scholarly journals Linalool Inhibits MCF-7 Tumor Growth in a Xenograft Model by Apoptosis Induction and Immune Modulation

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110151
Author(s):  
Yunqi Zhao ◽  
Xi Meng ◽  
Yan Zeng ◽  
Canbin Wang ◽  
Jiwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
B Cell ◽  
Peripheral Blood ◽  
Xenograft Model ◽  
Tunel Assay ◽  
Control Group ◽  
Apoptosis Induction ◽  
Ki 67 ◽  
Cell Counts ◽  
Mcf 7

In this study, the anti-cancer activity of linalool was investigated in MCF-7 breast cancer-bearing mice. Natural killer (NK) and B cell populations in peripheral blood were studied by flow cytometry. The expressions of proliferating cell nuclear antigen (PCNA) and Ki-67 in xenograft tumors were evaluated by immunohistochemistry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to investigate apoptosis induction in an in vivo model. The results indicated that linalool possesses an inhibitory effect on breast cancer growth in the xenograft model. Linalool reduced B cell counts, but increased NK cell counts in mice peripheral blood. The immunosignals of PCNA and Ki-67 were significantly lower in the linalool treatment group than those of the control group. The TUNEL assay showed that linalool significantly induced apoptosis compared to the control group. The findings of this study provide insight and evidence on the antiproliferative activity of linalool on human breast cancer.

scholarly journals Investigation of Breast Cancer Microstructure and Microvasculature from Time-Dependent DWI and CEST in Correlation with Histological Biomarkers

2021 ◽  
Author(s):  
Yuko Someya ◽  
Mami Iima ◽  
Hirohiko Imai ◽  
Akihiko Yoshizawa ◽  
Masako Kataoka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Xenograft Model ◽  
Time Dependent ◽  
Amide Proton ◽  
Strong Positive Correlation ◽  
Ki 67 ◽  
B Values ◽  
Positive Correlation ◽  
Non Gaussian ◽  
Mcf 7

Abstract We investigated the associations of time-dependent DWI, non-Gaussian DWI and CEST parameters with histological biomarkers in a breast cancer xenograft model. 22 xenograft mice (7 MCF-7 and 15 MDA-MB-231) were scanned at 2 diffusion times (Td= 2.5/ 5 ms) with 11 b values (0–600 s/mm2), and 9/ 27.6 ms with 17 b values (0–3000 s/mm2). The apparent diffusion coefficient, ADC0 − 600, shifted ADC, sADC200 − 1500 and the ADC change with Td, as well as IVIM and non-Gaussian diffusion parameters were estimated. CEST images were acquired and the amide proton transfer signal intensity (APT SI) were measured. The sADC200 − 1500 change and combined ADC change (ADC0 − 600, 2.5 ms with sADC200 − 1500, 27.6 ms) was significantly larger for MCF-7 group, and the combined ADC change was positively correlated with Ki67max and APT SI. ADC0 decreased significantly in MDA-MB-231 group and K increased significantly with Td in MCF-7 group. APT SI and cellular area had a moderately strong positive correlation in MDA-MB-231 and MCF-7 tumors combined, and there was a positive correlation in MDA-MB-231 tumors. There was a significant negative correlation between APT SI and the Ki-67-positive ratio in MDA-MB-231 tumors and when combined with MCF-7 tumors. The associations of combined ADC change and API SI with Ki-67 parameters indicate that the Td-dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.

