Systolic hypertension: an increasing clinical challenge in Asia

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients | Trials

A 57 year old woman is complaining of chest pain. her blood pressure is 109/88 and her respirations

1) Stress is not a state of _____________ or an abstract _____________
2) Chronic stress can kill __________________________________ cells.
3) Robert
…

Zapalsky is a Stanford University ________________ scientist.
4) Every so often he ships his lab 9,000 miles to ___________, East Africa to study wild
__________________________________________________
5) The two advantages of a blow gun are:
__________________________________________________________
6) With the baboons blood samples, the above gentleman measures these two things:
__________________________________________________
7) These two things occur when the baboon is stressed:
____________________________________________________________
8) The right amount of stress is very ________________________________
9) Three examples of the above are:
_________________________________________________________
10) The submissive baboon exhibits these four things:
__________________________________________________________
11) Kevin Brooks is a government ________________, level ___________ for the British Secret
Service.
12) The Whitehall Study found that the lower the rank of the individual the more
___________________ occurred and __________________ lives.
13) Way back when it was believed that stress caused _______________
14) It was later discovered by Australian scientists that _______________ caused the above malady.
15) _______________________ of the world’s population has the item above.
16) Social and psychological stress can definitely ____________ our arteries.
17) The two major hormones that are involved with stress are:
________________________________
18) Through research it was found that stresses rats brain cells are much _____________________
than unstressed rats.
19) The hippocampus part of the brain controls these two things:
__________________________________________
20) The hormone dopamine is responsible for our feelings of ____________________
21) Emmanuel Johnson was a ____________________________________
22) The above gentleman experienced these three things while doing his job:
__________________________________________________________________________________
______________________________________________________________
23) In the baboon hierarchy it was found that the subordinate monkeys have more
______________________________________________________________________
24) Stress fat is ________________________________________________________ fat.
25) The “Dutch Uncle Winter” in the 1940s dealt with a ____________________________
26) The Dutch study concluded that children born during the above period of time eventually
encountered ___________________________________________________
27) These three disabilities occur from early stress situations:
__________________________________________________________________________________
_________
28) Stressful events prior to _________________ can last a lifetime.
29) ______________________ protect the ends of our chromosomes.
30) The author believes that for every one year of caring for a special _______ child that the
individual ages __________________ years.
31) Connecting with and helping _______________ extends our ____________________
32) The baboons fed on human food that was tainted with _________________________ and died.
All the ______________________________________ males were gone.
33) Conditions where people ____________ and ____________ are vital.
34) More __________________ and more ____________________ make happy employees.
35) The proper __________________________________ style produces this environment.
36) The final question is “Are we brave enough to learn from a _______________________
plz answer only if you know

Which is an example of weak social behavior?
A.
asking your friend to do you a favor from time to time
B.
being both happy and a little upset when a
…

friend performs better than you at a task
C.
insisting on doing what you want to do whenever you’re with your friends
Which is an example of weak social behavior?

There’s a girl in my class thats always looking at me, i’ll be honest i sometimes do look at her but that’s only when i get a feel-ing she’s looking a
…

t me… one day she was walking in front of me walking sl-ow while staring out the side of her eyes at me and today i looked across the room bc the teacher called me she was staring at me and then moved behind some-one else so i wouldn’t see and through-out the class i would continue to see her looking at me…

Which is an illegal drug?
Prescription medication
Alcohol
Cocaine
Inhalants

the patient presents to the clinic with reports of irritability, being sleepy during the day, chronically not being able to fall asleep, and being tir
…

ed. which nursing diagnosis will the nurse document in the plan of care?

Hey what’s up all just wanting to say hi and c-h-a-t a bit and… f-r-e-e points to whoever wants them 100 points each I have too m
uch anyway…

que enfermedades pueden mejorar si se consume suficiente agua

at the end of which week does an embryo become a fetus?

standard precautions are used to prevent transmission of

how do bacteria survive for so long during harsh conditions until finding a host?

Frontiers | The Role of Metabolic Syndrome in Endometrial Cancer: A Review

Introduction

Endometrial cancer is one of the most common gynecological malignancies. The latest cancer statistics from the American Cancer Society showed that in 2018, the number of new cases of endometrial cancer in the United States was 63,230, and the number of deaths was 11,350. The incidence of malignant endometrial tumors in women ranked fourth, and the incidence of death from endometrial cancer ranked sixth (1). With the increasing incidence of metabolic diseases (obesity, diabetes and hypertension), the incidence of endometrial cancer is increasing, and affecting younger populations worldwide. It is estimated that the incidence of endometrial cancer will increase to 42.13 per 100,000 people in the United States by 2030 (2). In recent years, early diagnosis, surgery, radiotherapy and chemotherapy can significantly improve the therapeutic effect of patients, but the treatment of early lesions and the need to retain fertility, late and recurrent patients is still limited. A clinical analysis of 276 patients with endometrial cancer showed that the 5-year disease-free survival rate and the 5-year overall survival rate were 82.3 and 81%, respectively, and the recurrence rate and the cancer-related mortality rate were 14.5 and 15.9%, respectively (3).

Regarding the pathogenesis of endometrial cancer, the traditional view is that long-term non-progesterone estrogen overstimulation of the endometrium is the main cause of endometrial hyperplasia and endometrial cancer. Estrogen can bind with nuclear estrogen receptor (ER) and play a “genotype”-regulatory effect by regulating the transcription of specific target genes. Additionally, our previous studies have found that estrogen can also induce Ca²⁺ influx by binding to the G protein-coupled estrogen receptor (GPER) on the cell membrane surface, activating the calcium channel Cav1.3, and activating the downstream signal transduction pathway (MAPK/Erk) rapidly, thereby promoting the proliferation of endometrial cancer. This process does not involve gene transcription and protein synthesis; therefore, it is called the “non-gene-transcription effect” (4). At present, long-term progesterone is commonly used in the clinical treatment of endometrial cancer. However, the overall effective rate of progesterone therapy for primary endometrial cancer is only 50–70%, and the recurrence rate is as high as 40% (5, 6). The objective response rate of progesterone therapy for advanced and recurrent endometrial cancer is only 15–20% (7). Interestingly, recent studies have shown that serum estrogen levels in patients with endometrial hyperplasia and endometrial cancer are not elevated compared with those in the normal control group (8). Moreover, epidemiological studies have shown that long-term estrogen exposure in post-menopausal women does not increase the risk of endometrial cancer (9). Traditional views do not explain why endometrial cancer still occurs in post-menopausal women with low estrogen levels. These studies suggest that local estrogen sensitivity, rather than increased circulating estrogen, may drive the occurrence and development of endometrial cancer. At the same time, other factors besides estrogen may also induce the occurrence and development of endometrial cancer.

Endometrial cancer is often associated with obesity, diabetes, and hypertension. These conditions are commonly known as the metabolic triad of endometrial cancer. Epidemiological studies showed that the risk of endometrial cancer in diabetic patients was 2.12 times higher than that in normal patients, while the risk of endometrial cancer in those who were overweight (BMI ≥ 25 kg/m²) was 2.45 times higher than that in the control group. The risk of endometrial cancer in obese patients with hypertension was 3.5 times higher than that in the control group. Additionally, endometrial cancer is one of the cancers most closely related to metabolic diseases (10). Several studies have shown that metabolic syndrome caused by obesity, diabetes and hypertension is closely related to the incidence and adverse prognosis of endometrial cancer. A meta-analysis of six studies reported that metabolic syndrome is closely associated with increased risk of endometrial cancer in women (relative risk: 1.89, 95% CI 1.34–2.67) (11). A new research reported that there was a very high prevalence of metabolic syndrome in women newly diagnosed with endometrial cancer (12). A prospective case control study reported that women newly diagnosed with endometrial cancer have a higher prevalence of incident hyperglycemia, total: HDL cholesterol ratio, and three or more cardiovascular risk factors than women without endometrial cancer (13). All these studies suggest that metabolic syndrome is closely related to the incidence of endometrial cancer. However, the exact mechanism of metabolic syndrome affecting the occurrence and development of endometrial cancer has not been determined to date, which may be related to the elevation of such metabolites as blood sugar, insulin, insulin-like growth factor and triglyceride in serum (14, 15). The dynamic interaction between cells and the cell microenvironment plays an important role in regulating the growth of normal tissues and cancer cells. The tumor cell microenvironment includes tumor cells and other cells, such as fibroblasts, lymphocytes, macrophages, adipocytes, and other secreted factors, to form a unique tumor microenvironment system. An abnormal imbalance of the cell microenvironment often leads to tumorigenesis (16). It is suggested that molecules related to metabolic syndrome can accelerate the progression of endometrial cancer not only by acting directly on tumor cells but also by further remodeling the immune microenvironment of tumors.

In this review, we focus on the metabolic microenvironment of endometrial cancer and summarize the key molecular signaling pathways of obesity, diabetes and hypertension-related metabolic syndrome affecting the occurrence, development and prognosis of endometrial cancer, aiming to explore new methods of early prevention, and targeted treatment of endometrial cancer.

Molecular And Metabolic Mechanisms Underlying the Obesity-Endometrial Cancer Link

Epidemiological data showed that obesity is closely related to the increase in the incidence of various cancers. Some scholars have confirmed the causal relationship between obesity and breast cancer by constructing a genetically engineered mouse model and have shown that obesity is closely related to the increase in the survival rate of residual cancer cells (17). A meta-analysis of 26 studies in the United States showed that every five units increase in body mass index (BMI) increased the risk of endometrial cancer by 50% [relative risk [RR], 1.50; 95% CI, 1.42–1.59] (18). A study reported that a history of bariatric surgery and maintained normal weight after surgery is associated with a 71 and 81% reduced risk for uterine malignant tumors (19). These findings suggest that obesity may be a modifiable risk factor related to development of endometrial cancer. However, the mechanism by which obesity increases the risk of endometrial cancer has not been elucidated. At present, the possible mechanisms are as follows: obese patients are often accompanied by insulin resistance (hyperinsulinemia), abnormal fat metabolism (leptin, adiponectin disorders), hyperglycemia, hyperlipidemia, and chronic inflammation. These factors may promote the occurrence and development of tumors (Figure 1). To explore the key mechanism of obesity-induced endometrial cancer occurrence and development, it is helpful to provide a new intervention target for the treatment of patients with metabolic syndrome.

Figure 1. Dysfunctional adipose tissue in obesity.

Adipocyte-Derived Estrogen Signaling

Endometrium is a highly dynamic tissue controlled by ovarian steroids, estrogen and progesterone. Long-term estrogen stimulation without progesterone antagonism is a key factor in the occurrence of endometrial cancer. The decline of ovarian function in post-menopausal women is accompanied by a decrease in hormone levels. However, post-menopausal women are still prone to endometrial cancer. It has been reported that adipose-derived aromatase converts circulating androstenedione into estradiol, leading to elevated serum estradiol levels, which binds to estrogen receptors α and β (ERα and ERβ), eventually leading to recruitment of transcription factors, and gene transcription may be activated or repressed (20). Thus, in post-menopausal women, adipose tissue is the main source of estrogen biosynthesis. In addition, obesity can lead to hyperinsulinemia, which can reduce the synthesis of sex hormone binding protein (SHBG) by increasing the bioavailability of insulin-like growth factor-1 (IGF-1), thereby leading to an increase in estrogen levels. Therefore, obesity increases the risk of endometrial cancer, possibly by indirectly affecting estrogen levels. A meta-analysis showed that hormone replacement therapy (HRT) could modified the BMI-endometrial cancer risk association, however, menopausal status and histologic subtype did not significantly impact upon these associations (21). These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association. Additional studies are needed to explore the exact mechanism mediating the link between body adiposity and endometrial cancer.

