Search results for: estrogen receptor-α

Authors: Laura Ulitzky, Dougbeh-Chris Nyan, Manuel M. Lafer, Erica Silberstein, Nicoleta Cehan, Deborah R. Taylor

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Hepatitis C virus (HCV)-associated hepatocellular carcinoma, fibrosis and cirrhosis are more frequent in men and postmenopausal women than in premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol (estrogen) plays an innate role in preventing viral infection and liver disease. Estrogen classically acts through nuclear estrogen receptors or, alternatively, through the membrane-bound G-protein-coupled estrogen receptor (GPR30 or GPER). We observed a marked decrease in detectable virus when HCV-infected human hepatoma cells were treated with estrogen. The effect was mimicked by both Tamoxifen (Tam) and G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. Through GPR30, estrogen-mediated the down-regulation of occludin; a tight junction protein and HCV receptor, by promoting activation of matrix metalloproteinases (MMPs). Activated MMP-9 was secreted in response to estrogen, cleaving occludin in the extracellular Domain D, the motif required for HCV entry and spread. This pathway gives new insight into a novel innate immune pathway and the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.

Keywords: HCV, estrogen, occludin, MMPs

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Authors: Noha Mohamed Abdelhafez Dahy, Azza Abd El-Aziz, Eman Ahmed, Marwa El-Sayed

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Osteoporosis is a metabolic bone disease characterized by low bone mass, deterioration of bone tissue, and disruption of bone microarchitecture, which leads to compromised bone strength and an increased risk of fracture, commonly it occurs in women 10-15 years after menopause, the mean age of menopause is 51 years. Menopause is natural physiological changes primary because of decline of ovaries function with age which leads to decrease of estrogen hormone production which is the main hormone for bone continuous remodeling for bone density maintenance. Exercise increase stimulation of bone growth to keep bone mass by the effect of the mechanical stimulation, antigravity loading and stress exerted on musculoskeletal muscles. Purpose: This study aimed to determine the effect of aerobic exercise on estrogen hormone and bone mineral density (BMD) in osteoporotic women and the correlation between the estrogen and BMD.

Keywords: Osteoporosis, Postmenopause, Aerobic exercise, DEXA, Serum Estrogen

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Authors: Farideh K. Khosroushahi, Serkan Erdal, Mucip Geni̇şel

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Soil salinity is one of the major abiotic stress factors that restricts arable land and reduces crop productivity worldwide. High salt concentration adversely affects plant growth and development inducing water deficit, ionic toxicity, nutrient imbalance, and lead to oxidative stress. Although the stimulating role of mammalian sex hormones on various biological and biochemical processes under normal and stress condition have been proven, there is no study regarding with these hormone's effect on modulation of the alternative respiration pathway and AOX gene expression. In this study, changes in alternative respiration pathway in leaves of maize seedlings under salinity and the possible modulating effect of estrogen on these changes were investigated. Maize seedlings were grown in a hydroponic media for 11 days and then were exposed to salt stress for 3 days after being sprayed estrogen. The data obtained from oxygen consumption revealed that salt stress elevated cellular respiration value in the leaves. In addition, a marked increase was observed at alternative respiration level in salt-stressed seedlings. Compared to salt application alone, supplementation with estrogen resulted in a significant rise in alternative oxidase (AOX) activities. Similarly, while salt stress caused to rise in expressions of AOX gene compared to control seedlings, estrogen application resulted in further activation of these genes’ expression compared to stressed-seedlings alone. These data revealed that mitigating role of estrogen against the detrimental effects of salt stress is linked to modulation of alternative respiration pathway.

Keywords: alternative oxidase, estrogen, Ssalt stress, AOX, maize

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Authors: Remi Safi, Aline Hamade, Najat Bteich, Jamal El Saghir, Mona Diab Assaf, Marwan El-Sabban, Fadia Najjar

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Estrogen is considered a risk factor for breast cancer since it promotes breast-cell proliferation. The jaesckeanadiol-3-p-hydroxyphenylpropanoate, a hemi-synthetic analogue of the natural phytoestrogen ferutinin (jaesckeanadiol-p-hydroxybenzoate), is designed to be devoid of estrogenic activity. This analogue induces a cytotoxic effect 30 times higher than that of ferutinin towards MCF-7 breast cancer cell line. We compared these two compounds with respect to their effect on proliferation, cell cycle distribution and cancer stem-like cells in the MCF-7 cell line. Treatment with ferutinin (30 μM) and its analogue (1 μM) produced a significant accumulation of cells at the pre G0/G1 cell cycle phase and triggered apoptosis. Importantly, this compound retains its anti-proliferative activity against breast cancer stem/progenitor cells that are naturally insensitive to ferutinin at the same dose. These results position ferutinin analogue as an effective compound inhibiting the proliferation of estrogen-dependent breast cancer cells and consistently targeting their stem-like cells.

