells have been the cells most extensively studied, primarily because they constitute the predominant leukocyte population present in the endometrium at the time of implantation and in early pregnancy
-
parental chromosomal abnormalities, uterine anatomic anomalies, endometrial infections, endocrine etiologies (luteal phase defect, thyroid dysfunction, uncontrolled diabetes mellitus), antiphospholipid syndrome, inherited thrombophilias, and alloimmune causes
- ...28 more annotations...
-
In summary, in vivo animal experiments have shown an inhibitory role of estrogen on peripheral NK cell lytic activity, which is partly due to suppression of NK cell output by the bone marrow and partly due to suppression of individual NK cell cytotoxicity. However, in vitro studies so far have failed to show conclusively a direct effect of estrogen on NK cells.
-
At the progesterone concentrations believed to be present in the uterus [up to 10−5 m at the maternal-fetal interface (35)], studies consistently show inhibition of lymphocyte proliferation (33) and inhibition of NK cytolytic activity in vitro
-
The overall effects of estrogen on NK cells are likely multifactorial, therefore, and depend on the type of cell affected as well as the kind of ER expressed by that cell.
-
It is known that progesterone can directly affect T cell differentiation in vitro, suppressing development of the Th1 pathway and enhancing differentiation along the Th2 pathway (44)
-
Th1 cells predominantly produce interferon-γ (IFN-γ), IL-2, and TNF-β and are involved in cell-mediated immunity. Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13 and stimulate humoral immunity
-
Furthermore, in response to progesterone, γδ T cells produce progesterone-induced blocking factor (PIBF) (54
-
A defining characteristic of NK cells is their ability to lyse target cells without prior sensitization and without restriction by HLA antigens.
-
IL-2 causes both NK cell proliferation and enhanced cytotoxicity. IFN-γ augments NK cytolytic activity, but does not cause NK proliferation. The two cytokines act synergistically to augment NK cytotoxicity (6).
-
The largest leukocyte population in the endometrium consists of NK cells named large granulated lymphocytes
-
there is a significant increase in the number of uNK cells throughout the secretory phase, which peaks in early pregnancy when uNK cells comprise about 75% of uterine leukocytes (62)
-
general proinflammatory effect of estrogen, causing an influx of macrophages and neutrophils, which is antagonized by progesterone through its receptor (70, 71).
-
Through promotion of a uterine Th2 environment, progesterone could indirectly affect uNK cell function
-
The mechanism of this increase in uNK cell numbers has been addressed in both human and mouse models, and is likely the result of: 1) recruitment of peripheral NK cells to the uterus, and 2) proliferation of existing uNK cells
-
uNK cells express a different cytokine profile, compared with resting peripheral NK cells. mRNAs for granulocyte CSF, M-CSF, GM-CSF, TNF-α, IFN-γ, TGF-β, and leukemia inhibitory factor (LIF) have been found in decidual CD56+ cells
-
Their increased numbers in early pregnancy, their hormonal dependence, and their close proximity to the infiltrating trophoblast all suggest that they play an important role in the regulation of the maternal immune response to the fetal allograft and the control of trophoblast growth and invasion during human pregnancy
-
Th1 immunity to trophoblast is associated with RPL, whereas Th2 immunity is associated with a successful pregnancy
1More
shared by Nathan Goodyear on 21 Mar 14
- No Cached
The premenstrual endometrial pattern of women with breast cancer. A study of progestati... - 0 views
onlinelibrary.wiley.com/...abstract
breast cancer androgens Testosterone women female hormone hormones
![](/images/link.gif)
27More
Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation - 0 views
-
DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
- ...23 more annotations...
-
It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
-
The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
-
The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
-
Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
-
In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
-
It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
-
Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
-
HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
-
Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
-
In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
-
DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
-
Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
-
The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
-
The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
-
the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
-
In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
-
DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect
11More
The current state and future perspectives of cannabinoids in cancer biology - 0 views
-
The activation of each of them leads to an inhibition of adenylyl cyclase via G proteins (Gi/o), which in turn activates many metabolic pathways such as mitogen‐activated protein kinase pathway (MAPK), phosphoinositide 3‐kinase pathway (PI3K), cyclooxygenase‐2 pathway (COX‐2), accumulation of ceramide, modulation of protein kinase B (Akt), and ion channels
-
Action of THC in human organism relies on mimicking endogenous agonists of CB receptors—endocannabinoids
- ...8 more annotations...
-
The upregulated expression of CB receptors and the elevated levels of endocannabinoids have been observed in a variety of cancer cells (skin, prostate, and colon cancer, hepatocellular carcinoma, endometrial sarcoma, glioblastoma multiforme, meningioma and pituitary adenoma, Hodgkin lymphoma, chemically induced hepatocarcinoma, mantel cell lymphoma)
-
concentration of endocannabinoids, expression level of their receptors, and the enzymes involved in their metabolism frequently are associated with an aggressiveness of cancer
-
CB2 receptor contributes to human epidermal growth factor receptor (HER2) pro‐oncogenic signaling and an overexpression of CB2 increases susceptibility for leukemia development after leukemia viral infection
-
Many cannabinoids, ranging from phytocannabinoids (THC, CBD), endocannabinoids (2‐arachidonoylglycerol, anandamide), to synthetic cannabinoids (JWH‐133, WIN‐55,212‐2), have shown ability to inhibit proliferation, metastasis, and angiogenesis in a variety of models of cancer
-
Despite some inconsistent data, the main effect of cannabinoids in a tumor is the inhibition of cancer cells’ proliferation and induction of cancer cell death by apoptosis
-
CB1 and CB2 receptor agonists stimulate apoptotic cell death in glioma cells by induction of de novo synthesis of ceramide, sphingolipid with proapoptotic activity