scholarly journals Efficacy of fluvastatin and aspirin for prevention of hormonally insensitive breast cancer

2021 ◽  
Author(s):  
Anjana Bhardwaj ◽  
Matthew D. Embury ◽  
Raniv D. Rojo ◽  
Constance Albarracin ◽  
Isabelle Bedrosian
Keyword(s):  
Breast Cancer ◽  
Apoptotic Cell ◽  
Low Cost ◽  
Vehicle Control ◽  
Tumor Burden ◽  
Tumor Incidence ◽  
Breast Cancers ◽  
Tumor Multiplicity ◽  
Low Toxicity ◽  
Fluvastatin Treatment

Abstract Purpose Primary prevention of hormonally insensitive breast cancers remains an important clinical need and repurposing existing low-toxicity drugs represents a low-cost, efficient strategy for meeting this goal. This study targeted the cholesterol pathway using fluvastatin, a cholesterol-lowering drug, and aspirin, an AMPK activator that acts as a brake in the cholesterol pathway, in a transgenic mouse model of triple-negative breast cancer (TNBC). Methods Using SV40C3 TAg mice, the efficacy and mechanism of fluvastatin, aspirin, or both in combination were compared with vehicle alone. Results Sixteen-weeks of fluvastatin treatment resulted in significant delay in onset of tumors (20 weeks vs. 16.8 weeks in vehicle treatment, p = 0.01) and inhibited tumor incidence and tumor multiplicity by 50% relative to the vehicle control. In animals that developed tumors, fluvastatin treatment inhibited tumor weight by 75% relative to vehicle control. Aspirin alone did not significantly affect tumor latency, tumor incidence or tumor burden compared to vehicle control. Fluvastatin and aspirin in combination delayed the onset of tumors but failed to inhibit tumor incidence and tumor multiplicity. The growth-inhibitory effects of fluvastatin were mediated through increased FAS/FASL mediated apoptotic cell death that was characterized by increased cleaved PARP and driven in part by depletion of an isoprenoid, geranyl geranyl pyrophosphate (GGPP). Conclusions In line with NCI’s emphasis to repurpose low-toxicity drugs for prevention of cancer, fluvastatin was effective for prevention of TNBC and warrants further clinical testing. Aspirin did not provide chemopreventive benefit.

scholarly journals Multidisciplinary Approach to Neoadjuvant Endocrine Therapy in Breast Cancer: A Comprehensive Review

2016 ◽  
Vol 38 (12) ◽  
pp. 615-622 ◽  
Author(s):  
Tomás Reinert ◽  
Susana Ramalho ◽  
Rodrigo Gonçalves ◽  
Carlos Barrios ◽  
Marcia Graudenz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Low Income ◽  
Hormone Receptor ◽  
Urban Areas ◽  
Low Cost ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Breast Cancers ◽  
Neoadjuvant Endocrine Therapy

AbstractBreast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.

[10]-Gingerol Affects Multiple Metastatic Processes and Induces Apoptosis in MDAMB- 231 Breast Tumor Cells

2019 ◽  
Vol 19 (5) ◽  
pp. 645-654 ◽  
Author(s):  
Angelina M. Fuzer ◽  
Ana C.B.M. Martin ◽  
Amanda B. Becceneri ◽  
James A. da Silva ◽  
Paulo C. Vieira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Antitumor Agents ◽  
Apoptotic Cell ◽  
3D Culture ◽  
Primary Concern ◽  
Breast Cancers ◽  
Her2 Gene

Background: Triple Negative Breast Cancer (TNBC) represents the approximately 15% of breast cancers that lack expression of Estrogen (ER) and Progesterone Receptors (PR) and do not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene, imposing difficulties to treatment. Interactions between tumor cells and their microenvironment facilitate tumor cell invasion in the surrounding tissues, intravasation through newly formed vessels, and dissemination to form metastasis. To treat metastasis from breast and many other cancer types, chemotherapy is one of the most extensively used methods. However, its efficacy and safety remain a primary concern, as well as its toxicity and other side effects. Thus, there is increasing interest in natural antitumor agents. In a previous work, we have demonstrated that [10]-gingerol is able to revert malignant phenotype in breast cancer cells in 3D culture and, moreover, to inhibit the dissemination of TNBC to multiple organs including lung, bone and brain, in spontaneous and experimental in vivo metastasis assays in mouse model. Objective: This work aims to investigate the in vitro effects of [10]-gingerol, using human MDA-MB-231TNBC cells, in comparison to non-tumor MCF-10A breast cells, in order to understand the antitumor and antimetastatic effects found in vivo and in a 3D environment. Methods: We investigated different steps of the metastatic process in vitro, such as cell migration, invasion, adhesion and MMP activity. In addition, we analyzed the anti-apoptotic and genotoxic effects of [10]-gingerol using PEAnnexin, DNA fragmentation, TUNEL and comet assays, respectively. Results: [10]-gingerol was able to inhibit cell adhesion, migration, invasion and to induce apoptosis more effectively in TNBC cells, when compared to non-tumor cells, demonstrating that these mechanisms can be involved in the antitumor and antimetastatic effects of [10]-gingerol, found both in 3D culture and in vivo. Conclusion: Taken together, results found here are complementary to previous studies of our group and others and demonstrate that additional mechanisms, besides apoptotic cell death, is used by [10]-gingerol to accomplish its antitumor and antimetastatic effects. Our results indicate a potential for this natural compound as an antitumor molecule or as an adjuvant for chemotherapeutics already used in the clinic.

