Trends of Breast Cancer Incidence in Iran During 2004-2008: A Bayesian Space-time Model

Jafari-Koshki, Tohid,Schmid, Volker Johann,Mahaki, Behzad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Background: Breast cancer is the most frequently diagnosed cancer in women and estimating its relative risks and trends of incidence at the area-level is helpful for health policy makers. However, traditional methods of estimation which do not take spatial heterogeneity into account suffer from drawbacks and their results may be misleading, as the estimated maps of incidence vary dramatically in neighboring areas. Spatial methods have been proposed to overcome drawbacks of traditional methods by including spatial sources of variation in the model to produce smoother maps. Materials and Methods: In this study we analyzed the breast cancer data in Iran during 2004-2008. We used a method proposed to cover spatial and temporal effects simultaneously and their interactions to study trends of breast cancer incidence in Iran. Results: The results agree with previous studies but provide new information about two main issues regarding the trend of breast cancer in provinces of Iran. First, this model discovered provinces with high relative risks of breast cancer during the 5 years of the study. Second, new information was provided with respect to overall trend trends o. East-Azerbaijan, Golestan, North-Khorasan, and Khorasan-Razavi had the highest increases in rates of breast cancer incidence whilst Tehran, Isfahan, and Yazd had the highest incidence rates during 2004-2008. Conclusions: Using spatial methods can provide more accurate and detailed information about the incidence or prevalence of a disease. These models can specify provinces with different health priorities in terms of needs for therapy and drugs or demands for efficient education, screening, and preventive policy into action.

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Nejati-Koshki, Kazem,Akbarzadeh, Abolfazl,Pourhasan-Moghaddam, Mohammad,Abhari, Alireza,Dariushnejad, Hassan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

Exploring Factors Related to Metastasis Free Survival in Breast Cancer Patients Using Bayesian Cure Models

Jafari-Koshki, Tohid,Mansourian, Marjan,Mokarian, Fariborz Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: Breast cancer is a fatal disease and the most frequently diagnosed cancer in women with an increasing pattern worldwide. The burden is mostly attributed to metastatic cancers that occur in one-third of patients and the treatments are palliative. It is of great interest to determine factors affecting time from cancer diagnosis to secondary metastasis. Materials and Methods: Cure rate models assume a Poisson distribution for the number of unobservable metastatic-component cells that are completely deleted from the non-metastasis patient body but some may remain and result in metastasis. Time to metastasis is defined as a function of the number of these cells and the time for each cell to develop a detectable sign of metastasis. Covariates are introduced to the model via the rate of metastatic-component cells. We used non-mixture cure rate models with Weibull and log-logistic distributions in a Bayesian setting to assess the relationship between metastasis free survival and covariates. Results: The median of metastasis free survival was 76.9 months. Various models showed that from covariates in the study, lymph node involvement ratio and being progesterone receptor positive were significant, with an adverse and a beneficial effect on metastasis free survival, respectively. The estimated fraction of patients cured from metastasis was almost 48%. The Weibull model had a slightly better performance than log-logistic. Conclusions: Cure rate models are popular in survival studies and outperform other models under certain conditions. We explored the prognostic factors of metastatic breast cancer from a different viewpoint. In this study, metastasis sites were analyzed all together. Conducting similar studies in a larger sample of cancer patients as well as evaluating the prognostic value of covariates in metastasis to each site separately are recommended.

Curcumin and Silibinin Inhibit Telomerase Expression in T47D Human Breast Cancer Cells

Nasiri, Marzieh,Zarghami, Nosratollah,Koshki, Kazem Nejati,Mollazadeh, Mahdieh,Moghaddam, Mohammad Pourhassan,Yamchi, Mohammad Rahmati,Esfahlan, Rana Jahanban,Barkhordari, Amin,Alibakhshi, Abbas Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Background: Telomerase has been considered as an attractive molecular target for breast cancer therapy. The main objective of this work is to assess the inhibitory effects of silibinin and curcumin, two herbal substances, on telomerase gene expression in breast cancer cells. Materials and Methods: For determination of cell viability tetrazolium-based assays were conducted after 24, 48, and 72 h exposure times and expression of human telomerase reverse transcriptase gene was measured with real-time PCR. Results: Each compound exerted cytotoxic effects on T47D cells and inhibited telomerase gene expression, both in a time-and dose-dependent manner. The mixture of curcumin and silibinin showed relatively more inhibitory effect on growth of T47D cells and hTERT gene expression as compared with either agent alone. Conclusions: These findings suggest that cell viability along with hTERT gene expression in breast cancer cells could be reduced by curcumin and silibinin.

