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 Validation of transgenic models of breast cancer: ductal carcinoma in situ (DCIS) and Brca1-mutation-related breast cancer

2005 ◽  
Vol 8 (8) ◽  
Author(s):  
M. S. Frech ◽  
L. P. Jones ◽  
P. A. Furth
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mouse Model ◽  
Mouse Models ◽  
Ductal Carcinoma ◽  
Brca1 Mutation ◽  
Tumor Development ◽  
Estrogen Receptor Α ◽  
Mammary Tissue

Available mouse models of ductal carcinomain situ(DCIS) and BRCA1-mutation-related breast cancer are reviewed. The best validated mouse models of human DCIS are the conditional estrogen receptor α in mammary tissue (CERM) model initiated by deregulated estrogen receptor α and the serial explant mouse model initiated by p53 deficiency. At present the most useful and best validated mouse model of BRCA1-mutation-related breast cancer uses the cre-lox system to make a conditional Brca1 deletion targeted to mammary epithelial cells. The major shortcoming of the non-conditional Brca1 models is the high incidence of non-mammary tumor development. The use of mammary gland transplants or explants from these mice into nude hosts is one approach that could be used to circumvent this deficiency. Development and validation of a Brca1-mutation-related mouse model of basal cell breast cancer is an important next step.

Comparison of Mammography and Ultrasonography for Tumor Size of DCIS of Breast Cancer

2019 ◽  
Vol 15 (2) ◽  
pp. 209-213
Author(s):  
Yu Wang ◽  
Jiantao Wang ◽  
Haiping Wang ◽  
Xinyu Yang ◽  
Liming Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Correlation Coefficient ◽  
Tumor Size ◽  
Ductal Carcinoma ◽  
Pearson Correlation ◽  
Dense Breast ◽  
Pathological Examination ◽  
Negative Group ◽  
The Difference

Objective: Accurate assessment of breast tumor size preoperatively is important for the initial decision-making in surgical approach. Therefore, we aimed to compare efficacy of mammography and ultrasonography in ductal carcinoma in situ (DCIS) of breast cancer. Methods: Preoperative mammography and ultrasonography were performed on 104 women with DCIS of breast cancer. We compared the accuracy of each of the imaging modalities with pathological size by Pearson correlation. For each modality, it was considered concordant if the difference between imaging assessment and pathological measurement is less than 0.5cm. Results: At pathological examination tumor size ranged from 0.4cm to 7.2cm in largest diameter. For mammographically determined size versus pathological size, correlation coefficient of r was 0.786 and for ultrasonography it was 0.651. Grouped by breast composition, in almost entirely fatty and scattered areas of fibroglandular dense breast, correlation coefficient of r was 0.790 for mammography and 0.678 for ultrasonography; in heterogeneously dense and extremely dense breast, correlation coefficient of r was 0.770 for mammography and 0.548 for ultrasonography. In microcalcification positive group, coeffient of r was 0.772 for mammography and 0.570 for ultrasonography. In microcalcification negative group, coeffient of r was 0.806 for mammography and 0.783 for ultrasonography. Conclusion: Mammography was more accurate than ultrasonography in measuring the largest cancer diameter in DCIS of breast cancer. The correlation coefficient improved in the group of almost entirely fatty/ scattered areas of fibroglandular dense breast or in microcalcification negative group.

scholarly journals High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer

2021 ◽  
pp. jmedgenet-2020-107347
Author(s):  
D Gareth Evans ◽  
Elke Maria van Veen ◽  
Helen J Byers ◽  
Sarah J Evans ◽  
George J Burghel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Ductal Carcinoma ◽  
Cancer Genes ◽  
Early Onset Breast Cancer ◽  
Younger Women ◽  
Pathogenic Variants ◽  
Younger Age ◽  
Predisposition Genes

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

scholarly journals The Emerging Roles of Steroid Hormone Receptors in Ductal Carcinoma in Situ (DCIS) of the Breast

2018 ◽  
Vol 23 (4) ◽  
pp. 237-248 ◽  
Author(s):  
Hugo Villanueva ◽  
Sandra Grimm ◽  
Sagar Dhamne ◽  
Kimal Rajapakshe ◽  
Adriana Visbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Hormone Receptors ◽  
Ductal Carcinoma ◽  
Clinical Problem ◽  
Experimental Models ◽  
Steroid Hormone Receptors ◽  
Cancer Risk Factors

Abstract Ductal carcinoma in situ (DCIS) is a non-obligate precursor to most types of invasive breast cancer (IBC). Although it is estimated only one third of untreated patients with DCIS will progress to IBC, standard of care for treatment is surgery and radiation. This therapeutic approach combined with a lack of reliable biomarker panels to predict DCIS progression is a major clinical problem. DCIS shares the same molecular subtypes as IBC including estrogen receptor (ER) and progesterone receptor (PR) positive luminal subtypes, which encompass the majority (60–70%) of DCIS. Compared to the established roles of ER and PR in luminal IBC, much less is known about the roles and mechanism of action of estrogen (E2) and progesterone (P4) and their cognate receptors in the development and progression of DCIS. This is an underexplored area of research due in part to a paucity of suitable experimental models of ER+/PR + DCIS. This review summarizes information from clinical and observational studies on steroid hormones as breast cancer risk factors and ER and PR as biomarkers in DCIS. Lastly, we discuss emerging experimental models of ER+/PR+ DCIS.

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.

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