scholarly journals Mechanisms of Bone Metastasis of Malignancies of the Genito-Mammary Area

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 42
Author(s):  
R. Bohîlțea ◽  
N. Turcan ◽  
T.A. Georgescu ◽  
M.M. Cîrstoiu
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Molecular Mechanisms ◽  
Bone Matrix ◽  
Cell Activity ◽  
Hematopoietic Stem ◽  
Wnt Proteins ◽  
Increased Risk ◽  
Wide Range

Abstract Bone metastasis is a frequent complication of advanced genito-mammary cancer patients. Skeletal involvement is particularly common in breast cancer. Bone metastases induce a wide range of symptoms, lowering the quality of life and shortening survival. The normal bone remodeling process is deeply affected in all types of metastases: osteolytic, osteoblastic, and mixed. The main mechanisms involved in bone metastatic dissemination are the expression of adhesion tumor molecules and corresponding receptors within bone marrow and bone matrix cells; local growth factors, molecular mechanisms of remodeling the hematopoietic stem cell activity, and alteration of the expression of the post-transcriptional regulatory microRNAs of the gene expression are the new theories developed from recent studies. Abnormalities in the number of copies of the 16q23 gene explain the increased risk of bone metastasis of breast cancer compared to its dissemination to the other organs; the mutual interaction between tumor cells and the bone microenvironment constitutes the element that stimulates both bone destruction and tumor development. Endothelin -1, bone morphogenic proteins, platelet-derived growth factor, Wnt proteins stimulate proliferation and osteoblastic activity. Genomic and proteomic studies underlie the development of new therapeutic agents for the treatment and prevention of bone metastases.

PTHrP(12-48) for the diagnosis of breast cancer bone metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21039-e21039
Author(s):  
Charity L. Washam ◽  
Stephanie D. Byrum ◽  
Kim Leitzel ◽  
Ali M. Suhail ◽  
Allan Lipton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
Parathyroid Hormone Related Protein ◽  
Increased Risk ◽  
Breast Cancer Bone Metastasis

e21039 Background: Bone metastasis of breast cancer significantly compromises patient morbidity and mortality. Currently, no reliable methods detect or predict patients at increased risk for developing bone metastasis. We utilized 3 independent cohorts of breast cancer patients to validate a highly discriminatory plasma-based proteomic profile that identifies breast cancer bone metastasis. The identity of the most discriminatory protein component identified was a parathyroid hormone-related protein fragment, PTHrP(12-48). Methods: Plasma samples collected from 21 breast cancer patients with clinical evidence of a bone metastasis and 21 patients with no evidence of bone metastasis from time of diagnosis to clinical outcome were evaluated. A novel mass spectrometry-based assay using human serum spiked with synthetic PTHrP(12-48) was used to measure PTHrP(12-48) concentrations (pg/μl). Statistical significance was assessed by one-way ANOVA. ROC curves evaluated the diagnostic potential of PTHrP(12-48) and a simple logistic regression derived from the combined measurement of PTHrP(12-48) and NTx. Results: PTHrP(12-48) concentrations ranged between 11.6 and 92.1 pg/μl in bone metastasis patients and between 4.5 and 34.2 pg/μl in patients without bone metastases. PTHrP(12-48) was significantly increased in bone metastasis plasma (p < 0.05). No significant correlation was identified between PTHrP(12-48) and NTx. ROC analysis of PTHrP(12-48), threshold 18 pg/μl, classified the two groups with high accuracy. Class prediction by the PTHrP(12-48)/NTx logistic regression model increased diagnostic specificity. Conclusions: The measurement of PTHrP(12-48) in patient plasma has potential as a viable clinical measure of bone metastasis. In combination with serum NTx, PTHrP(12-48) may assist in identifying bone metastases in patients presenting with low to normal bone turnover markers.

