PHARMACOLOGICAL ACTIVITY OF AN AMINOCHROMENE DERIVATIVE IN THE TREATMENT OF BREAST CANCER (EXPERIMENTAL STUDY)

2021 ◽  
pp. 12-19
Author(s):  
Deryabina O.N. ◽  
Blinova Е.В. ◽  
Samyshina E.A. ◽  
Demura T.A. ◽  
Epishkina A.A. ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Antitumor Activity ◽  
Tumor Cells ◽  
Control Group ◽  
Atypical Cells ◽  
Axillary Region ◽  
Size And Morphology ◽  
The Right ◽  
Single Tumor

We studied an antitumor effect of a compound of 4-aminochromene derivatives (AX-554) in the tumor system of breast cancer Ca-755. We used C57Bl / 6 mice, which were subcutaneously injected with a suspension of Ca-755 tumor cells into the right axillary region in the amount of 1×106 cells in 199 solution. AX-554 was administered intragastrically through a tube once on the 48 hours after tumor transplantation, in comparison with reference antitumor drugs with proven antitumor activity, which were used as doxorubicin, paclitaxel. The antitumor activity was judged by the survival rate of animals, the size and morphology of the tumor node. It was shown that the 4-aminochromene derivative AX-554 increases the survival rate of animals with breast cancer by 30% compared with the control group and by 10% with the group receiving doxorubicin. with control. In the study of tumor sections stained with hemotoxylin and eosin in animals treated with AX-554, there were single tumor cells in a state of severe dystrophy, the necrosis zone was 90%, which indicates drug pathomorphosis of the 3rd degree. In animals treated with doxorubicin, atypical cells in the center of the tumor node retained their structure, in the periphery - cells in a state of dystrophy, foci of necrosis accounted for 60%. The morphological picture of the tumor in animals treated with paclitaxel was a drug pathomorphosis of the 2nd degree.

Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Chuan Chen ◽  
Ziyue Zhao ◽  
Qian Dong ◽  
XueHui Gao ◽  
Huibin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Oxidative Phosphorylation ◽  
Tumor Cells ◽  
Transcriptome Analysis ◽  
Mcf7 Cells ◽  
Er Positive ◽  
Induced Apoptosis ◽  
Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

scholarly journals Application of HER2 peptide vaccines in patients with breast cancer: a systematic review and meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zicong You ◽  
Weijun Zhou ◽  
Junyan Weng ◽  
Haizhan Feng ◽  
Peiqiao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
T Cell ◽  
Clinical Studies ◽  
Cd8 T Cell ◽  
Delayed Type Hypersensitivity ◽  
Cochrane Library ◽  
Control Group ◽  
Cell Numbers ◽  
Before And After

Abstract Background The E75 and GP2 vaccines are the few therapeutic vaccines targeting HER2 currently under clinical research for patients with breast cancer. Methods Databases, including the Cochrane Library, PubMed, Medline, Embase, and Web of Science, were used to retrieve clinical studies on E75 and GP2 vaccines. Retrieval time was from the beginning of database construction until May 31st, 2021. Results A total of 24 clinical studies were included in this analysis, including 1704 patients in the vaccinated group and 1248 patients in the control group. For the E75 vaccine, there were significant differences between the vaccinated group and the control group in the delayed-type hypersensitivity reaction (SMD = 0.685 95% CI 0.52–0.85, PHeterogeneity = 0.186, PDTH < 0.05) and the change in CD8+ T-cell numbers (SMD = − 0.864, 95% CI − 1.02 to − 0.709, PHeterogeneity = 0.085, PCD8+ T cell < 0.05) before and after injection. For the GP2 vaccine, there was a significant difference between the vaccinated group and the control group in the change in CD8+ T-cell numbers (SMD = − 0.584, 95% CI − 0.803 to − 0.294, PHeterogeneity = 0.397, PCD8+ T cell < 0.05) before and after injection. In addition, the clinical outcomes, including recurrence rate (RR = 0.568, 95% CI 0.444–0.727, PHeterogeneity = 0.955, PRecurrence < 0.05) and disease-free survival rate (RR = 1.149, 95% CI 1.050–1.256, PHeterogeneity = 0.003, PDFS < 0.05), of the E75-vaccinated group were different from those of the control group. However, we found that the overall survival rate with the E75 vaccine (RR = 1.032, 95% CI 0.998–1.067, PHeterogeneity = 0.476, POS > 0.05) was not different between the two groups. Local and systemic toxicity assessments of the two vaccines showed minimal side effects. Conclusions The E75 vaccine was effective and safe in patients with breast cancer. The GP2 vaccine could elicit a strong immune response, but more trials are needed to confirm its clinical efficacy.

