• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8395-8400
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• 2014

In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer death in the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate, these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. The present report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal and lobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors (age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety nine cases of breast tumors were recruited from the pathology department archive of King Abdulaziz University Hospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductal carcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59 (62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order. Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal and lobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 in Saudi female is different from that of Tunisian and Jordanian female populations and closer to the expression pattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found two IHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reported in other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation among Arabic female populations.

• Reproductive and Developmental Biology
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• v.35 no.1
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• pp.47-54
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• 2011

Endocrine disruptors bind to hormone receptors on sperm membrane, therefore spermatozoa are potentially a useful model for examining estrogenic activities of endocrine disruptors. The objective of this study was to compare the effects of two xenoestrogenic compounds [genistein (Gen) and 4-tert-octylphenol (OP)] to those of two steroids [estrogen ($E_2$) and progesterone ($P_4$)] on boar sperm % motility and motion kinematics of in vitro. Porcine spermatozoa were incubated with various concentrations ($0.001{\sim}100\;{\mu}M$) of each chemical for 15 or 30 min, and then assessed % motility and sperm motion kinematics using computer assisted sperm analyzer (CASA). Each chemical decreased sperm % motility, and OP decreased VSL and VAP compared with untreated control(p<0.05). $E_2$ stimulated the motion kinematic changes except VCL. Moreover, Gen had effects on VCL and VAP alterations after 30 min incubation. In summary, since all chemicals studied effectively altered sperm % motility and motion kinematics, it was concluded that porcine spermatozoa could be a useful model for in vitro screening of potential endocrine disruptors.

• Development and Reproduction
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• v.9 no.2
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• pp.85-93
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• 2005

Estrogens are known as the steroid hormones and essential regulators of developments, differentiations, and fertility in animals including humans. Recently, classic focus on estrogens which are considered as female hormone is changing in the whole field of reproductive endocrinology. Especially, interest in estrogen functions in male reproduction is increasing more and more, as numerous studies about the endocrine disruptors, interrupting the endocrine system, are being carried out. To understand exactly the function of estrogen in a male reproductive system, a summary for estrogen receptors upon developmental distributions in testis will be useful. In addition to the regulatory roles of estrogen in male, unexpected exposure to exogenous estrogens causes defects of differentiation of male reproductive system and an injury of spermatogenesis. Also, this review highlights the indicator of exogenous estrogens to perturb male fertility. These approaches would give tile practical information about estrogen roles in male development and reproduction.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.5019-5023
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• 2016

Background: In Mexico, breast cancer (BCa) is in first place regarding cancer mortality and has been established as a priority health issue. The incidence of metastasis from BCa is very high and presents as the principal mortality factor among women younger than 40 years of age. OBJECTIVE. To determine any associations between clinicopathological characteristics and metastasis in Mexican women under 40 years of age. Methods: During the 2010-2015 period, a total of 180 female BCa cases seen at the Navy General High Specialty Hospital, SEMAR, in Mexico City; we collected information on 20 patients with BCa younger than 40 years of age. Statistical analyses were conducted using the Kolmogorov-Smirnov, Students t, Fisher, Chi square, and Mantel-Haenszel tests. Results: The prevalence of women with BCa younger than the age of 40 years during the 2010-2015 period was 13.3%. We found a high frequency of obesity in of these cases (>75%); 100% of obese patients with a history of smoking presented with metastasis (p <0.05). In addition, the hormone phenotype was important; HER2-positive cases were 12 times more likely tto exhibit metastasis (p <0.05), while expression of estrogen and progesterone receptors appeared to be protective. Diabetes mellitus in combination with smoking was also a risk factor for development of metastasis (p <0.05). Conclusion: In this study, we obtained essential data regarding risk of metastasis in young breast cancer cases which could be useful for predicting disease evolution and treatment response.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.4
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• pp.275-281
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• 2000

Cholecystokinin (CCK) is a gastrointestinal hormone which plays an important role in satiety and gastric motility. It is also widely distributed throughout the central nervous system, where it appears to be involved in the central control of anxiety, feeding behavior and nociception. Two distinct CCK receptor types, $CCK_A$ and $CCK_B,$ have been found in the brain. Both CCK receptors coexist in the rat nucleus tractus solitarius (NTS), which is the primary center for the coordination of peripheral and central activities related to gastrointestinal, cardiovascular and respiratory functions. In order to study ionic actions of CCK on each type of receptor, we investigated the effects of CCK-8S on neurons located in the NTS of the rat using whole-cell patch-clamp recordings in brainstem slices. Application of CCK-8S, under current clamp, produced a membrane depolarization accompanied by action potential firing. This CCK-evoked excitation was dose-dependent $(10\;nM{\sim}10\;{\mu}M)$ and observed in more than 60% of NTS neurons. Under voltage clamp conditions, CCK-8S induced an inward current with a notably increased spontaneous excitatory synaptic activity. However, CCK-8S did not significantly change the amplitude of pharmacologically isolated and evoked EPSP(C)s. Using selective $CCK_A$ and $CCK_B$ receptor antagonists, we observed two different effects of CCK-8S, which suggest $CCK_A$ receptor-mediated inhibitory and $CCK_B$ receptor-mediated excitatory effects in the NTS. These results may help to explain the ability of CCK to modulate gastrointestinal and other reflex systems in the NTS.

