• Journal of Ginseng Research
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• v.43 no.3
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• pp.421-430
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• 2019

Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1003-1008
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• 2016

Breast cancer is now the leading cause of cancer death in women worldwide. Cancer progression is driven not only by cancer cell intrinsic alterations and interactions with tumor microenvironment, but also by systemic effects. Integration of multiple profiling data may provide insights into the underlying molecular mechanisms of complex systemic processes. We performed a bioinformatic analysis of two public available microarray datasets for breast tumor stroma and peripheral blood mononuclear cells, featuring integrated transcriptomics data, protein-protein interactions (PPIs) and protein subcellular localization, to identify genes and biological pathways that contribute to dialogue between tumor stroma and the peripheral circulation. Genes of the integrin family as well as CXCR4 proved to be hub nodes of the crosstalk network and may play an important role in response to stroma-derived chemoattractants. This study pointed to potential for development of therapeutic strategies that target systemic signals travelling through the circulation and interdict tumor cell recruitment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8339-8343
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• 2016

Background: To determine the outcome and cost saving by placing ultrasound guided surgical clips for tumor localization in patients undergoing neo-adjuvant chemotherapy for breast cancer. Materials and Methods: This retrospective cross sectional analytical study was conducted at the Department of Diagnostic Radiology, Aga Khan University Hospital, Karachi, Pakistan from January to December 2014. A sample of 25 women fulfilling our selection criteria was taken. All patients came to our department for ultrasound guided core biopsy of suspicious breast lesions and clip placement in the index lesion prior to neo-adjuvant chemotherapy. All the selected patients had biopsy proven breast cancer. Results: The mean age was $45{\pm}11.6years$. There were no complications seen after clip placement in terms of clip migration or hemorrhage. The cost of commercially available markers was approximately PKR 9,000 (US$ 90) and that of the surgical clip was PKR 900 (US$ 9). The cost of surgical clips in 25 patients was PKR 22,500 (US$ 225), when compared to the commercially available markers which may have incurred a cost of PKR 225,000 (US$ 2,250). The total cost saving for 25 patients was PKR 202,500 (US$ 2, 025), making it PKR 8100 (US$ 81) per patient. Conclusions: The results of our study show that ultrasound guided surgical clip placement in index lesions prior to neo-adjuvant therapy is a safe and cost effective method to identify tumor bed and response to treatment for further management.

• The Korean Journal of Cytopathology
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• v.9 no.2
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• pp.213-219
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• 1998

Glycogen-rich clear ceil carcinoma of the breast is an unusual variant of carcinoma with a recorded incidence of $1.4{\sim}3%$ of breast carcinomas. The cytologic characteristics have not been well described. We report two cases of glycogen-rich clear cell carcinoma with corresponding fine needle aspiration(FNA) cytologic findings and compare them to infiltrating ductal carcinoma and other clear ceil malignancies with a review of literature. One was a 62-year-old woman exhibiting a palpable mass of the right breast. The smears showed atypical tight cell clusters and individually scattered single cells containing leanly or clear abundant cytoplasm with well defined cytoplasmic margins. Mild to moderate nuclear pleomorphism and a prominent nucleolus were present. The other was a 42-year-old woman who was admitted with a right breast mass. The smears showed moderately cellular, tightly cohesive tumor cells. The cytoplasmic outline was generally well demarcated. The tumor cells Contained foamy to clear abundant cytoplasm with large and small vacuoles. The nuclear pleomorphism was marked. Both tumors resected by modified radical mastectomy, were diagnosed as glycogen-rich clear cell carcinoma. Histologically, the clear cell nature of tumor cells were not characteristic enough to predict this type of the tumor. Some cytologic features can be distinguished other clear cell breast cancer from glycogen-rich carcinoma. Recognition of these unusual patterns in a breast FNAC should raise the suspicion of a clear cell carcinoma including glycogen-rich subtype. Cytological localization of glycogen using PAS and D-PAS staining may permit the correct Identification and differential diagnosis of this tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1783-1789
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• 2014