scholarly journals Assessment of Postural Balance in Women Treated for Breast Cancer

Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 505
Author(s):  
Iwona Głowacka-Mrotek ◽  
Magdalena Tarkowska ◽  
Tomasz Nowikiewicz ◽  
Magdalena Hagner-Derengowska ◽  
Aleksander Goch
Keyword(s):  
Breast Cancer ◽  
Postural Balance ◽  
Path Length ◽  
Muscle Tension ◽  
The Body ◽  
Control Group ◽  
Foot Pressure ◽  
Static Test ◽  
Healthy Female ◽  
The Right

Background and objectives: Surgery is the primary and most effective treatment of breast cancer. Unilateral mastectomy disrupts the distribution of muscle tension between the right and the left sides of the body. The aim of the study was to evaluate postural balance in patients treated for breast cancer by mastectomy. Materials and methods: A controlled clinical study was conducted on 90 patients who have undergone surgical treatment for breast cancer (mastectomy) 5–6 years prior (Breast Group—BG). The control group (CG) consisted of 74 healthy female volunteers. Analysis of balance was performed using the Alfa stabilography platform. A static test (Romberg’s test) with open and closed eyes was used to assess balance. The following balance parameters were analyzed: path length, statokinesigram area, parameters of deflection and velocity of the foot pressure center. Results: The study demonstrated that patients from BG (5–6 years after surgery) obtained worse results in both tests with open (maximum back deviation, maximum forward deviation, average Y deviation, average Y velocity, path length and path surface area) (p < 0.05) as well as with closed eyes (maximum backward deviation, maximum forward deviation, mean Y deviation and path length) (p < 0.05). Conclusions: Our study demonstrated that women 5–6 years after surgery for breast cancer have impaired balance compared to healthy women, despite physiotherapy.

Molecular markers for circulating tumor cells in breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 223-223
Author(s):  
R. Zeillinger ◽  
E. Obermayr ◽  
A. Fink-Retter ◽  
G. Heinze ◽  
A. Reinthaller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Gene Panel ◽  
Control Group ◽  
Gene Marker ◽  
Breast Cancer Patients ◽  
Gene Markers ◽  
Blood Samples

223 Background: Recently, we identified a six gene panel (CCNE2, DKFZp762E1312, EMP2, MAL2, PPIC, and SLC6A8) for the RT-qPCR based detection of circulating tumor cells (CTC) in breast cancer patients. The aim of the present study was to evaluate the gene panel in further blood samples. Methods: Blood samples were taken from breast cancer patients with metastatic disease (MBC, N=10) or with no evidence of disease (NED, N=30). Putative CTC were enriched by Oncoquick density gradient centrifugation. Total RNA was isolated with RNeasy Micro Kit (QIAgen). Template cDNA was generated with M-MLV Reverse Transcriptase, RNase H Minus (Promega) and random nonamers as primers. RT-qPCR was performed in duplicate reactions using TaqMan Assays (Applied Biosystems) with default thermal cycling parameters. Raw data were analyzed with the AB7900 Sequence Detection Software version 2.2.2 using automatic baseline correction and manual cycle threshold setting. Gene expression was normalized to GAPDH expression. A threshold value TX for each gene X was set at two standard deviations above the mean dCtX value in the healthy control group. A patient was defined as CTC-positive, if at least one gene marker was over-expressed compared to the defined threshold. Results: The gene panel consisting of CCNE2, DKFZp762E1312, EMP2, MAL2, PPIC, and SLC6A8 identified 4/11 MBC but only 5/27 NED patients as CTC positive (p=0.163). By adding known CTC markers (SCGB2A2, TFF1, FXYD3, AGR2, S100A18, and EPCAM) to the panel, 7/11 MBC but only 6/27 NED patients were CTC positive (p=0.018). The presence of CTC in NED patients correlated with pN staging (p=0.026). Only one out of the six CTC positive NED patients relapsed within the observation period (median 35 months, range 25-39 months from blood sampling). We observed no correlation of CTC positivity and recurrence in NED patients. Conclusions: The sensitivity of the RT-qPCR based CTC detection in breast cancer patients may be enhanced by adding known CTC markers (SCGB2A2, TFF1, FXYD3, AGR2, S100A18, and EPCAM) to the six gene panel (CCNE2, DKFZp762E1312, EMP2, MAL2, PPIC, and SLC6A8). Longer follow-up times are needed to evaluate the predictive value of the gene markers on survival.

