breast tumor tissue
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2021 ◽  
Vol 12 (1) ◽  
pp. 4
Author(s):  
Tatiana Kalinina ◽  
Vladislav Kononchuk ◽  
Efim Alekseenok ◽  
Grigory Abdullin ◽  
Sergey Sidorov ◽  
...  

Despite the existing advances in the diagnosis and treatment of breast cancer (BC), the search for markers associated with the clinicopathological features of BC is still in demand. MiRNAs (miRs) have potential as markers, since a change in the miRNA expression profile accompanies the initiation and progression of malignant diseases. The receptors for estrogen, androgen, and progesterone (ER, AR, and PR) play an important role in breast carcinogenesis. Therefore, to search for miRNAs that may function as markers in BC, using bioinformatic analysis and the literature data, we selected 13 miRNAs whose promoter regions contain binding sites for ER or AR, or putative binding sites for ER, AR, and PR. We quantified their expression in MCF-7 cells treated with estradiol, progesterone, or testosterone. The levels of miRNAs sensitive to one or more of these hormones were quantified in BC samples (n = 196). We discovered that high expression levels of miR-190b in breast tumor tissue indicate a positive ER status, and miR-423 and miR-200b levels differ between patients with and without HER2 amplification. The miR-193b, -423, -190a, -324, and -200b levels were associated with tumor size or lymph node status in BC patients, but the presence of these associations depended on the status and expression level of ER, PR, HER2, and Ki-67. We also found that miR-21 expression depends on HER2 expression in ER- and/or PR-positive BC. The levels of miRNA were significantly different between HER2 0 and HER2 1+ tumors (p = 0.027), and between HER2 0 and HER2 2+, 3+ tumors (p = 0.005).


2021 ◽  
Vol 74 ◽  
pp. 101999
Author(s):  
Michelle R. Roberts ◽  
Gabrielle M. Baker ◽  
Yujing J. Heng ◽  
Michael E. Pyle ◽  
Kristina Astone ◽  
...  

2021 ◽  
Author(s):  
Ramla Shahid ◽  
Nabiha Bashir ◽  
Mehreen Ishfaq ◽  
Kehkashan Mazhar ◽  
Jahangir Sarwar Khan

Abstract BackgroundBiological treatment of many cancers currently targets membrane bound receptors located on a cell surface. We are in a great to need identify novel membrane proteins associated with migration and metastasis of breast cancer cells. CD271, a single transmembrane protein belongs to tumor necrosis factor receptor acts and play its role in proliferation of cancer cell. The purpose of this study is to investigate the role of CD271 in breast cancer. Methods and ResultsIn this study we analyzed the expression of CD271 in breast tumor tissue, breast cancer cell line MCF7 and isolated cancer stem cells (MCF7-CSCs) by quantitative real-time polymerase chain reaction (RT-qPCR). CD271 was upregulated among breast cancer patients in all age groups. Within the promoter region of CD271, there is a binding site for NF-κB1 which overlaps a putative quadraplex forming sequence. While CD271 also activates NF-κB pathway, down regulation of CD271 through quadraplex targeting resulted in inhibition of NF-κB and its downstream targets Nanog and Sox2ConclusionIn conclusion, CD271 and NF-κB are interrelated to each other. Upon CD271 inhibition, the NF-κB expression also reduces which then effected the cell proliferation and migration. These results suggest that NF-κB is regulated by CD271 is playing a crucial role in cancer development and could be a potential therapeutic target.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Heng-Huan Lee ◽  
Ying-Nai Wang ◽  
Wen-Hao Yang ◽  
Weiya Xia ◽  
Yongkun Wei ◽  
...  

AbstractHuman ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245930
Author(s):  
M. Wielema ◽  
P. E. Sijens ◽  
H. Dijkstra ◽  
G. H. De Bock ◽  
I. G. van Bruggen ◽  
...  

Objectives In breast diffusion weighted imaging (DWI) protocol standardization, it is recently shown that no breast tumor tissue selection (BTTS) method outperformed the others. The purpose of this study is to analyze the feasibility of three fixed-size breast tumor tissue selection (BTTS) methods based on the reproducibility, accuracy and time-measurement in comparison to the largest oval and manual delineation in breast diffusion weighted imaging data. Methods This study is performed with a consecutive dataset of 116 breast lesions (98 malignant) of at least 1.0 cm, scanned in accordance with the EUSOBI breast DWI working group recommendations. Reproducibility of the maximum size manual (BTTS1) and of the maximal size round/oval (BTTS2) methods were compared with three smaller fixed-size circular BTTS methods in the middle of each lesion (BTTS3, 0.12 cm3 volume) and at lowest apparent diffusion coefficient (ADC) (BTTS4, 0.12 cm3; BTTS5, 0.24 cm3). Mean ADC values, intraclass-correlation-coefficients (ICCs), area under the curve (AUC) and measurement times (sec) of the 5 BTTS methods were assessed by two observers. Results Excellent inter- and intra-observer agreement was found for any BTTS (with ICC 0.88–0.92 and 0.92–0.94, respectively). Significant difference in ADCmean between any pair of BTTS methods was shown (p = <0.001–0.009), except for BTTS2 vs. BTTS3 for observer 1 (p = 0.10). AUCs were comparable between BTTS methods, with highest AUC for BTTS2 (0.89–0.91) and lowest for BTTS4 (0.76–0.85). However, as an indicator of clinical feasibility, BTTS2-3 showed shortest measurement times (10–15 sec) compared to BTTS1, 4–5 (19–39 sec). Conclusion The performance of fixed-size BTTS methods, as a potential tool for clinical decision making, shows equal AUC but shorter ADC measurement time compared to manual or oval whole lesion measurements. The advantage of a fixed size BTTS method is the excellent reproducibility. A central fixed breast tumor tissue volume of 0.12 cm3 is the most feasible method for use in clinical practice.