Keywords: ferutinin, hemi-synthetic analogue, breast cancer, estrogen, stem/progenitor cells

Procedia PDF Downloads 152

Authors: Saeedeh Salimi, Farzaneh Farajian- Mashhadi, Ehsan Tabatabaei, Mahnaz Shahrakipoor, Minoo Yaghmaei, Mojgan Mokhtari

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Purpose: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore ERα gene could be a possible candidate for preeclampsia(PE) susceptibility. In the current study, we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. Methods: One hundred ninety-two pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by PCR-RFLP method. Results: The frequency of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; P = 0.02) and in severe PE compared to normotensive women [OR= 1.8(1.1-3), P=0.02] after adjusting for age, ethnicity and primiparity. Conclusions: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition.

Keywords: estrogen receptor-α, polymorphism, gene, preeclampsia

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Authors: K. Shafiei, A. Pirestani, G. Ghalamkari, S. Safavipour

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Use of GnRH or its agonists to increase conception rates should be based on an understanding of GnRH-induced biological effects on the reproductive-endocrine system. This effect may occur through GnRH-stimulated LH surge stimulating production of progesterone by corpus luteum.the aim of this study was to compare the effects on reproductive efficiency of a luteolytic dose of a synthetic prostaglandin Cloprostenol Sodium versus ainjectable progesterone and Luliberin- A on Follicle estrogen and progesterone levels.In this study, we used45 head of holstein dairy heifersin the three treatments, with 15 replicates per treatment were performed in random groups. all the heifers before the projects is began in two steps injection 3 mL CloprostenolSodium with an interval of 11 days been synchronized and 10 days later, second injection of prostaglandin was conducted after that we started below protocol:Control group (daily sodium chloride serum injection 1 cc), Group B: Day Zero, intramuscular injection of 15 mg Luliberin- A + every other day injection of 3 cc progesterone + day 7, injection of Cloprostenol Sodium+ day 9, injection of 15 mg Luliberin- A.Group C: similar to Grop B + daily injection of progesterone after that blood samples was collected and centrifuged.plasma were analysed by ELISA.the analysis of this study uses SPSS data software package and compared between the mean and LS Means LSD test at 5% significance level was used.The results of this study shows that maximum of progesterone plasma levels were in the control gruop (P ≥ 0.05).Therefore, daily injection of progesterone inhibit the growth CL. the most estrogen levels in plasma were in Group C (P ≥ 0.05) thus it can be concluded, rise in endogenous estrogen concentrations normally stimulates the preovulatory LH release in heifers.

Keywords: Luliberin- A, Cloprostenol Sodium, estrogen, progesterone, dairy heifers

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Authors: Uraporn Vongvatcharanon, Kochakorn Sukjan, Wandee Udomuksorn, Ekkasit Kumarnsit, Surapong Vongvatcharanon

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Sarcopenia is a loss of muscle mass, and strength frequently found in menopause. Estrogen replacement has been shown to improve such a loss of muscle functions. However, there is an increased risk of cancer that has to be considered because of the estrogen replacement therapy. Thus, phytoestrogen supplementation has been suggested as an alternative therapy. Pueraria mirifica (PM) is a plant in the family Leguminosae, that is known to be phytoestrogen-rich and has been traditionally used for the treatment of menopausal symptoms. It contains isoflavones and other compounds such as miroestrol and its derivatives. Parvalbumin (PV) is a calcium binding protein and functions as a relaxing factor in fast twitch muscle fibers. A decrease of the PV level results in a reduction of the speed of the twitch relaxation. Therefore, this study aimed to investigate the effect of an ethanolic extract from Pueraria mirifica on the estrogen levels, skeletal muscle functions and PV levels in the extensor digitorum longus (EDL) and gastrocnemius of ovariectomized rats. Twelve-week old female Wistar rats (200-250 g) were divided into 6 groups: SHAM (un-ovariectomized rats, that received double distilled water), PM-0 (ovariectomized rats, OVX, receiving double distilled water), E (OVX, receiving an estradiol benzoate dose of 0.04 mg/kg), PM-50 (OVX receiving PM 50 mg/kg), PM-500 (OVX receiving PM 500 mg/kg), PM-1000 (OVX receiving PM 1000 mg/kg) all for 90 days. The PM-0 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation and parvalbumin levels of both EDL and gastrocnemius that were significantly reduced compared to those of the SHAM group (p<0.05). Also the α and β estrogen receptor immunoreactivities and the parvalbumin immunoreactivities of both EDL and gastrocnemius were decreased in the PM-0 group. In contrast the E, PM-50, PM-500 and PM-1000 group had estrogen levels, uterus weights, muscle mass, myofiber cross-section areas, peak tension, fatigue resistance, speed of relaxation of both EDL and gastrocnemius that were significantly increased compared with PM-0 group (p<0.05). In addition, the α and β estrogen receptor immunoreactivities and parvalbumin immunoreactivity of both the EDL and gastrocnemius were increased in the E, PM-50, PM-500 and PM-1000 group. In addition the extract of Pueraria mirifica replacement group at 50 and 500 mg/kg had significantly increased parvalbumin levels in the EDL muscle but in the gastrocnemius, only the dose of 500 mg/kg increased the parvalbumin levels (p<0.05). These results have demonstrated that the use of the Pueraria mirifica extract as a replacement therapy for estrogen produced estrogenic activity that was similar to that produced by the estradiol benzoate replacement. It seems that the phytoestrogens could bind with the estrogen receptors and stimulate the transcriptional activity to synthesise muscle protein that caused an increase in muscle mass and parvalbumin levels. Thus, muscle synthesis may restore parvalbumin levels resulting in an enhanced relaxation efficiency that would lead to a shortened latent period before the next contraction.

