• Title/Summary/Keyword: Advanced breast cancer

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Breast Cancer in Tunisia: Association of Body Mass Index with Histopathological Aspects of Tumors

  • Bouguerra, Hichem;Guissouma, Hajer;Labidi, Soumaya;Stambouli, Nejla;Marrakchi, Raja;Chouaib, Salem;Elgaaied, Amel Ben Ammar;Boussen, Hammouda;Gati, Asma
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6805-6810
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    • 2014
  • Background: Previous studies have suggested a link between obesity and breast cancer (BC). However, there is no universal consensus, especially in population based studies. Because only few studies have been conducted on African women, we aimed here to assess the relationship between BMI at time of diagnosis and the BC histopathological features among Tunisian patients according to menopausal status using a hospital-based prospective cohort study. Materials and Methods: Clinical and pathological data were collected from 262 patients stratified on four groups according to their BMI. The relationship between BMI and histopathological features at diagnosis was analysed using univariate and multivariate analysis. Receiver-operating characteristic (ROC) curves were used to evaluate the performance of BMI in predicting of high tumor grade, in comparison to ki-67 index of proliferation. Results: Obesity was correlated with larger tumors, advanced grade and with ER-PR-Her2+ BC subtype. An association of BMI with tumor size and tumor grade was observed in both premenopausal and postmenopausal women. Additionally, a significant association between BMI and ER+, ER+PR+Her2+ and ER-PR-Her2+ status was revealed for premenopausal patients, while only ER+PR+Her2+ was associated with BMI for postmenopausal women. Finally, our results showed that compared to Ki67 proliferation index, BMI is a useful prognostic marker of high grade BC tumors. Conclusions: These data are the first to show that in Tunisia obese women suffering from BC have significantly larger tumors and advanced tumor grade and that higher BMI might influence tumor characteristics and behavior.

Egr-1 regulates the transcription of the BRCA1 gene by etoposide

  • Shin, Soon Young;Kim, Chang Gun;Lee, Young Han
    • BMB Reports
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    • v.46 no.2
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    • pp.92-96
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    • 2013
  • The breast cancer susceptibility gene BRCA1 encodes a nuclear protein, which functions as a tumor suppressor and is involved in gene transcription and DNA repair processes. Many families with inherited breast and ovarian cancers have mutations in the BRCA1 gene. However, only a few studies have reported on the mechanism underlying the regulation of BRCA1 expression in humans. In this study, we investigated the transcriptional regulation of BRCA1 in HeLa cells treated with etoposide. We found that three Egr-1-binding sequences (EBSs) were located at -1031, -1005, and -385 within the enhancer region of the BRCA1 gene. Forced expression of Egr-1 stimulated the BRCA1 promoter activity. EMSA data showed that Egr-1 bound directly to the EBS within the BRCA1 gene. Knockdown of Egr-1 through the expression of a small hairpin RNA (shRNA) attenuated etoposide-induced BRCA1 promoter activity. We conclude that Egr-1 targets the BRCA1 gene in HeLa cells exposed to etoposide.

Diffusion-Weighted Imaging as a Stand-Alone Breast Imaging Modality (독립적 검사 방법으로서의 확산강조 자기공명영상검사)

  • Hee Jung Shin;Su Hyun Lee;Woo Kyung Moon
    • Journal of the Korean Society of Radiology
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    • v.82 no.1
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    • pp.29-48
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    • 2021
  • Diffusion-weighted magnetic resonance imaging (DW MRI) is a fast unenhanced technique that shows promise as a stand-alone modality for cancer screening and characterization. Currently, DW MRI may have lower sensitivity than that of dynamic contrast-enhanced MRI as a standalone modality for breast cancer detection but superior to that of mammography, which may provide a useful alternative for supplemental screening. Standardized acquisition and interpretation of DW MRI can improve the image quality and reduce the variability of the results. Furthermore, high-resolution DW MRI, with advanced techniques and postprocessing, will facilitate better detection and characterization of subcentimeter cancers and reduce false-negatives and false-positives. Future results from ongoing prospective multicenter clinical trials using standardized and optimized protocols will facilitate the use of DW MRI as a stand-alone modality.

ANTICANCER EFFECT OF TAMOXIFEN IN ORAL CANCER CELL (구강암세포주에서의 Tamoxifen의 항암효과)

  • Jung, Jae-Hwa;Yun, Pil-Young;Myoung, Hoon;Shin, Jae-Il;Lee, Jong-Ho;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.29 no.6
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    • pp.365-373
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    • 2003
  • Tamoxifen is an selective estrogen receptor antagonist widely used in the management of patients with breast cancer for more than 30 years. It was thought to act primarily through occupying the estrogen receptor sites in ER positive breast cancer cells and directly on cancer cell proper. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanism of therapeutic action of tamoxifen. The purposes of this study were to identify ER in oral carcinoma cell lines and to evaluate ER independent cytotoxic effect of tamoxifen. KB(SCC), HSC-3(SCC) and A253(ACC) cell line were used and capacity of cell proliferation, apoptosis, in vitro invasion and gelatin zymography were tested. ER expression of each cell line were detected by RT-PCR and immunocytochemistry. Dose dependent inhibition of cell proliferation and inhibition of gelatinolytic activity were observed in all oral carcinoma cell lines and significant difference of apoptotic index were observed in A253 and KB. Tamoxifen inhibited in vitro invasion in all experimental groups. ER expression was detected in KB and A253. These data suggest that tamoxifen may play a role in management of oral carcinoma by independent cytotoxic effect and more advanced research must processed confirming ER-dependent cytotoxicity.

