Decreased blood pressure associated with in-vehicle exposure to carbon monoxide in Korean volunteers.

BACKGROUND: Carbon monoxide (CO) is one of the primary components of emissions from light-duty vehicles, and reportedly comprises 77% of all pollutants emitted in terms of concentration. Exposure to CO aggravates cardiovascular disease and causes other health disorders. The study was aimed to assess the negative effects by injecting different amounts of CO concentration directly to human volunteers boarding in the car. METHODS: Human volunteers were exposed to CO concentrations of 0, 33.2, and 72.4 ppm, respectively during the first test and 0, 30.3, and 48.8 ppm respectively during the second test while seated in the car. The volunteers were exposed to each concentration for approximately 45 min. After exposure, blood pressure measurement, blood collection (carboxyhemoglobin [COHb] analysis), medical interview, echocardiography test, and cognitive reaction test were performed. RESULT: In patients who were exposed to a mean concentration of CO for 72.4 ± 1.4 ppm during the first exposure test and 48.8 ± 3.7 ppm during the second exposure test, the COHb level exceeded 2%. Moreover, the diastolic blood pressure was decreased while increasing in CO concentration after exposure. The medical interview findings showed that the degree of fatigue was increased and the degree of concentration was reduced when the exposed concentration of CO was increased. CONCLUSION: Although the study had a limited sample size, we found that even a low concentration of CO flowing into a car could have a negative influence on human health, such as change of blood pressure and degree of fatigue.

The Effects of Tonsillectomy Education Using Smartphone Text Message for Mothers and Children Undergoing Tonsillectomy: A Randomized Controlled Trial.

BACKGROUND: Tonsillectomy is the most common type of surgical procedure performed in preschool children. Due to short period of hospitalization, mothers are expected to manage their children's care at home. However, they are rarely provided with sufficient information about postoperative management. This study aims to determine the effectiveness of providing caregivers with information on tonsillectomy care by smartphone text messaging in increasing their mothers' knowledge, reducing the anxiety, and improving the sick-role behavior of pediatric tonsillectomy patients. MATERIALS AND METHODS: A sample of 61 pediatric patients and their mothers was recruited. Participants were randomly assigned into either the experimental group (n = 27) or the control group (n = 34). The control group was given information about the tonsillectomy by conventional textual and verbal means, whereas the experimental group received the same information in the form of 10 text messages during the period from hospitalization to their first follow-up visits. RESULTS: Results of mixed design, two-way analysis of variance indicated significant interaction effects between time points and groups for mothers' knowledge (F = 4.26, p = 0.043) and children's anxiety (F = 3.32; p = 0.037). Thus, the results do support the effectiveness of tonsillectomy education using smartphone text messaging in increasing mothers' knowledge and reducing children's anxiety. CONCLUSIONS: These results can be applied to preoperative and postoperative interventions for children not only for tonsillectomy but also for many other operations. The development of various educational programs using smartphone text messaging for postoperative patient management would also be valuable.

Antimicrobial activities of active component isolated from Lawsonia inermis leaves and structure-activity relationships of its analogues against food-borne bacteria.

The antimicrobial activities of Lawsonia inermis leaf extract and 2-hydroxy-1,4-naphthoquinone analogues against food-borne bacteria. The antimicrobial activities of five fractions derived from the methanol extract of Lawsonia inermis leaves were evaluated against 7 food-borne bacteria. 2-Hydroxy-1,4-naphthoquinone was isolated by chromatographic analyses. 2-Hydroxy-1,4-naphthoquinone showed the strong activities against Bacillus cereus, Listeria monocytogenes, Salmonella enterica, Shigella sonnei, Staphylococcus epidermidis, and S. intermedius, but exerted no growth-inhibitory activities against S. typhimurium. The antimicrobial activities of the 2-hydroxy-1,4-naphthoquinone analogues were tested against 7 food-borne bacteria to establish structure-activity relationships. Hydroxyl (2-hydroxy-1,4-naphthoquinone and 5-hydroxy-1,4-naphthoquinone), methoxy (2-methoxy-1,4-naphthoquinone), and methyl (2-methyl-1,4-naphthoquinone, and 5-hydroxy-2-methyl-1,4-naphthoquinone) functional groups on the 1,4-naphthoquinone skeleton possessed potent activities, whereas bromo (2-bromo-1,4-naphthoquinone and 2,3-dibromo-1,4-naphthoquione) and chloro (2,3-dichloro-1,4-naphthoquinone) exhibited no activity against 7 food-borne bacteria. The L. inermis leaf extract and 2-hydroxy-1,4-naphthoquinone analogues should be useful as natural antimicrobial agents against food-borne bacteria.