Adipocyte-Derived Insulin Resistance

In obese patients, excessive accumulation of adipose tissue leads to elevated levels of circulating free fatty acids and increased expression of serum adipokines, such as leptin, visfatin, and cytokines, which ultimately leads to insulin resistance. Hyperinsulinemia with a decrease in the serum level of IGF-1 binding protein and an increase in IGF-1 is most often caused by insulin resistance. Obesity-induced chronic low-grade inflammation is an important factor leading to insulin resistance. Obesity-related inflammation is characterized by increased macrophage infiltration and increased expression of inflammatory cytokines in adipose tissue (22). Recently, studies have reported that endoplasmic reticulum chaperone 78 (GRP78) plays an important role in obesity-induced insulin resistance by regulating macrophages (23). The level of the proinflammatory cytokine TGF-α in adipose tissue of obese mice was significantly increased, which was closely related to insulin resistance (24). There are a large number of inflammatory mediators, such as C-reactive protein (CRP), interleukin-6 (IL-6), and plasminogen activator inhibitor-1 (PAI-1), that are elevated in the plasma of obese patients or animals and are closely related to insulin resistance (25). The obesity-induced inflammatory response inhibits insulin signaling in adipocytes and hepatocytes through a variety of signaling pathways, including inhibition of the expression of insulin receptor substrate 1 (IRS-1) and insulin receptor (IR) in insulin signaling pathways and inhibition of PPAR gamma function, and ultimately leads to insulin resistance (26, 27). Increased insulin and IGF-1 can stimulate the proliferation of endometrial cancer cells by binding to IR and IGF-1 receptors (IGF-1R) and activating downstream signaling pathways (28).

Synergistic Interaction of Estradiol and Insulin Signaling

There are both genotypic transcriptional and non-transcriptional effects in estrogen signal transduction: estrogen binds to ERα in the nucleus to exert genotypic effects, and the estrogen receptor GPER is located on the cell membrane to exert non-genotypic transcriptional effects. Studies have shown that estrogen combined with insulin can significantly promote the proliferation of endometrial cancer cells compared with estrogen or insulin alone (29). The combination of estrogen and a high-fat diet (mimic insulin resistance) could significantly stimulate the increase of endometrial glands in C57BL/6 mice. The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) and LXR/RXR signaling pathways may be involved in this process (30). Insulin upregulates TET1 and then upregulates GPER expression, which enhances the sensitivity of endometrial cancer cells to estrogen (31). Studies have found that estrogen and IGF-1 can synergistically promote the development of tumors in mice by activating MAPK and AKT signaling pathways (32). Other studies have found that estrogen may bind to IGF-1R and exert non-genetic transcriptional effects through the Ras/MAPK signaling pathway (33). How insulin and IGF-1 interact with estrogen in signaling pathways to promote the development of endometrial cancer warrants further investigation.

Adipose-Derived mTOR Signaling

Compared with non-obese patients, the activity of VEGF-mTOR in obese endometrial cancer patients increased significantly, suggesting that adipocyte-derived VEGF-mTOR signaling is a potential target for the treatment of obese women with endometrial cancer (34). Adipose tissue mesenchymal stem cell-derived medium can activate Akt/mTOR and promote the proliferation and invasion of cancer cells (35). A new bidirectional inhibitor of PI3K and mTOR is more effective than a simple inhibitor of mTOR (rapamycin) in inhibiting endometrial cancer (36). It is suggested that mTOR signaling may be a key pathway connecting obesity and endometrial cancer, which needs to be verified in a clinical trial.

Adipose-Derived Stem Cells

Adipose-derived stem cells play an important role in the tumor microenvironment. Obesity can promote the transformation of adipose-derived stem cells (ASCs) into cancer-related fibroblasts (CAFs), thereby promoting the proliferation and invasive phenotype of cancer cells (37). In addition, adipose-derived stem cells can promote ER + breast cancer cell metastasis independently of estrogen signaling (38). Leptin secreted by adipose-derived stem cells promotes the growth and metastasis of ER + breast cancer by increasing the expression of ER receptor and aromatase (39). It has been reported that ASCs can fuse with endometrial cancer cells, and the fused endometrial cancer cells present a fibroblast-like appearance of mesenchymal phenotype accompanied by downregulation of E-cadherin expression and upregulation of Vimentin expression (40). Further study of the role of ASCs in the occurrence of endometrial cancer will help to elucidate how obesity increases the risk of endometrial cancer.

Adipose-Derived Adipokines

Adiponectin

Adiponectin is a cytokine secreted mainly by adipocytes. Epidemiological studies have shown that adiponectin levels in the blood circulation of patients with endometrial cancer are decreased (41). Serum low adiponectin levels are closely related to insulin resistance, hyperinsulinemia, obesity, and hypertension (42). A meta-analysis showed that serum adiponectin levels were negatively correlated with the risk of endometrial cancer, especially in post-menopausal women who did not receive HRT (43). In a meta-analysis of 26 studies, for each 1 μg/ml increase of adiponectin, there was a 3% reduction of summary relative risk (SRR) in endometrial cancer risk, and a 14% reduction for each increase of 5 μg/ml (44). Abnormal expression of serum adiponectin is also closely related to the occurrence and development of prostate cancer, breast cancer and colon cancer (45–47). However, the antitumor effect of adiponectin on endometrial cancer mainly depends on the alteration of systemic metabolic state or the direct interaction with tumor cells warrants further study.

Adiponectin exerts its biological effects mainly by binding to adiponectin receptors. Three types of adiponectin receptors have been identified: adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2), and T-cadherin. AdipoR1 is mainly expressed in skeletal muscle and epithelial cells, and AdipoR2 is most abundant in the liver (48). AMPK is an important signaling pathway downstream of adiponectin. The adiponectin/AdipoR1 signaling axis can promote the phosphorylation of the AMPK Thr172 site by inducing phosphorylation of the tumor suppressor gene LKB1. AMPK phosphorylation also plays an important role in energy metabolism by activating the TSC2 tumor suppressor (49, 50). Studies have shown that there is no significant difference in the expression of AdipoR1 and AdipoR2 in normal endometrial tissues. In endometrial cancer tissues, the expression of AdipoR1 is higher than that of AdipoR2. Adiponectin/AdipoRs can inhibit the proliferation, adhesion and invasiveness of endometrial cancer cells by activating the downstream LKB1-AMPK/S6 signal axis (51). Adiponectin can not only inhibit the proliferation and migration of endometrial cancer cells through the AMPK/mTOR/S6K1 signaling pathway but can also enhance the sensitivity of endometrial cancer cells to insulin through the AMPK/S6K1/IRS1 signaling pathway (52). Adiponectin increases insulin sensitivity mainly by activating p38MAPK activity. It has been reported that the highly conserved 13-residue segment (ADP-1) of adiponectin can promote the translocation of glucose transporter 4 (GLUT4) to the cell membrane, reduce the blood sugar level of db/db mice and promote the secretion of insulin by pancreatic beta cells, thereby improving the metabolism of glucose and fatty acids (53). In addition, the anti-proliferative effect of adiponectin is related to a variety of cell cycle regulators, cyclin D1, D2, ERK1/2, and Akt.

It is worth noting that adiponectin not only affects the tumor cells themselves but also regulates the tumor immune microenvironment. In contrast, it has been reported that the deletion of adiponectin may promote the transformation of M2 tumor-associated macrophages to M1 type through the p38MAPK signaling pathway, thereby inhibiting the growth of tumors (54). Therefore, on the one hand, adiponectin can reduce the occurrence of endometrial cancer by changing the metabolic state of the whole body; on the other hand, it can directly inhibit the proliferation of endometrial cancer cells. The decrease in serum adiponectin levels in obese patients is closely related to the increased risk of endometrial cancer (44).

Visfatin

Visfatin is an insulin-like adipokine identified in recent years. Visfatin is highly expressed in many metabolically related tumors, and its increased expression is closely related to the increased risk of cancer (55). It has been reported that decreased serum adiponectin or increased visfatin levels are independent risk factors for endometrial cancer. The visfatin:adiponectin ratio in the endometrial cancer was significantly higher than the control, which has certain reference value for the diagnosis of endometrial cancer (56). With the increase of BMI, the level of visfatin in obese patients increases significantly. The increase in serum visfatin level is closely related with risk of myometrial invasion (OR: 1.091; 95%CI:1.021–1.166) and lymph node metastasis (OR: 1.018; 95%CI:1.000–1.035) of endometrial cancer. A high level of visfatin suggests poor prognosis in patients with endometrial cancer, which may be a potential therapeutic target for endometrial cancer (57, 58). Studies have shown that visfatin can upregulate the expression of IR and insulin receptor substrate (IRS) 1/2, and it can coactivate the PI3K/Akt and MAPK/ERK1/2 signaling pathways with insulin to promote the proliferation and inhibit apoptosis of endometrial cancer cells (59). Exogenous visfatin can promote the proliferation of breast cancer cells by promoting ERα phosphorylation and activating estrogen response element (ERE)-dependent signaling pathways (60). However, it has not been reported whether visfatin can also enhance estrogen-dependent ER signaling and accelerate the development of endometrial cancer. In addition, visfatin has been reported to be abnormally expressed in a variety of tumors, which can increase the risk of multiple tumors and become a potential molecular marker for the early detection of tumors (55). Therefore, the combination of visfatin and adiponectin may be a marker for the early clinical diagnosis of endometrial cancer and may provide new targets for clinical intervention.

Leptin

Leptin is an important adipokine encoded by the obesity gene. Leptin plays an important role in regulating food intake, energy consumption and promoting cell growth by combining with leptin receptor (ObR). Recent studies have found that abnormal expression of leptin and leptin receptor signaling related to obesity plays an important role in the development of breast, colon and endometrial cancer (61, 62). A meta-analysis showed that high levels of leptin can significantly increase the risk of endometrial cancer (risk ratio, RR = 2.55) and that high levels of leptin are an independent risk factor for endometrial cancer (63). The expression of leptin and ObR is positively correlated with the invasiveness of tumors and BMI of patients but is negatively correlated with histological grade. The elevated expression of leptin and ObR is closely related to lymph node metastasis and poor survival prognosis, as well as the positive expression of ERs (64). However, whether the leptin signaling pathway can influence the development of endometrial cancer by affecting the classical estrogen signaling pathway remains to be further confirmed. Studies have shown that the expression of ObR in poorly differentiated endometrial cancer tissues is significantly higher than that in well-differentiated endometrial cancer tissues, and leptin can inhibit the apoptosis of endometrial cancer cells by activating the NIK/IKK signaling pathway. Elevated leptin levels can influence epithelial polarity and promote malignant transformation through overactivation of the PI3K/Akt signaling pathway (65). Leptin also promotes the proliferation and invasion of endometrial cancer cells by activating STAT3 and ERK1/2, JNK signaling pathways. Correspondingly, this proliferation is inhibited when the JAK/STAT3 pathway is blocked (66). Other studies have reported that the leptin-2548 G/A SNP may be involved in the occurrence and development of endometrial cancer (67). It has been reported that leptin can upregulate the expression of STAT3-CPT1B and plays an important role in maintaining the stem and drug resistance of breast cancer cells (68). However, the role of leptin in the maintenance stem cell of endometrial cancer has not been determined to date and requires further study. Elevated leptin levels suggest the presence of endometrial cancer, and serum leptin levels may be an effective tool for assessing the clinical staging of endometrial cancer (69). Although elevated leptin level is a high-risk factor for endometrial cancer, whether it is the most critical molecule associated with obesity and endometrial cancer warrants further investigation.

Adipose-Derived Inflammatory Cytokines

Inflammation is the core stage of tumorigenesis and development. It has been reported that 18% of cancer cases worldwide are related to chronic infection, which implies a potential relationship between cancer and inflammation. In a lean state, a balance between adipocytes and immune cells can maintain normal metabolism throughout the body. However, in obese people, this balance translates into a markedly inflammatory adipose tissue microenvironment. Obesity-related adipose inflammation can increase the secretion of pro-inflammatory factors, cause systemic metabolic disorders, and change the microenvironment of tumors, thereby significantly increasing the risk of cancer in obese people. Several studies have confirmed that obesity-related inflammatory cytokines are involved in tumorigenesis.

IL-6

IL-6 is an inflammatory cytokine that plays an important role in many physiological and pathological processes. IL-6 is closely associated with a three times increased risk of mortality in overweight/obese patients (70). Studies have confirmed that IL-6 is closely related to the occurrence of a variety of tumors, including endometrial cancer. Adipose-derived IL-6 can promote the proliferation, invasion and angiogenesis of endometrial cancer cells by activating the JAK/STAT3 signaling pathway (71). The elevated plasma level of IL-6 is closely related to the poor prognosis of tumors (72). In addition, estrogen can promote the expression of IL-6 in endometrial cancer cells by binding to GPER on the cell surface (73). It has been reported that estrogen (E2) can promote the expression of IL-6 by binding with nuclear receptor ERα, and IL-6 can promote the synthesis of aromatase by binding with IL-6R of basal cells, thereby accelerating the synthesis of estrogen and forming a positive feedback loop (74). A new study confirms that blocking IL-6-driven inflammatory signaling can inhibit the spread of cancer cells to the liver (75). IL-6 is likely to play a prominent role in the development of endometrial cancer, and it appears to be one of the major mechanisms involved in the obesity-cancer link.

