scholarly journals The effects of pBudCE4.1-azurin-MAM-A recombinant vector on IL-2, IL-6, IL-7, and IL-10 expressions in laboratory mice

2020 ◽  
Vol 22 (1) ◽  
pp. 38-45
Author(s):  
Payam Ghasemi-Dehkordi ◽  
Abbas Doosti ◽  
Mohammad-Saeid Jami
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Thigh Muscle ◽  
Laboratory Mice ◽  
Expression Levels ◽  
Recombinant Vector ◽  
Molecular Tests ◽  
Serological Studies ◽  
Pcr Method ◽  
Blood Specimens

Background and aims: Breast cancer is one of the most common types of malignancy in women with morbidity and mortality (15.0%) in the world. The antitumor activity of azurin protein produced by Pseudomonas aeruginosa has been described before. Mammaglobin-A (MAM-A) protein is especially expressed in 40%-80% of breast cancer types and this protein is a very specific molecular marker for stimulating the immune system. Accordingly, this study investigated the effects of pBudCE4.1-azurin-MAM-A recombinant vector on the induction of the immune system in laboratory mice by the real-time polymerase chain reaction (PCR) method. Methods: The pBudCE4.1-azurin-MAM-A recombinant and empty vectors were purchased and then separately transformed into Escherichia coli for multiplying. Next, each plasmid was extracted and the accuracy of transformation was confirmed by the PCR. These recombinant and empty (control) vectors were separately infused into the thigh muscle of the animals and the healthy group was infused with phosphatebuffered saline. The infusion sites, blood specimens, as well as the serum of the animals were collected and examined by serological and molecular tests. Results: Molecular and serological studies showed that the serum and expression levels of IL-2, IL-6, IL-7, and IL-10 in infused mice with pBudCE4.1-azurin-MAM-A recombinant vector significantly increased compared to healthy animals and injected mice with an empty vector (P<0.05). Conclusion: In general, the findings revealed that the pBudCE4.1-azurin-MAM-A recombinant vector can stimulate the immune system of the mouse by an increase in the expression levels of IL-2, IL-6, IL-7, and IL-10. Thus, it would be better to examine the effects of this recombinant vector as a DNA vaccine on the prevention and treatment of breast cancer.

SOX4 Serves an Oncogenic Role in the Tumourigenesis of Human Breast Adenocarcinoma by Promoting Cell Proliferation, Migration and Inhibiting Apoptosis

2020 ◽  
Vol 15 (1) ◽  
pp. 49-58
Author(s):  
Junhe Zhang ◽  
Shujie Chai ◽  
Xinyu Ruan
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
Breast Adenocarcinoma ◽  
Migration Ability ◽  
Expression Levels ◽  
Apoptosis Rate ◽  
And Migration ◽  
Mcf 7 ◽  
Proliferation And Migration

Background: Breast cancer is among the most common malignant cancers worldwide, and breast adenocarcinoma in glandular tissue cells has excessive metastasis and invasion capability. However, little is known on the molecular process by which this disease develops and progresses. Objective: In this study, we explored the effects of sex-determining region Y-box 4 (SOX4) protein on proliferation, migration, apoptosis and tumourigenesis of breast adenocarcinoma and its possible mechanisms. Methods: The SOX4 overexpression or knockdown Michigan Cancer Foundation-7 (MCF-7) cell lines were established. Among the SOX4 overexpression or MCF-7 knockdown cell lines, proliferation, migration ability and apoptosis rate were detected. The expression levels of apoptosis-related proteins (Bax and Cleaved caspase-3) were analysed using Western blot. The effect of SOX4 on tumourigenesis was analysed using the clone formation assay in vitro and tumour xenograft experiment in nude mice. Results: Compared with the overexpression of control cells, proliferation and migration ability of SOX4 overexpression cells significantly increased, the apoptosis rate significantly decreased in addition to the expression levels of Bax and Cleaved caspase-3 (P < 0.05). Compared with the knockdown of control cells, proliferation and migration ability of SOX4 knockdown cells significantly decreased, and the apoptosis rate and expression levels of Bax and Cleaved caspase-3 significantly increased (P < 0.05). Clone formation and tumour growth abilities of SOX4 overexpression cells were significantly higher than those of the control cells (P < 0.05), whereas SOX4 knockdown cells had the opposite effect. Conclusion: SOX4 plays an oncogenic role in breast adenocarcinoma tumourigenesis by promoting cell proliferation, migration and inhibiting apoptosis. It can be used as a potential molecular target for breast cancer gene therapy.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

scholarly journals Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1128
Author(s):  
Amy Kwan ◽  
Natalie Winder ◽  
Munitta Muthana
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cell Death ◽  
Immune System ◽  
Menopausal Status ◽  
Oncolytic Virotherapy ◽  
Immunogenic Cell Death ◽  
Tumour Type ◽  
Common Cancer ◽  
Direct Cell