Application of Bayesian Multilevel Space-Time Models to Study Relative Risk of Esophageal Cancer in Iran 2005-2007 at a County Level

Rastaghi, Sedigheh,Jafari-Koshki, Tohid,Mahaki, Behzad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Reported age standardized incidence rates for esophageal cancer in Iran are 0.88 and 6.15 for females and males, at fifth and the eighth ranks, respectively, of cancers overall. The present study aimed to map relative risk using more realistic and less problematic methods than common estimators. Materials and Methods: In this ecological investigation, the studied population consisted of all esophageal cancer patients in Iran from 2005 to 2007. The Bayesian multilevel space-time model with three levels of county, province, and time was used to measure the relative risk of esophageal cancer. Analyses were conducted using R package INLA. Results: The total number of registered patients was 7,160. According to the results, the three-level model with adjustment for risk factors of physical activity and smoking had the best fit among all models. The overall temporal trend was significantly increasing. At county level, Ahar, Marand, Salmas, Bojnoord, Saghez, Sarakhs, Shahroud and Torbatejam had the highest relative risks. Physical activity was found to have significant direct association with risk of developing esophageal cancer. Conclusions: Given to great variation across geographical areas, many different factors affect the incidence of esophageal cancer. Conducting further studies at the individual level in areas with high incidence could provide more detailed information on risk factors of esophageal cancer.

Area-to-Area Poisson Kriging and Spatial Bayesian Analysis in Mapping of Gastric Cancer Incidence in Iran

Asmarian, Naeimehossadat,Jafari-Koshki, Tohid,Soleimani, Ali,Ayatollahi, Seyyed Mohammad Taghi Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.10

Background: In many countries gastric cancer has the highest incidence among the gastrointestinal cancers and is the second most common cancer in Iran. The aim of this study was to identify and map high risk gastric cancer regions at the county-level in Iran. Methods: In this study we analyzed gastric cancer data for Iran in the years 2003-2010. Area-to-area Poisson kriging and Besag, York and Mollie (BYM) spatial models were applied to smoothing the standardized incidence ratios of gastric cancer for the 373 counties surveyed in this study. The two methods were compared in term of accuracy and precision in identifying high risk regions. Result: The highest smoothed standardized incidence rate (SIR) according to area-to-area Poisson kriging was in Meshkinshahr county in Ardabil province in north-western Iran (2.4,SD=0.05), while the highest smoothed standardized incidence rate (SIR) according to the BYM model was in Ardabil, the capital of that province (2.9,SD=0.09). Conclusion: Both methods of mapping, ATA Poisson kriging and BYM, showed the gastric cancer incidence rate to be highest in north and north-west Iran. However, area-to-area Poisson kriging was more precise than the BYM model and required less smoothing. According to the results obtained, preventive measures and treatment programs should be focused on particular counties of Iran.

Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer

Zohre, Sadeghi,Kazem, Nejati-Koshki,Abolfazl, Akbarzadeh,Mohammad, Rahmati-Yamchi,Aliakbar, Movassaghpour,Effat, Alizadeh,Zahra, Davoudi,Hassan, Dariushnejad,Nosratollah, Zarghami Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-like factor 4 (klf4) is a zinc finger-containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. Aims: In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Results: Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Conclusions: Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.