Keywords: Puereria mirifica, Parvalbumin, estrogen, ovariectomized rats

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Ezeugwunne Ifeoma Priscilla, Charles Chinedum Onyenekwe, Joseph Eberendu Ahaneku, Rosemary Adanma Analike, Adesuwa Peace Eidangbe

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This study was designed to assess the effect of malaria parasitaemia on serum reproductive hormone levels of asymptomatic HIV adult subjects. A total of 271 participants aged between 17 and 58 ears were conveniently recruited. 135 asymptomatic HIV-infected subjects participated in the study; 67 of them had malaria parasitaemia. 136 HIV seropositive control subjects, 68 of them had malaria parasitaemia. Blood samples were collected from the participants for the determination of HIV status by immunoassay and immunochromatography. Enzyme-linked immunosorbent assay (ELISA) was used to assay for serum LH, FSH, Estrogen, testosterone, progesterone, prolactin, and PSA levels, CD4+T cell counts by Cyflow method, thick and thin films determination of malaria parasitaemia count and density by WHO. Student's t-tests and ANOVA were used to compare means. P<0.05 was considered statistically significant. The results showed significant differences in serum levels of LH, FSH, PSA, estrogen, progesterone, and testosterone amongst the groups at P<0.05, respectively. The serum levels of LH, FSH, and PSA were significantly higher in malaria-infected asymptomatic HIV subjects than in asymptomatic HIV subjects with malaria parasitaemia (P<0.05 in each case). Also, the serum levels of LH, FSH, PSA, estrogen, and progesterone were significantly higher in malaria-infected asymptomatic HIV subjects compared with malaria-infected HIV seronegative subjects (P<0.05, respectively). The mean MP counts and MP density were significantly higher in asymptomatic HIV subjects compared to HIV seronegative subjects (P<0.05, in each case). The mean serum levels of testosterone were significantly lower in both malaria-infected and malaria uninfected HIV seronegative subjects (P<0.05, in each case). In conclusion, Malaria and HIV co-infection might increase the burden of hypogonadism as well as primary testicular failure, hyperprogesteronaemia, elevated levels of estrogen, and PSA in adult males asymptomatic HIV subjects.

Keywords: malaria parasitaemia, HIV, CD4, reproductive hormones

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Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

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Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Ji Hye Im, Nguyen T. T. Phuong, Keon Wook Kang

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Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation.

Keywords: TAMR-MCF-7, CREB, estrogen receptor, aromatase

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Authors: Sandhyarani Guggilla

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For several reasons no two individuals can be considered identical and hence individualization of therapy is the current trend in treating the patients. Influence of menstrual cycle on the pharmacokinetics of Doxycycline. Twelve healthy female volunteers have been included in the study after obtaining written informed consent. The age ranged from 16 to 25 years. Experimental design: The volunteer selection and recruitment will be carried out after obtaining informed consent from each volunteer. The drug administration will be done to each volunteer at 7 a.m along with a glass of water after an overnight fasting on 3rd, 13th and 23rd day of menstrual cycle. These saliva samples will be stored under frozen conditions until HPLC analysis. Results: In the present study the changes in estrogen levels during ovulatory phase have not shown any influence onAUCo-t of Doxycycline. Only AUCo-t of doxycycline showed an increasing trend with increasing levels of estrogen in ovulatory phase, but not in other phases. Even though the FSH levels differed significantly among volunteers during different phases FSH does not seem to influence the overall pharmacokinetic behavior of Doxycycline during different phases. The present study indicated only the trend that the hormone levels may influence the pharmacokinetic behavior of the Doxycycline. Conclusion: In the present study the changes in hormones have shown an increasing C-max, increasing AUCo-t of Doxycycline pharmacokinetics significantly in follicular phase than ovulatory and luteal phases among volunteers during different phases. In other pharmacokinetic properties like clearance, biological half-life, volume of distribution, mean residence time the change was not significant.