2021 ◽  
Vol 67 (4) ◽  
pp. 360-365
Author(s):  
T.S. Kalinina ◽  
V.V. Kononchuk ◽  
S.V. Sidorov ◽  
D.A. Obukhova ◽  
G.R. Abdullin ◽  
...  

The oxytocin receptor (OXTR) plays an important role in childbirth, breastfeeding, and social interactions. There is emerging evidence that OXTR is associated with the breast cancer (BC) initiation and progression. However, the mechanisms leading to a change in its expression, the diagnostic or prognostic value of the receptor in BC are currently poorly understood. Here, we have evaluated the relative level of OXTR expression in BC samples (n=107), and also investigated the effect of estradiol on its expression in MCF-7 and MDA-MB-231 cells. The level of OXTR expression was significantly lower in breast tumor tissue than in normal tissue obtained from the same patient. The expression of OXTR was dependent on the status and expression of the estrogen receptor (ER): the level of OXTR mRNA was significantly lower in ER-negative BC samples compared to ER-positive BC samples. Moreover, OXTR expression was also lower in samples from patients with luminal subtype with a low value of ER expression (0-5 score according to the IHC assay, Allred scoring) compared with samples with high ER expression (6-8 score). In luminal BC, OXTR expression was associated with the HER2 expression level: the OXTR mRNA level was higher in tumors with a HER2 IHC score of 1+ as compared to cases with the HER2 expression score of 2+, 3+. We also showed that estradiol increased the level of OXTR mRNA in MCF-7 cells, but not in ER-negative MDA-MB-231 cells. These data indicate that changes in OXTR expression in BC tissues can be caused by increased ER expression. We found no association between OXTR and T or N stages and progesterone receptor expression.


2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Teng Zhang ◽  
Fangfang Duan ◽  
Danhua Su ◽  
Long Ma ◽  
Jiezuan Yang ◽  
...  

To study the homogeneity and heterogeneity of CD4+CD25+ T cells receptor β-chain complementarity determining region 3 (TCR β CDR3) repertoires in breast tumor tissues, lung metastatic tissues, and spleens from 4T1 tumor-bearing BALB/c mice. We used high-throughput sequencing to analyze the characteristics and changes of CD4+CD25+ TCR β CDR3 repertoires among tumor tissues, lung metastatic tissues, and spleens. The diversity of the CD4+CD25+ TCR β CDR3 repertoires in breast tumor tissue was similar to that of lung metastatic tissues and less pronounced than that of spleen tissues. Breast tumor tissues and lung metastatic tissues had a greater number of high-frequency CDR3 sequences and intermediate-frequency CDR3 sequences than those of spleens. The proportion of unique productive CDR3 sequences in breast tumor tissues and lung metastatic tissues was significantly greater than that in the spleens. The diversity and frequency of the CDR3 repertoires remained homogeneous in breast tumors and lung metastatic tissues and showed great heterogeneity in the spleens, which suggested that the breast tissues and lung metastatic tissues have characteristics of CD4+CD25+ T cells that relate to the tumor microenvironment. However, the number and characteristics of overlapping CDR3 sequences suggested that there were some different CD4+CD25+ T cells in tumors and in the circulatory immune system. The study may be used to further explore the characteristics of the CDR3 repertoires and determine the source of the CD4+CD25+ T cells in the breast cancer microenvironment.


F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 1770
Author(s):  
Rarastoeti Pratiwi ◽  
Nyoman Yudi Antara ◽  
Lalu Gunawan Fadliansyah ◽  
Syamsul Arif Ardiansyah ◽  
Luthfi Nurhidayat ◽  
...  