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

Immunotherapy: New insights in breast cancer treatment

2021 ◽  
pp. 1-10
Author(s):  
Bader Alshehri
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Immune System ◽  
Cancer Treatment ◽  
Immune Evasion ◽  
Breast Tumor ◽  
Parp Inhibitor ◽  
Breast Cancer Treatment ◽  
New Treatment

Breast cancer being the most malignant and lethal disease persistent among women globally. Immunotherapy as a new treatment modality has emerged in understanding the loopholes in the treatment of breast cancer which is mainly attributed to the potential of tumor cells to evade and survive the immune response by developing various strategies. Therefore, improved understanding of the immune evasion by cancer cells and the monoclonal antibodies against PD- and PD-L1 can help us in the diagnosis of this malignancy. Here in this article, I have highlighted that in addition to focusing on other strategies for breast cancer treatment, the involvement of immune system in breast cancer is vital for the understanding of this malignancy. Further, the complete involvement of immune system in the relapse or recurrence of the breast tumor and have also highlighted the role of vaccines, PD-1 and CTLA-4 with the recent advances in the field. Moreover, in addition to the application of immunotherapy as a sole therapy, combinations of immunotherapy with various strategies like targeting it with MEK inhibitors, Vaccines, chemotherapy and PARP inhibitor has shown to have significant benefits is also discussed in this article.

scholarly journals The Value of EphB2 Receptor and Cognate Ephrin Ligands in Prognostic and Predictive Assessments of Human Breast Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8098
Author(s):  
Abdul Shukkur Ebrahim ◽  
Zeyad Hailat ◽  
Sudeshna Bandyopadhyay ◽  
Daniel Neill ◽  
Mustapha Kandouz
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Predictive Value ◽  
Intracellular Signaling ◽  
Ductal Carcinoma ◽  
Cancer Development ◽  
Eph Receptors ◽  
Free Survival ◽  
Expression Levels ◽  
Ephrin Ligands

Cell–cell communication proteins Eph and ephrin constitute the largest family of receptor tyrosine kinases (RTKs). They are distinguished by the fact that both receptors and ligands are membrane-bound, and both can drive intracellular signaling in their respective cells. Ever since these RTKs have been found to be involved in cancer development, strategies to target them therapeutically have been actively pursued. However, before this goal can be rationally achieved, the contributions of either Eph receptors or their ephrin ligands to cancer development and progression should be scrutinized in depth. To assess the clinical pertinence of this concern, we performed a systematic review and meta-analysis of the prognostic/predictive value of EphB2 and its multiple cognate ephrin ligands in breast cancer. We found that EphB2 has prognostic value, as indicated by the association of higher EphB2 expression levels with lower distant metastasis-free survival (DMFS), and the association of lower EphB2 expression levels with poorer relapse-free survival (RFS). We also found that higher EphB2 expression could be a prognostic factor for distant metastasis, specifically in the luminal subtypes of breast cancer. EFNB2 showed a marked correlation between higher expression levels and shorter DMFS. EFNA5 or EFNB1 overexpression is correlated with longer RFS. Increased EFNB1 expression is correlated with longer OS in lymph node (LN)-negative patients and the luminal B subtype. Higher levels of EFNB2 or EFNA5 are significantly correlated with shorter RFS, regardless of LN status. However, while this correlation with shorter RFS is true for EFNB2 in all subtypes except basal, it is also true for EFNA5 in all subtypes except HER2+. The analysis also points to possible predictive value for EphB2. In systemically treated patients who have undergone either endocrine therapy or chemotherapy, we found that higher expression of EphB2 is correlated with better rates of RFS. Bearing in mind the limitations inherent to any mRNA-based profiling method, we complemented our analysis with an immunohistochemical assessment of expression levels of both the EphB2 receptor and cognate ephrin ligands. We found that the latter are significantly more expressed in cancers than in normal tissues, and even more so in invasive and metastatic samples than in ductal carcinoma in situ (DCIS). Finally, in an in vitro cellular model of breast cancer progression, based on H-Ras-transformation of the MCF10A benign mammary cell line, we observed dramatic increases in the mRNA expression of EphB2 receptor and EFNB1 and EFNB2 ligands in transformed and invasive cells in comparison with their benign counterparts. Taken together, these data show the clinical validity of a model whereby EphB2, along with its cognate ephrin ligands, have dual anti- and pro-tumor progression effects. In so doing, they reinforce the necessity of further biological investigations into Ephs and ephrins, prior to using them in targeted therapies.