Keywords: menstrual cycle, doxycycline, estrogen, FSH, ovulatory phase

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Authors: Nadine Abuqtaish

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Females’ participation in athletic sports events has increased in the last decades, and the discovery of eating disorders and menstrual dysfunction has been evident since the early 1980s. The term “Female athlete triad” was initially defined by the Task Force on Women’s Issues of the American College of Sports Medicine (ACSM) in 1992. Menstrual irregularities have been prevalent in competitive female athletes, especially in their adolescence and early adulthood age. Nutritional restrictions to maintain a certain physique and lean look are sought to be advantageous in female athletes such as gymnastics, cheerleading, or weight-sensitive sports such as endurance sports (cycling and marathoners). This stress places the female at risk of irregularities in their menstrual cycle which can lead them to lose their circadian estrogen levels. Estrogen is an important female reproductive hormone that plays a role in maintaining bone mass. Bone mineral density peaks by the age 25. Inadequate estrogen due to missed menstrual cycle or amenorrhea has been estimated to cause a yearly loss of 2% of bone mass, increasing the risk of osteoporosis in the postmenopausal phase. This paper is intended to have a better depth understanding of whether female athletes are being monitored by their official entities or coaches. A qualitative research method through online search engines and keywords “females, athletes, triad, amenorrhea, anorexia, osteoporosis” were used to collect the available primary sources from official public library databases. The latest consensus was published in 2014 by the Female Athlete Triad Coalition and the need for further research and emphasis on this issue is still lacking.

Keywords: female, athlete, triad, amenorrhea, anorexia, bone loss

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Authors: Amir Ghasemlouei, Alireza Khalaj

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In women, cancer of the breast is one of the most common incident cancer and cause of death from cancer .we reviewed the prevalence of obesity and its association with breast cancer. In this study, a total of 25 articles regarding the subject matter of the article have been presented in which 640 patients were examined that 320 patients with breast cancer and 320 were controls. The distribution of breast cancer patients and controls with respect to their anthropometric indices in patients with higher weight, which was statistically significant (60.2 ± 10.2 kg) compared with control group (56.1 ± 11.3 kg). The body mass index of patients was (26.06+/-3.42) and significantly higher than the control group (24.1+/-1.7). Obesity leads to increased levels of adipose tissue in the body that can be stored toxins and carcinogens to produce a continuous supply. Due to the high level of fat and the role of estrogen in a woman is endogenous estrogen of the tumor and regulate the activities of growth steroids, obesity is a risk factor for breast cancer is confirmed. Our study and other studies show that obesity is a risk factor for breast cancer. And with a weight loss intervention for breast cancer can be prevented in the future.

Keywords: breast cancer, review study, obesity, overweight

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Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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Authors: D. Pradhan, G. Tripathy, S. Pradhan

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Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Karthik Mittal

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This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

Procedia PDF Downloads 116

Authors: Anaelle Gabet, Helene Metivier, Christine De Brauer, Gilles Mailhot, Marcello Brigante

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The presence of micropollutants in surface waters has been widely reported around the world, particularly downstream from wastewater treatment plants (WWTPs). Rural WWTPs constitute more than 90 % of the total WWTPs in France. Like conventional ones, they are not able to fully remove micropollutants. Estrogens are excreted by human beings every day and several studies have highlighted their endocrine disruption properties on river wildlife. They are mainly estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2). Rural WWTPs require cheap and robust tertiary processes. UVC activation of H₂O₂ for HO· generation, a very reactive molecule, has demonstrated its effectiveness. However, UVC rays are dangerous to manipulate and energy-consuming. This is why the ability of UVA rays was investigated in this study. Moreover, the use of S₂O₈²⁻ for SO₄·- generation as an alternative to HO· has emerged in the last few years. Such processes have been widely studied on a lab scale. However, pilot-scale works constitute fewer studies. This study was carried out on a 20-L pilot composed of a 1.12-L UV reactor equipped with a polychromatic UVA lamp or a monochromatic (254 nm) UVC lamp fed in recirculation. Degradation rates of a mixture of spiked E1, E2 and EE2 (5 µM each) were followed by HPLC-UV. Results are expressed in UV dose (mJ.cm-2) received by the compounds of interest to compare UVC and UVA. In every system, estrogen degradation rates followed pseudo-first-order rates. First, experiments were carried out in tap water. All estrogens underwent photolysis under UVC rays, although E1 photolysis is higher. However, only very weak photolysis was observed under UVA rays. Preliminary studies on both oxidants have shown that S₂O₈²⁻ photolysis constants are higher than H₂O₂ under both UVA and UVC rays. Therefore, estrogen degradation rates are about ten times higher in the presence of 1 mM of S₂O₈²⁻ than with one mM of H₂O₂ under both radiations. In the same conditions, the mixture of interest required about 40 times higher UV dose when using UVA rays compared to UVC. However, the UVA/S₂O₈²⁻ system only requires four times more UV dose than the conventional UVC/H₂O₂ system. Further studies were carried out in WWTP effluent with the UVC lamp. When comparing these results to the tap water ones, estrogen degradation rates were more inhibited in the S₂O₈²⁻ system than with H₂O₂. It seems that SO₄·- undergo higher quenching by a real effluent than HO·. Preliminary experiments have shown that natural organic matter is mainly responsible for the radical quenching and that HO and SO₄ both had similar second-order reaction rate constants with dissolved organic matter. However, E1, E2 and EE2 second-order reaction rate constants are about ten times lower with SO₄ than with HO. In conclusion, the UVA/S₂O₈²⁻ system showed encouraging results for the use of UVA rays but further studies in WWTP effluent have to be carried out to confirm this interest. The efficiency of other pollutants in the real matrix also needs to be investigated.

