The immunotherapy candidate TNFSF4 may help the induction of a promising immunological response in breast carcinomas

AbstractImmune checkpoint blockade, an immunotherapy, has been applied in multiple systemic malignancies and has improved overall survival to a relatively great extent; whether it can be applied in breast cancer remains unknown. We endeavored to explore possible factors that may influence immunotherapy outcomes in breast cancer using several public databases. The possible treatment target TNF superfamily member 4 (TNFSF4) was selected from many candidates based on its abnormal expression profile, survival-associated status, and ability to predict immune system reactions. For the first time, we identified the oncogenic features of TNFSF4 in breast carcinoma. TNFSF4 was revealed to be closely related to treatment that induced antitumor immunity and to interact with multiple immune effector molecules and T cell signatures, which was independent of endocrine status and has not been reported previously. Moreover, the potential immunotherapeutic approach of TNFSF4 blockade showed underlying effects on stem cell expansion, which more strongly and specifically demonstrated the potential effects of applying TNFSF4 blockade-based immunotherapies in breast carcinomas. We identified potential targets that may contribute to breast cancer therapies through clinical analysis and real-world review and provided one potential but crucial tool for treating breast carcinoma that showed effects across subtypes and long-term effectiveness.

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Exploring the true immunotherapy candidates to acquire the promising immunological response in breast carcinomas

10.21203/rs.3.rs-150167/v1 ◽

2021 ◽

Author(s):

Xiang Li ◽

Lei Ma ◽

Ye Sun ◽

Kai Li ◽

Hong Ren ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Immune Therapy ◽

Immunological Response ◽

Immune Checkpoint Blockade ◽

Cancer Therapies ◽

Breast Carcinomas ◽

Immune Effector ◽

Immune Therapies ◽

First Time

Abstract Background: Immune checkpoint blockade of immune therapy has been applied in multiple systemic malignancies, and have improved the overall survival to a greater extent, whether it will apply to breast cancer remains unknown. Methods: We endeavored to explore the possible factors that may influence the breast carcinoma associated immune therapy outcomes with using several public databases. Results: The possible treating target of TNF superfamily member 4 (TNFSF4), was selected from massive candidates for its abnormal expression profile, survival associated status, immune system reactions predication. For the first time, we revealed the oncogenic features of TNFSF4 in breast carcinoma, and TNFSF4 was further revealed to be closely related to anti-tumor immunity treatment, including multiple immune effector molecules and T-cell signatures, which was independent on endocrine status, and has not ever been referred to. Moreover, the immune treatment of TNFSF4 blockade also indicated the underling effects on stem cells’ expansion, which more strongly and specifically demonstrated the powerful effects of applying the TNFSF4 blockade based immune therapies in breast carcinomas. Conclusions: For the first time, we aim to dig out the embedding stars that may contribute to breast cancer therapies, and provide one potential but crucial potent for treating breast carcinoma indistinguishably, and long-term effective.

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Estrogen responsive finger protein as a new potential biomarker for breast cancer

10.31234/osf.io/jnd29 ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Breast Carcinoma ◽

Cancer Patients ◽

Mrna Level ◽

Significant Prognostic Factor ◽

Breast Carcinomas ◽

Finger Protein ◽

Potential Biomarker ◽

Human Breast Carcinomas

Purpose: Estrogen-responsive finger protein (Efp) is amember ofRINGfinger-B box-Coiled Coilfamily and is also a downstream target of estrogen receptor a. Previously, Efp was shown tomediate estrogen-induced cell growth, which suggests possible involvement in the developmentof human breast carcinomas. In this study, we examined expression of Efp in breast carcinomatissues and correlated these findings with various clinicopathologic variables.Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistryand laser capture microdissection/real-time PCR of Efp. Immunohistochemistryfor Efp was also done in 151breast carcinoma specimens fixed with formalin and embedded inparaffinwax.Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantlyassociated with the mRNA level (n = 30). Efp immunoreactivity was positively associated withlymph node status or estrogen receptor a status and negatively correlated with histologic gradeor 14-3-3j immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlatedwith poor prognosis of breast cancer patients, and multivariate analyses of disease-freesurvival and overall survival for151breast cancer patients showed that Efp immunoreactivity wasthe independentmarker.Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor inbreast cancer patients. These findings may account for an oncogenic role of Efp in the tumorprogression of breast carcinoma.