Biological and Toxicological Evaluation of N-(4methyl-phenyl)-4-methylphthalimide on Bone Cancer in Mice

2019 ◽  
Vol 19 (5) ◽  
pp. 667-676
Author(s):  
José R. Santin ◽  
Gislaine F. da Silva ◽  
Maria V.D. Pastor ◽  
Milena F. Broering ◽  
Roberta Nunes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
In Silico ◽  
Bone Matrix ◽  
Micronucleus Assay ◽  
Repeated Treatment ◽  
Toxicological Evaluation ◽  
Toxicological Analysis ◽  
Breast Cancer Bone Metastasis

Background: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. Methods: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. Results: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. Conclusion: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.

Molecular Mechanisms Underlying the Anti-Breast Cancer Stem Cell Activity of Pterocladia capillacea and Corallina officinalis Polysaccharides

2021 ◽  
Vol 21 ◽  
Author(s):  
Hebatallah G. Hafez ◽  
Rafat M. Mohareb ◽  
Sohair M. Salem ◽  
Azza A. Matloub ◽  
Emad F. Eskander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protein Complexes ◽  
Cell Activity ◽  
Sulfated Polysaccharide ◽  
Corallina Officinalis ◽  
Stem Cell Activity ◽  
Mcf 7

Objective: This study aimed to appraise the activity of Pterocladia capillacea and Corallina officinalis polysaccharides against breast cancer stem cells (BCSCs). P. capillacea and C. officinalis polysaccharides were characterized to be sulfated polysaccharide-protein complexes. Methods: Cytotoxicity of the polysaccharides against MDA-MB-231 and MCF-7 cell lines along with their impact on CD44+/CD24− and aldehyde dehydrogenase 1(ALDH1) positive BCSC population were determined. Their effect on gene expression of CSC markers, Wnt/β-catenin and Notch signaling pathways was evaluated. Results: P. capillacea and C. officinalis polysaccharides inhibited the growth of breast cancer cells and reduced BCSC subpopulation. P. capillacea polysaccharides significantly down-regulated OCT4, SOX2, ALDH1A3 and vimentin in MDA-MB-231 as well as in MCF-7 cells except for vimentin that was up-regulated in MCF-7 cells. C. officinalis polysaccharides exhibited similar effects except for OCT4 that was up-regulated in MDA-MB-231 cells. Significant suppression of Cyclin D1 gene expression was noted in MDA-MB-231 and MCF-7 cells treated with P. capillacea or C. officinalis polysaccharides. β-catenin and c-Myc genes were significantly down-regulated in MDA-MB-231 cells treated with C. officinalis and P. capillacea polysaccharides, respectively, while being up-regulated in MCF-7 cells treated with either of them. Additionally, P. capillacea and C. officinalis polysaccharides significantly down-regulated Hes1 gene in MCF-7 cells despite increasing Notch1 gene expression level. However, significant down-regulation of Notch1 gene was observed in MDA-MB-231 cells treated with P. capillacea polysaccharides. Conclusion: Collectively, this study provides evidence for the effectiveness of P. capillacea and C. officinalis polysaccharides in targeting BCSCs through interfering with substantial signaling pathways contributing to their functionality.

scholarly journals TIE2 Induces Breast Cancer Cell Dormancy and Inhibits the Development of Osteolytic Bone Metastases

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 868
Author(s):  
Florian Drescher ◽  
Patricia Juárez ◽  
Danna L. Arellano ◽  
Nicolás Serafín-Higuera ◽  
Felipe Olvera-Rodriguez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Kinase Inhibitors ◽  
Disseminated Tumor Cells ◽  
Tyrosine Kinase Receptor ◽  
In Vivo Models ◽  
Hematopoietic Stem ◽  
Cell Dormancy

