Changes in glycosaminoglycans and proteoglycans of normal breast and fibroadenoma during the menstrual cycle

Lima, Cilene Rebouças de; Santos, José de Arimatéa dos; Nazário, Afonso Celso Pinto; Michelacci, Yára M.

doi:10.1016/j.bbagen.2012.04.010

Cited by 18 publications

(14 citation statements)

References 50 publications

(53 reference statements)

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“…Given the sample size (n = 10) of this initial study, it is difficult to control for age and menstrual cycle effects, which are known to modulate breast tissue density and composition (27). Further studies will include intra-scan registration to account for such effects.…”

Section: Discussionmentioning

confidence: 99%

Optimization of 7-T Chemical Exchange Saturation Transfer Parameters for Validation of Glycosaminoglycan and Amide Proton Transfer of Fibroglandular Breast Tissue

Dula¹,

Arlinghaus²,

Williams³

et al. 2015

Radiology

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Purpose The two purposes of this study were to: 1) implement simulation-optimized chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) and glycosaminoglycans (GAG) hydroxyl proton transfer effects in the human breast at 7 Tesla, and 2) determine the reliability of these techniques for evaluation of fibroglandular tissue in the healthy breast as a benchmark for future studies of pathology. Materials and Methods All human studies were IRB approved, HIPPA compliant, and included informed consent. The CEST parameters of saturation duration (25 ms) and amplitude (1 μT) were chosen based on simulation-driven optimization for APT contrast with the CEST effect quantified using residuals of a Lorentzian fit. Optimized parameters were implemented at 7 Tesla in ten healthy women in two separate scans to evaluate the reliability of CEST MRI measurements in the breast. CEST z-spectra were acquired over saturation offset frequencies ranging between ±40 ppm using a quadrature unilateral breast coil. The scan-rescan reliability was assessed in terms of the intraclass correlation coefficient, which indicates the ratio of between-subject variation to total variation. Results Simulations of the Bloch Equations with chemical exchange guided selection of optimal values for pulse duration and amplitude, 25 ms and 1 μT, respectively. Reliability was evaluated using intraclass correlation coefficients (95% confidence intervals) with acceptable results: 0.963 (0.852, 0.991) and 0.903 (0.609, 0.976) for APT and GAG, respectively. Conclusion We used simulations to derive optimal CEST preparation parameters to elicit maximal CEST contrast in healthy fibroglandular breast tissue due to APT at 7 T. We demonstrate that by using these parameters, obtaining reproducible values for both the amide and hydroxyl protons from of CEST MRI at 7 T is feasible in the human breast

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Section: Discussionmentioning

confidence: 99%

Optimization of 7-T Chemical Exchange Saturation Transfer Parameters for Validation of Glycosaminoglycan and Amide Proton Transfer of Fibroglandular Breast Tissue

Dula¹,

Arlinghaus²,

Williams³

et al. 2015

Radiology

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“…CS/DSPGs are involved in mammary gland development and may, consequently, be involved in breast cancer development [10]. DSPGs expression was described to be increased in breast cancer fibroadenoma compared to healthy tissue [11]. A common finding is that matrix secreted CS/DSPGs such as decorin and versican are deposited in tumor stroma [12, 13] and are related to aggressive phenotype in breast cancer [14–16].…”

Section: Extracellular Matrices In Breast Cancer: Focus On the Promentioning

confidence: 99%

“…It is accumulated in the preclinical phase of breast cancer in non-palpable breast carcinomas and is associated with risk factors such as increased mammographic density and malignant appearing microcalcifications [16]. Versican is increased in fibroadenoma [11] and the elevated levels of stromal versican are associated with increased risk and rate of relapse in women with node-negative breast cancer [14, 17]. Although all versican splice variants are markedly accumulated in breast tumors, highly glycanated V0 and V1 variants predominate in tumor stroma.…”

Section: Versican: a Tumor Stroma-associated Proteoglycan In Breasmentioning

confidence: 99%

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

Theocharis

Skandalis

Neill

et al. 2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

110

125

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Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer.

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“…Nevertheless, DSPGs expression were described to be increased in breast cancer fibroadenoma compared to healthy tissue [80], and, although the DSPG decorin was present in both healthy and tumor tissue, versican was exclusively detected in tumor samples.…”

Section: Heparan Sulfate In Breast Cancermentioning

confidence: 99%

Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression

Gomes

Stelling

Pavão

2013

BioMed Research International

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Breast cancer is defined as a cancer originating in tissues of the breast, frequently in ducts and lobules. During the last 30 years, studies to understand the biology and to treat breast tumor improved patients' survival rates. These studies have focused on genetic components involved in tumor progression and on tumor microenvironment. Heparan sulfate proteoglycans (HSPGs) are involved in cell signaling, adhesion, extracellular matrix assembly, and growth factors storage. As a central molecule, HSPG regulates cell behavior and tumor progression. HS accompanied by its glycosaminoglycan counterparts regulates tissue homeostasis and cancer development. These molecules present opposite effects according to tumor type or cancer model. Studies in this area may contribute to unveil glycosaminoglycan activities on cell dynamics during breast cancer exploring these polysaccharides as antitumor agents. Heparanase is a potent tumor modulator due to its protumorigenic, proangiogenic, and prometastatic activities. Several lines of evidence indicate that heparanase is upregulated in all human sarcomas and carcinomas. Heparanase seems to be related to several aspects regulating the potential of breast cancer metastasis. Due to its multiple roles, heparanase is seen as a target in cancer treatment. We will describe recent findings on the function of HSPGs and heparanase in breast cancer behavior and progression.

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Changes in glycosaminoglycans and proteoglycans of normal breast and fibroadenoma during the menstrual cycle

Abstract: PGs are increased in fibroadenoma, but their concentrations may be less sensitive to hormonal control.

Cited by 18 publications

References 50 publications

Optimization of 7-T Chemical Exchange Saturation Transfer Parameters for Validation of Glycosaminoglycan and Amide Proton Transfer of Fibroglandular Breast Tissue

Optimization of 7-T Chemical Exchange Saturation Transfer Parameters for Validation of Glycosaminoglycan and Amide Proton Transfer of Fibroglandular Breast Tissue

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

Heparan Sulfate and Heparanase as Modulators of Breast Cancer Progression

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