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Stromal CCL5 Promotes Breast Cancer Progression by Interacting with CCR3 in Tumor Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22041918 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1918

Author(s):

Mio Yamaguchi ◽

Kiyoshi Takagi ◽

Koki Narita ◽

Yasuhiro Miki ◽

Yoshiaki Onodera ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Tumor Progression ◽

Tumor Cells ◽

Cancer Progression ◽

Stromal Cells ◽

Human Breast Carcinoma ◽

Breast Cancer Patients ◽

Breast Carcinomas ◽

Human Breast

Chemokines secreted from stromal cells have important roles for interactions with carcinoma cells and regulating tumor progression. C-C motif chemokine ligand (CCL) 5 is expressed in various types of stromal cells and associated with tumor progression, interacting with C-C chemokine receptor (CCR) 1, 3 and 5 expressed in tumor cells. However, the expression on CCL5 and its receptors have so far not been well-examined in human breast carcinoma tissues. We therefore immunolocalized CCL5, as well as CCR1, 3 and 5, in 111 human breast carcinoma tissues and correlated them with clinicopathological characteristics. Stromal CCL5 immunoreactivity was significantly correlated with the aggressive phenotype of breast carcinomas. Importantly, this tendency was observed especially in the CCR3-positive group. Furthermore, the risk of recurrence was significantly higher in the patients with breast carcinomas positive for CCL5 and CCR3 but negative for CCR1 and CCR5, as compared with other patients. In summary, the CCL5-CCR3 axis might contribute to a worse prognosis in breast cancer patients, and these findings will contribute to a better understanding of the significance of the CCL5/CCRs axis in breast carcinoma microenvironment.

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Isolated right adrenal metastasis from an invasive ductal breast carcinoma.

10.32512/jmr/2.2.2019/10.13 ◽

2019 ◽

pp. 10-13

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Invasive Ductal Carcinoma ◽

Adrenal Glands ◽

Ductal Carcinoma ◽

Adrenal Metastasis ◽

Breast Carcinomas ◽

Invasive Ductal Breast Carcinoma ◽

Invasive Breast Carcinomas ◽

Histopathological Type

Invasive ductal carcinoma (IDC) is the most common histopathological type of breast cancer, accounting for up to 85% of all invasive breast carcinomas [1]. It spreads usually to the bone first. Solitary metastasis is commonly located in the lung, liver or brain [2]. Adrenal glands locations are extremely rare [3]. We report a case of isolated metachronous right adrenal metastasis, diagnosed four years after breast IDC management. The aim is to highlight clinical, diagnostic and therapeutic characteristics of this entity.

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Isolated right adrenal metastasis from an invasive ductal breast carcinoma.

10.32512/jmr/2.2.2019/10.12. ◽

2019 ◽

pp. 10-12

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Invasive Ductal Carcinoma ◽

Adrenal Glands ◽

Ductal Carcinoma ◽

Adrenal Metastasis ◽

Breast Carcinomas ◽

Invasive Ductal Breast Carcinoma ◽

Invasive Breast Carcinomas ◽

Histopathological Type

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Krüppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens

Endocrine Related Cancer ◽

10.1530/erc-12-0017 ◽

2012 ◽

Vol 19 (6) ◽

pp. 741-750 ◽

Cited By ~ 19

Author(s):

Kiyoshi Takagi ◽

Yasuhiro Miki ◽

Yoshiaki Onodera ◽

Yasuhiro Nakamura ◽

Takanori Ishida ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Breast Carcinoma ◽

Carcinoma Cells ◽

Human Breast Carcinoma ◽

Dependent Manner ◽

Breast Carcinomas ◽

Human Breast ◽

Breast Carcinoma Cells ◽

Mcf 7

Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associated with the status of androgen receptor. KLF5 immunoreactivity was also significantly associated with increased risk of recurrence and worse clinical outcome in breast cancer patients by univariate analyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients. We then examined possible regulation of KLF5 by androgen using MCF-7 breast carcinoma cells. KLF5 mRNA was induced by biologically active androgen 5α-dihydrotestosterone in a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfection experiments demonstrated that proliferation activity of MCF-7 cells was significantly associated with the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive gene in human breast carcinomas and play important roles in the progression of breast carcinomas. KLF5 immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.

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Isolated right adrenal metastasis from an invasive ductal breast carcinoma.

10.32512/jmr/2.2.2019l10.12 ◽

2019 ◽

pp. 10-12

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Invasive Ductal Carcinoma ◽

Adrenal Glands ◽

Ductal Carcinoma ◽

Adrenal Metastasis ◽

Breast Carcinomas ◽

Invasive Ductal Breast Carcinoma ◽

Invasive Breast Carcinomas ◽

Histopathological Type

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Matrix Metalloproteinase-2 Expression as a Prognostic Marker in Breast Carcinomas

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/47478.14835 ◽

2021 ◽

Author(s):

