scholarly journals Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

2014 ◽  
Vol 60 (1) ◽  
pp. 233-242 ◽  
Author(s):  
Yaojun Li ◽  
Yueguo Li ◽  
Tao Chen ◽  
Anna S Kuklina ◽  
Paul Bernard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ex Vivo ◽  
Human Cell Line ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Orthotopic Implantation ◽  
Peptide Cleavage ◽  
Clinical Patient ◽  
Tumor Tissues ◽  
Carboxypeptidase N

Abstract BACKGROUND Carboxypeptidase N (CPN) is important in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. We investigated whether circulating peptides specifically cleaved by CPN in the tumor microenvironment can be stage-specific indicators of breast cancer. METHODS CPN activity was measured using an ex vivo peptide cleavage assay by incubating synthesized C3f peptide (His6-C3f_S1304-R1320-His6) in interstitial fluids of breast tumors and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. The nature and extent of peptide cleavage by CPN was investigated by fragment profiling using nanopore fractionation and mass spectrometry. The fragment profiles in interstitial fluid correlated with concentrations of CPN-catalyzed peptides in blood samples taken from the tumor-bearing mice, healthy women, and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting. RESULTS We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, CPN was clearly increased in tumor tissues compared with normal breast tissue, whereas corresponding CPN abundance in blood remained constant. Concentrations of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n = 8) at 2 weeks after orthotopic implantation. Six homologous peptides displayed significantly higher expression in the patients' plasma as early as the first pathologic stage of breast cancer. CONCLUSIONS Circulating CPN-catalyzed peptide concentrations reflect the CPN activity in tumors. These biomarkers show strong potential for the noninvasive and early diagnosis of breast cancer.

scholarly journals Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Subtypes ◽  
Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

scholarly journals miR-205 in Breast Cancer: State of the Art

2020 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Ilaria Plantamura ◽  
Alessandra Cataldo ◽  
Giulia Cosentino ◽  
Marilena V. Iorio
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Normal Breast ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Open Questions ◽  
Tumor Tissues ◽  
Breast Physiology ◽  
Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

scholarly journals The Expression Pattern of Epidermal Differentiation Marker Keratin 10 in the Normal Human Breast and Breast Cancer Cells

2020 ◽  
Vol 68 (8) ◽  
pp. 561-570
Author(s):  
Jiyoung Kim ◽  
René Villadsen
Keyword(s):  
Breast Cancer ◽  
Expression Pattern ◽  
Breast Tissue ◽  
Normal Breast ◽  
Epidermal Differentiation ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Normal Human Breast ◽  
Differentiation Marker ◽  
Breast Gland

Cells of the human breast gland express an array of keratins, of which some are used for characterizing both normal and neoplastic breast tissue. However, the expression pattern of certain keratins has yet to be detailed. Here, the expression of a differentiation marker of epidermal epithelium, keratin 10 (K10), was investigated in the human breast gland. While in normal breast tissue generally less than 1% of luminal epithelial cells expressed K10, in women >30 years of age glandular structures with K10-positive (K10pos) cells were found at higher frequency than in younger women. K10pos cells belong to a mature luminal compartment as they were negative for cKIT, positive for Ks20.8, and mostly non-cycling. In breast cancer, around 16% of primary breast carcinomas tested were positive for K10 by immunohistochemistry. Interestingly, K10pos tumor cells generally exhibit features of differentiation similar to their normal counterparts. Although this suggests that K10 is a marker of tumor differentiation, data based on gene expression analysis imply that high levels of K10 dictate a worse outcome for breast cancer patients. These findings can form the basis of future studies that should unravel which role K10 may play as a marker of breast cancer:

Repression of protocadherin 17 is correlated with elevated angiogenesis and hypoxia markers in female patients with breast cancer

2021 ◽  
pp. 1-10
Author(s):  
Sanaa A. El-Benhawy ◽  
Samia A. Ebeid ◽  
Nadia A. Abd El Moneim ◽  
Rabie R. Abdel Wahed ◽  
Amal R.R. Arab
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Stage ◽  
Suppressor Gene ◽  
Normal Breast ◽  
Vital Role ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Cd34 Cells ◽  
Breast Tissues

BACKGROUND: Altered cadherin expression plays a vital role in tumorigenesis, angiogenesis and tumor progression. However, the function of protocadherin 17 (PCDH17) in breast cancer remains unclear. OBJECTIVE: Our target is to explore PCDH17 gene expression in breast carcinoma tissues and its relation to serum angiopoietin-2 (Ang-2), carbonic anhydrase IX (CAIX) and % of circulating CD34+ cells in breast cancer patients (BCPs). METHODS: This study included Fifty female BCPs and 50 healthy females as control group. Cancerous and neighboring normal breast tissues were collected from BCPs as well as blood samples at diagnosis PCDH17 gene expression was evaluated by RT-PCR. Serum Ang-2, CAIX levels were measured by ELISA and % CD34+ cells were assessed by flow cytometry. RESULTS: PCDH17 was downregulated in cancerous breast tissues and its repression was significantly correlated with advanced stage and larger tumor size. Low PCDH17 was significantly correlated with serum Ang-2, % CD34+ cells and serum CAIX levels. Serum CAIX, Ang-2 and % CD34+ cells levels were highly elevated in BCPs and significantly correlated with clinical stage. CONCLUSIONS: PCDH17 downregulation correlated significantly with increased angiogenic and hypoxia biomarkers. These results explore the role of PCDH17 as a tumor suppressor gene inhibiting tumor growth and proliferation.

scholarly journals Exosomes: A Forthcoming Era of Breast Cancer Therapeutics

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4672
Author(s):  
Banashree Bondhopadhyay ◽  
Sandeep Sisodiya ◽  
Faisal Abdulrahman Alzahrani ◽  
Muhammed A. Bakhrebah ◽  
Atul Chikara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapeutics ◽  
Therapeutic Strategies ◽  
Breast Cancer Patients ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Circulating Markers

Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies.

scholarly journals Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Breast Care ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Kheirollah Yari ◽  
Zohreh Rahimi
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Retinoic Acid Receptor ◽  
Methylation Status ◽  
Normal Breast ◽  
Breast Cancer Patients ◽  
Retinoic Acid Receptor Beta ◽  
Cancer Tissues ◽  
Breast Tissues ◽  
Receptor Beta

Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations. Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer.