Intronic miRNAs of Apoptosis Genes as Indicators of Cell Death

2019 ◽  
Vol 35 (6) ◽  
pp. 108-113
Author(s):  
J.A. Makarova ◽  
A.A. Poloznikov
Keyword(s):  
Breast Cancer ◽  
Cancer Cell Line ◽  
Ministry Of Education ◽  
Apoptosis Induction ◽  
Cell Models ◽  
Process Stage ◽  
Mature Micrornas ◽  
The Russian Federation ◽  
Apoptosis Level ◽  
Mcf 7

A method to assess the apoptosis level in cell models based on the analysis of the expression of micRNAs located in introns of apoptosis genes has been developed. Bioinformation analysis identified 536 genes associated with apoptosis; 30 of them contained 38 pre-microRNAs encoding 41 mature microRNAs. A significant change in the expression of hsa-miR-1244 and hsa-miR-4479 in response to apoptosis induction in the MCF-7 breast cancer cell line was revealed. A correlation was also found between the expression level of these miRNAs and the size of the primary tumor (process stage) in patients with breast cancer. apoptosis, microRNA, MCF7, breast cancer This work was supported by the Ministry of Education and Science of the Russian Federation (Project no. RFMEFI61618X0092).

scholarly journals Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells

2021 ◽  
Vol 14 (3) ◽  
pp. 254
Author(s):  
Afnan H. El-Gowily ◽  
Samah A. Loutfy ◽  
Ehab M. M. Ali ◽  
Tarek M. Mohamed ◽  
Mohammed A. Mansour
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Mtor Pathway ◽  
Tumor Growth Inhibition ◽  
Autophagic Flux ◽  
Ki 67 ◽  
Mcf 7

Cancer is a complex devastating disease with enormous treatment challenges, including chemo- and radiotherapeutic resistance. Combination therapy demonstrated a promising strategy to target hard-to-treat cancers and sensitize cancer cells to conventional anti-cancer drugs such as doxorubicin. This study aimed to establish molecular profiling and therapeutic efficacy assessment of chloroquine and/or tioconazole (TIC) combination with doxorubicin (DOX) as anew combination model in MCF-7 breast cancer. The drugs are tested against apoptotic/autophagic pathways and related redox status. Molecular docking revealed that chloroquine (CQ) and TIC could be potential PI3K and ATG4B pathway inhibitors. Combination therapy significantly inhibited cancer cell viability, PI3K/AkT/mTOR pathway, and tumor-supporting autophagic flux, however, induced apoptotic pathways and altered nuclear genotoxic feature. Our data revealed that the combination cocktail therapy markedly inhibited tumor proliferation marker (KI-67) and cell growth, along with the accumulation of autophagosomes and elevation of LC3-II and p62 levels indicated autophagic flux blockage and increased apoptosis. Additionally, CQ and/or TIC combination therapy with DOX exerts its activity on the redox balance of cancer cells mediated ROS-dependent apoptosis induction achieved by GPX3 suppression. Besides, Autophagy inhibition causes moderately upregulation in ATGs 5,7 redundant proteins strengthened combinations induced apoptosis, whereas inhibition of PI3K/AKT/mTOR pathway with Beclin-1 upregulation leading to cytodestructive autophagy with overcome drug resistance effectively in curing cancer. Notably, the tumor growth inhibition and various antioxidant effects were observed in vivo. These results suggest CQ and/or TIC combination with DOX could act as effective cocktail therapy targeting autophagy and PI3K/AKT/mTOR pathways in MCF-7 breast cancer cells and hence, sensitizes cancer cells to doxorubicin treatment and combat its toxicity.

scholarly journals Persistent Increased Frequency of Genomic Instability in Women Diagnosed with Breast Cancer: Before, during, and after Treatments

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
André Luiz Pinho Sobral ◽  
Jaqueline Nascimento Picada ◽  
Ivana Grivicich ◽  
Antonio Luiz Gomes Júnior ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Comet Assay ◽  
Peripheral Blood ◽  
Micronucleus Test ◽  
Cancer Control ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Buccal Cells ◽  
Oncological Treatment

This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient’s cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.

scholarly journals High expression of E-cadherin and Ki-67 associated with functional/dysfunctional phenotypes of tumor-infiltrating lymphocytes among Chinese patients with operable breast cancer