TNF-α

TNF-α is an inflammatory cytokine secreted by macrophages and adipocytes. It is an important regulator of adipose tissue metabolism and plays an important role in immune regulation, inflammatory response and anti-tumor response. However, recent studies have found that TNF-α is also an endogenous tumor-promoting factor that can promote the proliferation, invasion and metastasis of cancer cells. The level of TNF-α in circulating blood of obese patients is increased, and the increased level of TNF-α is closely related to the poor prognosis of endometrial cancer patients (76). In addition, studies have reported that 11 cancer markers in overweight patients are significantly higher than those in normal weight patients, including ANG-2, sFASL, HB-EGF, IL-8, PLGF, TGF-α, TNF-α, uPA, VEGF-A, VEGF-C, and VEGF-D (77). Compared with lean mice, C57BL/6 mice induced by a high-fat diet had higher levels of serum free fatty acids and TNF-α and higher accumulation of macrophages in adipose tissue (78). A case-control study showed that elevated levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) were associated with an increased risk of endometrial cancer [TNF-α-odds ratio [OR]: 1.73; sTNFR1-[OR]:1.68; sTNFR2-[OR]:1.53] (79). Regarding the mechanism of TNF-α in promoting tumorigenesis and development, it has been reported that chronic inflammation induced by obesity promotes the accumulation of macrophages in adipose tissue. TNF-α released by M1 macrophages can promote metastasis and inhibit apoptosis of ovarian cancer cells by activating the signaling pathway of NF-κB (80). TNF-α is also a key factor driving the expression of the aromatase gene, and IL-10 can regulate the expression of aromatase in adipose tissue by inhibiting the TNF-α signaling pathway (81). Moreover, TNF-α could induce serine phosphorylation of IRS-1 and inhibit its triggering of downstream signals, leading to insulin resistance. Insulin resistance-induced hyperinsulinemia and IGF-1 can further enhance the biological effects of TNF-α by activating the TNF-α signaling pathway (80). TNF-α inhibited apoptosis in cancer cells by activating the NF-κB signaling pathway. Although several pathways between TNF-α and tumors have been identified, the precise mechanism of obesity-related TNF-α involved in the development of endometrial cancer remains to be further investigated.

PAI-1

Plasminogen activator inhibitor-1 (PAI-1) is a protease inhibitor produced by vascular endothelial cells, stromal cells and adipocytes in adipose tissue. Recent studies have found that PAI-1 not only plays an important role in influencing insulin signaling but also plays an important biological role in influencing the invasion, invasion and metastasis of obesity-related tumors (82). PAI-1 is highly expressed in endometrial cancer tissues and is closely related to the poor prognosis of endometrial cancer (83). Studies have reported that PAI-1 may mediate the transcriptional regulation of adipose-derived stem cells in endometrial cancer (84). Therefore, PAI-1 represents a potential therapeutic target.

Effect of Obesity on the Tumor Immune Microenvironment

Obesity can promote adipocytes to secrete pro-inflammatory factors, such as TNF-α, IL-6, and IL-18. These pro-inflammatory cytokines can further enhance the infiltration of inflammatory cells, mainly macrophages and T lymphocytes, thereby promoting abnormal proliferation and transformation of normal cells (85). Studies have shown that 16 weeks of aerobic and endurance training can reduce the expression of inflammatory cytokines (IL-6 and TNF-α) in adipose tissue and induce the transformation of inflammatory M1 macrophages into anti-inflammatory M2 macrophages (86). It has been found that adipose tissue-derived leptin can promote the differentiation of Th27 cells and promote T cell function by regulating cell metabolic reprogramming (87). Recent studies have shown that obesity can increase the infiltration of tumor-related macrophages, upregulate the production of IL-1β, and promote angiogenesis and tumor progression (88). It has been reported that M2 macrophages infiltrated in the microenvironment of endometrial cancer can enhance the sensitivity of endometrial cancer cells to estrogen by releasing cytokine IL17A and upregulating the expression of ERα through TET1-mediated epigenetics (8). These studies indicated that obesity may further promote the occurrence and progression of endometrial cancer by affecting the immune microenvironment of tumors.

Type 2 Diabetes And Endometrial Cancer

Most epidemiological studies suggested that diabetes is a risk factor for endometrial cancer incidence; for example, a meta-analysis of 16 studies showed that diabetes was statistically significantly associated with an increased risk of endometrial cancer (summary RR 2.10, 95% CI 1.75–2.53), and there was a stronger association with a adjusting for age (RR 2.74, 95% CI 1.87–4.00) (89). Also, diabetes is closely related to increased cancer-specific mortality (HR 2.09, 95% CI 1.31–3.35) and mortality from non-cancer related causes in women with endometrial cancer (90). Therefore, these studies show that diabetes increases both the risk and mortality rates of endometrial cancer.

Effect of Hyperglycemia on Endometrial Cancer

Hyperglycemia is an important clinical characteristic of type 2 diabetes mellitus. Systemic hyperglycemia provides favorable conditions for energy metabolism of cancer cells. Previous studies have confirmed that elevated serum glucose can directly regulate cancer-related signaling pathways, especially to meet the needs of rapid proliferation of cancer cells, and can promote the process of glycometabolism reprogramming (91). Metabolic reprogramming is one of the important hallmarks of tumor cells, which are different from normal cells. Even in the presence of abundant oxygen, ~80% of tumor cells metabolize glucose and produce ATP mainly through aerobic glycolysis, also known as the Warburg effect. In addition to the rapid production of energy, glycolysis can also produce a large number of metabolic intermediates, which can be used to synthesize biological macromolecules needed for the rapid growth of tumors, including nucleotides, fatty acids, and proteins.

Glucose transporter (GLUT) is the main carrier of glucose uptake by cells. When glucose enters the cell, GLUT transports allosteric to transport glucose into the cell to support the high glycolysis rate. It has been reported that high glucose could promote the expression of vascular endothelial growth factor (VEGF)/VEGFR and the process of (epithelial-mesenchymal transition) EMT by regulating the expression of ERα/GLUT4, thereby promoting the proliferation and invasion of endometrial cancer cells (92). In addition, high glucose can increase the activity of glucose uptake and glycolysis by regulating AMPK/mTOR/S6 and MAPK pathways, thereby leading to increased invasiveness of endometrial cancer cells. Moreover, high glucose can promote the proliferation of endometrial cancer cells by activating STAT3 expression, which can be inhibited by metformin (93). The activity of glucose metabolism is closely related to the concentration of glucose outside the cell. However, it is not clear how cells perceive external glucose levels and regulate glycolysis pathway activity. AMPK, an adenylate-activated protein kinase, is a key protein for the perception of extracellular glucose concentration (94). It was reported that high extracellular glucose levels regulate the protein level of CARM1 by reducing AMPK phosphorylation, thereby inhibiting GAPDH methylation, which further promotes the activity of the GAPDH enzyme and glycolysis pathway (95). This study reveals the mechanism by which cells perceive extracellular glucose levels and regulate the rate of glycolysis, helping to elucidate the mechanism by which cancer cells perceive and utilize glucose.

Pyruvate kinase isozymes M2 (PKM2) is a key metabolic enzyme that promotes glycolysis and plays an important role in tumorigenesis through the Warburg effect. It has been reported that high glucose could promote the abnormal expression of PKM2. Overexpression of PKM2 could promote the accumulation of glycolysis intermediates (pyruvate and lactic acid), provide precursors for the synthesis of biomacromolecules, and lead to cell proliferation and tumorigenesis (96). Lactic acid is a key metabolite of glycolysis in cancer cells. The accumulation of extracellular lactic acid has an important impact on the metabolism of cancer cells and the transformation of non-cancer cells into cancer cells, including metabolic reprogramming, tumor inflammation, and angiogenesis. Recent studies have found that lactic acid produced by glycolysis of cancer cells can inhibit the function of macrophages through a hypoxia-inducible factor-mediated mechanism, induce the transformation of anti-tumor type M1 macrophages into M2, and promote the invasion and migration of cancer cells (97). Interestingly, M2 macrophages are the predominant tumor-associated macrophages in endometrial cancer and play an important role in the occurrence and development of endometrial cancer (98). Monocarboxylate Transporter 1 (MCT1) is an important protein for lactic acid and pyruvate uptake by cells, while MCT4 is an important protein for cell transport of lactic acid and pyruvate, which play an important role in regulating lactic acid metabolism. It has been reported that MCT1 was an independent prognostic biomarker in endometrial cancer (99). A recent study reported that the use of monocarboxylic acid transporter (MCT) inhibitors can reverse the inhibition of lactic acid on macrophage lysosomes (100). Therefore, MCT1 inhibition may have potential as a treatment for endometrial cancer. It is suggested that the enhancement of glycolysis activity and metabolites, such as lactic acid, in endometrial cancer under a high glucose environment may lead to acidification of the tumor microenvironment. The acidic environment may be perceived by tumor-related macrophages, which depend on the monocarboxylic acid transporter 1 (MCT1) pathway to induce macrophage transformation from M1 to M2, thus accelerating the progress of endometrial cancer. These studies suggested that managing hyperglycemia or targeting glycometabolism may be a potential therapeutic strategy for endometrial cancer.

Effect of Insulin Resistance on Endometrial Cancer

Insulin resistance and hyperinsulinemia are important characteristics of obesity and diabetes. The expression of insulin and IGF-1 was significantly increased in diabetic patients, and high insulin levels were an independent factor of endometrial cancer (28, 101, 102). High insulin and IGF-1/2 levels in diabetic patients can accelerate the transformation of androstenedione into estrogen by aromatase and increase estrogen levels by inhibiting the synthesis of SHBG. Long-term estrogen stimulation without progesterone antagonism can cause endometrial dysplasia or even malignant transformation (103). It has been reported that after adjusting for BMI, age and histological type, the high expression of IR/IGF-1R is closely related to prognostic high-risk factors, such as the progression of endometrial cancer and lymph node infiltration (104).

Insulin can activate the phosphoinositide 3-kinase (PI3K)/AKT or mitogen-activated protein kinase (MAPK)/extracellular signaled regulated kinase ERK signaling pathway through binding to IR/IGF-1R to promote EMT of endometrial cancer, which leads to increased proliferation and invasion of endometrial cancer cells, inhibits apoptosis of cancer cells and promotes angiogenesis of tumors (105). In addition, insulin could upregulate the expression of vascular endothelial growth factor, thereby stimulating angiogenesis, which is closely related to the occurrence and development of tumors (106). Recent studies have reported that insulin signal-dependent phosphorylation initiates glucose metabolism prior to glucose transport; thus, the metabolism of glucose is diverted to a specific direction of glycolysis (107). In this way, insulin signaling plays a key role in glycometabolism reprogramming, and insulin resistance can promote the occurrence and development of endometrial cancer through an indirect pathway or ligand-receptor direct pathway.

IR-A has high affinity for insulin and IGF-II but binds IGF-I with low affinity. IGF-1R has high affinity for IGFs. However, blocking IGF-IR and IR does not completely prevent the growth stimulation of insulin-like growth factor or insulin on cancer cells, suggesting that other receptors may be involved in complex signal transduction systems. Our previous studies found and confirmed for the first time the expression of Hybrid-R in endometrial cancer, which can promote the proliferation and inhibit apoptosis of endometrial cancer cells through the MAPK/ERK signaling pathway (22). Hybrid-R is expected to provide a new therapeutic target and strategy for the precise treatment of endometrial cancer patients with insulin resistance and hyperinsulinemia.

Metformin in the Treatment of Endometrial Cancer

Metformin, an insulin sensitizer, is considered a potential anticancer drug. Our previous clinical studies have found that metformin combined with progesterone treatment can significantly improve the efficacy of endometrial cancer patients with poor progesterone treatment (108). It has been reported that plasma hyperglycemia and high levels of IGF-1 in patients with endometrial cancer can be reversed by conventional doses of metformin (109). Metformin can significantly inhibit the proliferation of endometrial cancer cells, which may be related to the activation of AMPK signaling and the inhibition of the mTOR signaling pathway (110). In contrast, some studies have shown that metformin does not reduce the risk of endometrial cancer, nor can it improve the overall survival of patients (111). Correspondingly, studies have found that metformin does not affect the PI3K-Akt-mTOR and insulin signaling pathways and has no effect on weight loss (112). It is of great clinical significance to further study the mechanism of abnormal glucose metabolism promoting endometrial cancer, reveal the key molecule of endometrial cancer caused by metabolic diseases, and find new effective preventive or anti-cancer drugs that can replace metformin.