• BMB Reports
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• v.53 no.3
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• pp.166-171
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• 2020

A chemical library comprising 2,354 drug-like compounds was screened using a transcription and replication-competent viruslike particle (trVLP) system implementing the whole Ebola virus (EBOV) life cycle. Dose-dependent inhibition of Ebola trVLP replication was induced by 15 hit compounds, which primarily target different types of G protein-coupled receptors (GPCRs). Based on the chemical structure, the compounds were divided into three groups, diphenylmethane derivatives, promazine derivatives and chemicals with no conserved skeletons. The third group included sertindole, raloxifene, and ibutamoren showing prominent antiviral effects in cells. They downregulated the expression of viral proteins, including the VP40 matrix protein and the envelope glycoprotein. They also reduced the amount of EBOV-derived tetracistronic minigenome RNA incorporated into progeny trVLPs in the culture supernatant. Particularly, ibutamoren, which is a known agonist of growth hormone secretagogue receptor (GHSR), showed the most promising antiviral activity with a 50% effective concentration of 0.2 μM, a 50% cytotoxic concentration of 42.4 μM, and a selectivity index of 222.8. Here, we suggest a strategy for development of anti-EBOV therapeutics by adopting GHSR agonists as hit compounds.

• Toxicological Research
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• v.20 no.3
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• pp.205-211
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• 2004

Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2005.11a
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• pp.31-43
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• 2005

Isoflavones are naturally occurring plant chemicals belonging to the 'phytoestrogen' class. The isoflavones are strikingly similar in chemical structure to natural estrogens. The phenolic ring is a key structural element of most compounds that bind to estrogen receptors. Dietary components that recently have received attention for their action as phytoestrogens are soy isoflavones. Soy products are the most significant dietary sources of isoflavones. Recently It is concerned clinical nutrition of isoflavone that is driven by reason of alternative sources of exogenous estrogen are constantly being needed. Estrogen therapy after the menopause offers protection from cardiovascular disease, reduces the extent of osteoporosis and relieves menopausal symptoms. Exogenous estrogen treatment is a fear of possible increased risk of developing breast cancer and because of side effects. Daily intake of soybean or soy food can affirmative effect to disease occurrence, that is based on mechanical investigation, experimental results of animals and human. Research into isoflavone is going on various field to relieve hormone - dependent disease such as cancer, menopausal symptom, cardiovascular disease and osteoporosis. Isoflavone is plenty in soybean meal, soy by-product, but only limited information is available on isoflavone efficacy into animal husbandry. Thus we conducted three experiments to investigate the effects of dietary isoflavone on productivities, antioxidative responses and bone metabolism in poultry. Dietary supplementation of isoflavone resulted in preventing the lipid oxidation of plasma and egg yolk. Dietary isoflavone improved bone development in egg-type growing chicks and broilers in terms of tibial strength. It was suggested that the proper use of feed additives such as isoflavone might provide means of improving antioxidative effect, skeletal strength, egg and eggshell quality.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6529-6532
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• 2013

Background: Breast cancer is mostly the disease of postmenopausal women but very young affected women are seen more than occasionally in developing countries. We reviewed our cases of very young breast cancer in order to help in better understanding of such cases. Materials and Methods: The records of patients 25 years of age or less who had been admitted for breast cancer surgery in the Cancer Institute of Tehran from 1979 to 2012 were reviewed and relevant data were extracted. Results: From 5,265 cases of breast cancer, 62 patients had 25 years of age or less. There were 55 cases of breast adenocarcinoma, all female. More than 78% of the patients had presented with a palpable mass, the family history was positive in 2% of cases, and about 94% of the histologies were invasive ductal carcinoma. Gestational breast cancer constituted 10% of the cancers; another 10%were bilateral. The median size of the tumors was 5.72 centimeters, 63.2% of them had axillary lymphatic involvement, and more than half were negative for hormone receptors. Conclusions: Our study shows an incidence of 1.17% for very young breast cancer and a 10% rate of bilaterality which probably warrants special guidelines for contralateral screening. Cancer stage and features were poor in comparison with breast cancer in all ages.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3185-3189
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• 2014

Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and $6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and $25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and $IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an $IC_{50}$ value of $32.0{\mu}M$; in contrast with lapatinib the $IC_{50}$ was $136.6{\mu}M$. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.