Keywords: AOPs, decontamination, estrogens, radicals, wastewater

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Authors: Shih-cheng Li, Ming-Yi Chung, Mei-Lien Chen

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Background: Plasticizers, such as phthalates and adipates, were substances added to a material that provided flexibility and durability to plastics such as polyvinyl chloride (PVC). Phthalates were generally recognized as an endocrine disrupter due to their estrogenic and anti-androgenic activities. Phthalates had the capacity to bind to estrogen receptors, and hence they might prolong menstrual cycles and increase the proportion of premature menopause. Recently, adipates such as di-2-ethylhexyl adipate (DEHA) and di-isononyl adipate (DiNA) had replaced phthalates and were now used for food packaging. Methods: MCF-7 cell lines were treated with di-2-ethylhexyl phthalate (DEHP), di- 2-ethylhexyl adipate (DEHA), or di-isononyl adipate (DiNA) (10-6 , 10-5 , and 10-4 mol/l), using 17β-estradiol (10-8 mol/l) as a positive control. After incubations of 24, 48, 72, and 96 hours, the cells were tested using the alamarBlue assay. Results: The alamarBlue assay revealed that cell proliferation significantly increased after treatments of DEHP and DEHA for 24 hours at a concentration of 10-6, 10-5, and 10-4 mol/l. After more than 48 hours, cell proliferations in DEHP at 10-6, 10-5, and 10-4 mol/l significantly decreased compared to the control group. Conclusions: The present study demonstrates that adipates, as well as phthalates, were capable of inducing cell proliferation. We further used MDA-MB-231 cell lines to confirm that the proliferation effect was generated through binding to estrogen receptors.

Keywords: MCF-7, phthalate, adipate, endocrine disrupter

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Authors: Divya Vohora, Md. Jamir Anwar

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Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. Both phenytoin (PHT) and sodium valproate (SVP) inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with CVD supplementation, on PHT and SVP-induced alterations in bone in mice. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of AEDs was also investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and curative treatment with raloxifene ameliorated bony alterations and was more effective than CVD. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with their antiepileptic efficacy, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Keywords: antiepileptic drugs, osteoporosis, raloxifene, TGF-β3

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Authors: Guanghua Lu, Zhenhua Yan

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To investigate the estrogenic contamination and potential risk of Taihu Lake, eight active biomonitoring points in the northern section of Taihu Lake were set up and located in Wangyuhe River outlet (P1), Gonghu Bay (P2 and P3), Meiliang Bay (P4 and P5), Zhushan Bay (P6 and P7) and Lake Centre (P8). A suite of biomarkers in caged fish after in situ exposure for 28 days, coupled with six selected exogenous estrogens in water, were determined in May and December 2011. Six target estrogens, namely estrone (E1), 17b-estradiol (E2), ethinylestradiol (EE2), estriol (E3), diethylstilbestrol (DES) and bisphenol A (BPA), were quantified using UPLC/MS/MS. The concentrations of E1, E2, E3, EE2, DES and BPA ranged from ND to 3.61 ng/L, ND to 17.3 ng/L, ND to 1.65 ng/L, ND to 10.2 ng/L, ND to 34.6 ng/L, and 3.95 to 207 ng/L, respectively. BPA was detected at all sampling points at all test periods, E2 was detected at 95% of samples, E1 and EE2 was detected at 75% of samples, and E3 was detected only in December 2011 with quite low concentrations. Each individual estrogen concentration measured at each sampling point was multiplied by its relative potency to gain the estradiol equivalent (EEQ). The total EEQ values in all the monitoring points ranged from 5.69 to 17.8 ng/L in May 2011, and from 4.46 to 21.1 ng/L in December 2011. E2 and EE2 were thought to be the major causal agents responsible for the estrogenic activities. Serum vitellogenin and E2 levels, gonadal DNA damage, and gonadosomatic index were measured in the in situ exposed fish. An enhanced integrated biomarker response (EIBR) was calculated and used to evaluate potential feminization risk of fish in the polluted area of Taihu Lake. EIBR index showed good agreement with the observed total EEQ levels in water. Our results indicated that Gong bay and the lake center had a low estrogenic risk, whereas Wangyuhe River, Meiliang Bay, and Zhushan Bay might present a higher risk to fish.

