The Prevalence and Determinants of Vitamin D Status among Older Adults: Data from a Longitudinal Aging Study.

Background: Aging is identified as a risk factor for vitamin D deficiency (VDD) therefore this investigation was designed to determine the prevalence of VDD and its determinants in a sample of older adults. Methods: The data of this study were obtained from the baseline wave of the Longitudinal Aging Study (LAS). Demographic, past medical history, medication history, and smoking behavior were collected using an interview approach. The physical activity and nutritional status of the participants were assessed using a standard questionnaire. Anthropometric indices were measured according to a standard protocol then body mass index (BMI) was calculated. Serum vitamin D and calcium levels were measured by autoanalyzers. Univariate and multiple logistic regression models were applied to detect the associated factors with VDD. Results: Mean age of the participants was 71.82 (SD = 7.63) years. A total of 1319 people participated in our study, and 51.16% (n = 688) were female. A total of 8.42% (n = 111) of the participants had VDD and 17.06% of them (n = 225) had insufficient vitamin D levels. In the multivariable logistic regression model, the age group of 70-79 years in comparison with the age group of 60-69 years had a 43% less chance of VDD. Furthermore, being overweight (OR = 0.36, P = 0.01) and obese (OR = 0.35, P = 0.02), and taking vitamin D supplements (OR = 0.31, P = 0.04) were significantly associated with VDD. Conclusions: Our results showed that 25% of older adults had vitamin D deficiency or insufficiency. In addition, some modifiable lifestyle factors were associated with VDD. Given that, old age is considered a risk factor for VDD. Therefore, detection and improvement of VDD may be a preventive measure in at-risk subjects.

Artificial neural networks (ANNs) for modeling efficient factors in predicting pap smear screening behavior change stage.

Background and objectives: Cervical cancer is ranked as the third most prevalent cancer that affects women all over the world and Pap smear seems to be the single most critical intervention to prevent cervical cancer. In the present study, the effects of demographic factors (age, education level, job, income level, marriage age, pregnancy, child number, breastfeeding, and menopause), insurance type, disease history and screening (sono and mammography, breast problem) and cancer information on Pap smear screening and behavior stage of change were investigated and modeled using an artificial neural network model (ANN). Materials and methods: Data were collected from a descriptive-analytical cross-sectional study. This research was conducted on 1898 female employees of governmental agencies of Birjand, a city located in the east of Iran. The questionnaire consisted of four parts (socioeconomic, reproductive characteristics, information about cervical cancer screening, and stage of change for cervical cancer screening). Multilayer feed-forward back-propagation neural networks were used to detect the patterns between variables using a neural network with 14 inputs and one output. To find out the neural network with the minimum sum of squared errors, we evaluated the performance of all neural networks using varying algorithms and numbers of neurons in the hidden layer. For this purpose, the data collected from 1898 women were analyzed using SPSS-22 software. Results: In the optimal ANN model, the variables of marriage age, age, breastfeeding, and the number of children were identified as the most significant factors with 18.3, 16.3, 7.3, and 7.3 percent, respectively, whereas the history of cancer, job, pregnancy, and menopause had importance of lower than 5 percent. Conclusion: Our findings showed that among many associated variables, the marriage age, age, breastfeeding, and the number of children were the most important predictors for the behavioral stage of change. Thus, it seems, focusing on these factors may lead to the adoption of effective programs and policies to improve cervical cancer screening practices in women.

Effects of the COVID-19 pandemic on lifestyle among Iranian population: A multicenter cross-sectional study.

Background: Quarantine, an unpleasant experience, was implemented in many countries to limit the spread of Coronavirus disease 2019 (COVID-19), which it could associated whit lifestyle changes. The present study aimed to determine the changes in Iranian's lifestyle during COVID-19 pandemic. Materials and Methods: In the present cross-sectional study, 2710 Iranian people completed an online researcher-made questionnaire asking lifestyle regarding COVID-19, which includes five sections about physical activity, stress and anxiety, nutrition habit, sleep disorders, and interpersonal relationship in addition to demographic data from January to February 2021, using the multistage cluster sampling method. Results: The participants' mean age was 33.78 ± 11.50 years and 68.3% of them were female. Traveling, sightseeing, and family visits have been eliminated from 91%, 83.5%, and 77.5% of participants' lives, respectively. There were increase in stress level (P < 0.001), weight of the participants (P < 0.001), sleep problems (P < 0.001), and healthier foods (P < 0.001) but decrease in interpersonal communication (P < 0.001) and the amount of physical activity (P < 0.001). Conclusion: In summary, this study indicates some changes in lifestyle of Iranian people, including changes in some eating practices, physical activity, social communication, and sleeping habits during the pandemic. However, as the COVID-19 pandemic is ongoing, a comprehensive understanding of these behaviors and habits can help develop interventions to mitigate the negative lifestyle behaviors during COVID-19 pandemic.

