scholarly journals L-Dopa-Decarboxylase (DDC) Is a Positive Prognosticator for Breast Cancer Patients and Epinephrine Regulates Breast Cancer Cell (MCF7 and T47D) Growth In Vitro According to Their Different Expression of Gi- Protein- Coupled Receptors

2020 ◽  
Vol 21 (24) ◽  
pp. 9565
Author(s):  
Eileen Tremmel ◽  
Christina Kuhn ◽  
Till Kaltofen ◽  
Theresa Vilsmaier ◽  
Doris Mayr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Breast Cancer Incidence ◽  
Dopa Decarboxylase ◽  
Breast Cancer Patients ◽  
Mcf7 Cells ◽  
Viability Assay ◽  
Gi Protein ◽  
Novel Target

A coherence between thyroid dysfunction and breast cancer incidence exists. Thyroid hormone metabolites bind to TAAR1 (trace amine-associated receptor 1) and through that modulate the serotonergic and dopaminergic system. Catecholamines themselves are synthesized by the L-dopa decarboxylase (DDC). The aim of our study was to analyze the influence of catecholamines on the DDC expression in primary breast cancer patients and the role of DDC concerning overall survival (OS). DDC expression was analyzed by immunohistochemistry. The effect of epinephrine on the expression of DDC and the Gi- protein was analyzed on the protein level via Western blot. A viability assay was performed to test the metabolic cell viability. The overexpression of DDC in the primary tumor was associated with longer OS (p = 0.03). Stimulation with epinephrine induced the downregulation of DDC (p = 0.038) and significantly increased viability in T47D cells (p = 0.028). In contrast, epinephrine induced an upregulation of DDC and decreased the proliferation of MCF7 cells (p = 0.028). Epinephrine led to an upregulation of Gi protein expression in MCF7 cells (p = 0.008). DDC is a positive prognostic factor for OS in breast cancer patients, and it is regulated through epinephrine differently in MCF7 and T47D. DDC may represent a novel target for the treatment of breast cancer, especially concerning its interaction with epinephrine.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions

Oncogene ◽  
2021 ◽  
Author(s):  
Francesco Pantano ◽  
Martine Croset ◽  
Keltouma Driouch ◽  
Natalia Bednarz-Knoll ◽  
Michele Iuliani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Osteolytic Lesions ◽  
Cell Colonization

AbstractBone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028). Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. M200 also markedly reduced tumor outgrowth in experimental models of bone metastasis or tumorigenesis, and blunted cancer-associated bone destruction. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro. Overall, this study identifies ITGA5 as a mediator of breast-to-bone metastasis and raises the possibility that volociximab/M200 could be repurposed for the treatment of ITGA5-positive breast cancer patients with bone metastases.

scholarly journals Letrozole Accelerates Metabolic Remodeling through Activation of Glycolysis in Cardiomyocytes: A Role beyond Hormone Regulation

2022 ◽  
Vol 23 (1) ◽  
pp. 547
Author(s):  
Jun H. Heo ◽  
Sang R. Lee ◽  
Seong Lae Jo ◽  
Hyun Yang ◽  
Hye Won Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Patients ◽  
Cardiovascular Effects ◽  
Female Rats ◽  
Acid Oxidation ◽  
Hormone Regulation ◽  
Breast Cancer Patients ◽  
Metabolic Remodeling

Estrogen receptor-positive (ER+) breast cancer patients are recommended hormone therapy as a primary adjuvant treatment after surgery. Aromatase inhibitors (AIs) are widely administered to ER+ breast cancer patients as estrogen blockers; however, their safety remains controversial. The use of letrozole, an AI, has been reported to cause adverse cardiovascular effects. We aimed to elucidate the effects of letrozole on the cardiovascular system. Female rats exposed to letrozole for four weeks showed metabolic changes, i.e., decreased fatty acid oxidation, increased glycolysis, and hypertrophy in the left ventricle. Although lipid oxidation yields more ATP than carbohydrate metabolism, the latter predominates in the heart under pathological conditions. Reduced lipid metabolism is attributed to reduced β-oxidation due to low circulating estrogen levels. In letrozole-treated rats, glycolysis levels were found to be increased in the heart. Furthermore, the levels of glycolytic enzymes were increased (in a high glucose medium) and the glycolytic rate was increased in vitro (H9c2 cells); the same was not true in the case of estrogen treatment. Reduced lipid metabolism and increased glycolysis can lower energy supply to the heart, resulting in predisposition to heart failure. These data suggest that a letrozole-induced cardiac metabolic remodeling, i.e., a shift from β-oxidation to glycolysis, may induce cardiac structural remodeling.

scholarly journals Lifestyle breast cancer patients among Indonesian women: A nationwide survey

2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Solikhah Solikhah ◽  
Khairunnisaa Nuur Aliifah Setyawati ◽  
Monthida Sangruangake
Keyword(s):  
Breast Cancer ◽  
High School ◽  
Cancer Patients ◽  
Breast Cancer Incidence ◽  
Education Level ◽  
Lifestyle Changes ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Major Health Problem ◽  
Significance Level

Recently, cancer is a major health problem in the world. Lifestyle changes and growing urbanization likely led to increasing breast cancer incidence in such in Indonesia. Therefore, this study aimed to explore lifestyle breast cancer patients among Indonesian women. The investigation was a cross-sectional study distributed among 3,392 females drawn from 13 out of 27 provinces in Indonesia. Multiple binary logistic regressions were conducted to investigate breast cancer risk among Indonesian. A significance level of 0.05 was employed in all analysis. Of the 3,392 respondents included in the analysis, more than half (52.71%; n=1,788) was aged 40–49 years old. The most common marital status of the participants was married (98.20%; n=3,331), followed by no smoking (94.69%; n=3,212) and active exercise (62.12%; n=2,107). Education level was significantly associated with breast cancer (AdjOR_Junior high school=0.21; 95%CI=0.06 to 0.70; p<0.01 and AdjOR_senior high school=0.60; 95%CI=0.15 to 2.26; p<0.05). Education level was significantly related to breast cancer. Lifestyle such as smoking and physical activity was suspected to affect breast cancer indirectly.

scholarly journals Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2605-2610 ◽  
Author(s):  
AA Ross ◽  
BW Cooper ◽  
HM Lazarus ◽  
W Mackay ◽  
TJ Moss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Stem Cell ◽  
Breast Cancer Patients ◽  
Tumor Involvement

Abstract Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.

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