Background: The EMSY gene encodes a BRCA2-binding partner protein that represses the DNA repair function of BRCA2 in non-hereditary breast cancer. Although amplification of EMSY gene has been proposed to have prognostic value in breast cancer, no data have been available concerning EMSY tissue expression patterns and its associations with clinicopathological features. Materials and Methods: In the current study, we examined the expression and localization pattern of EMSY protein by immunohistochemistry and assessed its prognostic value in a well-characterized series of 116 unselected breast carcinomas with a mean follow up of 47 months using tissue microarray technique. Results: Immunohistochemical expression of EMSY protein was detected in 76% of primary breast tumors, localized in nuclear (18%), cytoplasmic (35%) or both cytoplasmic and nuclear sites (23%). Univariate analysis revealed a significant positive association between EMSY expression and lymph node metastasis (p value=0.045) and larger tumor size (p value=0.027), as well as a non-significant relation with increased risk of recurrence (p value=0.088), whereas no association with patients' survival (log rank test, p value=0.482), tumor grade or type was observed. Conclusions: Herein, we demonstrated for the first time the immunostaining pattern of EMSY protein in breast tumors. Our data imply that EMSY protein may have impact on clinicipathological parameters and could be considered as a potential target for breast cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7843-7847
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• 2014

Background: Although breast cancer (BC) is one of the most common malignant diseases in women, the majority of the studies describing the characteristics of BC in elderly patients have been limited to survival assessments or tumor features, without using younger BC patients as a reference group. The aim of our study was to describe and compare tumor characteristics and management patterns in elderly versus younger breast cancer patients in Turkey. Materials and Methods: We retrospectively analyzed 152 patients with invasive breast cancer who underwent surgery in our institution between 2002 and 2012. Patients were divided into 2 groups according to age at the time of diagnosis. Results: There were 62 patients in the elderly group (${\geq}65$ years) and 90 patients in the younger group (<65 years). Compared to the younger group, tumors in the elderly group were more likely to be larger (p=0.018), of lower grade (p=0.005), and hormone receptor-positive (p>0.001). There were no significant differences regarding histology, localization, lymph node involvement, or types of surgical procedures between the 2 groups. Comorbidities were more common in elderly patients (p<0.001). In addition, elderly patients were more likely to receive hormonal therapy (p<0.001) and less likely to receive radiotherapy (p=0.08) and chemotherapy (p=0.003). There was no difference in survival and locoregional recurrence rates between the groups. Conclusions: The results of this study demonstrate that breast cancer in elderly patients has more favorable tumor features, warranting less aggressive treatment regimens after surgery.

• Toxicological Research
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• v.14 no.2
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• pp.123-127
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• 1998

BRCA1 is a tumor suppresser gene in familial cases of breast cancer. It has been controversial whether the subcellular localization of BRCA1 is located in nuclei or cytoplasm in normal human breast cells. We found that a p220 protein was expressed in Type II Normal human breast epithelial cells (NHBEC) but not in Type I NHBEC in Western blot analysis using the 17F8 (3A2) antibody. Immunostaining using the same antibody revealed positive staining in nuclei, cytoplasm and perinuclei of Type II cells and negative staining in Type I NHBEC. The p220 protein, however, was expressed in SV40 immortalized Type I NHBEC and tumorigenic cells derived from them after x-ray and neu oncogene treatment. The subcelluar localization was mostly cytoplasmic and punctate in the nuclei. The breast carcinoma cell lines, MCF-7 and T47D, also expressed the p220 protein. Using RT-PCR, we observed the expression of BRCA1 mRNA in both Type I and Type II NHBEC. This result indicated that there might be mechanisms involved in post-translational or translational regulation of BRCA1 gene. It is speculated that the absence of BRCA1 protein expression in Type I NHBEC might playa role in their susceptibility to neoplastic transformation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4921-4926
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• 2015