Other Types OF Diseases OF Metabolic Syndrome And Endometrial Cancer

Dyslipidemia is closely related to the incidence of various cancers (113). It was reported that patients with hyperglycemia, hyperlipidemia and hypertension are twice as likely to develop endometrial cancer as normal people (114). The BMI of patients was positively correlated with serum palmitic acid, oleic acid and stearic acid levels. The increase of free fatty acids in obese patients can indirectly promote the proliferation of endometrial cancer cells by increasing the level of estradiol (115). The BMI of patients with endometrial cancer was significantly higher than that of normal controls. At present, there are many studies on the relationship between endometrial cancer and obesity and diabetes, but there are few studies on the relationship between endometrial cancer and hypertension and lipid disorders. The possible mechanisms of abnormal blood lipids associated with the risk of endometrial cancer are as follows: activation of fatty acid and amino hexose pathways leads to the production of reactive oxygen species (ROS) in mitochondria, which induces oxidative stress in cells. Excessive aggregation of ROS clusters interacts with lipids, proteins and DNA in cells, causing changes in membrane and enzyme functions, inducing cell damage, and ultimately leading to tumorigenesis (116). Recent studies have reported that serum cholesterol is elevated in obese people. Cholesterol activates the transcriptional activity of endometrial cancer cells through an ER-dependent pathway and promotes the proliferation of endometrial cancer cells (117). Moreover, recent studies have found that elevated circulating free fatty acids may be an important factor in linking obesity and tumorigenesis, which can promote the proliferation and invasion of breast cancer cells through ERα signaling and the mTOR signaling pathway (118). It has been reported that A-FABP released from adipose tissue can promote the dryness and invasiveness of breast cancer cells (119). Taken together, abnormal lipid metabolism, especially elevated free fatty acids, is closely related to the progression of endometrial cancer. Can fatty acids participate in the occurrence and development of endometrial cancer through an ER-dependent pathway remains to be thoroughly characterized.

Hypothyroidism is a type of reduced metabolic syndrome caused by a decrease in thyroid hormone synthesis and secretion or by inadequate physiological effects. Brinton et al. indicated that EC is related to previous diagnoses of thyroid diseases (RR = 1.52, 95% CI 1.17–1.98) (120). It has been reported that the incidence of hypothyroidism in EC patients is significantly increased. Serum TSH level before treatment is an independent risk factor for poor prognosis of EC (121). Additionally, elevated TSH levels have been reported to increase the incidence of MS (122). At present, there are few studies on thyroid function and endometrial cancer. Several studies have shown that hypothyroidism is closely related to MS, PCOS, elevated serum leptin levels, and dyslipidemia. Hypothyroidism may promote the occurrence and development of endometrial cancer by indirectly increasing the risk factors of endometrial cancer or through direct interaction (123). Studies examining the relationship between thyroid function (TSH level) and endometrial cancer will provide new insights into the mechanism of endometrial cancer.

Conclusion

Metabolic syndrome is a complex disorder defined by a cluster of metabolic risk factors that includes insulin resistance, hyperinsulinemia, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and visceral obesity. Obesity, diabetes and hypertension are the metabolic triad of endometrial cancer. There was a very high prevalence of metabolic syndrome in women newly diagnosed with endometrial cancer. In this article, we review potential pathways directly linking metabolic syndrome with cancer (Figure 2). Obesity-related insulin resistance, leptin and lactone levels are closely related to the occurrence and development of endometrial cancer. Decreased serum adiponectin levels and increased chronic inflammation in obese patients are important factors for increasing the risk of endometrial cancer. Obesity and diabetes have many common pathological characteristics: insulin resistance (hyperinsulinemia), abnormal fat metabolism (elevated leptin, decreased adiponectin), hyperglycemia, hyperlipidemia and chronic inflammation. Many studies have reported that these characteristics can promote the occurrence and development of endometrial cancer by directly acting on tumor cells or regulating the tumor microenvironment. Therefore, there is an urgent need to intervene in chronic diseases related to metabolic syndrome to reduce the incidence of endometrial cancer. A commentary by MacKintosh et al. indicated obese undergoing bariatric surgery or medical weight loss management could reduce the risk of endometrial cancer and hyperplastic abnormalities of the endometrium may be reversible through weight loss (124). Studies have assessed the effects of obesity and weight-loss surgery on endometrial morphology and molecular signaling pathways in endometrial cancer. It was found that insulin resistance (HbA1c, HOMA-IR) and inflammation (hsCRP, IL-6) circulating biomarkers decreased, while reproductive biomarkers (LH, FSH, SHBG) increased significantly (125). C-peptide, insulin, C-reactive protein, leptin, IL-1Ralpha, and IL-6 decreased significantly, while SHBG, IGFBP1, and adiponectin increased significantly in weight-loss interventions in endometrial cancer (126). Thus, bariatric surgery may reduce the risk of endometrial cancer by improving obesity-induced inflammation. However, the role of bariatric surgery in the treatment of endometrial hyperplasia still need conclusive or convincing evidence. Recently, seven markers based on the BMI-sensitive pathway of insulin resistance, adipoR1, adipoR2, ObR, IRβ, IRS-1, IGF-1R, and IGF-2R, have been proposed to develop a new molecular typing system for endometrial cancer. However, no effective molecular typing system and molecular typing markers have been found for endometrial cancer (127). A research proposed a pragmatic endometrial cancer risk prediction model, which included obesity, reproduction, insulin resistance, and genetic risk. This model plays an important role in identifying individuals at high risk of endometrial cancer and guiding preventive treatment of specific disease targets (128). Except for obesity, reproduction, insulin resistance, and genetic risk, the other metabolic syndrome related high risk factors for endometrial cancer as mentioned in the text should also be considered and a large prospective cohort of asymptomatic women is required. Similarly, studies incorporating biomarkers (adiponectin, estradiol, interleukin-1 receptor antagonist, tumor necrosis factor-and triglyceride) into the risk prediction model of endometrial cancer have found that they can modestly improve the predictive ability of endometrial cancer (129). Despite different studies, new molecular markers have been reported, but to date, no reliable molecular markers have been applied to clinical molecular typing. Our recent study found that serum total calcium may be a more sensitive metabolic syndrome parameter than hyperlipidemia in patients with endometrioid cancer (130).

Figure 2. Potential pathways directly linking metabolic syndrome with endometrial cancer.

Therefore, it is necessary to screen new markers based on systemic metabolomic changes and to reveal new molecular typing methods and risk prognostic models of endometrial cancer based on serum metabolomic changes. With the frequent application of proteomics, metabolomics, and transcriptomes, the role of key molecules in identifying metabolic syndrome-related diseases in endometrial cancer is of great significance for the early prevention and treatment of endometrial cancer. In conclusion, endometrial cancer is a type of metabolic disease-related tumor. Elucidating the specific roles and mechanisms of metabolic syndrome-related diseases in endometrial cancer is expected to provide a new target for the early prevention and treatment of endometrial cancer. Although the study of the association between metabolic syndrome and cancer may provide an effective therapeutic target for endometrial cancer, improving lifestyle is still the most important component in preventing the morbidity and mortality of endometrial cancer associated with metabolic syndrome. Further in vivo and clinical studies are needed to investigate the therapeutic targeting of the metabolic microenvironment in metabolic syndrome-related endometrial cancer.

Author Contributions

XY and JW wrote and approved the final version of this manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (grant nos. 81672571 and 81874108), Special Projects for Strengthening Basic Research of Peking University (grant no. BMU2018JC005), and National Key Technology Research and Development Program (grant no. 2015BAI13B06).

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

2. Sheikh MA, Althouse AD, Freese KE, Soisson S, Edwards RP, Welburn S, et al. USA endometrial cancer projections to 2030: should we be concerned? Future Oncol. (2014) 10:2561–8. doi: 10.2217/fon.14.192

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Tejerizo-Garcia A, Jimenez-Lopez JS, Munoz-Gonzalez JL, Bartolome-Sotillos S, Marqueta-Marques L, Lopez-Gonzalez G, et al. Overall survival and disease-free survival in endometrial cancer: prognostic factors in 276 patients. Onco Targets Ther. (2013) 9:1305–13. doi: 10.2147/OTT.S51532

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Hao J, Bao X, Jin B, Wang X, Mao Z, Li X, et al. Ca2+ channel subunit alpha 1D promotes proliferation and migration of endometrial cancer cells mediated by 17beta-estradiol via the G protein-coupled estrogen receptor. FASEB J. (2015) 29:2883–93. doi: 10.1096/fj.14-265603

PubMed Abstract | CrossRef Full Text | Google Scholar

7. Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. (1999) 17:1736–44. doi: 10.1200/JCO.1999.17.6.1736

PubMed Abstract | CrossRef Full Text | Google Scholar

8. Ning C, Xie B, Zhang L, Li C, Shan W, Yang B, et al. Infiltrating macrophages induce ERalpha expression through an IL17A-mediated epigenetic mechanism to sensitize endometrial cancer cells to estrogen. Cancer Res. (2016) 76:1354–66. doi: 10.1158/0008-5472.CAN-15-1260

PubMed Abstract | CrossRef Full Text | Google Scholar

9. Cherry N, McNamee R, Heagerty A, Kitchener H, Hannaford P. Long-term safety of unopposed estrogen used by women surviving myocardial infarction: 14-year follow-up of the ESPRIT randomised controlled trial. BJOG. (2014) 121:700–5. Discussion 5. doi: 10.1111/1471-0528.12598

PubMed Abstract | CrossRef Full Text | Google Scholar

11. Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Giugliano D. Metabolic syndrome and endometrial cancer: a meta-analysis. Endocrine. (2014) 45:28–36. doi: 10.1007/s12020-013-9973-3

PubMed Abstract | CrossRef Full Text | Google Scholar

12. Kitson SJ, Lindsay J, Sivalingam VN, Rutter MK, Crosbie EJ. High prevalence of metabolic syndrome in women newly diagnosed with endometrial cancer. Gynecol Oncol Rep. (2018) 26:109–10. doi: 10.1016/j.gore.2018.08.006

PubMed Abstract | CrossRef Full Text | Google Scholar

13. Kitson SJ, Lindsay J, Sivalingam VN, Lunt M, Ryan NAJ, Edmondson RJ, et al. The unrecognized burden of cardiovascular risk factors in women newly diagnosed with endometrial cancer: a prospective case control study. Gynecol Oncol. (2018) 148:154–60. doi: 10.1016/j.ygyno.2017.11.019

PubMed Abstract | CrossRef Full Text | Google Scholar

14. Trabert B, Wentzensen N, Felix AS, Yang HP, Sherman ME, Brinton LA. Metabolic syndrome and risk of endometrial cancer in the United States: a study in the SEER-medicare linked database. Cancer Epidemiol Biomarkers Prev. (2015) 24:261–7. doi: 10.1158/1055-9965.EPI-14-0923

PubMed Abstract | CrossRef Full Text | Google Scholar

15. Nead KT, Sharp SJ, Thompson DJ, Painter JN, Savage DB, Semple RK, et al. Evidence of a causal association between insulinemia and endometrial cancer: a mendelian randomization analysis. J Natl Cancer Inst. (2015) 107:djv178. doi: 10.1093/jnci/djv178

PubMed Abstract | CrossRef Full Text | Google Scholar

16. Cuny T, de Herder W, Barlier A, Hofland LJ. Role of the tumor microenvironment in digestive neuroendocrine tumors. Endocr Relat Cancer. (2018) 25:R519–44. doi: 10.1530/ERC-18-0025

PubMed Abstract | CrossRef Full Text | Google Scholar

17. Ecker BL, Lee JY, Sterner CJ, Solomon AC, Pant DK, Shen F, et al. Impact of obesity on breast cancer recurrence and minimal residual disease. Breast Cancer Res. (2019) 21:41. doi: 10.1186/s13058-018-1087-7

PubMed Abstract | CrossRef Full Text | Google Scholar

18. World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food, Nutrition, Physical Activity, and the Prevention of Endometrial Cancer. (2013). Available online at: http://www.dietandcancerreport.org (accessed August 1, 2019).