How to get the most from microarray data: advice from reverse genomics.

BACKGROUND: Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data-derived predictor of known cancer associated genes. RESULTS: We found that the traditional approach of identifying cancer genes--identifying differentially expressed genes--is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results were consistent across 4 major types of cancer: breast, colorectal, lung, and prostate. We used recently reported cancer-associated genes (2011-2012) for validation and found that novel cancer-associated genes can be best identified by elevated variance of the gene expression in tumor samples. CONCLUSIONS: The observation that the high interindividual variation of gene expression in tumor tissues is the best predictor of cancer-associated genes is likely a result of tumor heterogeneity on gene level. Computer simulation demonstrates that in the case of heterogeneity, an assessment of variance in tumors provides a better identification of cancer genes than does the comparison of the expression in normal and tumor tissues. Our results thus challenge the current paradigm that comparing the mean expression between normal and tumorous tissues is the best approach to identifying cancer-associated genes; we found that the high interindividual variation in expression is a better approach, and that using variation would improve our chances of identifying cancer-associated genes.

Acaricidal activities against house dust mites of spearmint oil and its constituents.

The aim of this study was to evaluate the acaricidal activities of spearmint oil and carvone derivatives against house dust mites using contact and fumigant toxicity bioassays to replace benzyl benzoate as a synthetic acaricide. Based on the LD50 values, the contact toxicity bioassay revealed that dihydrocarvone (0.95 and 0.88 µg/cm2) was 7.7 and 6.8 times more toxic than benzyl benzoate (7.33 and 6.01 µg/cm2) against Dermatophagoides farinae and Dermatophagoides pteronyssinus, respectively, followed by carvone (3.78 and 3.23 µg/cm2), spearmint oil (5.16 and 4.64 µg/cm2), carveol (6.00 and 5.80 µg/cm2), and dihydrocarveol (8.23 and 7.10 µg/cm2). Results of the fumigant toxicity bioassay showed that dihydrocarvone (2.73 and 2.16 µg/cm2) was approximately 4.0 and 4.8 times more effective than benzyl benzoate (11.00 and 10.27 µg/cm2), followed by carvone (6.63 and 5.78 µg/cm2), carveol (7.58 and 7.24 µg/cm2), spearmint oil (9.55 and 8.10 µg/cm2), and dihydrocarveol (9.79 and 8.14 µg/cm2). Taken together, spearmint oil and carvone derivatives are a likely viable alternative to synthetic acaricides for managing house dust mites.

Antimicrobial potentials of active component isolated from Citrullus colocynthis fruits and structure-activity relationships of its analogues against foodborne bacteria.

