-
Signal Transduction and Targeted Therapy May 2020Although targeted therapy has been extensively investigated for breast cancers, a molecular target with broad application is currently unavailable due to the high...
Although targeted therapy has been extensively investigated for breast cancers, a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers. Mammaglobin-A (Mam-A), which is overexpressed in most breast carcinomas, has been proposed as a promising target. However, the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study. Here, seven potential epitopes of Mam-A were disclosed, and a unique epitope was then identified in most types of breast cancers, despite the genotypic heterogeneity. With phage display technology, the epitope was determined to be N-terminal amino acids 42-51 of Mam-A (N). Then, the N epitope-specific monoclonal antibody, mAb785, was conjugated to poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with therapeutic agents, thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers. The computer simulation of the N epitope and the mAb785 structures, as well as their interactions, further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Breast Neoplasms; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Epitopes; Female; Humans; Mammaglobin A; Nanoparticles; Neoplasm Proteins; T-Lymphocytes, Cytotoxic
PubMed: 32467564
DOI: 10.1038/s41392-020-0183-1 -
La Tunisie Medicale Feb 2020Mammary analogue secretory carcinoma is a rare new entity of low-grade malignant tumor of salivary glands. It shared the same histologic features and the chromosomal...
BACKGROUND
Mammary analogue secretory carcinoma is a rare new entity of low-grade malignant tumor of salivary glands. It shared the same histologic features and the chromosomal translocation t(12;15)(p13;q25) as secretory carcinoma of the breast.
AIM
To highlight the diagnosis approaches and the attitude of management in a case of MASC which is the first case reported in Tunisia. Reported case: A case of MASC of the lower left jugal mucosa was reviewed for its microscopic and immunohistochemical features. Fluorescence in situ hybridization (FISH) for the ETV6-NTRK3 translocation was performed. Surgery was the only treatment required in this case. No signs of local or regional recurrence during the one-year follow-up were noticed.
COMMENTARIES
Secretory carcinoma was confused with other salivary gland tumors especially acinic cell carcinoma due to their morphological similarities, making diagnosis dilemma. Fluorescence in-situ hybridization (FISH) is the one definitive finding to confirm the diagnosis of MASC and to differentiate it from the other types of salivary gland tumor. At the present time, no specific therapy is available for patients with MASC.
Topics: Anoctamin-1; Cheek; Cytogenetic Analysis; Diagnosis, Differential; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Mammaglobin A; Mammary Analogue Secretory Carcinoma; Mouth Mucosa; Neoplasm Proteins; Oncogene Proteins, Fusion; S100 Proteins; Tunisia
PubMed: 32395809
DOI: No ID Found -
Histopathology Dec 2020Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3),...
AIMS
Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10).
METHODS AND RESULTS
We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P < 0.001), whereas all other traditional markers were associated with non-TNBC (P < 0.001 for all). In addition, SOX10 was more correlated to basal-like breast cancer (BLBC) (P = 0.001) than five-marker-negative subtype among the TNBCs. A high expression rate of SOX10 (81%) was confirmed in the validation cohort. Additionally, SOX10 expression was inversely correlated with GATA3 and GCDFP15 expression, so they may complement each other in TNBC detection. The SOX10-GATA3 combination yielded a sensitivity of 60.3% for TNBC detection in the test cohort.
CONCLUSION
SOX10 is a reliable marker for identifying TNBC, and complements GATA3. The SOX10-GATA3 combination may be used as a sensitive TNBC marker.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Female; GATA3 Transcription Factor; Humans; Mammaglobin A; Middle Aged; SOXE Transcription Factors; Triple Negative Breast Neoplasms; Young Adult
PubMed: 32304249
DOI: 10.1111/his.14118 -
ACS Sensors Feb 2020The detection of circulating tumor cells (CTCs), which are responsible for metastasis in several forms of cancer, represents an important goal in oncological diagnosis...
The detection of circulating tumor cells (CTCs), which are responsible for metastasis in several forms of cancer, represents an important goal in oncological diagnosis and treatment. These cells remain extremely challenging to detect, despite numerous previous studies, due to their low concentration (1-10 cells/mL of blood). In this work, an all-fiber plasmonic aptasensor featuring multiple narrowband resonances in the near-infrared wavelength range was developed to detect metastatic breast cancer cells. To this aim, specific aptamers against mammaglobin-A were selected and immobilized as receptors on the sensor surface. In vitro assays confirm that the label-free and real-time detection of cancer cells [limit of detection (LOD) of 49 cells/mL] occurs within 5 min, while the additional use of functionalized gold nanoparticles allows a 2-fold amplification of the biosensor response. Differential measurements on selected optical resonances were used to process the sensor response, and results were confirmed by microscopy. The detection of only 10 cancer cells/mL was achieved with relevant specificity against control cells and with quick response time.