Google Scholar

19. Ward KK, Roncancio AM, Shah NR, Davis MA, Saenz CC, McHale MT, et al. Bariatric surgery decreases the risk of uterine malignancy. Gynecol Oncol. (2014) 133:63–6. doi: 10.1016/j.ygyno.2013.11.012

PubMed Abstract | CrossRef Full Text | Google Scholar

21. Crosbie EJ, Zwahlen M, Kitchener HC, Egger M, Renehan AG. Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. (2010) 19:3119–30. doi: 10.1158/1055-9965.EPI-10-0832

PubMed Abstract | CrossRef Full Text | Google Scholar

22. Ye J, McGuinness OP. Inflammation during obesity is not all bad: evidence from animal and human studies. Am J Physiol Endocrinol Metab. (2013) 304:E466–77. doi: 10.1152/ajpendo.00266.2012

CrossRef Full Text | Google Scholar

23. Kim JH, Lee E, Friedline RH, Suk S, Jung DY, Dagdeviren S, et al. Endoplasmic reticulum chaperone GRP78 regulates macrophage function and insulin resistance in diet-induced obesity. FASEB J. (2018) 32:2292–304. doi: 10.1096/fj.201701017R

PubMed Abstract | CrossRef Full Text | Google Scholar

24. Szeto HH, Liu S, Soong Y, Alam N, Prusky GT, Seshan SV. Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury. Kidney Int. (2016) 90:997–1011. doi: 10.1016/j.kint.2016.06.013

PubMed Abstract | CrossRef Full Text | Google Scholar

26. Perrotta F, Nigro E, Mollica M, Costigliola A, D’Agnano V, Daniele A, et al. Pulmonary hypertension and obesity: focus on adiponectin. Int J Mol Sci. (2019) 20:E912. doi: 10.3390/ijms20040912

PubMed Abstract | CrossRef Full Text | Google Scholar

27. Liu Z, Wang N, Ma Y, Wen D. Hydroxytyrosol improves obesity and insulin resistance by modulating gut microbiota in high-fat diet-induced obese mice. Front Microbiol. (2019) 10:390. doi: 10.3389/fmicb.2019.00390

PubMed Abstract | CrossRef Full Text | Google Scholar

29. Tian W, Teng F, Zhao J, Gao J, Gao C, Sun D, et al. Estrogen and insulin synergistically promote type 1 endometrial cancer progression. Cancer Biol Ther. (2017) 18:1000–10. doi: 10.1080/15384047.2017.1394547

PubMed Abstract | CrossRef Full Text | Google Scholar

30. Cheng Y, Lv Q, Xie B, Yang B, Shan W, Ning C, et al. Estrogen and high-fat diet induced alterations in C57BL/6 mice endometrial transcriptome profile. Endocr Connect. (2018) 7:36–46. doi: 10.1530/EC-17-0315

PubMed Abstract | CrossRef Full Text | Google Scholar

31. Xie BY, Lv QY, Ning CC, Yang BY, Shan WW, Cheng YL, et al. TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation. Biochem Biophys Res Commun. (2017) 482:857–62. doi: 10.1016/j.bbrc.2016.11.124

PubMed Abstract | CrossRef Full Text | Google Scholar

32. Tang H, Liao Y, Xu L, Zhang C, Liu Z, Deng Y, et al. Estrogen and insulin-like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice. Int J Cancer. (2013) 133:2473–82. doi: 10.1002/ijc.28262

PubMed Abstract | CrossRef Full Text | Google Scholar

33. Kamanga-Sollo E, White ME, Hathaway MR, Chung KY, Johnson BJ, Dayton WR. Roles of IGF-I and the estrogen, androgen and IGF-I receptors in estradiol-17beta- and trenbolone acetate-stimulated proliferation of cultured bovine satellite cells. Domest Anim Endocrinol. (2008) 35:88–97. doi: 10.1016/j.domaniend.2008.02.003

PubMed Abstract | CrossRef Full Text | Google Scholar

34. Sahoo SS, Lombard JM, Ius Y, O’Sullivan R, Wood LG, Nahar P, et al. Adipose-derived VEGF-mTOR signaling promotes endometrial hyperplasia and cancer: implications for obese women. Mol Cancer Res. (2018) 16:309–21. doi: 10.1158/1541-7786.MCR-17-0466

PubMed Abstract | CrossRef Full Text | Google Scholar

35. Ko JH, Um JY, Lee SG, Yang WM, Sethi G, Ahn KS. Conditioned media from adipocytes promote proliferation, migration, and invasion in melanoma and colorectal cancer cells. J Cell Physiol. (2019) 234:18249–61. doi: 10.1002/jcp.28456

PubMed Abstract | CrossRef Full Text | Google Scholar

36. Chen J, Zhao KN, Li R, Shao R, Chen C. Activation of PI3K/Akt/mTOR pathway and dual inhibitors of PI3K and mTOR in endometrial cancer. Curr Med Chem. (2014) 21:3070–80. doi: 10.2174/0929867321666140414095605

PubMed Abstract | CrossRef Full Text | Google Scholar

37. Strong AL, Pei DT, Hurst CG, Gimble JM, Burow ME, Bunnell BA. Obesity enhances the conversion of adipose-derived stromal/stem cells into carcinoma-associated fibroblast leading to cancer cell proliferation and progression to an invasive phenotype. Stem Cells Int. (2017) 2017:9216502. doi: 10.1155/2017/9216502

PubMed Abstract | CrossRef Full Text | Google Scholar

38. Sabol RA, Beighley A, Giacomelli P, Wise RM, Harrison MAA, O’Donnnell BA, et al. Obesity-altered adipose stem cells promote ER(+) breast cancer metastasis through estrogen independent pathways. Int J Mol Sci. (2019) 20:E1419. doi: 10.3390/ijms20061419

PubMed Abstract | CrossRef Full Text | Google Scholar

39. Strong AL, Strong TA, Rhodes LV, Semon JA, Zhang X, Shi Z, et al. Obesity associated alterations in the biology of adipose stem cells mediate enhanced tumorigenesis by estrogen dependent pathways. Breast Cancer Res. (2013) 15:R102. doi: 10.1186/bcr3569

PubMed Abstract | CrossRef Full Text | Google Scholar

40. Li M, Li X, Zhao L, Zhou J, Cheng Y, Xu B, et al. Spontaneous formation of tumorigenic hybrids between human omental adipose-derived stromal cells and endometrial cancer cells increased motility and heterogeneity of cancer cells. Cell Cycle. (2019) 18:320–32. doi: 10.1080/15384101.2019.1568743

PubMed Abstract | CrossRef Full Text | Google Scholar

41. Rzepka-Gorska I, Bedner R, Cymbaluk-Ploska A, Chudecka-Glaz A. Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia with atypia in obese women. Eur J Gynaecol Oncol. (2008) 29:594–7.

PubMed Abstract | Google Scholar

42. Aggeloussi S, Theodorou AA, Paschalis V, Nikolaidis MG, Fatouros IG, Owolabi EO, et al. Adipocytokine levels in children: effects of fatness and training. Pediatr Exerc Sci. (2012) 24:461–71. doi: 10.1123/pes.24.3.461

PubMed Abstract | CrossRef Full Text | Google Scholar

43. Zeng F, Shi J, Long Y, Tian H, Li X, Zhao AZ, et al. Adiponectin and endometrial cancer: a systematic review and meta-analysis. Cell Physiol Biochem. (2015) 36:1670–8. doi: 10.1159/000430327

PubMed Abstract | CrossRef Full Text | Google Scholar

45. Karnati HK, Panigrahi MK, Li Y, Tweedie D, Greig NH. Adiponectin as a potential therapeutic target for prostate cancer. Curr Pharm Des. (2017) 23:4170–9. doi: 10.2174/1381612823666170208123553

PubMed Abstract | CrossRef Full Text | Google Scholar

47. Nigro E, Schettino P, Polito R, Scudiero O, Monaco ML, De Palma GD, et al. Adiponectin and colon cancer: evidence for inhibitory effects on viability and migration of human colorectal cell lines. Mol Cell Biochem. (2018) 448:125–35. doi: 10.1007/s11010-018-3319-7

PubMed Abstract | CrossRef Full Text | Google Scholar

48. Panno ML, Naimo GD, Spina E, Ando S, Mauro L. Different molecular signaling sustaining adiponectin action in breast cancer. Curr Opin Pharmacol. (2016) 31:1–7. doi: 10.1016/j.coph.2016.08.001

PubMed Abstract | CrossRef Full Text | Google Scholar

50. Wang Y, Xu W, Yan Z, Zhao W, Mi J, Li J, et al. Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways. J Exp Clin Cancer Res. (2018) 37:63. doi: 10.1186/s13046-018-0731-5

PubMed Abstract | CrossRef Full Text | Google Scholar

51. Moon HS, Chamberland JP, Aronis K, Tseleni-Balafouta S, Mantzoros CS. Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans. Mol Cancer Ther. (2011) 10:2234–43. doi: 10.1158/1535-7163.MCT-11-0545

PubMed Abstract | CrossRef Full Text | Google Scholar

52. Cai ZF, Deng L, Wang MM, Zhang JQ, Li L. [Effect of AMPK/mTOR/S6K1 pathways and the insulin-sensitizing effect for adiponectin in endometrial cancer cells]. Zhonghua Fu Chan Ke Za Zhi. (2018) 53:554–60. doi: 10.3760/cma.j.issn.0529-567x.2018.08.008

PubMed Abstract | CrossRef Full Text | Google Scholar

53. Sayeed M, Gautam S, Verma DP, Afshan T, Kumari T, Srivastava AK, et al. A collagen domain-derived short adiponectin peptide activates APPL1 and AMPK signaling pathways and improves glucose and fatty acid metabolisms. J Biol Chem. (2018) 293:13509–23. doi: 10.1074/jbc.RA118.001801

PubMed Abstract | CrossRef Full Text | Google Scholar

54. Peng J, Tsang JY, Ho DH, Zhang R, Xiao H, Li D, et al. Modulatory effects of adiponectin on the polarization of tumor-associated macrophages. Int J Cancer. (2015) 137:848–58. doi: 10.1002/ijc.29485

PubMed Abstract | CrossRef Full Text | Google Scholar

55. Mohammadi M, Mianabadi F, Mehrad-Majd H. Circulating visfatin levels and cancers risk: a systematic review and meta-analysis. J Cell Physiol. (2019) 234:5011–22. doi: 10.1002/jcp.27302

PubMed Abstract | CrossRef Full Text | Google Scholar

56. Wang Z, Gao S, Sun C, Li J, Gao W, Yu L. Clinical significance of serum adiponectin and visfatin levels in endometrial cancer. Int J Gynaecol Obstet. (2019) 145:34–9. doi: 10.1002/ijgo.12772

PubMed Abstract | CrossRef Full Text | Google Scholar

57. Ilhan TT, Kebapcilar A, Yilmaz SA, Ilhan T, Kerimoglu OS, Pekin AT, et al. Relations of serum visfatin and resistin levels with endometrial cancer and factors associated with its prognosis. Asian Pac J Cancer Prev. (2015) 16:4503–8. doi: 10.7314/APJCP.2015.16.11.4503

PubMed Abstract | CrossRef Full Text | Google Scholar

58. Cymbaluk-Ploska A, Chudecka-Glaz A, Pius-Sadowska E, Sompolska-Rzechula A, Machalinski B, Menkiszak J. Circulating serum level of visfatin in patients with endometrial cancer. Biomed Res Int. (2018) 2018:8576179. doi: 10.1155/2018/8576179

PubMed Abstract | CrossRef Full Text | Google Scholar

59. Wang Y, Gao C, Zhang Y, Gao J, Teng F, Tian W, et al. Visfatin stimulates endometrial cancer cell proliferation via activation of PI3K/Akt and MAPK/ERK1/2 signalling pathways. Gynecol Oncol. (2016) 143:168–78. doi: 10.1016/j.ygyno.2016.07.109

PubMed Abstract | CrossRef Full Text | Google Scholar

60. Zangooei M, Nourbakhsh M, Ghahremani MH, Meshkani R, Khedri A, Shadboorestan A, et al. Investigating the effect of visfatin on ERalpha phosphorylation (Ser118 and Ser167) and ERE-dependent transcriptional activity. EXCLI J. (2018) 17:516–25. doi: 10.17179/excli2018-1299