B Jayashree ◽

Priyathersini Nagarajan ◽

Thanka Johnson

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Matrix Metalloproteinase ◽

Prognostic Marker ◽

Poor Prognosis ◽

Invasive Breast Carcinoma ◽

Disease Stage ◽

Clinical Staging ◽

Matrix Metalloproteinase 2 ◽

Breast Carcinomas

Introduction: Matrix Metalloproteinase-2 (MMP-2) is over expressed in a variety of malignant tumours and their expression and activity are often associated with tumour aggressiveness and a poor prognosis. It serves as a prognostic marker in breast carcinoma regardless of patient age, disease stage, malignancy grade, or hormone receptor status and modulation of MMP-2 expression and activation provides a new mechanism for breast cancer treatment. Aim: To evaluate the expression of MMP-2 in breast carcinoma tumour cells and peritumoural stroma and also to analyse the findings with the existing other prognostic markers of mammary carcinoma. Materials and Methods: The present study was a retrospective study conducted on paraffin blocks of 90 cases of invasive breast carcinoma specimens received in the Department of Pathology, Sri Raamachandra Institute of Higher Education and Research a tertiary care centre in Chennai, Tamil Nadu, India, from January 2012 to June 2017. Immunohistochemical staining for MMP-2, Oestrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) was done. Statistical analysis was done on the data collected by using the software GNU-PSPP version 0.10.1. Pearson Chi-square test was used to determine significant clinicopathological differences between MMP-2 expression in positive and negative tumours. Differences were considered statistically significant when p-value was <0.05. Results: The study included 90 cases of histological proven invasive breast carcinoma. The study parameters include age, clinical staging, histopathological grade, lymphnode status, molecular subtype and MMP-2 expression in invasive breast carcinoma. Out of 90 cases, 62 cases were positive for MMP-2 and 18 cases were positive for peritumoural stroma, 30 cases were negative for MMP-2 in tumoural cells and 72 cases were negative surrounding the peritumoural stroma. Conclusion:Present study showed high MMP-2 immunohistochemical expression in breast carcinomas. There was a statistically significant association of increased MMP-2 expression with tumour stage. There was also a statistically significant association of MMP-2 in the tumour and stroma with High Grade Ductal Carcinoma In Situ (HGDCIS). There was an increased expression of MMP-2 in Luminal A subtype. Low expression was seen in the other molecular subtypes. In view of these findings and association with other studies in the literature, the present study demonstrates that the expression of MMP-2 in tumour and stromal cells could serve as a parameter of poor prognosis in breast cancer.

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Three- Dmensi0nal(3d) Relationships Between Tumor Cell Proliferation and its Anigiogensis in Human Breast Cancer by Confocal Laser Scanning Miroscopy(CLSM) with Triple-Labeling Immunohistochemistry.

Microscopy and Microanalysis ◽

10.1017/s1431927600007030 ◽

1997 ◽

Vol 3 (S2) ◽

pp. 29-30

Author(s):

J. Itoh ◽

K. Yasumura ◽

K. Ogawa ◽

K. Kawai ◽

A. Serizawa ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Breast Carcinoma ◽

Tumor Cell ◽

Lymph Node Status ◽

Computer Assisted ◽

Tumor Cell Proliferation ◽

Breast Carcinomas ◽

Human Breast ◽

Human Breast Carcinomas

There have been considerable interests in the relationship between tumor cell proliferation and angiogenesis. In human breast carcinomas, it has been reported that angiogenesis is an independent prognostic factor and that proliferating factors are closely related with lymph node status. Therefore, the demonstration of proliferating and angiogenetic factors as well as the tumor blood vessels in human breast carcinoma simultaneously is important for clinical evaluation of breast cancer patients.CLSM has been an exciting new apparatus because of it's more powerful resolution than conventional light microscopy and the high-performance on 3D optical sectioning. Images taken with CLSM can be digitized and made variable for image analysis manipulation and computer-assisted 3D reconstructions.In the present study, we employed immunohistochemical comparative 3D visualization of proliferating and angiogenstic factors with microvessels in human breast carcinomas by CLSM.The tissues from the surgically resected breast carcinoma were fixed in cold 4 % paraformaldehyde(PFA) and routinely processed in paraffin wax.

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Apoptosis gene signature of Survivin and its splice variant expression in breast carcinoma

Endocrine Related Cancer ◽

10.1530/erc-11-0105 ◽

2011 ◽

Vol 18 (6) ◽

pp. 783-792 ◽

Cited By ~ 21

Author(s):

Frédérique Végran ◽

Romain Boidot ◽

Franck Bonnetain ◽

Muriel Cadouot ◽

Sandy Chevrier ◽

...

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Gene Signature ◽

Breast Carcinomas ◽

Apoptotic Pathway ◽

Apoptotic Genes ◽

Apoptosis Gene ◽

Induced Apoptosis ◽

High Level

Survivin, an anti-apoptotic protein, was described as strongly expressed in human cancers including breast cancer. However, little is known about the association between Survivin variants (Survivin-2B, Survivin-ΔEx3, Survivin-3B, and Survivin-2α) and the other apoptotic-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Human Apoptosis Gene Arrays were used to screen genes that could be associated with Survivin variants. Expression of the five transcripts was measured by RT-PCR in 135 breast carcinomas and Cox survival analysis was analyzed according to the patient outcome. Significant associations between Survivin transcripts and apoptotic genes were found. Interestingly, Survivin-3B variant showed major inverse correlations with pro-apoptotic genes. In addition, in vitro results indicated that overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/cyclophosphamide-induced apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of Survivin-3B expression had a shorter overall (P=0.030 and P=0.042 respectively), and disease-free (P=0.024 and P=0.009) survival. Our data suggest that Survivin-3B contributes to cell survival through the anti-apoptotic pathway and that its expression level could be an important factor in determining therapeutic strategies for breast carcinoma.

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