Breast cancer (BCa) cells disseminating to the bone can remain dormant and resistant to treatments for many years until relapsing as bone metastases. The tyrosine kinase receptor TIE2 induces the dormancy of hematopoietic stem cells, and could also induce the dormancy of BCa cells. However, TIE2 is also a target for anti-angiogenic treatments in ongoing clinical trials, and its inhibition could then restart the proliferation of dormant BCa cells in bone. In this study, we used a combination of patient data, in vitro, and in vivo models to investigate the effect of TIE2 in the dormancy of bone metastases. In BCa patients, we found that a higher TIE2 expression is associated with an increased time to metastases and survival. In vitro, TIE2 decreased cell proliferation as it increased the expression of cyclin-dependent kinase inhibitors CDKN1A and CDKN1B and arrested cells in the G0/G1 phase. Expression of TIE2 also increased the resistance to the chemotherapeutic 5-Fluorouracil. In mice, TIE2 expression reduced tumor growth and the formation of osteolytic bone metastasis. Together, these results show that TIE2 is sufficient to induce dormancy in vitro and in vivo, and could be a useful prognostic marker for patients. Our data also suggest being cautious when using TIE2 inhibitors in the clinic, as they could awaken dormant disseminated tumor cells.

scholarly journals Bone Metastasis Prognostic Factors in Breast Cancer

2019 ◽  
Vol 13 ◽  
pp. 117822341983097 ◽  
Author(s):  
Akram Yazdani ◽  
Sara Dorri ◽  
Alireza Atashi ◽  
Hoda Shirafkan ◽  
Hedieh Zabolinezhad
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Bone Metastasis ◽  
Lymph Nodes ◽  
Bone Metastases ◽  
Tumor Size ◽  
Menopausal Status ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Factors Associated

Objective: Bone is the most common site of metastasis in breast cancer. Prognostic factors for predicting bone metastases in breast cancer are controversial yet. In this study, we investigated clinical factors associated with secondary bone metastasis of breast cancer. Methods: In total, 1690 patients with breast cancer recorded between 2002 and 2012 in Motamed Cancer Institute, Tehran, Iran entered in the retrospective study. We studied age, menopausal status, histologic type, tumor size, number of cancerous axillary lymph nodes, serum concentrations of alkaline phosphatase (ALP), carcinogenicity antigen (CEA), cancer antigen (CA)-153, and hemoglobin (HB) in 2 groups with bone metastases (n = 123) and without it, respectively. We applied logistic regression to identify bone metastasis prognostic factors in breast cancer patients and calculated the cut-off value, sensitivity, and characteristics of independent prognostic factors using receiver operating characteristic (ROC) curve analysis. Results: Menopause, larger tumor size, and the greater number of cancerous axillary lymph nodes increased the chance of bone metastases significantly ( P < .05). There was no significant difference between mean groups with and without bone metastases regarding serum concentration of CEA, CA-153, HB, and histopathologic type ( P > .05). Logistic regression showed that age (odds ratio (OR) = 1.021), menopausal status (OR = 1.854), number of cancerous axillary lymph nodes (OR = 1.065), a tumor size between 2 and 5 cm diameter (OR = 2.002) and more than 5 cm diameter (OR = 4.009), and ALP (OR = 1.005) are independent prognostic factors associated with bone metastases. The ROC curve showed that the abovementioned factors have comparable predictive accuracy for bone metastases. Conclusions: Age, menopausal status, number of axillary lymph node metastases, tumor size, and ALP were identified as prognostic factors for bone metastasis in patients with breast cancer. So patients with these characteristics should be monitored more precisely with regular follow-ups.

scholarly journals Obesity and Breast Cancer: A Case of Inflamed Adipose Tissue

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1686 ◽  
Author(s):  
Ryan Kolb ◽  
Weizhou Zhang
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Breast Cancer Incidence ◽  
Menopausal Status ◽  
Epidemiological Data ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Cancer Subtypes ◽  
Increased Risk

Obesity is associated with an increased risk of estrogen receptor-positive breast cancer in postmenopausal women and a worse prognosis for all major breast cancer subtypes regardless of menopausal status. While the link between obesity and the pathogenesis of breast cancer is clear, the molecular mechanism of this association is not completely understood due to the complexity of both obesity and breast cancer. The aim of this review is to highlight the association between obesity and breast cancer and discuss the literature, which indicates that this association is due to chronic adipose tissue inflammation. We will discuss the epidemiological data for the association between breast cancer incidence and progression as well as the potential molecular mechanisms for this association. We will focus on the role of inflammation within the adipose tissue during the pathogenesis of breast cancer. A better understanding of how obesity and adipose tissue inflammation affects the pathogenesis of breast cancer will lead to new strategies to reduce breast cancer risk and improve patient outcomes for obese patients.