Keywords: active biomonitoring, estrogen, feminization risk, Taihu Lake

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Authors: Sayantika Biswas, Dipanshu Sur, Amitoj Athwal, Ratnabali Chakravorty

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Title: Impact of serum estrogen and progesterone levels in the outcome pregnancy rate in frozen embryo transfer cycles. A prospective cohort study Objective: The aim of the current study was to evaluate the effect of serum estradiol (E2) and progesterone (P4) levels at different time points on pregnancy outcomes in frozen embryo transfer (FET) cycles. Materials & Method: A prospective cohort study was performed in patients undergoing frozen embryo transfer. Patients under age 37 years of age with at least one good blastocyst or three good day 3 embryos were included in the study. For endometrial preparation, 14 days of oral estradiol use (2X2 mg for 5 days. 3X2 mg for 4 days, and 4X2 mg for 5 days) was followed by vaginal progesterone twice a day and 50 mg intramuscular progesterone twice a day. Embryo transfer was scheduled 72-76 hrs or 116-120hrs after the initiation of progesterone. Serum E2 and P4 levels were examined at 4 times a) at the start of the menstrual cycle prior to the hormone supplementation. b) on the day of P4 start. c) on the day of ET. d) on the third day after ET. Result: A total 41 women were included in this study (mean age 31.8; SD 2.8). Clinical pregnancy rate was 65.55%. Serum E2 levels on at the start of the menstrual cycle prior to the hormone supplementation and on the day of P4 start were high in patients who achieved pregnancy compared to who did not (P=0.005 and P=0.019 respectively). P4 levels on on the day of ET were also high in patients with clinical pregnancy. On the day of P4 start, a serum E2 threshold of 186.4 pg/ml had a sensitivity of 82%, and P4 had a sensitivity of 71% for the prediction of clinical pregnancy at the threshold value 16.00 ng/ml. Conclusion: In women undergoing FET with hormone replacement, serum E2 level >186.4 pg/ml on the day of the start of progesterone and serum P4 levels >16.00 ng/ml on embryo transfer day are associated with clinical pregnancy.

Keywords: serum estradiol, serum progesterone, clinical pregnancy, frozen embryo transfer

Procedia PDF Downloads 44

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer occupies the first place among the cancer in women in the world. It is urgent today to study the role of molecular markers which are capable of predicting the dynamics and outcome of the disease. The aim of this study is to define the prognostic value of the content of estrogen receptor (ER), progesterone receptor (PgR), and amplification of HER-2 / neu oncoprotein by studying 3 and 5-year overall and relapse-free survival in 470 patients with primary operable and 280 patients with locally–advanced breast cancer. Materials and methods: Study results of 3 and 5-year overall and relapse-free survival, depending on the content of RE, PgR in primary operable patients showed that ER positive (+) and PgR (+) survival was 100 (96.2%) and 97.3 (94.6%), for ER negative (-) and PgR (-) - 69.2 (60.3%) and 65.4 (57.7%), for ER positive (+) and negative PgR (-) 87.4 (80.1%) and 81.5 (79.3%), for ER negative (-) and positive PgR (+) - 97.4 (93.4%) and 90.4 (88.5%), respectively. Survival results depended also on the level of HER-2 / neu expression. In patients with HER-2 / neu negative the survival rates were as follows: 98.6 (94.7%) and 96.2 (92.3%). In group of patients with the level of HER-2 / neu (2+) expression these figures were: 45.3 (44.3%) and 45.1 (40.2%), and in group of patients with the level of HER-2 / neu (3+) expression - 41.2 (33.1%) and 34.3 (29.4%). The combination of ER negative (-), PgR (-), HER-2 / neu (-) they were 27.2 (25.4%) and 19.5 (15.3%), respectively. In patients with locally-advanced breast cancer the results of 3 and 5-year OS and RFS for ER (+) and PgR (+) were 76.3 (69.3%) and 62.2 (61.4%), for ER (-) and RP (-) 29.1 (23.7%) and 18.3 (12.6%), for ER (+) and PgR (-) 61.2 (47.2%) and 39.4 (25.6%), for ER (-) and PgR (+) 54.3 (43.1%) and 41.3 (18.3%), respectively. The level of HER-2 / neu expression also affected the survival results. Therefore, in HER-2/ neu negative patients the survival rate was 74.1 (67.6%) and 65.1 (57.3%), with the level of expression (2+) 20.4 (14.2%) and 8.6 (6.4%), with the level of expression (3+) 6.2 (3.1%) and 1.2 (1.5%), respectively. The combination for ER, PgR, HER-2 / neu negative was 22.1 (14.3%) and 8.4 (1.2%). Conclusion: Thus, the presence of steroid hormone receptors in breast tumor tissues at primary operable and locally- advanced process as the lack of HER-2/neu oncoprotein correlates with the highest rates of 3- and 5-year overall and relapse-free survival. The absence of steroid hormone receptors as well as of HER-2/neu overexpression in malignant breast tissues significantly degrades the 3- and 5-year overall and relapse-free survival. Tumors with ER, PgR and HER-2/neu negative have the most unfavorable prognostics.