Effects of Michigan Cancer Foundation-7/A New Adriamycin Cell-Derived Exosomes on MCF-7 Cell Apoptosis and Drug Sensitivity Through Ubiquitin Carboxyl-Terminal Hydrolase L1

2020 ◽  
Vol 10 (12) ◽  
pp. 1780-1785
Author(s):  
Chen Li ◽  
Yu Wang ◽  
Na Xu ◽  
Xin Liu
Keyword(s):  
Breast Cancer ◽  
Cell Apoptosis ◽  
Drug Sensitivity ◽  
Mrna Level ◽  
Cancer Cell Line ◽  
Normal Breast ◽  
Control Group ◽  
Experiment Control ◽  
Size And Morphology ◽  
Mcf 7

Exosomes secreted by adriamycin-resistant human breast cancer cell line MCF-7/ADR can promote the resistance of normal breast cancer cells. However, the exosomes? contents remain unclear. This article investigated the effect of UCHL1 in MCF-7/ADR-derived exosomes on MCF-7 cell apoptosis and drug sensitivity. In this experiment, control group (NC group), Exosome group, Exosome+ siRNA-UCHL1 group were set followed by analysis of exosomes morphology by electron microscope, UCHL1 and Tubulin level by Western Blot, UCHL1 level by immunofluorescence, UCHL1 mRNA level by qRT-PCR, cell apoptosis by flow cytometry, and drug sensitivity by MTT assay. The size and morphology of exosomes were normal with high expression of UCHL1 and CD63. Compared to NC group, UCHL1 level in Exosome group was significantly increased, while siRNAUCHL1 could reduce UCHL1 level; in addition, Exosome group showed significantly decreased cell apoptosis (P < 0.01) which was elevated in Exosome+siRNA-UCHL1 group (P < 0.05); finally, drug sensitivity in Exosome group was significantly increased (P < 0.01) and decreased in the Exosome+siRNA-UCHL1 group (P < 0.05). MCF-7/ADR-derived UCHL1 in exosome can increase UCHL1 level in MCF-7 cells, reduce cell apoptosis and drug sensitivity of cells.

scholarly journals A CASE OF ACCESSORY BREAST CANCER IN THE RIGHT AXILLARY REGION

1994 ◽  
Vol 55 (11) ◽  
pp. 2815-2818
Author(s):  
Yutaka KIMURA ◽  
Keisuke MIYAUCHI ◽  
Motohiro HIRAO ◽  
Hiroshi MIYATA ◽  
Tarou AOKI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Accessory Breast ◽  
Axillary Region ◽  
The Right

scholarly journals Enhancement of antitumor activity by using 5-ALA–mediated sonodynamic therapy to induce apoptosis in malignant gliomas: significance of high-intensity focused ultrasound on 5-ALA-SDT in a mouse glioma model

2018 ◽  
Vol 129 (6) ◽  
pp. 1416-1428 ◽  
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Daisuke Yamashita ◽  
Shohei Kohno ◽  
Akihiro Inoue ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cells ◽  
High Intensity ◽  
Focused Ultrasound ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Tunel Staining ◽  
Sonodynamic Therapy