scholarly journals Serum Long Non-Coding RNAs PVT1, HOTAIR, and NEAT1 as Potential Biomarkers in Egyptian Women with Breast Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 301
Author(s):  
Amal Ahmed Abd El-Fattah ◽  
Nermin Abdel Hamid Sadik ◽  
Olfat Gamil Shaker ◽  
Amal Mohamed Kamal ◽  
Nancy Nabil Shahin
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Cancer Patients ◽  
Breast Cancer Diagnosis ◽  
Serum Levels ◽  
Breast Cancer Patients ◽  
Multivariate Logistic Regression ◽  
Expression Levels ◽  
Non Coding Rnas ◽  
Pai 1

Long non-coding RNAs play an important role in tumor growth, angiogenesis, and metastasis in several types of cancer. However, the clinical significance of using lncRNAs as biomarkers for breast cancer diagnosis and prognosis is still poorly investigated. In this study, we analyzed the serum expression levels of lncRNAs PVT1, HOTAIR, NEAT1, and MALAT1, and their associated proteins, PAI-1, and OPN, in breast cancer patients compared to fibroadenoma patients and healthy subjects. Using quantitative real-time PCR (qRT-PCR), we compared the serum expression levels of the four circulating lncRNAs in patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The serum levels of PAI-1 and OPN were measured using ELISA. Receiveroperating-characteristic (ROC) analysis and multivariate logistic regression were used to evaluate the diagnostic value of the selected parameters. The serum levels of HOTAIR, PAI-1, and OPN were significantly higher in breast cancer patients compared to controls and fibroadenoma patients. The serum level of PVT1 was significantly higher in breast cancer patients than in the controls, while that of NEAT1 was significantly lower in breast cancer patients compared to controls and fibroadenoma patients. Both ROC and multivariate logistic regression analyses revealed that PAI-1 has the greatest power in discriminating breast cancer from the control, whereas HOTAIR, PAI-1, and OPN have the greatest power in discriminating breast cancer from fibroadenoma patients. In conclusion, our data suggest that the serum levels of PVT1, HOTAIR, NEAT1, PAI-1, and OPN could serve as promising diagnostic biomarkers for breast cancer.

scholarly journals Study of Gene Expression of Programmed Cell Death Ligand 1 (PD-L1) in Breast Cancer Patients

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 2-2
Author(s):  
H Gadelrab ◽  
M Mokhtar ◽  
H Morsy ◽  
M Elnaggar
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Patients ◽  
Therapeutic Response ◽  
Female Breast Cancer ◽  
Clinicopathological Parameters ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
Female Breast

Introduction: Breast cancer is the most frequently occurring cancer among females and the second most common cancer overall. Programmed Cell Death Ligand 1 (PD-L1) plays an important role in blocking ‘cancer-immunity cycle’ and is considered as a major inhibitory pathway. The aim of the present study was to clarify the alterations of expression of PD-L1 in peripheral blood mononuclear cytes (PBMCs) of female breast cancer patients and analyze its association with clinico-pathological criteria as well as therapeutic response. Materials and Methods: The study was conducted on 45 female breast cancer patients and 45 female controls. Blood samples were collected followed by PBMCs isolation, total RNA extraction, reverse transcription and finally, quantitative polymerase chain reaction (qPCR) using SYBR Green DNA binding dye. Expression levels of PD-L1 were calculated and then compared with clinicopathological parameters of the patients in addition to initial therapeutic response. Results: A significant difference was detected for PD-L1 expression levels in breast cancer patients compared to controls. A significant association with age, metastatic breast cancer, estrogen receptor (ER) negative status as well as high concentrations of cancer antigen 15-3 (CA15-3) was detected. On the other hand, no significant association was recognized with tumor size, lymph nodal status, histopathological type, grade, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER-2) status, triple negative, among de novo and recurrent metastatic patients and for the number of metastatic sites as well as the therapeutic response. Conclusions: This study paves the way of the use of PD-L1 as a noninvasive prognostic and diagnostic biomarker for poor prognosis of breast cancer.