Keywords: breast cancer, estrogen receptor, oncoprotein, progesterone receptor

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Authors: M. Ouassaf, S. Belaidi

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Aromatase is an estrogen biosynthetic enzyme belonging to the cytochrome P450 family, which catalyzes the limiting step in the conversion of androgens to estrogens. As it is relevant for the promotion of tumor cell growth. A set of thirty 1,2,3-triazole derivatives was used in the quantitative structure activity relationship (QSAR) study using regression multiple linear (MLR), We divided the data into two training and testing groups. The results showed a good predictive ability of the MLR model, the models were statistically robust internally (R² = 0.982) and the predictability of the model was tested by several parameters. including external criteria (R²pred = 0.851, CCC = 0.946). The knowledge gained in this study should provide relevant information that contributes to the origins of aromatase inhibitory activity and, therefore, facilitates our ongoing quest for aromatase inhibitors with robust properties.

Keywords: aromatase inhibitors, QSAR, MLR, 1, 2, 3-triazole

Procedia PDF Downloads 81

Authors: N. Szczepanska, B. Kudlak, G. Yotova, S. Tsakovski, J. Namiesnik

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In the scientific literature related to the widely understood issue of packaging materials designed to have contact with food (food contact materials), there is much information on raw materials used for their production, as well as their physiochemical properties, types, and parameters. However, not much attention is given to the issues concerning migration of toxic substances from packaging and its actual influence on the health of the final consumer, even though health protection and food safety are the priority tasks. The goal of this study was to estimate the impact of particular foodstuff packaging type, food production, and storage conditions on the degree of leaching of potentially toxic compounds and endocrine disruptors to foodstuffs using the acute toxicity test Microtox and XenoScreen YES YAS assay. The selected foodstuff packaging materials were metal cans used for fish storage and tetrapak. Five stimulants respectful to specific kinds of food were chosen in order to assess global migration: distilled water for aqueous foods with a pH above 4.5; acetic acid at 3% in distilled water for acidic aqueous food with pH below 4.5; ethanol at 5% for any food that may contain alcohol; dimethyl sulfoxide (DMSO) and artificial saliva were used in regard to the possibility of using it as an simulation medium. For each packaging three independent variables (temperature and contact time) factorial design simulant was performed. Xenobiotics migration from epoxy resins was studied at three different temperatures (25°C, 65°C, and 121°C) and extraction time of 12h, 48h and 2 weeks. Such experimental design leads to 9 experiments for each food simulant as conditions for each experiment are obtained by combination of temperature and contact time levels. Each experiment was run in triplicate for acute toxicity and in duplicate for estrogen disruption potential determination. Multi-factor analysis of variation (MANOVA) was used to evaluate the effects of the three main factors solvent, temperature (temperature regime for cup), contact time and their interactions on the respected dependent variable (acute toxicity or estrogen disruption potential). From all stimulants studied the most toxic were can and tetrapak lining acetic acid extracts that are indication for significant migration of toxic compounds. This migration increased with increase of contact time and temperature and justified the hypothesis that food products with low pH values cause significant damage internal resin filling. Can lining extracts of all simulation medias excluding distilled water and artificial saliva proved to contain androgen agonists even at 25°C and extraction time of 12h. For tetrapak extracts significant endocrine potential for acetic acid, DMSO and saliva were detected.