OBJECTIVEHigh invasiveness of malignant gliomas frequently causes early local recurrence of the tumor, resulting in extremely poor outcome. To control such recurrence, novel therapies targeted toward infiltrating glioma cells around the tumor border are required. Here, the authors investigated the antitumor activity of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of 5-ALA–mediated SDT (5-ALA-SDT).METHODSIn vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined by analysis of the effect of pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated.RESULTSThe 5-ALA-SDT inhibited cell growth and changed cell morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the control group, and inhibition of ROS generation by edaravone completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. The proliferative activity of the entire tumor was markedly decreased. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact.CONCLUSIONSThe 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field, whereas the surrounding brain tissue remained normal, resulting in longer survival of the HIFU-treated mice compared with that of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

Alendronate/folic acid-decorated polymeric nanoparticles for hierarchically targetable chemotherapy against bone metastatic breast cancer

2020 ◽  
Vol 8 (17) ◽  
pp. 3789-3800 ◽  
Author(s):  
Shih-Hong Chen ◽  
Te-I Liu ◽  
Cheng-Lin Chuang ◽  
Hsin-Hung Chen ◽  
Wen-Hsuan Chiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Folic Acid ◽  
Metastatic Breast Cancer ◽  
Survival Rate ◽  
Bone Metastases ◽  
Tumor Cells ◽  
Polymeric Nanoparticles ◽  
Bone Matrix ◽  
Metastatic Breast

Through hierarchically targeting bone matrix and tumor cells, PTX-carrying ALN/FA-nanoparticles substantially accumulate in bone metastases and improve mice survival rate.

scholarly journals Action of tacrolimus on Wistar rat kidneys implanted with Walker 256 carcinosarcoma

2010 ◽  
Vol 25 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Cristiano Machado Inácio ◽  
Ulrich Andréas Dietz ◽  
Osvaldo Malafaia ◽  
Jurandir Marcondes Ribas Filho ◽  
Paulo Afonso Nunes Nassif ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Wistar Rats ◽  
Histological Analysis ◽  
Statistical Significance ◽  
Control Group ◽  
Walker 256 Carcinosarcoma ◽  
Tumor Group ◽  
Male Wistar Rats ◽  
Walker 256 ◽  
The Right

PURPOSE: To evaluate the development of Walker 256 tumor in male Wistar rats treated with tacrolimus using an experimental kidney tumor model. METHODS: 40 male Wistar rats were divided into four groups: Tumor group (TU) (n=10), Tacrolimus-Tumor group (TT) (n=10), Tacrolimus group (TC) (n=10) and Control group (C) (n=10). Treatment with tacrolimus was performed in groups TT and TC. Under anesthesia, the right kidney of each animal of TU and TT was accessed through a supraumbilical incision and inoculated with a 0.1mL solution containing 2x10(6) tumor cells (Walker 256 carcinosarcoma tumor cells). Group TC was treated with a saline solution. All the animals of groups TC and TT were treated with tacrolimus (5mg/kg/day) by gavage for 15 days. TU group animals received saline by gavage for 15 days. On the 15th postoperative day, all animals were submitted to euthanasia and blood sampling for analysis of serum creatinine (Cr) and blood urea nitrogen (BUN). Abdominal gross examination was performed, the right kidney removed and prepared for histological analysis by hematoxylin-eosin staining. The resulting data were submitted to statistical analysis by ANOVA. RESULTS: Statistical significance was found when comparing creatinine level between groups TU, TT and TC -TT group culminated with a marked increased in creatinine levels (Cr=1.013 ± 0.3028 mg/mL), TU group (Cr=0.5670 ± 0.03536 mg/dL) P=0.00256, TC group (Cr =0.711 ± 0.1653 mg/mL) P= 0.02832. Statistical significance was found when comparing BUN levels in TT group (71.32 ± 17.14 mg/mL), compared with TU group (45.83 ± 5.046 mg/dL), P=0.000318. There were no statistically significant differences between groups TT and TC (61.23 ± 9.503 mg/mL) P=0.7242. Histological analysis showed a poor evolution in TT group with multiple foci of hemorrhage and cortical invasion by the Walker tumor. CONCLUSION: The Tacrolimus-treated group developed a more aggressive tumor and a drug-related nephrotoxic effect.

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