PubMed Abstract | CrossRef Full Text | Google Scholar

61. Zahid H, Subbaramaiah K, Iyengar NM, Zhou XK, Chen IC, Bhardwaj P, et al. Leptin regulation of the p53-HIF1alpha/PKM2-aromatase axis in breast adipose stromal cells: a novel mechanism for the obesity-breast cancer link. Int J Obes. (2018) 42:711–20. doi: 10.1038/ijo.2017.273

PubMed Abstract | CrossRef Full Text | Google Scholar

62. Song NY, Lee YH, Na HK, Baek JH, Surh YJ. Leptin induces SIRT1 expression through activation of NF-E2-related factor 2: implications for obesity-associated colon carcinogenesis. Biochem Pharmacol. (2018) 153:282–91. doi: 10.1016/j.bcp.2018.02.001

PubMed Abstract | CrossRef Full Text | Google Scholar

63. Wang PP, He XY, Wang R, Wang Z, Wang YG. High leptin level is an independent risk factor of endometrial cancer: a meta-analysis. Cell Physiol Biochem. (2014) 34:1477–84. doi: 10.1159/000366352

PubMed Abstract | CrossRef Full Text | Google Scholar

64. Zhang Y, Liu L, Li C, Ai H. Correlation analysis between the expressions of leptin and its receptor (ObR) and clinicopathology in endometrial cancer. Cancer Biomark. (2014) 14:353–9. doi: 10.3233/CBM-140415

PubMed Abstract | CrossRef Full Text | Google Scholar

65. Tenvooren I, Jenks MZ, Rashid H, Cook KL, Muhlemann JK, Sistrunk C, et al. Elevated leptin disrupts epithelial polarity and promotes premalignant alterations in the mammary gland. Oncogene. (2019) 38:3855–70. doi: 10.1038/s41388-019-0687-8

PubMed Abstract | CrossRef Full Text | Google Scholar

66. Liu Y, Lv L, Xiao W, Gong C, Yin J, Wang D, et al. Leptin activates STAT3 and ERK1/2 pathways and induces endometrial cancer cell proliferation. J Huazhong Univ Sci Technolog Med Sci. (2011) 31:365. doi: 10.1007/s11596-011-0382-7

PubMed Abstract | CrossRef Full Text | Google Scholar

67. Bienkiewicz J, Romanowicz H, Malinowski A, Smolarz B. Association of Single Nucleotide Polymorphism−2548 G/A (rs12112075) of leptin gene with endometrial cancer and uterine leiomyomas. Eur J Obstet Gynecol Reprod Biol. (2017) 218:113–8. doi: 10.1016/j.ejogrb.2017.09.022

PubMed Abstract | CrossRef Full Text | Google Scholar

68. Wang T, Fahrmann JF, Lee H, Li YJ, Tripathi SC, Yue C, et al. JAK/STAT3-regulated fatty acid beta-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab. (2018) 27:136–50 e5. doi: 10.1016/j.cmet.2017.11.001

CrossRef Full Text | Google Scholar

69. Cymbaluk-Ploska A, Chudecka-Glaz A, Jagodzinska A, Pius-Sadowska E, Sompolska-Rzechula A, Machalinski B, et al. Evaluation of biologically active substances promoting the development of or protecting against endometrial cancer. Onco Targets Ther. (2018) 11:1363–72. doi: 10.2147/OTT.S155942

PubMed Abstract | CrossRef Full Text | Google Scholar

70. Dibaba DT, Judd SE, Gilchrist SC, Cushman M, Pisu M, Safford M, et al. Association between obesity and biomarkers of inflammation and metabolism with cancer mortality in a prospective cohort study. Metabolism. (2019) 94:69–76. doi: 10.1016/j.metabol.2019.01.007

PubMed Abstract | CrossRef Full Text | Google Scholar

71. Chu Y, Wang Y, Peng W, Xu L, Liu M, Li J, et al. STAT3 activation by IL-6 from adipose-derived stem cells promotes endometrial carcinoma proliferation and metastasis. Biochem Biophys Res Commun. (2018) 500:626–31. doi: 10.1016/j.bbrc.2018.04.121

PubMed Abstract | CrossRef Full Text | Google Scholar

73. He YY, Cai B, Yang YX, Liu XL, Wan XP. Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci. (2009) 100:1051–61. doi: 10.1111/j.1349-7006.2009.01148.x

PubMed Abstract | CrossRef Full Text | Google Scholar

74. Che Q, Liu BY, Liao Y, Zhang HJ, Yang TT, He YY, et al. Activation of a positive feedback loop involving IL-6 and aromatase promotes intratumoral 17beta-estradiol biosynthesis in endometrial carcinoma microenvironment. Int J Cancer. (2014) 135:282–94. doi: 10.1002/ijc.28679

PubMed Abstract | CrossRef Full Text | Google Scholar

75. Lee JW, Stone ML, Porrett PM, Thomas SK, Komar CA, Li JH, et al. Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature. (2019) 567:249–52. doi: 10.1038/s41586-019-1004-y

PubMed Abstract | CrossRef Full Text | Google Scholar

76. Smith HO, Stephens ND, Qualls CR, Fligelman T, Wang T, Lin CY, et al. The clinical significance of inflammatory cytokines in primary cell culture in endometrial carcinoma. Mol Oncol. (2013) 7:41–54. doi: 10.1016/j.molonc.2012.07.002

PubMed Abstract | CrossRef Full Text | Google Scholar

77. Ku SC, Ho PS, Tseng YT, Yeh TC, Cheng SL, Liang CS. Benzodiazepine-associated carcinogenesis: focus on lorazepam-associated cancer biomarker changes in overweight individuals. Psychiatry Investig. (2018) 15:900–6. doi: 10.30773/pi.2018.05.02.1

PubMed Abstract | CrossRef Full Text | Google Scholar

78. Ahmad R, Al-Roub A, Kochumon S, Akther N, Thomas R, Kumari M, et al. The synergy between palmitate and TNF-alpha for CCL2 production is dependent on the TRIF/IRF3 pathway: implications for metabolic inflammation. J Immunol. (2018) 200:3599–611. doi: 10.4049/jimmunol.1701552

PubMed Abstract | CrossRef Full Text | Google Scholar

79. Dossus L, Becker S, Rinaldi S, Lukanova A, Tjonneland A, Olsen A, et al. Tumor necrosis factor (TNF)-alpha, soluble TNF receptors and endometrial cancer risk: the EPIC study. Int J Cancer. (2011) 129:2032–7. doi: 10.1002/ijc.25840

PubMed Abstract | CrossRef Full Text | Google Scholar

80. Alipourfard I, Datukishvili N, Mikeladze D. TNF-alpha downregulation modifies Insulin Receptor Substrate 1 (IRS-1) in metabolic signaling of diabetic insulin-resistant hepatocytes. Mediat Inflamm. (2019) 2019:3560819. doi: 10.1155/2019/3560819

PubMed Abstract | CrossRef Full Text | Google Scholar

81. Martinez-Chacon G, Brown KA, Docanto MM, Kumar H, Salminen S, Saarinen N, et al. IL-10 suppresses TNF-alpha-induced expression of human aromatase gene in mammary adipose tissue. FASEB J. (2018) 32:3361–70. doi: 10.1096/fj.201700938RRR

PubMed Abstract | CrossRef Full Text | Google Scholar

82. Vousden KA, Lundqvist T, Popovic B, Naiman B, Carruthers AM, Newton P, et al. Discovery and characterisation of an antibody that selectively modulates the inhibitory activity of plasminogen activator inhibitor-1. Sci Rep. (2019) 9:1605. doi: 10.2210/pdb6i8s/pdb

PubMed Abstract | CrossRef Full Text | Google Scholar

83. Steiner E, Pollow K, Hasenclever D, Schormann W, Hermes M, Schmidt M, et al. Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer. Gynecol Oncol. (2008) 108:569–76. doi: 10.1016/j.ygyno.2007.11.025

PubMed Abstract | CrossRef Full Text | Google Scholar

84. Polusani SR, Huang YW, Huang G, Chen CW, Wang CM, Lin LL, et al. Adipokines deregulate cellular communication via epigenetic repression of gap junction loci in obese endometrial cancer. Cancer Res. (2019) 79:196–208. doi: 10.1158/0008-5472.CAN-18-1615

PubMed Abstract | CrossRef Full Text | Google Scholar

86. Dieli-Conwright CM, Parmentier JH, Sami N, Lee K, Spicer D, Mack WJ, et al. Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention. Breast Cancer Res Treat. (2018) 168:147–57. doi: 10.1007/s10549-017-4576-y

PubMed Abstract | CrossRef Full Text | Google Scholar

87. Saucillo DC, Gerriets VA, Sheng J, Rathmell JC, Maciver NJ. Leptin metabolically licenses T cells for activation to link nutrition and immunity. J Immunol. (2014) 192:136–44. doi: 10.4049/jimmunol.1301158

PubMed Abstract | CrossRef Full Text | Google Scholar

88. Kolb R, Kluz P, Tan ZW, Borcherding N, Bormann N, Vishwakarma A, et al. Obesity-associated inflammation promotes angiogenesis and breast cancer via angiopoietin-like 4. Oncogene. (2019) 38:2351–63. doi: 10.1038/s41388-018-0592-6

PubMed Abstract | CrossRef Full Text | Google Scholar

90. Nagle CM, Crosbie EJ, Brand A, Obermair A, Oehler MK, Quinn M, et al. The association between diabetes, comorbidities, body mass index and all-cause and cause-specific mortality among women with endometrial cancer. Gynecol Oncol. (2018) 150:99–105. doi: 10.1016/j.ygyno.2018.04.006

PubMed Abstract | CrossRef Full Text | Google Scholar

92. Gu CJ, Xie F, Zhang B, Yang HL, Cheng J, He YY, et al. High glucose promotes epithelial-mesenchymal transition of uterus endometrial cancer cells by increasing ER/GLUT4-mediated VEGF secretion. Cell Physiol Biochem. (2018) 50:706–20. doi: 10.1159/000494237

PubMed Abstract | CrossRef Full Text | Google Scholar

93. Wallbillich JJ, Josyula S, Saini U, Zingarelli RA, Dorayappan KD, Riley MK, et al. High glucose-mediated STAT3 activation in endometrial cancer is inhibited by metformin: therapeutic implications for endometrial cancer. PLoS ONE. (2017) 12:e0170318. doi: 10.1371/journal.pone.0170318

PubMed Abstract | CrossRef Full Text | Google Scholar

95. Zhong XY, Yuan XM, Xu YY, Yin M, Yan WW, Zou SW, et al. CARM1 methylates GAPDH to regulate glucose metabolism and is suppressed in liver cancer. Cell Rep. (2018) 24:3207–23. doi: 10.1016/j.celrep.2018.08.066

PubMed Abstract | CrossRef Full Text | Google Scholar

96. Wei Y, Wang D, Jin F, Bian Z, Li L, Liang H, et al. Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Nat Commun. (2017) 8:14041. doi: 10.1038/ncomms14041

PubMed Abstract | CrossRef Full Text | Google Scholar

97. Bohn T, Rapp S, Luther N, Klein M, Bruehl TJ, Kojima N, et al. Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nat Immunol. (2018) 19:1319–29. doi: 10.1038/s41590-018-0226-8

PubMed Abstract | CrossRef Full Text | Google Scholar

98. Gu S, Ni T, Wang J, Liu Y, Fan Q, Wang Y, et al. CD47 blockade inhibits tumor progression through promoting phagocytosis of tumor cells by M2 polarized macrophages in endometrial cancer. J Immunol Res. (2018) 2018:6156757. doi: 10.1155/2018/6156757

PubMed Abstract | CrossRef Full Text | Google Scholar

99. Latif A, Chadwick AL, Kitson SJ, Gregson HJ, Sivalingam VN, Bolton J, et al. Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer. BMC Clin Pathol. (2017) 17:27. doi: 10.1186/s12907-017-0067-7

PubMed Abstract | CrossRef Full Text | Google Scholar

100. Liu N, Luo J, Kuang D, Xu S, Duan Y, Xia Y, et al. Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2alpha-mediated tumor progression. J Clin Invest. (2019) 129:631–46. doi: 10.1172/JCI123027

PubMed Abstract | CrossRef Full Text | Google Scholar

101. Friedenreich CM, Langley AR, Speidel TP, Lau DC, Courneya KS, Csizmadi I, et al. Case-control study of markers of insulin resistance and endometrial cancer risk. Endocr Relat Cancer. (2012) 19:785–92. doi: 10.1530/ERC-12-0211