scholarly journals Newly Synthesized Imino-Derivatives Analogues of Resveratrol Exert Inhibitory Effects in Breast Tumor Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7797
Author(s):  
Domenico Iacopetta ◽  
Rosamaria Lappano ◽  
Annaluisa Mariconda ◽  
Jessica Ceramella ◽  
Maria Stefania Sinicropi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anticancer Agents ◽  
Breast Tumor ◽  
Topoisomerase Ii ◽  
Apoptotic Cell ◽  
Beneficial Effects ◽  
Small Series ◽  
Low Toxicity ◽  
Anti Tumor Activity

Breast cancer represents the most frequently diagnosed malignancy in women worldwide. Various therapeutics are currently used in order to halt the progression of breast tumor, even though certain side effects may limit the beneficial effects. In recent years, many efforts have been addressed to the usefulness of natural compounds as anticancer agents due to their low toxicity. Resveratrol, a stilbene found in grapes, berries, peanuts and soybeans, has raised a notable interest for its antioxidant, anti-inflammatory, and antitumor properties. Here, we report the design, the synthesis and the characterization of the anticancer activity of a small series of imino N-aryl-substituted compounds that are analogues of resveratrol. In particular, the most active compound, named 3, exhibited anti-tumor activity in diverse types of breast cancer cells through the inhibition of the human topoisomerase II and the induction of apoptotic cell death. Therefore, the abovementioned compound maybe considered as a promising agent in more comprehensive treatments of breast cancer.

scholarly journals Inhibition of Cell Growth and Induction of Apoptosis byAntrodia camphoratain HER-2/neu-Overexpressing Breast Cancer Cells through the Induction of ROS, Depletion of HER-2/neu, and Disruption of the PI3K/Akt Signaling Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Chuan-Chen Lee ◽  
Hsin-Ling Yang ◽  
Tzong-Der Way ◽  
K. J. Senthil Kumar ◽  
Ying-Chen Juan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Apoptotic Cell ◽  
Immunoblot Analysis ◽  
Ros Generation ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Her 2

Previously, we demonstrated that a submerged fermentation culture ofAntrodia camphorata(AC) promotes cell-cycle arrest and apoptosis in human estrogen receptor-positive/negative breast cancer cells. However, whether AC is effective against HER-2/neu-overexpressing breast cancers has not been thoroughly elucidated. In the present study, we showed that AC exhibited a significant cytotoxic effect against HER-2/neu-overexpressing MDA-MB-453 and BT-474 cells. Immunoblot analysis demonstrated that HER-2/neuand their tyrosine phosphorylation were inhibited by AC in a dose-dependent manner. An increase in intracellular reactive oxygen species (ROS) was observed in AC-treated cells, whereas antioxidantN-acetylcysteine (NAC) significantly prevented AC induced HER-2/neudepletion and cell death, which directly indicates that AC-induced HER-2/neudepletion and cell death was mediated by ROS generation. Also, AC significantly downregulated the expression of cyclin D1, cyclin E, and CDK4 followed by the suppression of PI3K/Akt, and their downstream effectors GSK-3βandβ-catenin. Notably, AC-treatment induced apoptotic cell death, which was associated with sub-G1 accumulation, DNA fragmentation, mitochondrial dysfunction, cytochromecrelease, caspase-3/-9 activation, PARP degradation, and Bcl-2/Bax dysregulation. Assays for colony formation also confirmed the growth-inhibitory effects of AC. This is the first report confirming the anticancer activity of this potentially beneficial mushroom against human HER-2/neu-overexpressing breast cancers.

scholarly journals DNA–affibody nanoparticle delivery system for cisplatin-based breast cancer chemotherapy

RSC Advances ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 1982-1989 ◽  
Author(s):  
Chao Zhang ◽  
HongLei Zhang ◽  
MengNan Han ◽  
XueLi Yang ◽  
ChaoHong Pei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Delivery System ◽  
High Specificity ◽  
The Novel ◽  
Breast Cancers ◽  
High Efficacy ◽  
Breast Cancer Chemotherapy ◽  
Nanoparticle Delivery ◽  
Dna Tetrahedron ◽  
Low Toxicity

The novel nano-drug cisplatin-DNA tetrahedron-affibody has high specificity, high efficacy, and low toxicity for the treatment of HER2-overexpressing breast cancers.