Evaluation of mRNA markers for micrometastases detection by RT-PCR in lymph nodes (LN), peripheral blood (PB) and bone marrow (BM) of breast cancer patients (pts)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20068-20068
Author(s):  
A. M. Morelle ◽  
A. Frasson ◽  
F. Zerwes ◽  
S. Alves ◽  
G. Devenz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Normal Breast ◽  
Variable Number ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Rt Pcr ◽  
Normal Gland ◽  
Cea Mrna ◽  
Mrna Markers

20068 Background: Previous RT-PCR study showed that hMAM and CEA mRNA could be detected in 95% and 78% breast carcinomas, respectively. Analyzed in normal LN, these two markers were the only ones not expressed, compared to other mRNA markers which could be detected in a variable number of cases (Marchetti 2001). We evaluate the expression of CEA and hMAM mRNA in breast cancer pts in order to investigate if the identification of these transcripts could be correlated to in the LN, PB and BM. Methods: Tumor, normal gland, LN and PB were obtained from 49 breast cancer pts who have been referred to surgery during the period of Jun/2000 to Jan/2004.BM could be obtained from 21 of these cases. Before the manipulation of the tumor, 5 mL of PB was collected and 5 mL of BM was aspirated from the iliac crest. First level axillary LN were sectioned in two. One of the halves was immediately frozen in liquid nitrogen. CEA and hMAM transcripts have been analysed by RT-PCR. Results: Tumors were positive for CEA in 38 (77.6%) cases and LN were positive in 15 cases (36.7%). 6/49 pts expressed CEA in normal breast (12.2%). Five of these, tumor also expressed CEA. Two pts (4.1%) showed CEA expression in PB and in BM. One patient expressed CEA in BM but not in PB. All pts that showed expression in PB, BM and LN, also showed transcript of CEA in tumor. hMAM transcripts were found in 39 (79.6%) normal gland tissue and in 41 of tumor samples (85.7%). LN were positive to hMAM in 12 cases (24.5%). 5 of these (10.2%) were also positive in PB and BM samples. The pts showing hMAM expression in PB, BM and LN also showed its expression in neoplasic tissue. Analyzing both markers, two pts showed the expression of CEA and hMAM in the PB and BM samples. In 21 of the 49 cases the comparison of hMAM and CEA was possible to be performed in all tissues. CEA and hMAM expression associated to larger number of LN affected. Conclusions: CEA and hMAM transcripts can be detected in majority of breast cancer tissue. Specificity of hMAM seems to be higher than CEA, which can be detected in more than 10% of non-tumor breast tissue. Synchronicity of CEA or hMAM expression in the tumor and in extra-mammary sites was high, suggesting that these markers may provide an interesting strategy for follow-up micrometastatic disease. No significant financial relationships to disclose.

Activation by zoledoronic acid and IL-18 of γδ T cells from early-stage breast cancer patients in the context of helper NK cells.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21004-e21004
Author(s):  
Tomoharu Sugie ◽  
Kaoru Murata-Hirai ◽  
Masashi Iwasaki ◽  
Craig T Morita ◽  
Wen Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Nk Cells ◽  
Cancer Patients ◽  
Ex Vivo ◽  
Early Stage ◽  
Γδ T Cells ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients ◽  
Vγ2vδ2 T Cells

e21004 Background: Human γδ T cells display potent cytotoxicity against various tumor cells pretreated with zoledronic acid (Zol). Zol has shown benefits when added to adjuvant endocrine therapy for patients with early-stage breast cancer or to standard chemotherapy for patients with multiple myeloma. Although γδ T cells may contribute to this additive effect, the responsiveness of γδ T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of Vγ2Vδ2 T cells from early- and late-stage breast cancer patients and examined the effect of IL-18 on their ex vivo expansion. Methods: Breast cancer patients (n=80) were enrolled after institutional review board approval and with written informed consent. Peripheral blood mononuclear cells (PBMC) were purified and stimulated with Zol/IL-2 or Zol/IL-2/IL-18 for 2 to 10 days. The expanded cells were assessed on flow cytometry and the production of IFN-γ and TNF-α measured through ELISA. Results: The responsiveness of Vγ2Vδ2 T cells from patients with low frequencies of Vγ2Vδ2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of Vγ2Vδ2T cells and helper NK cells (CD3-CD56brightCD11c+CD14-CD16+NKGD2+NKp44low) from patients with either low or high frequencies of Vγ2Vδ2 T cells. Cell-to-cell contact between γδ T and helper NK cells appeared to promote expansion of γδ T cells. Exogenous IL-18 markedly enhanced IFN-γ and TNF-α production from PBMC stimulated by Zol/IL-2, whereas the addition of an anti-IL-18Rα mAb reduced cytokine production. Conclusions: These results demonstrate that Zol elicits immunological responses by γδ T cells from early-stage breast cancer patients and IL-18 enhances proliferative responses and effector functions of γδ T cells in the context of helper NK cells.

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