PubMed Abstract | CrossRef Full Text | Google Scholar

102. Kabat GC, Kim MY, Lane DS, Zaslavsky O, Ho GYF, Luo J, et al. Serum glucose and insulin and risk of cancers of the breast, endometrium, and ovary in postmenopausal women. Eur J Cancer Prev. (2018) 27:261–8. doi: 10.1097/CEJ.0000000000000435

PubMed Abstract | CrossRef Full Text | Google Scholar

104. Joehlin-Price AS, Stephens JA, Zhang J, Backes FJ, Cohn DE, Suarez AA. Endometrial cancer Insulin-Like Growth Factor 1 Receptor (IGF1R) expression increases with body mass index and is associated with pathologic extent and prognosis. Cancer Epidemiol Biomarkers Prev. (2016) 25:438–45. doi: 10.1158/1055-9965.EPI-15-1145

PubMed Abstract | CrossRef Full Text | Google Scholar

105. Wang C, Su K, Zhang Y, Zhang W, Zhao Q, Chu D, et al. IR-A/IGF-1R-mediated signals promote epithelial-mesenchymal transition of endometrial carcinoma cells by activating PI3K/AKT and ERK pathways. Cancer Biol Ther. (2019) 20:295–306. doi: 10.1080/15384047.2018.1529096

PubMed Abstract | CrossRef Full Text | Google Scholar

106. Zhang H, Fagan DH, Zeng X, Freeman KT, Sachdev D, Yee D. Inhibition of cancer cell proliferation and metastasis by insulin receptor downregulation. Oncogene. (2010) 29:2517–27. doi: 10.1038/onc.2010.17

PubMed Abstract | CrossRef Full Text | Google Scholar

107. Krycer JR, Yugi K, Hirayama A, Fazakerley DJ, Quek LE, Scalzo R, et al. Dynamic metabolomics reveals that insulin primes the adipocyte for glucose metabolism. Cell Rep. (2017) 21:3536–47. doi: 10.1016/j.celrep.2017.11.085

PubMed Abstract | CrossRef Full Text | Google Scholar

108. Zhou R, Yang Y, Lu Q, Wang J, Miao Y, Wang S, et al. Prognostic factors of oncological and reproductive outcomes in fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin in Chinese patients. Gynecol Oncol. (2015) 139:424–8. doi: 10.1016/j.ygyno.2015.09.078

PubMed Abstract | CrossRef Full Text | Google Scholar

109. Kheirandish M, Mahboobi H, Yazdanparast M, Kamal W, Kamal MA. Anti-cancer effects of metformin: recent evidences for its role in prevention and treatment of cancer. Curr Drug Metab. (2018) 19:793–7. doi: 10.2174/1389200219666180416161846

PubMed Abstract | CrossRef Full Text | Google Scholar

110. Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA, Bae-Jump VL. Metformin is a potent inhibitor of endometrial cancer cell proliferation–implications for a novel treatment strategy. Gynecol Oncol. (2010) 116:92–8. doi: 10.1016/j.ygyno.2009.09.024

PubMed Abstract | CrossRef Full Text | Google Scholar

111. Nevadunsky NS, Van Arsdale A, Strickler HD, Moadel A, Kaur G, Frimer M, et al. Metformin use and endometrial cancer survival. Gynecol Oncol. (2014) 132:236–40. doi: 10.1016/j.ygyno.2013.10.026

PubMed Abstract | CrossRef Full Text | Google Scholar

112. Kitson SJ, Maskell Z, Sivalingam VN, Allen JL, Ali S, Burns S, et al. PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase III trial. Clin Cancer Res. (2019) 25:2424–32. doi: 10.1158/1078-0432.CCR-18-3339

PubMed Abstract | CrossRef Full Text | Google Scholar

113. Arthur R, Moller H, Garmo H, Haggstrom C, Holmberg L, Stattin P, et al. Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study. Cancer Causes Control. (2019) 30:195–206. doi: 10.1007/s10552-018-1093-1

PubMed Abstract | CrossRef Full Text | Google Scholar

114. Arthur RS, Kabat GC, Kim MY, Wild RA, Shadyab AH, Wactawski-Wende J, et al. Metabolic syndrome and risk of endometrial cancer in postmenopausal women: a prospective study. Cancer Causes Control. (2019) 30:355–63. doi: 10.1007/s10552-019-01139-5

PubMed Abstract | CrossRef Full Text | Google Scholar

115. Bruning PF, Bonfrer JM. Free fatty acid concentrations correlated with the available fraction of estradiol in human plasma. Cancer Res. (1986) 46:2606–9.

PubMed Abstract | Google Scholar

116. Schmandt RE, Iglesias DA, Co NN, Lu KH. Understanding obesity and endometrial cancer risk: opportunities for prevention. Am J Obstet Gynecol. (2011) 205:518–25. doi: 10.1016/j.ajog.2011.05.042

PubMed Abstract | CrossRef Full Text | Google Scholar

117. Gibson DA, Collins F, Cousins FL, Esnal Zufiaurre A, Saunders PTK. The impact of 27-hydroxycholesterol on endometrial cancer proliferation. Endocr Relat Cancer. (2018) 25:381–91. doi: 10.1530/ERC-17-0449

PubMed Abstract | CrossRef Full Text | Google Scholar

118. Madak-Erdogan Z, Band S, Zhao YC, Smith BP, Kulkoyluoglu-Cotul E, Zuo Q, et al. Free fatty acids rewire cancer metabolism in obesity-associated breast cancer via estrogen receptor and mTOR signaling. Cancer Res. (2019) 79:2494–510. doi: 10.1158/0008-5472.CAN-18-2849

PubMed Abstract | CrossRef Full Text | Google Scholar

119. Hao J, Zhang Y, Yan X, Yan F, Sun Y, Zeng J, et al. Circulating adipose fatty acid binding protein is a new link underlying obesity-associated breast/mammary tumor development. Cell Metab. (2018) 28:689–705 e5. doi: 10.1016/j.cmet.2018.07.006

PubMed Abstract | CrossRef Full Text | Google Scholar

120. Brinton LA, Sakoda LC, Frederiksen K, Sherman ME, Kjaer SK, Graubard BI, et al. Relationships of uterine and ovarian tumors to pre-existing chronic conditions. Gynecol Oncol. (2007) 107:487–94. doi: 10.1016/j.ygyno.2007.08.002

PubMed Abstract | CrossRef Full Text | Google Scholar

121. Seebacher V, Hofstetter G, Polterauer S, Reinthaller A, Grimm C, Schwameis R, et al. Does thyroid-stimulating hormone influence the prognosis of patients with endometrial cancer? A multicentre trial. Br J Cancer. (2013) 109:215–8. doi: 10.1038/bjc.2013.282

PubMed Abstract | CrossRef Full Text | Google Scholar

122. Shinkov A, Borissova AM, Kovatcheva R, Atanassova I, Vlahov J, Dakovska L. The prevalence of the metabolic syndrome increases through the quartiles of thyroid stimulating hormone in a population-based sample of euthyroid subjects. Arq Bras Endocrinol Metabol. (2014) 58:926–32. doi: 10.1590/0004-2730000003538

PubMed Abstract | CrossRef Full Text | Google Scholar

125. MacKintosh ML, Derbyshire AE, McVey RJ, Bolton J, Nickkho-Amiry M, Higgins CL, et al. The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk. Int J Cancer. (2019) 144:641–50. doi: 10.1002/ijc.31913

PubMed Abstract | CrossRef Full Text | Google Scholar

126. Linkov F, Goughnour SL, Ma T, Xu Z, Edwards RP, Lokshin AE, et al. Changes in inflammatory endometrial cancer risk biomarkers in individuals undergoing surgical weight loss. Gynecol Oncol. (2017) 147:133–8. doi: 10.1016/j.ygyno.2017.07.144

PubMed Abstract | CrossRef Full Text | Google Scholar

127. Busch EL, Crous-Bou M, Prescott J, Downing MJ, Rosner BA, Mutter GL, et al. Adiponectin, leptin, and insulin-pathway receptors as endometrial cancer subtyping markers. Horm Cancer. (2018) 9:33–9. doi: 10.1007/s12672-017-0318-1

PubMed Abstract | CrossRef Full Text | Google Scholar

128. Kitson SJ, Evans DG, Crosbie EJ. Identifying high-risk women for endometrial cancer prevention strategies: proposal of an endometrial cancer risk prediction model. Cancer Prev Res. (2017) 10:1–13. doi: 10.1158/1940-6207.CAPR-16-0224

PubMed Abstract | CrossRef Full Text | Google Scholar

129. Fortner RT, Husing A, Kuhn T, Konar M, Overvad K, Tjonneland A, et al. Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort. Int J Cancer. (2017) 140:1317–23. doi: 10.1002/ijc.30560

PubMed Abstract | CrossRef Full Text | Google Scholar

130. Lin Y, Zhou J, Cao L, Xu Q, Hao J, Zhao L, et al. Serum calcium is a novel parameter to assess metabolic syndrome in endometrial carcinoma. J Gynecol Oncol. (2019) 30:e12. doi: 10.3802/jgo.2019.30.e12

PubMed Abstract | CrossRef Full Text | Google Scholar

An Error Occurred Setting Your User Cookie

This site uses cookies to improve performance. If your browser does not accept cookies, you cannot view this site.

Setting Your Browser to Accept Cookies

There are many reasons why a cookie could not be set correctly. Below are the most common reasons:

• You have cookies disabled in your browser. You need to reset your browser to accept cookies or to ask you if you want to accept cookies.
• Your browser asks you whether you want to accept cookies and you declined.
  To accept cookies from this site, use the Back button and accept the cookie.
• Your browser does not support cookies. Try a different browser if you suspect this.
• The date on your computer is in the past. If your computer’s clock shows a date before 1 Jan 1970,
  the browser will automatically forget the cookie. To fix this, set the correct time and date on your computer.
• You have installed an application that monitors or blocks cookies from being set.
  You must disable the application while logging in or check with your system administrator.

Why Does this Site Require Cookies?

This site uses cookies to improve performance by remembering that you are logged in when you go from page to page. To provide access without cookies
would require the site to create a new session for every page you visit, which slows the system down to an unacceptable level.

What Gets Stored in a Cookie?

This site stores nothing other than an automatically generated session ID in the cookie; no other information is captured.

In general, only the information that you provide, or the choices you make while visiting a web site, can be stored in a cookie. For example, the site
cannot determine your email name unless you choose to type it. Allowing a website to create a cookie does not give that or any other site access to the
rest of your computer, and only the site that created the cookie can read it.

Er dit blodtryk 109 over 57 (109/57)?

Blodtryk 109 over 57 skrives som 109/57.

Dit blodtryk er: For lavt – Hypotoni!

Med hensyn til din systoliske værdi (øvre tryk) er dit blodtryk: Idealt!

Hvis du har en blodtryksmåling placeret inden for to forskellige klassificeringsresultater, skal du bruge resultatet, der er inden for det højere interval. For eksempel, hvis din systoliske værdi er ‘høj-normal’ og din diastoliske værdi er ‘hypotension klasse 1’, skal du bedømme ‘hypotension klasse 1’ som din nuværende klassificering.

Hvad dine værdier betyder for dit helbred:

Din blodtryksværdi på 109 over 57 (109/57) angiver et ideelt blodtryk. Kravene til denne klassifikation er opfyldt med en systolisk værdi lavere end 120 mmHg og en diastolisk værdi lavere end 80 mmHg, dvs. lavere end 120/80.

Dette blodtryksniveau er ideelt til at undgå skader på kar og organer. Et ideelt blodtryk øger normalt din levetid.

Indhold

1. Blodtryk 109 over 57 (109/57) i diagram og skala
2. Hvad menes med klassifikation “Idealt blodtryk”?
3. Virtuel blodtryksmåler til 109/57
4. Kontroller en anden værdi

Blodtryk 109 over 57 (109/57) i diagram

Blodtryk 109 over 57 (109/57) i skala

0

10

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

Systolisk værdi
(øvre tryk)

0

10

20

30

40

50

60

70

80

90

100

110

120

130

140

150

Diastolisk værdi
(lavere tryk)

Betydningen af Idealt blodtryk

Dit blodtryk er ideelt.

Betingelsen for et ideelt blodtryk er en værdi, der er lavere end 120 over 80 (120/80).

