scholarly journals The CHARACTERIZATION OF SYNERGISTIC EFFECT OF CRILIN AND NANOCURCUMIN ON TREATMENT FOR 7, 12 DIMETHYLBENZ [A] ATHRACENE (DMBA)-INDUCED BREAST CANCER MICE

2018 ◽  
Vol 34 (1) ◽  
pp. 61
Author(s):  
Gia-Buu Tran
Keyword(s):  
Breast Cancer ◽  
Synergistic Effect ◽  
Tumor Volume ◽  
Ductal Carcinoma ◽  
Inhibitory Effect ◽  
Carcinoma Cells ◽  
Herbal Remedies ◽  
Surrounding Tissue ◽  
Neoplastic Disease

Breast cancer is the neoplastic disease which is characterized by unregulated ductal and lobular hyperplasia. Some herbal remedies have been researched and proved the inhibitory effect on breast cancer such as, Crilin-extracted from Cirnum latifolum and curcumin-isolated from Cucuma longa. However, the synergistic effect of crilin and nanocurcumin have not been studied yet. In this study, we established the mouse model of breast cancer induced by DMBA and evaluated the effectiveness of combination of crilin and nanocurcumin on treatment of breast cancer. After 12 weeks, co-administration of crilin and nanocurcumin inversed alteration of body weight, the number of erythrocytes and leukocytes induced by DMBA. Furthermore, the synergistic effect of crilin and nanocucumin on reduction of tumor volume was proven. Histological analysis revealed that co-administration of crilin and nanocurcumin inhibited invasion of mammary ductal carcinoma cells into surrounding tissue, recovered lobular cells structure, and diminished leukocyte composition. Thereby, the combination of crilin and nanocurcumin recovers immune system and prevent the development of breast cancer.

scholarly journals Molecular and Cellular Characterization of Two Patient-Derived Ductal Carcinoma in Situ (DCIS) Cell Lines, ETCC-006 and ETCC-010

2020 ◽  
Author(s):  
Julia Samson ◽  
Kellie Dean
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Ductal Carcinoma ◽  
Breast Cancer Cell Lines ◽  
Breast Epithelial Cell ◽  
Anchorage Independent Growth

Abstract Background: Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010. Methods: Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile. Results: ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in receptor tyrosine kinase pathways and DNA replication/cell cycle programs. Conclusions: For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.

scholarly journals Molecular and cellular characterization of two patient-derived ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Julia Samson ◽  
Magdalina Derlipanska ◽  
Oza Zaheed ◽  
Kellie Dean
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Line ◽  
Cell Lines ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Anchorage Independent Growth

Abstract Background Currently it is unclear how in situ breast cancer progresses to invasive disease; therefore, a better understanding of the events that occur during the transition to invasive carcinoma is warranted. Here we have conducted a detailed molecular and cellular characterization of two, patient-derived, ductal carcinoma in situ (DCIS) cell lines, ETCC-006 and ETCC-010. Methods Human DCIS cell lines, ETCC-006 and ETCC-010, were compared against a panel of cell lines including the immortalized, breast epithelial cell line, MCF10A, breast cancer cell lines, MCF7 and MDA-MB-231, and another DCIS line, MCF10DCIS.com. Cell morphology, hormone and HER2/ERBB2 receptor status, cell proliferation, survival, migration, anchorage-independent growth, indicators of EMT, cell signalling pathways and cell cycle proteins were examined using immunostaining, immunoblots, and quantitative, reverse transcriptase PCR (qRT-PCR), along with clonogenic, wound-closure and soft agar assays. RNA sequencing (RNAseq) was used to provide a transcriptomic profile. Results ETCC-006 and ETCC-010 cells displayed notable differences to another DCIS cell line, MCF10DCIS.com, in terms of morphology, steroid-receptor/HER status and markers of EMT. The ETCC cell lines lack ER/PR and HER, form colonies in clonogenic assays, have migratory capacity and are capable of anchorage-independent growth. Despite being isogenic, less than 30% of differentially expressed transcripts overlapped between the two lines, with enrichment in pathways involving receptor tyrosine kinases and DNA replication/cell cycle programs and in gene sets responsible for extracellular matrix organisation and ion transport. Conclusions For the first time, we provide a molecular and cellular characterization of two, patient-derived DCIS cell lines, ETCC-006 and ETCC-010, facilitating future investigations into the molecular basis of DCIS to invasive ductal carcinoma transition.