scholarly journals Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Rachel Eyre ◽  
Denis G. Alférez ◽  
Angélica Santiago-Gómez ◽  
Kath Spence ◽  
James C. McConnell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Colony Formation ◽  
Breast Cancer Cells ◽  
Wnt Signalling ◽  
Early Event ◽  
Metastatic Lesions ◽  
Breast Cancer Bone Metastasis

Abstract Dissemination of tumour cells to the bone marrow is an early event in breast cancer, however cells may lie dormant for many years before bone metastases develop. Treatment for bone metastases is not curative, therefore new adjuvant therapies which prevent the colonisation of disseminated cells into metastatic lesions are required. There is evidence that cancer stem cells (CSCs) within breast tumours are capable of metastasis, but the mechanism by which these colonise bone is unknown. Here, we establish that bone marrow-derived IL1β stimulates breast cancer cell colonisation in the bone by inducing intracellular NFkB and CREB signalling in breast cancer cells, leading to autocrine Wnt signalling and CSC colony formation. Importantly, we show that inhibition of this pathway prevents both CSC colony formation in the bone environment, and bone metastasis. These findings establish that targeting IL1β-NFKB/CREB-Wnt signalling should be considered for adjuvant therapy to prevent breast cancer bone metastasis.

CA 15.3 with Urinary Calcium Excretion is Useful in the Diagnosis and Monitoring of Bone Metastases from Breast Cancer

1993 ◽  
Vol 8 (4) ◽  
pp. 208-214
Author(s):  
G.C. Yadav ◽  
A. Rao ◽  
M.M. Motawy ◽  
N. Safadi ◽  
M. Jameel Ahmed
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Serum Levels ◽  
Urinary Calcium ◽  
Response To Therapy ◽  
Urinary Calcium Excretion ◽  
Calcium Excretion ◽  
Diagnostic Efficacy ◽  
Ca 15.3

Serum levels of breast carcinoma antigen (CA 15.3) and urinary calcium excretion (UCa) were determined in 73 patients with breast cancer: 36 without bone metastases (stage I-IV) and 37 with bone metastases. The patients in the latter group were further investigated at 2,4 and 6 months from the start of treatment. Both markers showed significant elevations in the group with bone metastases (CA 15.3: P = 1.0×10–6, UCa: P = 8.6×10–9). The bone metastasis index (BMI), which represents the combination of the markers, had better diagnostic efficacy (90%) than CA 15.3 alone (84%) or UCa alone (82%). During treatment of bone metastasis, the longitudinal levels of the markers showed a highly significant association with the therapeutic response assessed by the UICC criteria. For identifying progression of disease, the diagnostic efficacy of CA 15.3, UCa and a combination of both, the so-called Biochemical Index of Response (BIR), was 65%, 70% and 79%, respectively, at two months and 89%, 84% and 92% at four months. Application of the tandem, CA 15.3 with UCa, was very useful for the detection of bone metastases and the prediction of response to therapy.

Multicenter Italian bone metastasis database: First prospective data on breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13072-e13072
Author(s):  
Alberto Bongiovanni ◽  
Flavia Foca ◽  
Manuela Fantini ◽  
Rosachiara Forcignano ◽  
Fabrizio Artioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Disease Diagnosis ◽  
Stage Iii ◽  
Breast Cancer Patients ◽  
Prospective Data ◽  
Luminal B

