Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

Muhammadnejad, Samad,Muhammadnejad, Ahad,Haddadi, Mahnaz,Oghabian, Mohammad-Ali,Mohagheghi, Mohammad-Ali,Tirgari, Farrokh,Sadeghi-Fazel, Fariba,Amanpour, Saeid Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.

Systematic Review of Available Guidelines on Fertility Preservation of Young Patients with Breast Cancer

Haddadi, Mahnaz,Muhammadnejad, Samad,Sadeghi-Fazel, Fariba,Zandieh, Zahra,Rahimi, Gohar,Sadighi, Sanambar,Akbari, Parya,Mohagheghi, Mohammad-Ali,Mosavi-Jarrahi, Alireza,Amanpour, Saeid Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: Since the survival rate of breast cancer patients has improved, harmful effects of new treatment modalities on fertility of the young breast cancer patients has become a focus of attention. This study aimed to systematically review and critically appraise all available guidelines for fertility preservation in young breast cancer patients. Materials and Methods: Major citation databases were searched for treatment guidelines. Experts from relevant disciplines appraised the available guidelines. The AGREE II Instrument that includes 23 criteria in seven domains (scope and purpose of the guidelines, stakeholder involvement, rigor of development, clarity, applicability, editorial independence, and overall quality) was used to apprise and score the guidelines. Results: The search strategy retrieved 2,606 citations; 72 were considered for full-text screening and seven guidelines were included in the study. There was variability in the scores assigned to different domains among the guidelines. ASCO (2013), with an overall score of 68.0%, had the highest score, and St Gallen, with an overall score of 24.7%, had the lowest scores among the guidelines. Conclusions: With the promising survival rate among breast cancer patients, more attention should be given to include specific fertility preservation recommendations for young breast cancer patients.

Lack of Metformin Effects on Different Molecular Subtypes of Breast Cancer under Normoglycemic Conditions: An in vitro Study

Sadighi, Sanambar,Amanpour, Saeid,Behrouzi, Bita,Khorgami, Zhinoos,Muhammadnejad, Samad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.

in vitro Assessment of Antineoplastic Effects of Deuterium Depleted Water

Soleyman-Jahi, Saeed,Zendehdel, Kazem,Akbarzadeh, Kambiz,Haddadi, Mahnaz,Amanpour, Saeid,Muhammadnejad, Samad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5

Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines. Materials and Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis. Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases. Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials.

Development of Gold-Coated Magnetic Nanoparticles as a Potential MRI Contrast Agent

Ali Reza Montazerabadi,Mohammad Ali Oghabian,Rasoul Irajirad,Samad Muhammadnejad,Davoud Ahmadvand,Hamid Delavari H,Seyed Rabie Mahdavi 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2015 NANO Vol.10 No.4

Gold-coated superparamagnetic iron oxide nanoparticles (SPIONs) coated with methylpolyethylene glycol (mPEG) are synthesized and investigated as a magnetic resonance (MR) imaging contrast agent. The synthesized mPEG-core@shells are characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometry (VSM), zeta-potential analysis and X-ray diffraction (XRD). In addition, the transverse relaxivity of the mPEG-core@shells is measured using a 3 T MRI scanner. The cytotoxicity of the mPEG-core@shells is tested in the LNCaP cell line using an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results show that the mPEG-core@shell particles are semispherical with hydrodynamic size of ~65 nm and a transverse relaxivity of 162.3 mM-1 S-1. The mPEG-core@shell particles demonstrate good stability in biological media without any significant in vitro cytotoxicity under high cellular uptake conditions. Finally, in vivo imaging shows that mPEG-core@shells are a potential contrast agent for use in early-stage detection.