Crosstalk between obesity and cancer: a role for adipokines.

Adipose tissue is a complex organ that is increasingly being recognised as the largest endocrine organ in the body. Adipocytes among multiple cell types of adipose tissue can secrete a variety of adipokines, which are involved in signalling pathways and these can be changed by obesity and cancer. There are proposed mechanisms to link obesity/adiposity to cancer development including adipocytokine dysregulation. Among these adipokines, leptin acts through multiple pathways including the STAT3, MAPK, and PI3K pathways involved in cell growth. Adiponectin has the opposite action from leptin in tumour growth partly because of increased apoptotic responses of p53 and Bax. Visfatin increases cancer cell proliferation through ERK1/2, PI3K/AKT, and p38 which are stimulated by proinflammatory cytokines. Omentin through the PI3K/Akt-Nos pathway is involved in cancer-tumour development. Apelin might be involved through angiogenesis in tumour progressions. PAI-1 via its anti-fibrinolytic activity on cell adhesion and uPA/uPAR activity influence cancer cell growth.

Prevalence of anemia and associated factors among the elderly population in South Khorasan, Birjand, 2019.

Background: Anemia is a multifactorial and common public health problem in geriatric age groups, especially in developing countries. Therefore, this study was designed to study the prevalence of anemia and associated factors among the elderly population in Birjand, Iran, in 2019. Methods: This was a cross-sectional approach to the baseline data of the Birjand longitudinal aging study (BLAS) in which 1396 people aged ≥ 60 years were screened for the presence of anemia based on the World Health Organization (WHO) criteria. For each participant, a standard questionnaire was administered. Furthermore, the height, weight, and body mass index (BMI) were calculated. Blood samples were obtained from each participant for hematological examination. Hemoglobin, hematocrit, and other indices of cell blood count were measured using an automatic cell counter. The prevalence rates were estimated using survey analysis with the weight of Birjand county older population. Univariate and multivariable logistic regression analyses were applied to detect the associated factor with anemia. Results: The mean age of the participants was 69.73±7.66 years. The crude prevalence of anemia was 11.10%, and the age-standardized prevalence based on the standard WHO population 2000-2025 was equal to 16.78% (12.81%-21.66%) (15.95% [10.41%-23.69%] in women and 17.32% (12.65%-23.25%) in men. Mild and normocytic anemia were the predominant types. The mean hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were lower in women than in men and the mean platelet count in women was higher (p<0.001). In the final multivariate logistic regression model, only age groups, BMI, fish consumption, and chronic kidney disease (CKD) were related to anemia. Conclusion: In conclusion, our findings showed the association of anemia with some risk factors and diseases. Anemia in geriatric age groups is often underdiagnosed; hence, identification of subgroups at risk for anemia and its associated risk factors in geriatric groups has a paramount importance in preventing adverse outcomes.

Crossroad between Obesity and Gastrointestinal Cancers: A Review of Molecular Mechanisms and Interventions.

The burden of gastrointestinal (GI) cancer is increasing worldwide, and in the past decade, cancer had entered the list of chronic debilitating diseases whose risk is substantially increased by hypernutrition. Obesity may increase the risk of cancer by the imbalance of various mechanisms including insulin and insulin-like growth factor1 (IGF-I) signaling, systemic inflammation, immune dysregulation, tumor angiogenesis, adipokines secretion, and intestinal microbiota that usually act interdependently. An increased understanding of the mechanisms underlying obesity-GI cancer link can provide multiple opportunities for cancer prevention. This review discusses various mechanisms involved molecular mechanisms linking obesity with GI cancers including esophagus, stomach, colorectal and hepatocellular. Furthermore, an optional intervention such as diet restriction and exercise is described, which may be preventive or therapeutic in GI cancer.

Breast cancer screening behavior and its associated factors in female employees in South Khorasan.