e13072 Background: Bone Metastases (BM) are still the main cause of morbidity and morbility in cancer patients because of their complications defined as skeletal-related events (SREs).SREs reduce pts quality of life and are associated with an increasing in social and health costs. At present, data concerning BM are mainly obtained retrospectively from monocentric experiences. Methods: We performed a multicentre prospective observational study of patients with BM from breast cancer (BC) with at least 6 month (m)'s follow-up who were registered in a prospective BM database (BMDB). Detailed information on patients at first diagnosis of BM was recorded in a custom-built software system, updated every 6 m by participating centres and reviewed by the coordinator centre.All pts have signed an informed consent. Results: Since October 2014,618 pts with BM from solid tumors were enrolled of whom 220 have BC as primitive site with a 6 m follow-up. Median age was 62 y (range 26-86). Median Follow up was 34 m (6-149). At enrolment 109 (50%) had only BM and 109 (50%) pts had concomitant visceral and BM. Median time to first BM was 47 m (range 0-312) in Bone only disease and 78.6 m in pts with visceral bone metastases. Disease Free interval (DFI) was different according to BC molecular subtypes and stage. The univariate hazard ratio (HR) for visceral or bone metastasis was higher in luminal B tumors (1.56, 95% confidence interval [CI]:1.1-2.3) (p = 0.002), basal-like (2.50, 95% CI:1.1-6.0) (p = 0.043), and HER2-enriched tumors (1.37, 95% CI:0.78-2.4) (p = 0.273). DFI for pts with stage I disease at diagnosis of primary BC was longer than that for stage III pts (median 67.2 m, 95%CI:53.1-96.1, vs. 58.1 m, 95%CI:41.9-73.4), with a HR of 1.84 (95% CI:1.1-3.0) (p = 0.015) for the stage III group, and 0.98 (95% C.I.:0.6-1.5) (p = 0.930) for the stage II group. During BM disease, 98 pts had at least 1 SREs . Zoledronate was used in 69.1% and Denosumab in 28.3% of cases. First line treatment was hormone-based (n = 105, 50.7%) chemo-based therapy (n = 80, 38.7%) and chemo+ormono based (n = 20, 9.7%). During follow up progression disease occurred in 167 pts. Median progression-free (mPFS) and overall survival calculated from metastatic disease diagnosis (mOS) were 15.1 m (95%CI 12.6-18.4) and 66.8 m (95%CI 52.1-79.2),respectively. Conclusions: This study presents prospective data about a cohort of BC pts enrolled at the first BM occurrence and followed over the time, extrapolated by the multicentric observational BMDB in order to better understed the clinical history of breast cancer and bone metastases.

scholarly journals The Role of Ovarian Sex Steroids in Metabolic Homeostasis, Obesity, and Postmenopausal Breast Cancer: Molecular Mechanisms and Therapeutic Implications

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Viroj Boonyaratanakornkit ◽  
Prangwan Pateetin
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Postmenopausal Breast Cancer ◽  
Cellular Metabolism ◽  
Obese Women ◽  
Therapeutic Implications ◽  
Estrogen Production ◽  
Increased Risk

Obese postmenopausal women have an increased risk of breast cancer and are likely to have a worse prognosis than nonobese postmenopausal women. The cessation of ovarian function after menopause results in withdrawal of ovarian sex steroid hormones, estrogen, and progesterone. Accumulating evidence suggests that the withdrawal of estrogen and progesterone causes homeostasis imbalances, including decreases in insulin sensitivity and leptin secretion and changes in glucose and lipid metabolism, resulting in a total reduction in energy expenditure. Together with a decrease in physical activity and consumption of a high fat diet, these factors significantly contribute to obesity in postmenopausal women. Obesity may contribute to breast cancer development through several mechanisms. Obesity causes localized inflammation, an increase in local estrogen production, and changes in cellular metabolism. In addition, obese women have a higher risk of insulin insensitivity, and an increase in insulin and other growth factor secretion. In this review, we describe our current understanding of the molecular actions of estrogen and progesterone and their contributions to cellular metabolism, obesity, inflammation, and postmenopausal breast cancer. We also discuss how modifications of estrogen and progesterone actions might be used as a therapeutic approach for obesity and postmenopausal breast cancer.

Sign in / Sign up

Export Citation Format

Share Document