Keywords: food packaging, extraction, migration, toxicity, biotest

Procedia PDF Downloads 155

Authors: Olfat Mohamed Hussien Yousef

Abstract:

Tamoxifen (TM) is a synthetic non-steroidal antiestrogen. It is one of the most effective drugs for treatment of estrogen-dependent cancer by binding to estrogen receptors, suppressing of epithelial proliferation and as a chemotherapeutic agent. Recently, more attention has been paid to the protective effects of natural antioxidants against toxicities induced by anti-cancer drugs involving free radical-mediated oxidative stress and tissue injury. Vitamin C is a potent antioxidant that has the ability to scavenge factors causing free radical formation in animals receiving tamoxifen. The present study aims at pinpointing the TM-induced histopathological and ultrastructural changes in the kidneys and to assess the possible chemoprotective role of vitamin C against such TM-induced microscopic changes. Thirty adult male CD-1 mice, 25-30 g in weight and 3 months old, were divided into three groups. The first group served as control. The second group received the therapeutic dose of TM at daily oral dose of 40 mg/kg body weight for 28 days. The third group received the therapeutic dose of vitamin C at a daily dose of 500 mg/kg body weight simultaneously with the therapeutic dose of TM used in group two for 28 days. Animals were sacrificed and kidney samples were obtained and processed for histological and ultrastructural examination. Histological changes induced by TM included damage of the renal corpuscles including obliteration of the subcapsular space, congestion of the glomerular blood capillaries, segmental mesangial cell proliferation with matrix expansion, capsular adhesions with the glomerular tuft especially at the urinary pole of the corpuscles. Moreover, some proximal and distal tubules suffered various degrees of degeneration in some lining cells. Haemorrhage and inflammatory cell infiltration were also observed in the intertubular spaces. Ultrastructural observations revealed damage of the parietal epithelium of Bowman’s capsule, fusion and destruction of the foot processes of podocytes and great increase of mesangial cells and mesangial matrix. The cells of the proximal convoluted tubules displayed marked destruction of the microvilli constituting the brush borders and degeneration of the mitochondria; besides, abundant lysosomes, numerous vacuoles and pyknotic nuclei were observed. The distal convoluted tubules displayed marked distruction of both the basal infolding and the mitochondria in some areas. Histological and ultrastructural results revealed that treatment of male mice with TM simultaneously with vitamin C led to apparent repair of the injured renal tissue. This might suggest that vitamin C (an antioxidant agent) can minimize the toxic effects of TM (an antiestrogen).

Keywords: tamoxifen, vitamin c, mammalian kidney, histology, ultrastructure

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Authors: Seyedeh Faranak Baniahmad, Soroor Yousefi

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Osteoporosis is a bone disease which increases the bone fracture risk, reduces the bone mineral density (BMD) and alters the amount and variety of proteins in bones. Antiresorptive therapy is one the most popular Osteoporosis treatment methods. In this method the bisphosphonates, hormones, calcitonin or the selective estrogen receptor modulators is replaced. In order to reduce undesirable effects and to increase the bioavailability of drug agents, the controlled drug delivery systems have been utilized. In current study, the controlled release of Alendronate from LDH-PCL with (0, 5, 10, 15 % wt. of LDH) was investigated. The results showed that the release of alendronate from the lamellar LDH incorporated into the PCL matrix is much slower than the release of alendronate from the PCL. Therefore such systems are very promising, in which the antiresorptive drug has to remain in the matrix for longer time and can be released in controlled manner.

Keywords: osteoporosis, alendronate, poly (ε–caprolactone), layered double hydroxide

Procedia PDF Downloads 349

Authors: A. H. Shaikat, M. B. Hossain, S. K. M. A. Islam, M. M. Hassan, S. A. Khan, A. K. M. Saifuddin, M. N. Islam, M. A. Hoque

Abstract:

A total of eighteen (18) sex reversed chickens with unusual phenotypic characteristics of male birds were identified over 2000 Hyline layer chickens at Motaher Poultry Farm, Ramu, Cox’s Bazar. Chickens were subdivided into two groups (case = 18, control = 20) based on the appearance of sex-reversed secondary sexual characteristics. Phenotypic traits of studied chickens were measured with farm management details. Hormone assay using ELISA, autopsy followed by gross examination of viscera was performed. The study found higher body weight (gm) (1579.3; 95% CI: 1561.7-1596.8), comb length (cm) (12.2; 11.5-12.8), comb width (cm) (7.9; 7.7-8.2), wattle length (cm) (4.9; 4.8-5.1) distinct spur, and shortened pubic bones distance, suggesting decrease oviposition in sex-reversed chickens. Testosterone concentration (ng/ml) (8.5; 6.4-10.6) was significantly higher (p<0.001) along with decrease estrogen (pg/ml) (5.1; 4.9-5.5) and progesterone concentration (pg/ml) (310.9; 289.4-332.5) in sex-reversed chickens. Mass abdominal fat deposition with atrophied ovary was found upon exploration of viscera.

Keywords: ovary, phenotypic traits, sex hormone, sex reversal

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