Mastectomy rates in relation to adoption of a margin guideline.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 508-508
Author(s):  
Monica Morrow ◽  
Steven J. Katz ◽  
Reshma Jagsi
Keyword(s):  
Breast Cancer ◽  
Los Angeles ◽  
Surgical Procedure ◽  
Low Cost ◽  
Negative Margin ◽  
Breast Cancers ◽  
Multinomial Regression ◽  
Survey Period ◽  
Additional Surgery ◽  
The Impact

508 Background: Surgery after initial lumpectomy to obtain a bigger negative margin is common and may lead to mastectomy. The impact of a 2014 consensus statement endorsing a minimal negative margin for invasive breast cancer on surgeon attitudes, re-excision rates, and final surgical procedure is uncertain. Methods: Women with stage I and II breast cancer diagnosed between 7/13–8/15 and reported to the Los Angeles and Detroit SEER registries were surveyed about 2 months post diagnosis, and 70% responded; 3729 comprise the analytic sample. All attending surgeons identified by the patients (n=489) were sent a questionnaire at the end of the patient survey period, and 376 (77%) responded. Pathology reports were reviewed for margin status. Multinomial regression models were used to assess trends. Results: The 67% initial lumpectomy rate was unchanged during the study. The final lumpectomy rate increased by 13% (to 65% from 52%) from 2013–2015, accompanied by a decrease in unilateral (to 18% from 27%) and bilateral (to 16% from 21%) mastectomy (p=0.002). Surgery after lumpectomy, both re-excision and mastectomy, declined by 16% (p<0.001). Pathology review showed no association between date of treatment and positive margins. Patient report of surgeon-recommended mastectomy after initial lumpectomy declined to 8% from 20% (p<0.001). 69% of surgeons endorsed a margin of no ink on tumor to avoid re-excision in ER+PR+ cancer and 63% for ER-PR- cancer. Surgeons treating >50 breast cancers annually were more likely to accept this margin than those treating <20 cases (p<0.001). Conclusions: Additional surgery after initial lumpectomy markedly decreased between 2013‒2015 after publication of a margin guideline endorsinga minimal negative margin. This resulted in a substantial increase in lumpectomy as the definitive surgical procedure, which illustrates that guidelines can be an effective, low-cost approach to addressing clinical controversies.

scholarly journals Vitamin D Metabolite Profile in Cholecalciferol- or Calcitriol-Supplemented Healthy and Mammary Gland Tumor-Bearing Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3416
Author(s):  
Artur Anisiewicz ◽  
Konrad Kowalski ◽  
Joanna Banach ◽  
Natalia Łabędź ◽  
Martyna Stachowicz-Suhs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Tumor Growth ◽  
Vitamin D3 ◽  
Metabolite Profile ◽  
Tumor Burden ◽  
Breast Cancers ◽  
Tumor Bearing ◽  
4T1 Breast Cancer ◽  
The Impact

To analyze if the prometastatic activity of calcitriol (active vitamin D3 metabolite), which was previously observed in a 4T1 breast cancer model, is also found in other breast cancers, and to assess the impact of various schemes of vitamin D supply, we used 4T1 and E0771 mouse metastatic and 67NR nonmetastatic cells in this study. BALB/c and C57BL/6 healthy and tumor-bearing mice were exposed to a control (1000 IU), low- (100 IU), and high- (5000 IU) vitamin D3 diets. Additionally, from day 7 of tumor transplantation, the 1000 and 100 IU groups were gavaged with calcitriol (+cal). After 8 weeks of feeding, plasma levels of 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 were significantly lower in calcitriol-treated and vitamin D-deficient groups than in the control, whereas the levels of all metabolites were increased in the 5000 IU group. The ratio of 25(OH)D3:24,25(OH)2D3 was increased in both calcitriol-treated groups, whereas the ratio of 25(OH)D3:3-epi-25(OH)D3 was increased only in the 100 IU group but decreased in the 5000 IU group. In contrast to E0771, 4T1 lung metastasis was accelerated in all vitamin D-supplemented mice, as well as in the deficient group with an increased inflammatory response. 67NR tumor growth was transiently inhibited in the 1000 IU+cal group, but single metastases were observed in the 5000 and 100 IU groups. Based on the results, we conclude that various schemes of vitamin D supply and vitamin D deficiency led to similar metabolite profiles irrespective of the mice strain and tumor burden. However, depending on the type of breast cancer, different effects on tumor growth and metastasis were noticed.