Spatiotemporal modeling with SimBioSys TumorScope to predict chemotherapeutic response in breast tumor microenvironments.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12656-e12656
Author(s):  
Chaitanya K Mamillapalli ◽  
Timothy K Markwell ◽  
Jason K Ellis ◽  
John Pfiefer ◽  
Tushar Pandey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Correlation Coefficient ◽  
Real World ◽  
Tumor Volume ◽  
Pearson Correlation ◽  
Tumor Therapy ◽  
Standard Of Care ◽  
Surrounding Tissue ◽  
Pearson Correlation Coefficient ◽  
Clinical Records

e12656 Background: Predictive models of the efficacy of different tumor therapies will provide significant enhancements to current standard of care practices. Predicting a given tumor’s growth and treatment response, however, is an intricate process that requires not only an understanding of the tumor's intrinsic characteristics, but also spatial- and temporal-resolved tumor shape descriptions, surrounding tissue dynamics, and a complete account for the milieu of diffusible molecules that drive tumor behaviors and interactions. Here we report an ongoing retrospective study designed to validate SimBioSys TumorScope as a computational tumor therapy prediction model in a real-world clinical setting. Methods: Fully-deidentified and HIPAA-compliant data were assessed from real-world clinical records and cases. Subjects comprised early stage breast cancer patients who were treated with neoadjuvant chemotherapy (NACT) and subsequent surgical resection. Data fields included imaging data, biomarker status, tumor sizing, demographic data, digital pathology, and genetic lab test data. Half of the data, including all data fields, were used as a training dataset for TumorScope. The second half of the data, with blinded diagnoses and results, will be used to test TumorScope’s prediction accuracy. Simulations will be initialized with pre-treatment MRI data and processed through the entirety of each patient's specified treatment regimen. Predicted tumor volume and longest dimension will be compared against measured values at several time-points after therapy initiation. Overall accuracy will be statistically assessed by the Pearson correlation coefficient between predicted and measured tumor volume and longest dimension at each time-point, as well as their root-mean-squared-errors. Results: Final statistical analysis is currently underway. Thus far, SimBioSys TumorScope has trended high accuracy levels with the non-blinded “training” cohort just as it has in previous database studies, with a Pearson correlation coefficient greater than 0.94. Conclusions: SimBioSys TumorScope for Breast Cancer accurately predicts patient NACT responses via spatio-temporal modeling of drug and nutrient perfusion, metabolic behavior, and the physio-chemical interactions between surrounding tissues. Future prospective studies may assess TumorScope’s capacity to support efficient patient treatments and enhance overall standard of care.

scholarly journals Patched Targeting Peptides for Imaging and Treatment of Hedgehog Positive Breast Tumors

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Daniel Smith ◽  
Fanlin Kong ◽  
David Yang ◽  
Richard Larson ◽  
Jennifer Sims-Mourtada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Inhibition ◽  
Hedgehog Signaling ◽  
Ductal Carcinoma ◽  
Inhibitory Effect ◽  
Receptor Expression ◽  
Breast Cancer Cell Lines ◽  
Cancer Therapies

High tumor hedgehog expression is correlated with poor prognosis in invasive ductal carcinoma. Peptides which bind the patched receptor have recently been reported to have a growth inhibitory effect in tumors with activated hedgehog signaling. We sought to examine growth inhibition with these peptides in breast cancer cells and use these peptides as molecular imaging probes to follow changes in hedgehog expression after chemotherapy. Significant growth inhibition was observed in breast cancer cell lines treated with PTCH-blocking peptides. Significantin vitrouptake was observed with both FITC- and99mTc-EC-peptide conjugates.In vivoimaging studies displayed greater accumulation of99mTc-labeled peptides within tumors as compared to adjacent muscle tissue. Patched receptor expression increased after treatment and this correlated with an increase in tumor radiotracer uptake. These studies suggest that peptides which bind the sonic hedgehog docking site in patched receptor correlate with patched expression and can be used to image patchedin vivo. Further, our data suggest that radiolabeled peptides may enable us to examine the activity of the hedgehog signaling pathway and to evaluate response to anti-cancer therapies.

scholarly journals Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 807
Author(s):  
Usha Sundralingam ◽  
Srikumar Chakravarthi ◽  
Ammu Kutty Radhakrishnan ◽  
Saravanan Muniyandy ◽  
Uma D. Palanisamy
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Tumor Volume ◽  
Ductal Carcinoma ◽  
Plasma Concentrations ◽  
Comparable Efficacy ◽  
Emu Oil ◽  
Syngeneic Mouse Model ◽  
Potential Use

Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC–MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.

scholarly journals Treatment of breast cancer in vivo by dual photodynamic and photothermal approaches with the aid of curcumin photosensitizer and magnetic nanoparticles

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ali Ashkbar ◽  
Fatemeh Rezaei ◽  
Farnoosh Attari ◽  
Saboura Ashkevarian
Keyword(s):  
Breast Cancer ◽  
Breast Tumor ◽  
Near Infrared ◽  
Tumor Volume ◽  
Control Group ◽  
Neoplastic Disease ◽  
Mice Model ◽  
Minimal Invasiveness ◽  
Uv Visible