2018 ◽  
Vol 46 (12) ◽  
pp. 5219-5227 ◽  
Author(s):  
Ruibin Wang ◽  
Feng Shi ◽  
Lin Zhao ◽  
Yanjie Zhao ◽  
Guangjiang Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Cross Sectional Study ◽  
Clinicopathological Features ◽  
Chinese Patients ◽  
Ki 67 ◽  
Cross Sectional ◽  
Cell Counts ◽  
Infiltrating Lymphocytes ◽  
E Cadherin

Objective Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1)+/PD-1− tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer. Methods In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment. Results The median cell counts of the overall TILs, PD-1+ TILs, and PD-1− TILs were 80, 18, and 55/HPF, respectively. The number of PD-1− TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1− TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1+ TILs, and the correlation coefficient was 0.29. Conclusions PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1− TILs; however, Ki-67 expression was associated with PD-1+ TILs.

scholarly journals Mummy Induces Apoptosis Through Inhibiting of Epithelial-Mesenchymal Transition (EMT) in Human Breast Cancer Cells

2020 ◽  
Vol 9 ◽  
pp. 1812
Author(s):  
Solmaz Rahmani Barouji ◽  
Arman Shahabi ◽  
Mohammadali Torbati ◽  
Seyyed Mohammad Bagher Fazljou ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Mcf 7

Background: Mummy (Iranian pure shilajit) is a remedy with possessing anti-inflammatory, antioxidant and anticancer activities. This study aimed to examine mummy effects on epithelial-mesenchymal transition (EMT) and invasiveness of MCF-7 and MDA-MB-231 breast cancer (BC) cell lines with underlying its mechanism. Materials and Methods: The dose-dependent inhibitory effect of the mummy on cell proliferation in vitro was determined using the MTT assay.  Flow cytometry and 4’,6-diamidino-2-phenylindole dihydrochloride staining were respectively used for quantitative and qualitative analysis of cellular apoptosis, and gene expression analysis was conducted using real-time PCR. Results: MDA-MB-231 showed more sensitivity than the MCF-7 cell line to the anticancer activity of mummy, while mummy did not exhibit significant cell cytotoxicity against human normal cells (MCF-10A). The gene expression profile demonstrated a significant decrease in TGF-β1, TGF-βR1, TWIST1, NOTCH1, CTNNB1, SRC along with an increase in E-cadherin mRNA levels in mummy treated cells compared to the untreated control group (P≤0.05). Conclusion: Mummy triggers inhibition of EMT and metastasis in breast cancer cells mainly through the downregulation of TGFβ1 activity, and more studies required to find its specific anticancer activity with details. [GMJ.2020;9:e1812]

scholarly journals PGV-0 AND PGV-1 INCREASED APOPTOSIS INDUCTION OF DOXORUBICIN ON MCF-7 BREAST CANCER CELLS

2015 ◽  
Vol 12 (2) ◽  
pp. 55-59
Author(s):  
Edy Meiyanto
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Chemotherapeutic Agent ◽  
Apoptosis Induction ◽  
Single Treatment ◽  
Cell Cycle Modulation ◽  
Induced Apoptosis ◽  
Mcf 7

As chemotherapeutic backbone for breast cancer therapy, doxorubicin showed various side effects and induced resistancy of breast cancer cells. Development of targeted therapy on breast cancer focused on combinatorial therapy of doxorubicin and molecular targeted agents. PGV-0 and PGV-1, a curcumin analogue showed potency as co-chemotherapeutic agent with doxorubicin. Our previous study of PGV-0 and PGV-1 showed cytotoxic activity in T47D cells. Therefore, the aim of this research is to examine the synergistic effect of PGV-0, PGV-1 on the cytotoxic activity of doxorubicin through cell cycle modulation and apoptotic induction on MCF-7 breast cancer cell lines. The cytotoxic assay of PGV-0, PGV-1, doxorubicin, and their combination were carried out by using MTT assay. Cell cycle distribution and apoptosis were determined by flowcytometer FACS-Calibur and the flowcytometry data was analyzed using Cell Quest program. Single treatment of PGV-0, PGV-1 and doxorubicin showed cytotoxic effect on MCF-7 with cell viability IC50 value 50 µM, 6 µM and 350 nM respectively. Single treatment of Doxorubicin 175 nM induced G2/M arrest. Single treatment of PGV-0 5 µM induced G2/M arrest while in higher dose 12.5  µM, PGV-0 induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 5 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 12.5 µM also increased apoptosis induction. Single treatment of PGV-1 0.6 µM induced G1 arrest while in higher dose 1.5  µM, PGV-1 induced apoptosis. Combination of doxorubicin 175 nM and PGV-1 0.6 µM induced apoptosis. Combination of doxorubicin 175 nM and PGV-0 1.5 µM also increased apoptosis induction. PGV-0 and PGV-1 are potential to be delevoped as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle modulation, but the molecular mechanism need to be explored detail.  Key words: PGV-0, PGV-1, doxorubicin, co-chemotherapy, breast cancer, cell cycle arrest, apoptosis