BACKGROUND: Breast cancer is a preventable disease, using three secondary preventive methods of mammography, clinical breast examination (CBE), and breast self-examination (BSE) that can lead to early detection of breast cancer. This study was designed to assess breast cancer screening behavior and its associated factors in females employed in South Khorasan. MATERIALS AND METHODS: In this analytic-descriptive study, 2256 female personnel of governmental organizations were investigated in Birjand city in 2016-2017. The data collection tool was a three-part questionnaire: sociodemographic characteristics, knowledge about breast cancer screening methods plus women's performance, and stage of change regarding screening behaviors of mammography, CBE, and BSE. The data were analyzed by SPSS 16 and one-way analysis variance, Tukey's post hoc, and multiple logistic regression model statistical tests. RESULTS: The mean ± standard deviation score of knowledge of the women was 3.45 ± 1.5. There was a significant difference of the mean score of knowledge between the single and married (P = 0.03) and age group (P = 0.04). The stage action of mammography, CBE, and BSE was 6.8%, 12.3%, and 16.8%, respectively. Logistic regression model showed that variables such as age and family history of breast cancer were highly significant related to mammography and also CBE. Knowledge was also highly significant in mammography, CBE, and BSE. Education level in CBE, marital status in BSE and mammography, and job in BSE were also significant (P < 0.001). CONCLUSIONS: This study reveals insufficient knowledge of female workers about breast cancer and the negative influence of low knowledge on the practice of breast cancer screening behavior. Therefore, the establishment and maintenance of regular educational courses for female employees is essential.

Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic.

The industrial activities of the last century have caused massive increases in human exposure to heavy metals. Mercury, lead, chromium, cadmium, and arsenic have been the most common heavy metals that induced human poisonings. Here, we reviewed the mechanistic action of these heavy metals according to the available animal and human studies. Acute or chronic poisonings may occur following exposure through water, air, and food. Bioaccumulation of these heavy metals leads to a diversity of toxic effects on a variety of body tissues and organs. Heavy metals disrupt cellular events including growth, proliferation, differentiation, damage-repairing processes, and apoptosis. Comparison of the mechanisms of action reveals similar pathways for these metals to induce toxicity including ROS generation, weakening of the antioxidant defense, enzyme inactivation, and oxidative stress. On the other hand, some of them have selective binding to specific macromolecules. The interaction of lead with aminolevulinic acid dehydratase and ferrochelatase is within this context. Reactions of other heavy metals with certain proteins were discussed as well. Some toxic metals including chromium, cadmium, and arsenic cause genomic instability. Defects in DNA repair following the induction of oxidative stress and DNA damage by the three metals have been considered as the cause of their carcinogenicity. Even with the current knowledge of hazards of heavy metals, the incidence of poisoning remains considerable and requires preventive and effective treatment. The application of chelation therapy for the management of metal poisoning could be another aspect of heavy metals to be reviewed in the future.

The relation of visfatin with nausea and vomiting in the pregnancy.

BACKGROUND: The etiology of nausea and vomiting during pregnancy (NVP) is unclear and appears multifactorial. It has been shown that the physiological changes associated with NVP include changes in the levels of adipocytokines. Therefore, we investigated the association of nausea and vomiting during pregnancy with visfatin, ß-human chorionic gonadotropin (ßHCG), and perceived stress. MATERIALS AND METHODS: In this cross-sectional study, 100 nulliparous pregnant women aged 18-45 years were evaluated. Participants completed two questionnaires including the Index of Nausea, Vomiting, and Retching (INVR) and Perceived Stress Scale (PSS) in the three trimesters of pregnancy. They also referred to the laboratory to conduct the biochemical examinations including serum visfatin and ßHCG levels in three trimesters. The obtained data were analyzed by SPSS 16 using statistical repeated-measures analysis of variance, Friedman, Bonferroni, and Wilcoxon post hoc tests. Marginal model (method generalized estimating equation [GEE]) was performed to assess the predictors of the INVR in the participants. RESULTS: INVR, PSS, visfatin, and ßHCG levels significantly decreased from the first trimester to the third trimester of pregnancy (P ≤ 0.001). As a result of simple marginal model (GEE method), visfatin was predicted log ßHCG (P = 0.035). Furthermore, the multiple marginal model revealed that the two predictors of ßHCG (P = 0.01) and PSS (P ≤ 0.001) were positively correlated with the INVR. Furthermore, visfatin had an indirect positive effect on INVR. CONCLUSION: The present study showed that visfatin can be indirectly related with nausea and vomiting throughout pregnancy. Furthermore, it seems that fluctuations in visfatin levels are independent of weight gain during pregnancy.