scholarly journals Overexpression of β-Arrestins inhibits proliferation and motility in triple negative breast cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saber Yari Bostanabad ◽  
Senem Noyan ◽  
Bala Gur Dedeoglu ◽  
Hakan Gurdal
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Function ◽  
Expression Profiles ◽  
Tissue Samples ◽  
Expression Levels ◽  
Cell Cycle Genes

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

scholarly journals The BIRC Family Genes Expression in Patients with Triple Negative Breast Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 1820
Author(s):  
Anna Makuch-Kocka ◽  
Janusz Kocki ◽  
Anna Brzozowska ◽  
Jacek Bogucki ◽  
Przemysław Kołodziej ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Data ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lymphatic Vessels ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Cancer Tissue ◽  
Expression Levels

The BIRC (baculoviral IAP repeat-containing; BIRC) family genes encode for Inhibitor of Apoptosis (IAP) proteins. The dysregulation of the expression levels of the genes in question in cancer tissue as compared to normal tissue suggests that the apoptosis process in cancer cells was disturbed, which may be associated with the development and chemoresistance of triple negative breast cancer (TNBC). In our study, we determined the expression level of eight genes from the BIRC family using the Real-Time PCR method in patients with TNBC and compared the obtained results with clinical data. Additionally, using bioinformatics tools (Ualcan and The Breast Cancer Gene-Expression Miner v4.5 (bc-GenExMiner v4.5)), we compared our data with the data in the Cancer Genome Atlas (TCGA) database. We observed diverse expression pattern among the studied genes in breast cancer tissue. Comparing the expression level of the studied genes with the clinical data, we found that in patients diagnosed with breast cancer under the age of 50, the expression levels of all studied genes were higher compared to patients diagnosed after the age of 50. We observed that in patients with invasion of neoplastic cells into lymphatic vessels and fat tissue, the expression levels of BIRC family genes were lower compared to patients in whom these features were not noted. Statistically significant differences in gene expression were also noted in patients classified into three groups depending on the basis of the Scarff-Bloom and Richardson (SBR) Grading System.

scholarly journals Activated STAT3 Is a Novel Regulator of the XRCC1 Promoter and Selectively Increases XRCC1 Protein Levels in Triple Negative Breast Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5475
Author(s):  
Griffin Wright ◽  
Manoj Sonavane ◽  
Natalie R. Gassman
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Excision Repair ◽  
Strand Break ◽  
Xrcc1 Gene ◽  
Single Strand Break ◽  
Expression Levels ◽  
Constitutive Activation ◽  
Gene And Protein Expression

Base Excision Repair (BER) addresses base lesions and abasic sites induced by exogenous and endogenous stressors. X-ray cross complementing group 1 (XRCC1) functions as a scaffold protein in BER and single-strand break repair (SSBR), facilitating and coordinating repair through its interaction with a host of critical repair proteins. Alterations of XRCC1 protein and gene expression levels are observed in many cancers, including colorectal, ovarian, and breast cancer. While increases in the expression level of XRCC1 are reported, the transcription factors responsible for this up-regulation are not known. In this study, we identify the signal transducer and activator of transcription 3 (STAT3) as a novel regulator of XRCC1 through chromatin immunoprecipitation. Activation of STAT3 through phosphorylation at Y705 by cytokine (IL-6) signaling increases the expression of XRCC1 and the occupancy of STAT3 within the XRCC1 promoter. In triple negative breast cancer, the constitutive activation of STAT3 upregulates XRCC1 gene and protein expression levels. Increased expression of XRCC1 is associated with aggressiveness and resistance to DNA damaging chemotherapeutics. Thus, we propose that activated STAT3 regulates XRCC1 under stress and growth conditions, but constitutive activation in cancers results in dysregulation of XRCC1 and subsequently BER and SSBR.

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