PAMAM Dendrimers Augment Inhibitory Effects of Curcumin on Cancer Cell Proliferation: Possible Inhibition of Telomerase

Mollazade, Mahdie,Nejati-Koshki, Kazem,Akbarzadeh, Abolfazl,Zarghami, Nosratollah,Nasiri, Marzieh,Jahanban-Esfahlan, Rana,Alibakhshi, Abbas Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Despite numerous useful anticancer properties of curcumin, its utility is limited due to its hydrophobic structure. In this study, we investigated the comparative antiproliferative effect of PAMAM encapsulating curcumin with naked curcumin on the T47D breast cancer cell line. Materials and Methods: Cytotoxic effects of PAMAM dendrimers encapsulating curcumin and curcumin alone were investigated by MTT assay. After treating cells with different concentrations of both curcumin alone and curcumin encapsulated for 24h, telomerase activity was determined by TRAP assay. Results: While PAMAM dendrimers encapsulating curcumin had no cytotoxicity on cancer cells, they decreased the $IC_{50}$ for proliferation and also increased the inhibitory effect on telomerase activity. Conclusions: Considering the non-toxicity in addition to effectiveness for enhancing curcumin anticancer properties, dendrimers could be considered good therapeutic vehicles for this hydrophobic agent.

Inhibitory Effects of β-Cyclodextrin-Helenalin Complexes on H-TERT Gene Expression in the T47D Breast Cancer Cell Line - Results of Real Time Quantitative PCR

Ghasemali, Samaneh,Nejati-Koshki, Kazem,Akbarzadeh, Abolfazl,Tafsiri, Elham,Zarghami, Nosratollah,Rahmati-Yamchi, Mohamad,Alizadeh, Effat,Barkhordari, Amin,Tozihi, Majid,Kordi, Shirafkan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Nowadays, the encapsulation of cytotoxic chemotherapeutic agents is attracting interest as a method for drug delivery. We hypothesized that the efficiency of helenalin might be maximized by encapsulation in ${\beta}$-cyclodextrin nanoparticles. Helenalin, with a hydrophobic structure obtained from flowers of Arnica chamissonis and Arnica Montana, has anti-cancer and anti-inflammatory activity but low water solubility and bioavailability. ${\beta}$-Cyclodextrin (${\beta}$-CD) is a cyclic oligosaccharide comprising seven D-glucopyranoside units, linked through 1,4-glycosidic bonds. Materials and Methods: To test our hypothesis, we prepared ${\beta}$-cyclodextrin-helenalin complexes to determine their inhibitory effects on telomerase gene expression by real-time polymerase chain reaction (q-PCR) and cytotoxic effects by colorimetric cell viability (MTT) assay. Results: MTT assay showed that not only ${\beta}$-cyclodextrin has no cytotoxic effect on its own but also it demonstrated that ${\beta}$-cyclodextrin-helenalin complexes inhibited the growth of the T47D breast cancer cell line in a time and dose-dependent manner. Our q-PCR results showed that the expression of telomerase gene was effectively reduced as the concentration of ${\beta}$-cyclodextrin-helenalin complexes increased. Conclusions: ${\beta}$-Cyclodextrin-helenalin complexes exerted cytotoxic effects on T47D cells through down-regulation of telomerase expression and by enhancing Helenalin uptake by cells. Therefore, ${\beta}$-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

Investigating the Incidence of Prostate Cancer in Iran 2005-2008 using Bayesian Spatial Ecological Regression Models

Haddad-Khoshkar, Ahmad,Koshki, TohidJafari,Mahaki, Behzad Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Prostate cancer is the most commonly diagnosed form of cancer and the sixth leading cause of cancer-related deaths among men in the entire world. Reported standardized incidence rates are 12.6, 61.7, 11.9 and 27.9 in Iran, developed countries, developing countries and the entire world, respectively. The present study investigated the relative risk of PC in Iran at the province level and also explored the impact of some factors by the use of Bayesian models. Materials and Methods: Our study population was all men with PC in Iran from 2005 to 2008. Considered risk factors were smoking, fruit and vegetable intake, physical activity, obesity and human development index. We used empirical and full Bayesian models to study the relative risk in Iran at province level to estimate the risk of PC more accurately. Results: In Iran from 2005 to 2008 the total number of known PC cases was 10,361 with most cases found in Fars and Tehran and the least in Ilam. In all models just human development index was found to be significantly related to PC risk Conclusions: In the unadjusted model, Fars, Semnam, Isfahan and Tehran provinces have the highest and Sistan-and-Baluchestan has the least risk of PC. In general, central provinces have high risk. After adjusting for covariates, Fars and Zanjan provinces have the highest relative risk and Kerman, Northern Khorasan, Kohgiluyeh Boyer Ahmad, Ghazvin and Kermanshah have the lowest relative risk. According to the results, the incidence of PC in provinces with higher human development index is higher.