Chemo preventive potential of Methanolic extract of bark of Albizia lebbeck (L.) benth on n-methyl-n-nitrosourea induced mammary carcinoma in female sprague dawley rats

2021 ◽  
pp. 5985-5990
Author(s):  
Ariharasivakumar G. ◽  
Dithu Thekkekkara
Keyword(s):  
Breast Cancer ◽  
Methanolic Extract ◽  
Tumor Burden ◽  
The Body ◽  
Biologically Active ◽  
Tumor Incidence ◽  
Albizia Lebbeck ◽  
Sprague Dawley ◽  
Duct Carcinoma ◽  
Sprague Dawley Rats

Introduction: Use of plants as a source of medicine has been inherited and is an important component of the health care system. Plants are a good source of biologically active compounds known as phytochemicals. The search for anticancer agents from plant sources started in 1950s with the discovery and development of vinca alkaloids, vincristine and vinblastine and the isolation of cytotoxic podophyllotoxin. Many chemotherapeutic agents are avilable their usage is limited due to development of side effects. Recent research demonstrates that plant based phytonutrients are effective in combating the incidence of carcinogenesis. So the purpose of this study is to reveal the relationship between breast cancer and chemopreventive effect of bark of Albizia lebbeck benth to protect against NMU induced mammary cancer in female spraque- dawley rats, and would foster further studies that could ultimately lead to prevention and therapy for breast cancer. Materials and methods: Virgin Female Sprague-Dawley rats were grouped into 5 groups (n=6). Thirty days before the induction of tumor the animals were treated with extracts. At the end of the 30th day tumor was induced by administrating NMU (50 mg/ kg i.p) was induced by single i.p injection, and then the treatment is continued up to a period of 120 days. At the end of the 120th day the animals were sacrificed through cervical decapitation, the mammary tumors were excised out and various parameters were studied such as tumor incidence, tumor burden, tumor volume, tumor weight and tumor latency. Also immunohistochemistry and histopathology were performed. Result: The i.p administration of NMU to the rats showed significant decrease in the body weight compared to normal control rats. After the administration of methanolic extract of Albizia lebbeck benth at different doses showed considerable prevention of weight loss when compared to NMU control rats. Also,in treated groups tumor incidence and tumor burden was decreased and tumor latency got increased. In addition histopathological studies supported significant decrease in formation of infiltrating duct carcinoma in mammory tissue sections. Conclusion: In the present study, methanolic extract of Albizia lebbeck benth showed protective effect against N-methyl-N-nitrosourea induced breast cancer.

Performance of a semi-automatic machine leaning method for discriminating HER2 2+ status of breast cancers based on DCE-MRI (Preprint)

2019 ◽  
Author(s):  
Lirong Song ◽  
Zejun Jiang ◽  
Hecheng Lu ◽  
Jiandong Yin
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Low Cost ◽  
Principal Component ◽  
Texture Features ◽  
Classification Performance ◽  
Image Features ◽  
Support Vector ◽  
Breast Cancers ◽  
Dce Mri

BACKGROUND Amplification status of human epidermal growth factor receptor2 (HER2) 2+ is currently tested by fluorescence in situ hybridization (FISH). However, the FISH technique is expensive, time consuming, and requires off-site testing. The requirement for alternative low-cost and accurate surrogate measures to formal genetic analysis is urgent. In addition, machine learning is broadly accepted for its ability to decipher complicated connections between medical image features and gene expression status. OBJECTIVE To investigate the potential association between texture features extracted from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and HER2 2+ amplification status of breast cancer. METHODS 92 patients with HER2 2+ breast cancer who underwent 3T MRI and FISH detection in 2018 were retrospectively selected, including 52 HER2 2+ positive and 40 negative cases. The lesion area was delineated semi-automatically with MATLAB, and a total of 307 texture features were extracted from precontrast, postcontrast, and subtraction images, independently. The Student’s t-test or Mann-Whitney U test was performed to identify significant features between different HER2 2+ amplification status. Principal component analysis was used to eliminate the feature correlations. Three machine learning classifiers, logistic regression analysis, quadratic discriminant analysis, and support vector machine (SVM), were with a leave-one-outcross validation method used to establish the classification models of HER2 2+ amplification status. Classification performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS Texture features calculated from subtraction images showed more promising results than those obtained from pre- and postcontrast images. The model with the SVM based on features from subtraction image achieved the best performance, with an area under the ROC curve of 0.890, sensitivity of 80.77%, specificity of 85.00%, and accuracy of 82.61%. CONCLUSIONS To a certain extent, texture features of breast cancer extracted from DCE-MRI are associated with HER2 2+ amplification status. Additional studies are necessary to confirm the present preliminary findings.

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