BACKGROUND: Synthetic preservatives have been consistently used to maintain the quality of food products. However, the degree of danger to human health cannot be ignored. In this study, the antimicrobial activities of Citrullus colocynthis fruits and 4-methylquinoline analogues were investigated to develop natural preservatives against foodborne bacteria. RESULTS: Antimicrobial activities of the methanol extract and five fractions derived from C. colocynthis fruits were evaluated against five foodborne bacteria. The chloroform fraction possessed strong activities against five foodborne bacteria. 4-Methylquinoline was isolated by chromatographic analyses. To establish the structure-activity relationships, the antimicrobial activities of 4-methylquinoline analogues (2-hydroxyquinoline, 4-hydroxyquinoline, 6-hydroxyquinoline, 2-methylquinoline, 6-methyquinoline, 8-methylquinoline and 2-methyl-8-hydroxyquinoline) were tested against food-borne bacteria. When employing the agar diffusion method, 2-methyl-8-hydroxyquinoline was found to have potent activities against the five foodborne bacteria. In terms of minimum bactericidal concentration or minimum inhibitory concentration, 2-methyl-8-hydroxyquinoline had significantly higher antimicrobial activity against the five foodborne bacteria. CONCLUSION: Citrullus colocynthis fruits and 4-methylquinoline analogues could be useful for the development of eco-friendly food supplemental agents and pharmaceuticals.

Acaricidal toxicities of 1-hydroxynaphthalene from Scutellaria barbata and its derivatives against house dust and storage mites.

The essential oil of Scutellaria barbata was extracted using a steam distillation and then evaluated via fumigant and contact toxicity bioassays against Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Tyrophagus putrescentiae. The acaricidal toxicities of 1-hydroxynaphthalene from S. barbata oil and its derivatives were determined and compared with those of benzyl benzoate. Based on the LD50 values of 1-hydroxynaphthalene derivatives against D. farinae, D. pteronyssinus, and T. putrescentiae, obtained using a fumigant toxicity bioassay, the acaricidal activity of 1-hydroxynaphthalene (2.11, 2.37, and 4.50 µg/cm2) was 4.76, 6.00, and 2.68 times higher than that of benzyl benzoate (10.05, 9.50, and 12.50 µg/cm2) in the corresponding order, which was followed by that of 2-hydroxynaphthalene (9.50, 9.00, and 11.50 µg/cm2). On the contact toxicity bioassay, the acaricidal activity of 1-hydroxynaphthalene (0.79, 0.92, and 2.50 µg/cm2) was 9.49, 6.52, and 3.76 times higher than that of benzyl benzoate (7.50, 6.00, and 9.41 µg/cm2), which was followed by that of 2-hydroxynaphthalene (4.21, 4.80, and 6.50 µg/cm2). In conclusion, our results indicate that S. barbata oil and 1-hydroxynaphthalene derivatives might be effective natural agents for the management of house dust and storage mites.

Application of an Antioxidant Response Element-Nuclear Factor Erythroid 2 Luciferase Assay for Assessing the Skin Sensitization Potential of Agrochemicals.

The skin sensitization potential of agrochemicals can be assessed using laboratory methods such as the keratinocyte activation assay so that their use in regulatory toxicology might replace experimental animal testing. Here, we evaluated the skin sensitization potential of 11 agrochemicals by using an antioxidant response element-nuclear factor erythroid 2 luciferase assay in KeratinoSens and LuSens cells and applying a skin sensitization adverse outcome pathway (AOP). The KeratinoSens and LuSens assays consistently evaluated the skin sensitization potential of 10/11 agrochemicals with reference to animal testing databases. Benomyl, pretilachlor, fluazinam, terbufos, butachlor, and carbosulfan were correctly detected as sensitizers, and glufosinate ammonium, oxiadiazon, tebuconazole, and etofenprox were correctly detected as non-sensitizers. For diazinon, the skin sensitizing potential was positive in the KeratinoSens assay but not in the LuSens assay. These results suggest that the evaluation of in vitro skin sensitization using the AOP mechanism can be applied to assess active agrochemicals.

Evaluation of transdermal exposure of phthalates in children's products.