Topics: Biosensing Techniques; Breast Neoplasms; Female; Humans; Optical Fibers
PubMed: 31967461
DOI: 10.1021/acssensors.9b02155 -
Oncology Letters Dec 2019Previous phase I DNA-vaccine based clinical trials using Mammaglobin-A (Mam-A), a human breast tumor associated antigen (TAA), demonstrated that this agent was safe and...
Previous phase I DNA-vaccine based clinical trials using Mammaglobin-A (Mam-A), a human breast tumor associated antigen (TAA), demonstrated that this agent was safe and efficient at treating patients with stage IV breast cancer. The long-term success of cancer vaccines is limited by the diminished expression of human leukocyte antigen (HLA) class I molecules in the tumor microenvironment. The current study assessed the impact of various selenocompounds on the expression of HLA class I molecules in THP-1 cells, an apparent proficient antigen that presents a human monocyte-like cell line, and their eventual activation of MamA2.1 (HLA-A2 immunodominant epitope of Mam-A) specific cytotoxic CD8 T lymphocytes (CTLs). The results revealed that, following treatment with methylselenol producing compounds [methylselenic acid (MSA) and dimethylselenide (DMDSe)], the expression of HLA class-I was increased and components involved with the antigen presentation machinery of THP-1 cells were upregulated. Furthermore, CTLs activated by MamA2.1 peptide presenting THP-1 cells, pre-treated with MSA and DMDSe, demonstrated an enhanced cytotoxicity in HLA-A2/Mam-A AU565 and UACC-812 breast cancer cell lines when compared with CTLs activated by THP-1 cells without drug treatment. However, no significant cytotoxicity was observed under similar conditions in HLA-A2/Mam-A MCF-7 and MDA-MB-231 breast cancer cell lines. The results indicated that treatment with methylselenol producing compounds retained antigen-dependent activation of CD8 T cells. The data of the current study demonstrated that MSA and DMDSe potentiated effector cytotoxic responses following TAA specific activation of CTLs, indicating their future role as vaccine adjuvants in cancer immunotherapy.
PubMed: 31807192
DOI: 10.3892/ol.2019.11010 -
Human Pathology Oct 2019Mammaglobin is expressed in breast and salivary gland secretory carcinomas; however, its expression in salivary duct carcinomas (SDCs) still not well established....
Mammaglobin is expressed in breast and salivary gland secretory carcinomas; however, its expression in salivary duct carcinomas (SDCs) still not well established. Therefore, the aim of this study was to investigate the presence and distribution of mammaglobin immunoexpression in SDC ex-PA in different phases of the adenoma to carcinoma sequence evaluating its possible involvement in carcinogenesis and tumor progression, as well as to determine its expression in SDC de novo. Mammaglobin immunohistochemistry was performed in 84 SG tumors, including 41 pleomorphic adenomas (PA) without malignant transformation, 13 intracapsular SDC ex-PA, 5 frankly invasive SDC ex-PA, 25 SDC de novo and 10 secretory carcinomas. The reactions were qualitatively analyzed and digitally scored. Positive immunostaining for mammaglobin was observed in 37 out of 84 SG tumors evaluated (44.1%), but strong staining was consistently seen only in secretory carcinomas, SDC de novo and frankly invasive SDC ex-PA, while it was weaker in intracapsular SDC ex-PA and PA. In PA, mammaglobin expression was significantly associated with recurrence. This study has confirmed that the mammaglobin is commonly expressed in SDC de novo and secretory carcinomas. Its expression was higher in SDC ex-PA than in PA, suggesting that mammaglobin may play a role in its malignant transformation.
Topics: Adenoma, Pleomorphic; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Disease Progression; Female; Humans; Immunohistochemistry; Male; Mammaglobin A; Middle Aged; Salivary Ducts; Salivary Gland Neoplasms; Young Adult
PubMed: 31400353
DOI: 10.1016/j.humpath.2019.08.001 -
Breast Cancer : Basic and Clinical... 2019This study determines the co-expression of mammaglobin-A, vascular endothelial growth factor receptor-3 (VEGFR3) and Ki67 by immunohistochemistry (IHC) in tissue samples...
BACKGROUND/METHODS
This study determines the co-expression of mammaglobin-A, vascular endothelial growth factor receptor-3 (VEGFR3) and Ki67 by immunohistochemistry (IHC) in tissue samples from 80 patients undergoing breast surgery (cancer or benign disease). The tissue expression was compared with the tumour histopathology and Kaplan Meier 5-year survival analysis was performed.
RESULTS
Positive breast tissue expression was observed in 53% samples for mammaglobin, 41% Ki67 and 65% VEGFR3 with a significant positive correlation between Ki67 and VEGFR3 co-expression. Ki67 and VEGFR3 expression correlated with the breast tumour grade and Ki67 expression also correlated with oestrogen receptor (ER) status. At 5 years post-operatively, 6/80 patients had died and 3 patients were alive but had cancer recurrence. High Ki67 expression significantly correlated with poor survival (disease-free and overall).