Development of orally bioavailable prodrugs of fulvestrant for the treatment of metastatic/advanced breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13027-e13027
Author(s):  
Parva Purohit ◽  
Pathik Brahmkshatriya ◽  
Vishalgiri Goswami
Keyword(s):  
Breast Cancer ◽  
Oral Delivery ◽  
Tumor Volume ◽  
Estrogen Therapy ◽  
Xenograft Model ◽  
Fold Increase ◽  
Tumor Growth Inhibition ◽  
Pharmacokinetic Studies ◽  
Hormone Receptor Positive ◽  
Mcf 7

e13027 Background: Fulvestrant, a potent, selective estrogen receptor degrader, is a primary drug of choice for treating advanced metastatic hormone receptor-positive breast cancer in postmenopausal women following anti-estrogen therapy. However, the existing therapy limits to inconvenient intramuscular injections due to low solubility, weak permeation, high metabolism, and poor pharmacokinetics profile. Additionally, it takes 30 days to reach maximal steady-state plasma concentration, limiting clinical efficacy. To overcome these issues, we modulated physicochemical properties of fulvestrant, enabling its oral delivery to improve bioavailability. Methods: Structurally diverse pro-moieties were appended on fulvestrant to improve solubility and ADME profile. Thermodynamic solubility, plasma/liver microsomal stability, and Caco-2 permeability studies were performed to identify lead molecules. Pharmacokinetic studies were performed for selected molecules in mice. Antitumor activity of once-daily oral dose of three molecules was evaluated in female nude mice using the MCF-7 xenograft model. The efficacy of lead molecules was compared with subcutaneously administered faslodex in terms of percentage tumor growth inhibition. Results: Several prodrugs of fulvestrant were synthesized and evaluated for their intrinsic properties suitable for increasing bioavailability of fulvestrant. Remarkable improvements (̃500 to 2000-fold increase) were achieved in solubility and permeability. The PoC established an increase in systemic plasma exposure of fulvestrant upon oral administration of prodrugs in mice with enhanced bioavailability (1.5-8.7-fold) as compared to fulvestrant given subcutaneously (Table). Herewith, we report the identification of KSHN001022, KSHN001075, and KSHN001126, the prodrugs of fulvestrant, which showed enhanced efficacy with better tumor volume reduction (̃48-88% regression in tumor volume) as compared to that of fulvestrant (78%) in the estrogen-dependent MCF-7 xenograft model. Conclusions: KSHN001 lead candidates demonstrated significantly higher bioavailability, hence, provides a novel strategy to deliver fulvestrant orally to pursue the potential benefits in patients with advanced metastatic disease.[Table: see text]

scholarly journals Immunostimulatory properties of bigroot geranium (Geranium macrorrhizum L.) extract

Medicina ◽  
2007 ◽  
Vol 43 (1) ◽  
pp. 60 ◽  
Author(s):  
Vilma Jurkštienė ◽  
Anatolijus Kondrotas ◽  
Egidijus Kėvelaitis
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Leukocyte Count ◽  
Ethanol Extract ◽  
Food Supplement ◽  
Total Leukocyte Count ◽  
Control Group ◽  
Case Group ◽  
Cell Counts