The effect of methadone on blood glucose, lipids and glucose-modulating hormones in methadone-dependent Wistar rats.

A growing body of evidence indicates that opioids regulate mechanisms activated during the stress response. This study was aimed to investigate the effect of methadone dependency on blood glucose, lipids and glucose-modulating hormones in male and female Wistar rats.This study was performed on 40 Wistar rats weighing 150-350 g, in four methadone exposure and control groups of both males and females. All rats were weighed at the beginning and end of the study and their fasting blood glucose was measured using a glucometer. In order to induce addiction, methadone was injected intraperitoneal for 10 consecutive days at 5 mg/kg dose. The control group received the same volume of only normal saline. At the end of the study, the rats were sacrificed and their blood serum collected to measure cortisol, glucagon, adrenaline and lipid profile levels.There was a significant decrease in the mean final blood glucose of methadone-treated versus control male rats (p = 0.02). There was no significant glucose difference, however, in female rats. Furthermore, a decrease in the mean serum levels of triglyceride, cortisol, and adrenaline occurred in male rats of methadone-dependent compared with control animals, but there was no significant difference in these values in female rats. Our results showed that methadone significantly reduced serum glucose as well as triglyceride levels only in male rats, this being associated with a reduction in the level of counter-regulating hormones of carbohydrate metabolism. Changes in lipid profiles, however, occurred independently of gender.

Association of serum levels of vascular endothelial growth factor and thrombospondin-1 to body mass index in polycystic ovary syndrome: a case-control study.

PURPOSE: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder that is characterized by disturbances in ovarian blood flow and angiogenesis. The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) serum levels with the body mass index (BMI) in patients with PCOS compared with healthy subjects. METHODS: The study was conducted with 80 subjects in 3 PCOS groups, including normal weight, overweight, and obese PCOS groups, and a control group of healthy subjects (n=20). The participants in all groups completed a questionnaire comprising sociodemographic and obstetric questions. The PCOS diagnosis in the study subjects was confirmed based on the Rotterdam criteria, BMI was determined according to the World Health Organization guidelines, and the lipid accumulation product index was calculated for all groups. Venous blood samples were collected from all participants after fasting to measure the serum levels of fasting blood glucose (FBG), lipids, insulin, VEGF, TSP-1, and leptin. RESULTS: Our findings showed that the serum VEGF level was significantly higher in the normal BMI PCOS group than that in the control group (P=0.03), and the TSP-1 level was significantly lower in the obese PCOS group than that in the control group (P=0.04). CONCLUSIONS: Our study demonstrated that alterations in VEGF and TSP-1 concentrations are dependent on BMI. Because abnormal ovarian angiogenesis is considered to be the main feature of PCOS, the study of ovarian angiogenic imbalance is proposed as a new tool for PCOS diagnosis and management.

Metabolic Syndrome and the Risk of Gastrointestinal Cancer: a Case-Control Study

Background: The metabolic syndrome and its concomitant complications are a major public health challenge worldwide. Growing evidence implies associations with cancer development and progression. Since there has been no report on this subject in South Khorasan, we studied metabolic syndrome components in gastrointestinal (GI) cancer patients for comparison with a control group in this province. Materials and methods: This case-control study was performed on 68 patients with histopathologically proven gastrointestinal cancers, referred to the oncology center in Birjand city (capital of South Khorasan province, Iran) in 2016-2017, and 100 control subjects without disease. Patients and control subjects completed a researcher-made questionnaire covering demographic characteristics, physical activities and food intake. Also, blood samples were obtained from both patients and control subjects after overnight fast. Anthropometric measurements of height, weight, body mass index, waist circumference and blood pressure were additionally performed. Results: Significant differences in the levels of blood glucose and serum HDL were noted between the two groups (P≤0.001). Also, the percentage of pre-diabetic and diabetic patients in the case group was higher than the control group (17.6 and 16.2% vs. 10.3 and 2.9%) (P=0.009). Multiple logistic regression showed that the risk of gastrointestinal cancer in people with high blood glucose was 3.35 times that in those with normal blood glucose (OR3.35, 95%CI,1.41-7.94; P=0.006) , 2.37 times higher in subjects with lower HDL (OR 2.37, 95%CI,1.18- 4.78), 10.4 times higher in overweight people (OR10.4, 95%CI,2.23-48.5) and 4.3 times higher in individuals with an opium addiction(OR4.3, 95%CI, 1.6-11.5) than those without. The mean consumption of fish (P=0.03) and vegetables and fruits (P=0.027) in the case group was significantly lower than in the control group. Conclusion: Emerging evidence indicates that the metabolic syndrome or its individual components may be important in the etiology and progression of GI cancer. Research to work toward preventing cancers should thus focus on nutritional and lifestyle modifications which may alleviate the metabolic syndrome.