CONCLUSIONS
In this study, VEGFR3 and Ki67 expression but not mammaglobin-A correlated with breast tumour pathology. Positive Ki67 expression was also associated with a poor 5-year survival outcome.
PubMed: 31263371
DOI: 10.1177/1178223419858957 -
3 Biotech Jul 2019In the present study, the simultaneous application of gene of and - antigen on the induction of immune responses against breast cancer tumors was investigated in...
In the present study, the simultaneous application of gene of and - antigen on the induction of immune responses against breast cancer tumors was investigated in BALB/c mice. The pBudCE4.1-azurin-MAM-A recombinant vector was generated and prepared at a large scale. This recombinant vector alone or combined with chitosan nanoparticles was infused into the hip muscle of animals. Animals were divided into the "prevention" and "therapy" categories. The animals of prevention category were first, immunized by a recombinant vector and then exposed to chemical cancer inducers; while the animals in the therapy category were first treated with chemical compounds and then infused by a recombinant plasmid. The tumor tissues, infusion sites, and blood specimens were collected and examined by serological, molecular, and histological tests. The breast tumor incidence in the infused animals by recombinant plasmid alone or combined with nanoparticles (in both prevention and therapy categories) compared with infused mice by empty pBudCE4.1 vector was significantly decreased (< 0.05). These results were supported by histological studies using H&E staining. The ELISA and q-real-time PCR techniques showed the range of IFN-γ, IL-12, IL-4, and IL-17A cytokines in the infused mice by recombinant vector alone or combined with nanoparticles compared to the healthy mice and infused animals by intact pBudCE4.1 were significantly increased (< 0.05). Accordingly, the expression of the tumor markers , , and were significantly decreased in treated mice either by the sole recombinant vector or combined with nanoparticles (< 0.05). These findings indicated that pBudCE4.1-azurin-MAM-A recombinant vector plays an essential role against the formation and expansion of breast tumors in the animal model. In addition, this recombinant vector is safe and has the proper ability to stimulate the immune system. In addition, the chitosan nanoparticle represents a promising adjuvant for DNA vaccine delivery, which improves the immune system stimulation and boosts the vaccine performance.
PubMed: 31245235
DOI: 10.1007/s13205-019-1804-7 -
Acta Otorhinolaryngologica Italica :... Jun 2019
Topics: Adolescent; Adult; Aged; Aquaporin 5; Caveolin 1; Chronic Disease; Cyclooxygenase 2; Cytokines; Epithelial Cells; Gene Expression; Gene Expression Profiling; Humans; Lactoferrin; Mammaglobin A; Middle Aged; Mucin 5AC; Nasal Polyps; Retrospective Studies; Rhinitis; Sinusitis; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 31131836
DOI: 10.14639/0392-100X-2361 -
PloS One 2019This meta-analysis presents evidence regarding the diagnostic accuracy of mammaglobin detected using the RT-PCR technique, related to the presence of sentinel node... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis presents evidence regarding the diagnostic accuracy of mammaglobin detected using the RT-PCR technique, related to the presence of sentinel node metastasis in breast cancer patients.
METHODS
The following databases were consulted: Cochrane, Lilacs, Scielo, Hinary, PubMed, Elsevier, Embase, ProQuest, the Universidad del Rosario´s Centro de Recursos Para el Aprendizaje y la Investigación (CRAI-UR) [Resource Center for Learning and Research], and the Google Scholar search engine. The quality of the studies was assessed using the QUADAS-2 and CASpe tools. The selected studies presented the necessary data to calculate diagnostic validity index of mammaglobin detection using RT-PCR, compared with the reference standard test. Global values for the sensitivity, specificity, positive predictive value, negative predictive value, probability ratios, diagnostic ORs, and summary ROC curves of this meta-analysis were obtained using the Meta-DiSc 1.4 program.
RESULTS
Initially, 731 articles were obtained; but only 25 were included in the meta-analysis. Sensitivity was 84% (95% CI: 83% - 86%), and specificity was 92% (95% CI: 91% - 93%). Positive and negative predictive values were 9.26 (95% CI: 6.47-13.26) and 0.17 (95% CI: 0.13-0.23), respectively. The diagnostic OR was 66.34 (95% CI: 42.52-103.52). The predictive area under the sROC curve was 94.78 (Q = 0.8876).
CONCLUSIONS
The evaluated diagnostic index showed that the expression of the mammaglobin biomarker has diagnostic prediction for detecting lymph node metastasis in breast cancer patients, when analyzed using RT-PCR, although more than 50% heterogeneity was found.
Topics: Biomarkers, Tumor; Breast Neoplasms; Cluster Analysis; Female; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Metastasis; Mammaglobin A; Observational Studies as Topic; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; ROC Curve; Reproducibility of Results; Sensitivity and Specificity
PubMed: 31120936
DOI: 10.1371/journal.pone.0216989