In this study, 16 children's products with the highest detection potential of phthalates were selected, and a phthalate assay and transdermal delivery analysis (NIER, US EPA Wipe [stress condition], US EPA Wipe [physiological condition], and US EPA Hand Wipe) were conducted with these products. The content of 6 controlled phthalates (DBP, BBP, DEHP, DNOP, DINP, and DIDP) was measured and most products contained more phthalates than the regulated guidelines (a total content of 6 phthalates to be ≤0.1%). For transdermal delivery, all items were found to be lower in the NIER transdermal delivery test method compared to the US EPA Hand Wipe (stress condition and physiological condition) transdermal delivery test method. For the US EPA Hand Wipe (stress condition and physiological condition) transdermal delivery test method, a similar result was observed, except for DINP. The average daily dose (ADD) estimated by determining the exposure algorithm for each transdermal delivery test method was highest in mats with a large contacting surface area and a long exposure time in the respective test methods. Conclusively, there was a difference between the NIER transdermal delivery test method and the US EPA Wipe transdermal delivery test method.

Significant association between IL-17F promoter region polymorphism and susceptibility to asthma in a Korean population.

BACKGROUND: Individual differences in susceptibility to asthma would be expected because of common DNA variants of single nucleotide polymorphisms (SNPs) across populations. The pro-inflammatory cytokine IL-17F has homology with the IL-17 motif and induces the expression of other inflammatory cytokines in airway epithelial cells. This study aimed to identify IL-17F gene polymorphisms and to determine a possible association between these polymorphisms and susceptibility to asthma through a case-control study in a Korean population. METHODS: We identified SNPs in the IL-17F gene by sequencing. Genotyping was conducted using the high-resolution melting (HRM) method on 424 asthma patients and 548 healthy controls. RESULTS: The genotype and allele frequencies of rs1889570 SNP were significantly different between asthma patients and healthy controls (p = 0.001 and 0.002, respectively). The rs1889570 SNP genotype was also positively associated with the number of peripheral blood eosinophils in asthma patients (p = 0.03). The frequencies of haplotypes AA (p = 0.01), GG (p = 0.01) and AG (p = 0.006) were significantly different between asthma patients and healthy controls. CONCLUSIONS: In this study, we confirmed that the rs1889570 polymorphism of the IL-17F gene is associated with susceptibility to asthma in a Korean population.

A multistep protein lysate array quantification method and its statistical properties.

The protein lysate array is an emerging technology for quantifying the protein concentration ratios in multiple biological samples. Statistical inference for a parametric quantification procedure has been inadequately addressed in the literature, mainly because the appropriate asymptotic theory involves a problem with the number of parameters increasing with the number of observations. In this article, we develop a multistep procedure for the Sigmoidal models, ensuring consistent estimation of the concentration levels with full asymptotic efficiency. The results obtained in the article justify inferential procedures based on large sample approximations. Simulation studies and real data analysis are used in the article to illustrate the performance of the proposed method in finite samples. The multistep procedure is convenient to work with asymptotically, and is recommended for its statistical efficiency in protein concentration estimation and improved numerical stability by focusing on optimization of lower-dimensional objective functions.

Evaluating the PM damage cost due to urban air pollution and vehicle emissions in Seoul, Korea.

This study evaluated the prospective damage costs of PM(2.5) inhalation. We performed a health risk assessment based on an exposure-response function to estimate the annual population risk in the Seoul metropolitan city, Korea. Also, we estimated a willingness-to-pay (WTP) amount for reducing the mortality rate in order to evaluate a statistical life value. We combined the annual population risk and the value-of-statistical-life to calculate the damage cost estimate. In the health risk assessment, we applied the PM(2.5) relative risk to evaluate the annual population risk. We targeted an exposure population of 5,401,369 persons who were over the age of 30. Using a Monte-Carlo simulation for uncertainty analysis, we estimated that the population risk of PM(2.5) inhalation during a year in Seoul is 2181 premature deaths for acute exposure and 18,510 premature deaths for chronic exposure. The monthly average WTP for 5/1000 mortality reduction over ten years is $20.20 USD (95% C.I: $16.60-24.50) and the implied value-of-statistical-life (VSL) is $485,000 USD (95% C.I: $398,000-588,000). The damage cost estimate due to risk from PM(2.5) inhalation in Seoul is about $1057 million USD per year for acute exposure, and $8972 million USD per year for chronic exposure. It is important to note that this cost estimate does not reflect all health damage cost estimates in this urban area. This recommendation is a model for evaluating a mortality risk reduction and as such we must re-evaluate an integrated application of morbidity risk.

p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance.