The aim of the study was to investigate the immunostimulatory properties of bigroot geranium. Material and methods. Possible nonspecific characteristics of bigroot geranium were evaluated by the total leukocyte count in the peripheral blood, and qualitative changes of blood were assessed using Shilling’s formula by evaluating changes in lymphocyte counts. In addition, we also studied changes in the counts of Tcell precursors in the thymus and B lymphocytes in the spleen. Ethanol extract of the leaves of bigroot geranium was produced at the Department of Food Technology, Kaunas University of Technology. Studies were performed on mice Bl 57 (n=21). The control group (n=7) received distilled water at a dose of 1 mL/day. The second and third groups received 1% and 10% extract of bigroot geranium, respectively, as a food supplement. Changes in cell counts were investigated after 4 weeks following the initiation of the trial. Results. After a 4-week administration of 1% extract of bigroot geranium (1 mL/day) (mice group, n=7), leukocyte count in the peripheral blood increased to 6.1×109 cells/L, and lymphocyte count – to 70%, but changes were not statistically significant. The other case group of mice (n=7) received 10% extract of bigroot geranium for 4 weeks at a dose of 1 mL/day. In this group, leukocyte count in the peripheral blood increased statistically significantly from 4.4×109 cells/L to 7.2×109 cells/L (p<0.01), and lymphocyte percentage – from 52% to 80% (p<0.001), as compared to control. Thymocyte (T lymphocytes) counts in thymus and splenocyte (B lymphocytes) counts in the spleen showed a tendency to increase after the administration of 1% and 10% extracts. After a 4-week administration of 1% extract of bigroot geranium, thymocyte and splenocyte counts increased from 0.342×106 cells to 0.372×106 cells per mg of tissue and from 0.395×106 cells to 0.405×106 cells per mg of tissue, respectively, as compared to control group (p>0.1). After the administration of 10% extract of bigroot geranium, thymocyte count increased to 0.488×106 cells per mg of tissue (p<0.01), and splenocyte count – to 0.504×106 cells per mg of tissue (p<0.01). Conclusion. The extracts of the leaves of bigroot geranium increased leukocyte count and lymphocyte percentage in the peripheral blood, and after a 4-week administration of 10% extract of bigroot geranium, a statistically significant increase in the counts of T lymphocytes (in the thymus) and B lymphocytes (in the spleen) was observed. The immunostimulatory effect depends on the dose of the extract.

scholarly journals Cell Counts, rather than Proportion, of CD8/PD-1 Tumor-Infiltrating Lymphocytes in a Tumor Microenvironment Associated with Pathological Characteristics of Chinese Invasive Ductal Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Qingkun Song ◽  
Feng Shi ◽  
Maya Adair ◽  
Hong Chang ◽  
Xiudong Guan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Axillary Lymph Node ◽  
Tumor Infiltrating Lymphocytes ◽  
Axillary Lymph Node Metastasis ◽  
Axillary Lymph ◽  
Ki 67 ◽  
Invasive Ductal Breast Cancer ◽  
Cell Counts ◽  
Infiltrating Lymphocytes

Objective. This study is aimed at investigating the association of exhausted CD8+ tumor-infiltrating lymphocytes with clinic-pathological factors. Methods. 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results. The proportion of CD8+/PD-1- TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8+/PD-1- TILs than elderly patients (18/HPF vs. 9/HPF, p<0.05). Patients with axillary lymph node metastasis had less CD8+/PD-1- TILs than those without metastasis (11/HPF vs. 27/HPF, p<0.05). Median counts of CD8+/PD-1- TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8+/PD-1+ TILs and CD8+/PD-1- TILs, and the correlation coefficients were 0.19 and 0.21 (p<0.05), respectively. Conclusion. The proportion of CD8+/PD-1- TILs was related with metastatic status of the axillary lymph node but cell counts of CD8+/PD-1- TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.

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