Background: Noncontact Electro Capacitive Cancer Therapy (ECCT) is a novel treatment modality in cancer. Chemokine (C-C motif) ligand 2 (CCL2) has a major role in the outgrowth of metastatic breast cancer. Interleukin 18 (IL18) plays a role in macrophage alteration, which leads to excessive angiogenesis. This study aims to elaborate on the association of CCL2, IL18, IL23α, and TNF-α (tumor necrosis factor-alpha) expression with the anti-proliferative effect of ECCT in rat breast tumor tissue.   Methods: Low intensity (18 Vpp) and intermediate frequency (150 kHz) alternating current-electric field (AC-EF) between two capacitive electrodes were exposed as external EF to a rat cage. Twenty-four rats were divided into four groups of six replicates. Breast tumor tissues were collected from 7, 12-dimethylbenz[a]anthracene (DMBA)-induced rats. Two groups were non DMBA-induced rats without ECCT exposure (NINT) and with (NIT). The other two groups were DMBA-induced rats without ECCT exposure (INT) and with (IT). Mammary glands and breast tumor tissues were collected from each group and preserved. Hematoxylin-eosin and immunohistochemistry staining were performed on paraffin sections of tissues using anti-PCNA, anti-ErbB2, anti-Caspase3, and anti-CD68. CCL2, IL18, IL23α, and TNF-α mRNA relative expressions were analyzed using qRT-PCR. Results: ECCT exposure may cause the reduction of PCNA protein expression as well as ErbB2 on breast tumor tissues, but it causes the increase of Caspase3 and macrophage CD68 protein. In rat breast tumor tissues of IT groups, the mRNA expression of CCL2 and IL18 are significantly down-regulated, in contrast with the up-regulated expression of these cytokines in tumor tissues of the INT group. IL23α and TNF- α expression remained similar in both groups. Conclusion: CCL2 and IL18 expressions have an association with the inhibition of breast tumor cell proliferation affected by ECCT exposure


Author(s):  
М.М. Цыганов ◽  
М.К. Ибрагимова ◽  
А.М. Певзнер ◽  
Е.Ю. Гарбуков ◽  
К.А. Гаптулбарова ◽  
...  

Целью работы явилась оценка связи хромосомных аберраций генов BRCA1, NF-κB1, PARP1 в опухолевой ткани молочной железы с эффектом химиотерапии и прогнозом заболевания. В исследование включены 85 больных люминальным В раком молочной железы IIA-IIIB стадии, с морфологически верифицированным диагнозом, в возрасте 25-68 лет (47,8±1,1). Было установлено, что наибольшая частота делеций наблюдается в гене BRCA1 (36%, 30 случаев из 85). Частота амплификаций PARP1 в исследуемой группе больных РМЖ достигает 62% (53 случая из 85). Наименьшее число хромосомных аберраций наблюдается в гене NF-κB1, всего у 22 больных наблюдаются делеции и амплификации данного гена (26%). Показано, что делеция гена BRCA1 сопряжена с хорошим ответом на неоадъювантную химиотерапию вне зависимости от наличия хромосомных аберраций других генов. При этом амплификация PARP1 связана с плохим прогнозом заболевания. The aim of the work was to assess the relationship of chromosomal aberrations of the BRCA1, NF-κB1, PARP1 genes in breast tumor tissue with the effect of chemotherapy and prognosis of the disease. The study included 85 patients with luminal stage IIA-IIIB breast cancer, with a morphologically verified diagnosis, aged 25-68 years (47.8±1.1). As a result of the study, the CNA frequency of the studied genes was estimated. It was found that the highest deletion rate is observed in the BRCA1 gene (36%, 30 cases out of 85). The frequency of amplification of PARP1 in the studied group of breast cancer patients reaches 62% (53 cases out of 85). The smallest number of chromosomal aberrations is observed in the NF-κB1 gene; in only 22 patients, deletions and amplifications of this gene are observed (26%). it was found that the deletion of the BRCA1 gene is associated with a good response to neoadjuvant chemotherapy, regardless of the presence of chromosomal aberrations of other genes. Moreover, amplification of PARP1 is associated with a poor prognosis of the disease.


Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2918
Author(s):  
Matteo Lazzeroni ◽  
Giovanna Petrangolini ◽  
José Antonio Legarreta Iriberri ◽  
Jaume Pascual Avellana ◽  
Digna Tost Robusté ◽  
...  

Silybin is a flavonolignan extracted from Silybum marianum with chemopreventive activity against various cancers, including breast. This study was designed to develop an HPLC-MS/MS method for the determination of silybin in human plasma, urine and breast tissue in early breast cancer patients undergoing Siliphos® supplementation, an oral silybin-phosphatidylcholine complex. The determination of silybin was carried out by liquid–liquid extraction with methyl-tert-butyl ether (MTBE); total silybin concentration was determined by treating the samples with β–glucuronidase, while for the determination of free silybin, the hydrolytic step was omitted. Naringenin and naproxen were selected as internal standards. The detection of the analyte was carried out by mass spectrometry and by chromatography. The HPLC-MS/MS method was evaluated in terms of selectivity, linearity, limit of quantification, precision and accuracy, and carryover. The method proved to be selective, linear, precise and accurate for the determination of silybin. To the best of our knowledge, this presents the first analytical method with the capacity to quantify the major bioactive components of milk thistle in three different biological matrices with a lower limit of quantification of 0.5 ng/mL for plasma. Silybin phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue.


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