BACKGROUND: Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells. METHODS: Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated. RESULTS: YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics. CONCLUSION: Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists.

The Mediating Roles of Happiness and Cohesion in the Relationship between Employee Volunteerism and Job Performance.

This study investigated the mediating effects of happiness and cohesion in the relationship between employee volunteerism, in-role behavior, and helping behavior. The study surveyed 312 full-time employees in South Korea, and regression analyses and the bootstrapping method were used to test the hypotheses. The study found happiness and cohesion to mediate the relationships between employee volunteerism and in-role and helping behavior. The findings suggest that employee volunteerism can promote a healthy working environment through increased feelings of happiness and cohesion as well as by improving performance behaviors.

Expression and characterization of trehalose biosynthetic modules in the adjacent locus of the salbostatin gene cluster.

The pseudodisaccharide salbostatin, which consists of valienamine linked to 2-amino-1,5-anhydro-2-deoxyglucitol, is a strong trehalase inhibitor. From our Streptomyces albus ATCC 21838 genomic library, we identified thirty-nine ORFs in a 40-kb gene cluster. Twenty-one genes are supposed to be a complete set of modules responsible for the salbostatin biosynthesis. Through sequence analysis of the gene cluster, some of the upstream gene products (SalB, SalC, SalD, SalE, and SalF) revealed functional resemblance with trehalose biosynthetic enzymes. On the basis of this rationale, we isolated the five genes (salB, salC, salD, salE, and salF) from the S. albus ATCC 21838 and cloned them into the expression vector pWHM3. We demonstrated the noticeable expression and accumulation of trehalose, using only the five upstream biosynthetic gene cluster of salbostatin, in the transformed Streptomyces lividans TK24. Finally, 490 mg/l trehalose was produced by fermentation of the transformant with sucrosedepleted R2YE media.

Relation of rice intake and biomarkers of cadmium for general population in Korea.

Environmental exposure to cadmium can cause renal damage. Foods containing cadmium are generally regarded as the main environmental sources of human exposure to cadmium. In this study, foods that are ingested in large amounts, including rice and other types of food with a high concentration of cadmium, were investigated to determine the correlation between the foods' cadmium content and biomarkers. The datasets required for this study, including blood cadmium concentration, biomarker concentration, and data on the amount of consumption by food item, were obtained from KNHNES. Furthermore, data on food groups with high daily exposure to hazardous amounts of cadmium were obtained by monitoring raw food sources from 2010 to 2012. The investigation was then followed by correlation analysis, which was performed to assess the relationship between the amount of rice consumption and cadmium concentration. The Pearson coefficient analysis on the relationship between the amount of food consumption and the biomarker showed that the correlation between foods' cadmium content and blood cadmium and that of between foods' cadmium content and other biomarkers were confirmed as statistically significant in the case of the cadmium content of white rice, while, in the case of brown rice, it was confirmed by a few biomarkers.

Inhibitory Potential of Constituents from Osmanthus fragrans and Structural Analogues Against Advanced Glycation End Products, α-Amylase, α-Glucosidase, and Oxidative Stress.