From obesity to cancer: a review on proposed mechanisms.

Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity-cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment. We review here the epidemiological and experimental evidences for the association between obesity and cancer. Specifically, we discuss potential mechanisms focusing how dysfunctional angiogenesis, chronic inflammation, interaction of proinflammatory cytokines, endocrine hormones, and adipokines including leptin, adiponectin insulin, growth factors, estrogen, and progesterone and strikingly, cell metabolism alteration in obesity participate in tumor development and progression, resistance to chemotherapy, and targeted therapies such as antiangiogenic and immune therapies.

Serum inflammatory markers in obese mice: Effect of ghrelin.

BACKGROUND: Ghrelin is involved in modulation of food intake and energy homeostasis; however, it may play a role in cardiovascular system and atherosclerosis process. This study aimed to investigate the effect of ghrelin on serum inflammatory markers in control and obese mice. MATERIALS AND METHODS: Ghrelin (100 mg/kg/day, twice daily) was administered interaperitoneally to control and diet-induced obese mice. After 10 days, blood samples were taken. RESULTS: Results showed that administration of ghrelin did not change serum hsCRP level; however, it reduced serum IL-6 concentration in obese mice (P < 0.05). CONCLUSION: It seems that the exact role and mechanism of ghrelin in prevention or treatment of atherosclerosis needs more studies.

"Ziziphus jujuba": A red fruit with promising anticancer activities.

Ziziphus jujuba Mill. (Z. jujuba) is a traditional herb with a long history of use for nutrition and the treatment of a broad spectrum of diseases. It grows mostly in South and East Asia, as well as in Australia and Europe. Mounting evidence shows the health benefits of Z. jujuba, including anticancer, anti-inflammation, antiobesity, antioxidant, and hepato- and gastrointestinal protective properties, which are due to its bioactive compounds. Chemotherapy, such as with cis-diamminedichloroplatinium (CDDP, cisplatin) and its derivatives, is widely used in cancer treatment. It is an effective treatment for human cancers, including ovarian cancer; however, drug resistance is a major obstacle to successful treatment. A better understanding of the mechanisms and strategies for overcoming chemoresistance can greatly improve therapeutic outcomes for patients. In this review article, the bioactive compounds present in Z. jujuba are explained. The high prevalence of many different cancers worldwide has recently attracted the attention of many researchers. This is why our research group focused on studying the anticancer activity of Z. jujuba as well as its impact on chemoresistance both in vivo and in vitro. We hope that these studies can lead to a promising future for cancer patients.

Leptin and its cardiovascular effects: Focus on angiogenesis.

Leptin is an endocrine hormone synthesized by adipocytes. It plays a key role in the energy homeostasis in central and peripheral tissues and has additional roles are attributed to it, such as the regulation of reproduction, immune function, bone homeostasis, and angiogenesis. The plasma concentration of leptin significantly increases in obese individuals. In the present review, we give an introduction concerning leptin, its receptors, signaling pathways, and its effect on cardiovascular system, especially on angiogenesis.

Ghrelin Does not Alter Aortic Intima-Media Thickness and Adipose Tissue Characteristics in Control and Obese Mice.