AbstractBreast cancer is a neoplastic disease with a high mortality rate among women. Recently, photodynamic therapy (PDT) and photothermal therapy (PTT) attracted considerable attention because of their minimal invasiveness. The PTT approach works based on hyperthermia generation, and PDT approach employs laser irradiation to activate a reagent named photosensitizer. Therefore, in the current paper, a dual-functioned nanocomposite (NC) was designed for the treatment of breast cancer model in Balb/c mice with the combination of photodynamic and photothermal approaches. Transmission electron microscopy, UV–visible spectroscopy, FTIR, and XRD were employed to validate the nanostructure and silica coating and curcumin (CUR) immobilization on the Fe3O4 nanoparticles. The effect of Fe3O4/SiO2-CUR combined with PDT and PTT was assessed in vivo on the breast tumor mice model, and immunohistochemistry (IHC) was employed to evaluate the expression of apoptotic Bax and Caspase3 proteins. The TEM images, UV–visible absorption, and FTIR spectra demonstrated the successful immobilization of curcumin molecules on the surface of Fe3O4/SiO2. Also, MTT assay confirmed the nontoxic nature of Fe3O4/SiO2 nanoparticles in vitro. In the breast tumor mice model, we have assessed six treatment groups, including control, CUR + PDT, Blue + NIR (near-infrared) lasers, NC, NC + PTT, and NC + PDT + PTT. The tumor volume in the NC + PDT + PTT group showed a significant reduction compared to other groups (p < 0.05). More interestingly, the tumor volume of NC + PDT + PTT group showed a 27% decrease compared to its initial amount. It should be noted that no detectable weight loss or adverse effects on the vital organs was observed due to the treatments. Additionally, the IHC data represented that the expression of proapoptotic Bax and Caspase3 proteins were significantly higher in the NC + PDT + PTT group compared to the control group, indicative of apoptosis. To conclude, our data supported the fact that the NC + PDT + PTT strategy might hold a promising substitute for chemotherapy for the treatment of triple-negative breast cancers.

scholarly journals An Organotypic Mammary Duct Model Capturing Distinct Events of DCIS Progression

2020 ◽  
Author(s):  
Jonathan Kulwatno ◽  
Xiangyu Gong ◽  
Rebecca DeVaux ◽  
Jason I. Herschkowitz ◽  
Kristen Lynn Mills
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Ductal Carcinoma ◽  
Biomechanical Properties ◽  
Breast Cancer Progression ◽  
Surrounding Tissue ◽  
Mammary Duct ◽  
The Matrix

ABSTRACTDuctal carcinoma in situ (DCIS) is a pre-cancerous stage breast cancer, where abnormal cells are contained within the duct, but have not invaded into the surrounding tissue. However, only 30-40% of DCIS cases are likely to progress into an invasive ductal carcinoma (IDC), while the remainder are innocuous. Since little is known about what contributes to the transition from DCIS to IDC, clinicians and patients tend to opt for treatment, leading to concerns of overdiagnosis and overtreatment. In vitro models are currently being used to probe how DCIS transitions into IDC, but many models do not take into consideration the macroscopic tissue architecture and the biomechanical properties of the microenvironment. Here, we developed an organotypic mammary duct model by molding a channel within a collagen matrix and lining it with a basement membrane. By adjusting the concentration of collagen, we effectively modulated the stiffness and morphological properties of the matrix and examined how an assortment of breast cells responded to changing density and stiffness of the matrix. We first validated the model using two established, phenotypically divergent breast cancer cell lines by demonstrating the ability of the cells to either invade (MDA-MB-231) or cluster (MCF7). We then examined how cells of the isogenic MCF10 series—spanning the range from healthy to aggressive—behaved within our model and observed distinct characteristics of breast cancer progression such as hyperplasia and invasion, in response to collagen concentration. Our results show that the model can recapitulate different stages of breast cancer progression and that the MCF10 series is adaptable to physiologically relevant in vitro studies, demonstrating the potential of both the model and cell lines to elucidate key factors that may contribute to understanding the transition from DCIS to IDC.IMPACT STATEMENTThe success of early preventative measures for breast cancer has left patients susceptible to overdiagnosis and overtreatment. Limited knowledge of factors driving an invasive transition has inspired the development of in vitro models that accurately capture this phenomenon. However, current models tend to neglect the macroscopic architecture and biomechanical properties of the mammary duct. Here, we introduce an organotypic model that recapitulates the cylindrical geometry of the tissue and the altered stroma seen in tumor microenvironments. Our model was able to capture distinct features associated with breast cancer progression, demonstrating its potential to uncover novel insights into disease progression.

Characterization of Thromboxane A2/Prostaglandin H2 Receptors in Porcine Coronary Artery -The Inhibitory Effect of a Novel Dibenzoxepin Derivative, KW-3635

1992 ◽  
Vol 67 (05) ◽  
pp. 582-584 ◽  
Author(s):  
Ichiro Miki ◽  
Akio Ishii
Keyword(s):  
Coronary Artery ◽  
Binding Sites ◽  
Thromboxane A2 ◽  
Inhibitory Effect ◽  
Scatchard Analysis ◽  
Single Class ◽  
Porcine Coronary Artery ◽  
Equilibrium Binding ◽  
H2 Receptors

SummaryWe characterized the thromboxane A2/prostaglandin H2 receptors in porcine coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to coronary arterial membranes was saturable and displaceable. Scatchard analysis of equilibrium binding showed a single class of high affinity binding sites with a dissociation constant of 18.5 ±1.0 nM and the maximum binding of 80.7 ± 5.2 fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to thromboxane A2/prosta-glandin H2 receptors in coronary artery with an inhibition constant of 6.0 ± 0.69 nM (mean ± S.E.M.).

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