Inhibition of α-amylase and α-glucosidase, advanced glycation end products (AGEs) formation, and oxidative stress by isolated active constituents of Osmanthus fragrans flowers (9,12-octadecadienoic acid and 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one) and their structural analogues were evaluated. 9,12-Octadecadienoic acid was 10.02 and 22.21 times more active against α-amylase and α-glucosidase, respectively, than acarbose and ascorbic acid, followed by 9,12,15-octadecatrienoic acid, 9-octadecenoic acid, 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one, 4-(2,6,6-trimethyl-2-cyclohexenyl)-3-buten-2-one, 1-heptadecanecarboxylic acid, and 1-pentadecanecarboxylic acid. Concerning the inhibition of AGEs formation, similar with data for 2,2'-diphenyl-1-picrylhydrazl radical scavenging activities, 9,12-octadecadienoic acid was 3.54 times more active than aminoguanidine, followed by 9,12,15-octadecatrienoic acid, and 9-octadecenoic acid. These results indicate that 4-(2,6,6-trimethyl-1-cyclohexenyl)-3-buten-2-one, 9,12-octadecadienoic acid and their analogues inhibit α-amylase and α-glucosidase, AGEs formation, and oxidative stress have potential value in alleviating diabetic pathological conditions.

Antimicrobial Effects of 7,8-Dihydroxy-6-Methoxycoumarin and 7-Hydroxy-6-Methoxycoumarin Analogues against Foodborne Pathogens and the Antimicrobial Mechanisms Associated with Membrane Permeability.

The antimicrobial effects of 7,8-dihydroxy-6-methoxycoumarin and 7-hydroxy-6-methoxycoumarin isolated from Fraxinus rhynchophylla bark and of their structural analogues were determined in an attempt to develop natural antimicrobial agents against the foodborne pathogens Escherichia coli, Bacillus cereus, Staphylococcus intermedius, and Listeria monocytogenes. To elucidate the relationship between structure and antimicrobial activity for the coumarin analogues, isolated constituents and their structural analogues were evaluated against foodborne pathogens. Based on the culture plate inhibition zones and MICs, 6,7-dimethoxycoumarin, 7,8-dihydroxy-6-methoxycoumarin, 7-hydroxy-6-methoxycoumarin, and 7-methoxycoumarin, containing a methoxy functional group on the coumarin skeleton, had the notable antimicrobial activity against foodborne pathogens. However, 7-hydroxycoumarin and 6,7-dihydroxycoumarin, which contained a hydroxyl functional group on the coumarin skeleton, had no antimicrobial activity against these pathogens. An increase in cell membrane permeability was confirmed by electron microscopy observations, and release of extracellular ATP and cell constituents followed treatment with the ethyl acetate fraction of F. rhynchophylla extract. These findings indicate that F. rhynchophylla extract and coumarin analogues have potential for use as antimicrobial agents against foodborne pathogens and that the antimicrobial mechanisms are associated with the loss of cell membrane integrity.

YAP/TAZ-Mediated Upregulation of GAB2 Leads to Increased Sensitivity to Growth Factor-Induced Activation of the PI3K Pathway.

The transcription regulators YAP and TAZ function as effectors of the HIPPO signaling cascade, critical for organismal development, cell growth, and cellular reprogramming, and YAP/TAZ is commonly misregulated in human cancers. The precise mechanism by which aberrant YAP/TAZ promotes tumor growth remains unclear. The HIPPO tumor suppressor pathway phosphorylates YAP and TAZ, resulting in cytosolic sequestration with subsequent degradation. Here, we report that the PI3K/AKT pathway, which is critically involved in the pathophysiology of endometrial cancer, interacts with the HIPPO pathway at multiple levels. Strikingly, coordinate knockdown of YAP and TAZ, mimicking activation of the HIPPO pathway, markedly decreased both constitutive and growth factor-induced PI3K pathway activation by decreasing levels of the GAB2 linker molecule in endometrial cancer lines. Furthermore, targeting YAP/TAZ decreased endometrial cancer tumor growth in vivo In addition, YAP and TAZ total and phosphoprotein levels correlated with clinical characteristics and outcomes in endometrial cancer. Thus, YAP and TAZ, which are inhibited by the HIPPO tumor suppressor pathway, modify PI3K/AKT pathway signaling in endometrial cancer. The cross-talk between these key pathways identifies potential new biomarkers and therapeutic targets in endometrial cancer. Cancer Res; 77(7); 1637-48. ©2017 AACR.