OBJECTIVE(S): Atherosclerosis is a chronic immune-inflammatory disease that generally leads to ischemic heart disease. Ghrelin has several modulatory effects on cardiovascular system. In this study, we investigated the effect of ghrelin on aortic intima-media thickness, size and the number of adipocyte cells in obese and control mice. MATERIALS AND METHODS: This study was conducted on 24 male C57BL/6 mice. The animals were divided into four groups: control, obese (received high fat diet), control+ghrelin (injected with 100 µg/Kg subcutaneously, bid) and obese+ghrelin (n=6 each). After 10 days, animals were sacrificed and epididymal adipose tissue and thoracic aortae were removed. Adipocyte cell number, size and aortic intima-media thickness were evaluated. RESULTS: Ghrelin did not change adipocyte cell number and size and aortic intima-media thickness in obese and control mice. In this study, high fat diet significantly decreased the number of adipocyte cells while increased their size (P<0.05). Ghrelin administration had no significant effect on adipocyte cell number and size in obese and control groups (P >0.05). In addition, it could not alter aortic intima-media thickness in both groups. CONCLUSION: Although ghrelin has several cardiovascular effects, it seems that it could not alter the size and number of adipocyte cells and aortic intima-media thickness in diet-induced obese mice.

The relationship between inflammatory markers, angiogenesis, and obesity.

Obesity is recognized as a chronic low grade and systemic inflammatory disease. Angiogenesis is critical for adipose tissue expansion. Several evidences have demonstrated that angiogenesis sustains inflammation by preparing oxygen and nutrients for inflammatory cells and inflammation in turn can cause insulin resistance, type 2 diabetes, and cardiovascular disease. The understanding of mechanisms of obesity especially main roles of inflammation and angiogenesis in fat mass expansion can lead to therapeutic approaches in growing field of obesity and its related disorders. In this review, we studied the relationship between obesity, angiogenesis, and inflammation.

Ghrelin does not modulate angiogenesis in matrigel plug in normal and diet-induced obese mice.

BACKGROUND: The reciprocal interaction between adipocytes and angiogenesis is considered as an essential component in the development and expansion of adipose tissue. The aim of this study was to evaluate the effect of ghrelin on angiogenic response using in vivo angiogenesis assay of matrigel plug and its correlation with serum leptin levels in normal and diet-induced obese mice. MATERIALS AND METHODS: This experimental study has been done on 24 male C57BL/6 mice which were randomly divided into four groups: Normal diet (ND) or control, ND + ghrelin, high-fat-diet (HFD) or obese and HFD + ghrelin (n = 6/group). Obese and control groups received HFD or standard diet for 14 weeks. Then, growth factor reduced matrigel plug (500 µl) containing bFGF (basic fibroblast growth factor; 100 ng) with or without ghrelin (100 µg/kg) was injected subcutaneously in the mid-ventral abdominal region of each mice. After 10 days, blood samples were taken and matrigel plugs were removed under anesthesia and angiogenic response was assessed by immunohisochemical staining. RESULTS: HFD significantly increased angiogenesis in matrigel plug as expressed as the number of CD31-positive cells than standard diet (43 ± 5 vs. 13 ± 2.5 CD31(+) cells/field). Ghrelin did not alter angiogenesis in matrigel plug in both obese and control groups. There was a strong positive correlation between the number of CD31-positive cells and serum leptin concentration (r = 0.91). CONCLUSION: Leptin as an angiogenic factor has a positive correlation with angiogenesis in matrigel plug model of angiogenesis and ghrelin could not alter angiogenesis.

Effect of DAPT, a gamma secretase inhibitor, on tumor angiogenesis in control mice.

BACKGROUND: Notch signaling is a key factor for angiogenesis in physiological and pathological condition and γ-secretase is the regulator of Notch signaling. The main goal of this study was to assess the effect of (N-[N-(3,5-Diflurophenaacetyl-L-alanyl)]-S-phenylglycine t-Butyl Ester) DAPT, a γ-secretase inhibitor, on serum angiogenic biomarkers, and tumor angiogenesis in control mice. MATERIALS AND METHODS: Tumor was induced by inoculation of colon adenocarcinoma cells (CT26) in 12 male Balb/C mice. When tumors size is reached to a 350 ± 50 mm(3), the animals were randomly divided into two groups: control and DAPT (n = 6/group). DAPT was injected subcutaneously 10 mg/kg/day. After 14 days, blood samples were taken and the tumors were harvested for immunohistochemical staining. RESULTS: Administration of DAPT significantly increased serum nitric oxide concentration and reduced vascular endothelial growth factor receptors-1 (VEGFR1) concentration without changes on serum VEGF concentration. DAPT reduced tumor vascular density in control mice (280.6 ± 81 vs. 386 ± 59.9 CD31 positive cells/mm(2)), although, it was not statistically significant. CONCLUSION: It seems that γ-secretase inhibitors can be considered for treatment of disorders with abnormal angiogenesis such as tumor angiogenesis.