Anti Proliferative Properties of Melissa officinalis in Different Human Cancer Cells

  • Jahanban-Esfahlan, Akram;Modaeinama, Sina;Abasi, Mozhgan;Abbasi, Mehran Mesgari;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5703-5707
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    • 2015
  • Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of their antioxidative properties. Melissa officinalis L. (MO), an aromatic and medicinal plant, is well known in thios context. However, toxicity against cancer cells has not been fully studied. Here, we investigated the selective anticancer effects of an MO extract (MOE) in different human cancer cells. Materials and Methods: a hydro-alcoholic extract of MO was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. MTT assays were used to evaluate cytotoxicity of different doses of MOE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer cells), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, MOE reduced the cell viability to values below 33%, even at the lowest doses. In all cases, $IC_{50}$ values were below $5{\mu}g/ml$. The mean growth inhibition was 73.1%, 86.7%, 79.9% and 77.8% in SKOV3, MCF-7 and PC-3 and A549 cells, respectively. Conclusions: Our results indicate that a hydro-alcoholic extract of MO possess a high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important than a maximally tolerated one. Moreover, the antiprolifreative effect of MO seems to be tumor type specific, as hormone dependant cancers were more sensitive to antitumoral effects of MOE.

Result of Neoadjuvant Chemotherapy, Surgery and Radiation Therapy in Locally Advanced Breast Cancer (국소 진행성 유방암 환자에서 선행 항암화학요법의 치료결과)

  • Bae, Sun-Hyun;Park, Won;Huh, Seung-Jae;Choi, Doo-Ho;Nam, Hee-Rim;Yang, Jung-Hyun;Nam, Seok-Jin;Lee, Jeong-Eon;Im,, Young-Hyuck;Ahn, Jin-Seok;Park, Yeon-Hee
    • Radiation Oncology Journal
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    • v.28 no.2
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    • pp.71-78
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    • 2010
  • Purpose: To evaluate the result of neoadjuvant chemotherapy, surgery, and radiation therapy in locally advanced breast cancer as well as analyze the prognostic factors affecting survival. Materials and Methods: One hundred fifty-nine patients with breast cancer were treated by neoadjuvant chemotherapy between April 1995 and November 2006 at the Samsung Medical Center. Among these patients, we retrospectively reviewed 105 patients treated with neoadjuvant chemotherapy followed by surgery and radiation therapy for a cure with an initial tumor size >5 cm or clinically positive lymph nodes. All patients received anthracycline based chemotherapy except for 2 patients. According to clinical tumor stage, 3 patients (3%) were cT1, 26 (25%) were cT2, 39 (37%) were T3 and 37 (35%) were T4. Initially, 98 patients (93%) showed axillary lymph node metastasis. The follow-up periods ranged from 7~142 months (median, 41 months) after the beginning of neoadjuvant chemotherapy. Results: Locoregional failure free survival rate and distant metastasis free survival rate at 5 years were 82.1% and 69.9%, respectively. Disease free survival rate and overall survival rate at 5 years were 66.1% and 77.1%, respectively. The results of a univariate analysis indicate that clinical tumor stage, pathologic tumor stage, pathologic nodal stage and pathologic TNM stage were statistically significant factors for disease free survival rate and overall survival rate. Whereas, a multivariate analysis indicated that only hormone therapy was a statistically significant factor for survival. Conclusion: The current study results were comparable to other published studies for neoadjuvant chemotherapy for breast cancer. Hormone therapy was a statistically significant prognostic factor. The patients with early clinical or pathologic stage had a tendency to improve their survival rate.

Study for the Synthesis of $[^{123}I]$Idoxifene and Its Uptake in the Breast Cancer Cell ($[^{123}I]$Idoxifene 합성과 유방암의 세포섭취에 관한 연구)

  • Cho, Young-Sub;Yang, Seung-Dae;Suh, Yong-Sup;Chun, Kwon-Soo;Ahn, Soon-Hyuk;Lim, Soo-Jung;Lim, Sang-Moo;Yu, Kook-Hyun
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.5
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    • pp.410-417
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    • 2000
  • Purpose: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using $[^{123}I]$ provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using $[^{123}I]$ and to determine its cell uptake of breast cancer cell line. Materials and Methods: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino-4-iodotamoxifen (idoxifene). $[^{123}I]$Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (${\pm}$)-2-phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). Results and Conclusion: Acylation of (2-chloroethoxy)benzene with (${\pm}$)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.

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Vascular Morphometric Changes During Tumor Growth and Chemotherapy in a Murine Mammary Tumor Model Using OCT Angiography: a Preliminary Study

  • Kim, Hoonsup;Eom, Tae Joong;Kim, Jae Gwan
    • Current Optics and Photonics
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    • v.3 no.1
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    • pp.54-65
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    • 2019
  • To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.