Hvis din systoliske værdi stiger med 11 mmHg till 120 mmHg, og din diastoliske værdi stiger med 23 mmHg till 80 mmHg, er dit blodtryk ikke længere ‘ideelt’, men klassificeres nu som ‘normalt’.

Et normalt systolisk blodtryk er mellem 120 til 130 mmHg, mens det diastoliske tryk er mellem 80 til 85 mmHg.

Lær mere om din klassificering Idealt blodtryk her.

Virtuel Blodtryksmåler

Tjek en anden værdi

Påvirker dit blodtryk

Advarselstegn

Klassifikation af blodtryk

Blood Sugar Glucose Converter for Diabetes

Convert blood sugar/glucose from mmol/L (UK standard) to mg/dL (US standard) and vice versa using our blood sugar converter.

Enter mg/dL or mmol/L value for conversion:

Download a mg/dL to mmol/L conversion chart

Download PDF

Your blood sugars are:

To check your blood sugar level ranges use the blood sugar checker

Fill out the following form to download your FREE mg/dl to mmol/L conversion chart

Whats the difference between mmol/L and mg/dL?

Both sets of units are used to measure blood sugar levels and both give a measurement of the concentration of glucose in the blood, albeit in slightly different ways.

mmol/L gives the molarity, which is the number of molecules of a substance within a specified volumen, in this case within 1 litre. mg/dL gives the concentration by the ratio of weight to volumen, in this case milligrams per decilitre.

mmol/L is the most common measurement used in the UK with mg/dL predominantly used in the USA and continental Europe.

Blood glucose typically varies from 4 mmol/L to 6 mmol/L for people without diabetes.

Blood sugar (also called blood glucose) needs to be tightly controlled in the human body to minimise the risk of complications developing.

• Formula to calculate mmol/l from mg/dl: mmol/l = mg/dl / 18
• Formula to calculate mg/dl from mmol/l: mg/dl = 18 × mmol/l

Can I change the units given by my blood glucose meter?

This can depend on which blood glucose meter you have. Some meters allow you to change the units from mg/dL to mmol/L and vice versa whether some meters are only set up to display one set of units.

Check the meter’s manual for whether it is possible to change the units. If you don’t have or cannot find the manual, contact the manufacturer.

Why are blood sugar levels important?

Measuring blood sugar levels and understanding what your glucose levels should be is an essential part of diabetes treatment for many people with diabetes.

Blood sugar level refers to the total amount of glucose circulating in the blood. In different parts of the world, different units for measuring blood glucose are standard.

90,000 Human pressure: age indicators, how to measure it correctly and the reasons for deviations from the norm

Arterial blood pressure is a purely individual indicator and depends on many factors. And, nevertheless, there is a certain average medical norm. That is why deviations from the accepted indicators allow the doctor to suspect malfunctions in the body’s systems.

Continuation of the article is under advertising

Advertising

However, it must be remembered that indicators can change.It depends, for example, on the time of day, as well as the age of the person. So, the pressure of a person is the norm by age, what is it, what does it depend on and why can it deviate? Portal davlenie.org tells.

What is blood pressure?

Behind this concept lies the force that the blood flow exerts on the walls of the vessels. Blood pressure indicators depend on the speed and strength of a person’s heart, as well as the total volume of blood that it is able to pass through itself within a minute.

And the recognized norm of pressure by age is one of the medical indicators of the correct functioning of the heart, the autonomic nervous system, and also the endocrine system.

Pressure standard

Foto: PantherMedia / Scanpix

Normal pressure in an adult should be determined only at rest, since any stress (both physical and emotional) has a huge impact on his performance. The human body independently controls blood pressure, and with a moderate load, its indicators rise by about 20 mm.Hg This is due to the fact that the muscles and organs involved in the work require a better blood supply.

If we talk about what blood pressure is considered normal, then at the moment the medicine recognized indicators in the range 91 … 139/61 … 89 mm Hg. In this case, the absolute norm is considered to be blood pressure 120/80 mm Hg, slightly increased – 130/85 mm Hg, increased normal – 139/89 mm Hg. An increase in numbers higher than 140/90 mm Hg already indicates the presence of pathology.

With age, irreversible processes occur in the human body, which provoke an increase in pressure throughout life. The older a person is, the higher his blood pressure readings.

Blood pressure: norm by age

What is normal human blood pressure? The question is somewhat abstract, since the norm for each person, most often, is individual. Educational medical literature suggests taking the figure of 120/80 mm as the norm.Hg It is these indicators that are recorded in people aged 20 … 40 years.

Normal blood pressure for a person aged 16 … 20 may be slightly lowered. This applies to both systolic and diastolic values. In general, the pressure at rest is 100/70 mm Hg. is a physiological norm.

Norms of pressure by age (the table is presented a little below) are determined by the following indicators:

Foto: Publicitātes attēli

As the table of human pressure shows, age-related changes relate to both upper and lower blood pressure.But you need to remember that these are just average clinical indicators.

But not only an increase, but also a decrease in blood pressure indicators is a sure sign of a deterioration in the activity of body systems. That is why the ability to use a tonometer can be attributed to a good prevention of almost all diseases. And in order to track the dynamics of pressure changes, it is necessary to keep a special diary.

How to measure pressure correctly?

There is a special device for measuring blood pressure – a tonometer.At home, it is most convenient to use automatic or semi-automatic devices, since measuring with a manual tonometer requires a certain skill.

To obtain correct results, the following recommendations must be observed:

• exercise must be completely eliminated before measuring blood pressure;
• smoking is prohibited;
• measuring blood pressure immediately after eating will also give incorrect results;
• measure blood pressure while sitting in a comfortable chair;
• the back must be supported;
• The hand on which the measurement is taken must be located at the level of the heart, i.e.e. pressure is measured while sitting at the table;
• when measuring pressure, you must remain motionless and not talk;
• readings are taken from both hands (measurement interval is 10 minutes).

Significant deviations from the norm require the obligatory consultation of a specialist doctor. Only a doctor, after going through all the diagnostic procedures, will be able to choose an adequate treatment for the existing problem.

Abnormality: probable causes

Foto: Shutterstock

There are many reasons that can provoke changes in blood pressure.But the most common ones are the following:

• Inability of the heart to work in the same mode and with the required strength.
• Change in blood quality. With age, it becomes thicker. And the thicker the blood, the more difficult it is for it to flow through the vessels. The cause of thickening can be, for example, such complex diseases as diabetes mellitus or autoimmune pathologies.
• Decreased vascular elasticity. This leads to an incorrect nutritional system, increased loads, certain medications.
• Formation of atherosclerotic plaques that form when the level of “bad” cholesterol in the blood is increased.
• A sharp change in the lumen of the vessel caused by hormones.
• Incorrect work of the endocrine glands.

Most of the causes of pressure surges can be eliminated on your own, which will allow you to maintain health as long as possible. Correctly selected diet, leading an active lifestyle, a calm attitude to life, which allows you to avoid stressful situations.Compliance with these simple rules allows you to normalize blood pressure.

Pulse, as an indicator of health

The next indicator of health, along with the numbers of blood pressure, is the pulse. A pulse in the range of 60… 80 beats / min is considered normal. The more intensive the metabolism takes place, the higher the number of beats per minute.

As well as for blood pressure indicators, there are averaged norms for different age categories.

Foto: Publicitātes attēli

By measuring your heart rate, you can learn to recognize an impending problem.For example, if the number of heart beats increases 2-3 hours after a meal, then poisoning can be suspected.

A magnetic storm in people who are acutely reacting to a sharp change in weather causes a decrease in blood pressure. The body reacts to this by increasing the heart rate in order to maintain the optimal blood pressure level.

An intense pulse, the blows of which a person feels very clearly, indicates a sharp increase in blood pressure.

90,000 OFFICIAL DOCUMENTS – AZERTAC – Azerbaijan State News Agency

28.10.2021 [14:31]

Dear Mr. President,
Dear brother,
On my own behalf and on behalf of the people of Azerbaijan, I am glad to convey to you and in your person to all of your …

10/27/2021 [15:07]

Dear Mr. President,
On my own behalf and on behalf of the people of Azerbaijan, I cordially congratulate you and in your person all your people on the national holiday of your country …

10/25/2021 [16:30]

Dear Shavkat Miromonovich,
I cordially congratulate you on your re-election to the post of President of the Republic of Uzbekistan.Your convincing electoral victory …

10/25/2021 [16:09]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide …

22.10.2021 [15:42]

Dear Mr. President,
On my own behalf and on behalf of the people of Azerbaijan, I convey to you and your people heartfelt congratulations and good wishes on the occasion of the national holiday of Hungary …

20.10.2021 [20:46]

The military aggression of Armenia against the Republic of Azerbaijan, along with the violation of human rights and numerous norms of international law, socio-economic consequences and damage to the cultural heritage, led to unprecedented environmental terror…

20.10.2021 [18:49]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide …

19.10.2021 [19:06]

Dear Mr. President,
Dear brother,
I am extremely saddened by the news of the death of Ozdemir Bayraktar, Chairman of the Management Board of Baykar …

19.10.2021 [15:33]

Guided by paragraph 23 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide…

19.10.2021 [15:19]

Guided by paragraph 23 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide …

17.10.2021 [18:26]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide: …

16.10.2021 [16:47]

Improving the welfare of the country’s population is one of the important priorities of the current socio-economic policy. In recent years, serious progress has been achieved in this direction, consistent steps have been taken to strengthen it…

10/16/2021 [15:35]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide
…

16.10.2021 [14:38]

Guided by paragraph 23 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide: …

15.10.2021 [21:55]

The National Council of the Azerbaijan Democratic Republic, having signed the Declaration of Independence on May 28, 1918, proclaimed the independence of Azerbaijan to the whole world, continued the centuries-old traditions of the statehood of our people…

10/14/2021 [14:22]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, I decide
…

13.10.2021 [20:05]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, in order to encourage investment in the non-oil sector of the economy, optimize and increase the efficiency of the management system …

13.10.2021 [19:30]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, in order to improve the mechanisms of management, regulation, control in the field of maritime transport, to optimize work…

10/13/2021 [19:14]

Guided by paragraph 32 of Article 109 of the Constitution of the Republic of Azerbaijan, in order to improve the mechanisms of management, regulation and control in the field of road transport, improve the quality of services for passenger and cargo transportation by road …

90,000 Promotion “Know your blood pressure numbers”

The first World Hypertension Day was held on May 14, 2005.Since 2006, World Hypertension Day has been held on the second Saturday in May at the initiative of the World Health Organization (WHO). Arterial hypertension (AH) is a persistent increase in blood pressure (BP) from 140/90 mm Hg.

The purpose of the World Hypertension Day is to inform the general public about the danger of this disease, the severity of complications, risk factors for the development of hypertension, as well as to raise public awareness about methods of prevention and early diagnosis.

According to the definition of the WHO and the International Society of Hypertension, essential hypertension is a condition in which the systolic blood pressure is 140 mm Hg. and higher, and diastolic blood pressure – 90 mm Hg. and higher in individuals not receiving antihypertensive therapy.

INDICATORS:

• 120-129 / 80-84 – normal blood pressure
• 130-139 / 85-89 – high normal blood pressure
• 140-159 / 90-95 – 1 degree AG
• 160-179 / 100-109 – II degree AG
• ≥180 / ≥110 – III degree AH

Elevated blood pressure has a negative effect on internal organs and systems, the so-called target organs, and can cause cerebral strokes, myocardial infarction, arrhythmias, renal failure, Alzheimer’s disease.Untreated or uncontrolled arterial hypertension in 50% is the cause of cerebral stroke, in 50% – acute myocardial infarction, in 30% – the cause of chronic hemodialysis in patients with renal failure.

Therefore, the main principle of hypertension treatment is constancy! You need to be treated all your life! It is imperative to follow the prescriptions of the attending physician, as well as to combine medication and non-medication methods of treatment.

Within the framework of the World Day against Arterial Hypertension, the Regional Clinical Hospital No. 1 named after Professor S.I. Sergeeva On May 15, an “Open Day” was organized with the possibility of measuring one’s blood pressure, acquiring practical skills for correct blood pressure measurement, recommendations on a healthy lifestyle, risk factors and prevention of hypertension.

The action “Know the numbers of your blood pressure”, distribution of information material is held on May 15 from 9.00 to 12.00 on the 1st and 2nd floors of the regional consultative and diagnostic polyclinic of the Regional Clinical Hospital No.