Background: Breast cancer is the most common cancer type among women with increasing incidence rates, improved prognosis and survival. According to the localization of the tumor, breast cancer is designated as unilateral (UBC) or bilateral (BBC). BBC can be classified as synchronous (SBBC) or metachronous (MBBC) based on the time interval between the diagnosis of the first and the secondary tumors. According to the guideline of WHO 2012, BBC is generally defined as SBBC when contralateral breast carcinoma is diagnosed within 3 months. The aim of this study was to compare the characteristics and patterns of metastasis of BBC patients with UBC. Materials and Methods: A cohort of 768 patients with breast cancer treated at the Turkish Ministry of Health-Izmir Bozyaka Research and Training Hospital between 1976 and 2012 were studied. Survival analysis was performed comparing UBC and BBC patients. In addition, evaluations were performed in patients with SBBC and MBBC sub-groups. We used a 3-months interval to distinguish metachronous from synchronous. Results: When clinical and histopathological parameters were statistically evaluated, ER status, event-free and overall survival were found to be significant between UBC and BBC patients. In comparison of SBBC and MBBC patients, age, histological type of tumor, event-free and overall survival were found to be significant. Conclusions: BBC cases were found to show worse prognosis than UBC cases. Among BBC, SBBC had the worst prognosis based on overall survival rates.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3699-3703
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• 2013

Background: This study aimed to show the localization of estrogen / progesterone receptors, human epidermal growth factor receptor 2 (Her-2) and protein 53 (p53) by immunohistochemistry in a series of consecutive breast cancer patients. Materials and Methods: The study covered invasive breast cancers from 299 patients presenting at the Oncogenetic Clinic and Pathology Centers of Ahwaz Jondishapour University of Medical Sciences Hospital in Iran during the time period from 2009 to 2011. The Scarff-Bloom Richardson scoring method was used. Results: Of the 299, 27% (80/299) were <40, 33% (100/299) were 41-50, and the remaining 40% (119/299) were>50 years old. The highest incidence of breast cancer in this study population was in the group of more than 50 year age, and the most common histological type of breast cancer was the invasive ductal carcinoma, which accounted for 68% (203/299) of the cases. Out of possible total of 207, 6% (13/207), 41% (85/207), and 53% (109/207) were scored as grade I, II, III, respectively. Conclusion: Our findings demonstrated a lack of association between labeling for the markers studied and tumor size and age of the patients. We confirmed an association between ER labeling and nuclear grade of breast cancer. The conflicting results obtained compared with the literature be because of differences in the immunohistochemical techniques applied in the various studies and to the scoring systems used.

• The Korean Journal of Nuclear Medicine
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• v.32 no.4
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• pp.374-381
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• 1998

Purpose: I-131 labeled (2'-deoxy-2'-iodo-${\beta}$-D-arabinofuranosyl) adenine (IAD) may be involved in DNA synthesis during active proliferation of tumor cells. We conducted this study to find out the biodistribution of IAD and it's feasibility for scintigraphic tumor imaging. Materials and Methods: Tosyl acetyl-adenosine was dissolved in acetonitrile, and I-131-NaI was added and heated to synthesize IAD. Female Fisher 344 rats innoculated with breast tumor cells were injected with 0.27 MBq of IAD. Rats were sacrificed at 0.5, 1, 2, 4, 24h and the % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy, rats bearing breast cancer were administered with 1.11 MBq of IAD and imaging was performed after 2 and 24h. Then, rat body was fixed and microtomized slice was placed on radiographic film for autoradiography. Results: %ID/g of tumor was 0.74 (0.5h),0.73 (1h), 0.55 (2h), 0.38 (4h), and 0.05 (24h), respectively. At 1h after injection, %ID/g of tumor was higher than that of heart (0.34), liver (0.42), spleen (0.47), kidney (0.69), muscle (0.14), bone (0.33) and intestine (0.51). However, %ID/g of tumor was lower than blood (1.06), lung (0.77), and thyroid (177.71). At 4h, %ID/g of tumor in comparison with other tissue did not change. Tumor contrast expressed by tumor to blood ratio was 0.69 and tumor to muscle ratio was 5.11 at 1h. However, these ratios did not improve through 24h. On autoradiogram and scintigraphy at 2 and 24 hour, the tumor was well visualized. Conclusion: This results suggest that IAD may have a potential for tumor scintigraphy. However, further work is needed to improve localization in tumor tissue.