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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 -
Histopathology Jan 2013In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to...
AIMS
In addition to oestrogen and progesterone receptors, gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are the most common markers used to identify breast origin by immunohistochemistry. GCDFP-15 expression has been reported in approximately 60% of breast carcinomas and MAM expression in approximately 80%. Data on their expression in triple-negative breast cancer (TNBC) are very limited. The aim of this study was to examine the expression of these markers in TNBC to determine their utility in pathological diagnosis.
METHODS AND RESULTS
We studied the immunohistochemical (IHC) expression of GCDFP-15 and MAM in 63 primary and 118 metastatic TNBCs. GCDFP-15 staining was present in 14% of primary and 21% of metastatic TNBCs. MAM staining was present in 25% of primary and 41% of metastatic TNBCs. The frequency of expression of GCDFP-15 and/or MAM was 30% in primary and 43% in metastatic TNBCs, and many positive tumours had only focal staining.
CONCLUSIONS
Staining for GCDFP-15 and/or MAM in triple-negative carcinomas helps to confirm breast origin, but most tumours in this subgroup of breast carcinomas lack expression of either marker.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Female; Glycoproteins; Humans; Immunohistochemistry; Mammaglobin A; Membrane Transport Proteins; Middle Aged; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone
PubMed: 22963676
DOI: 10.1111/j.1365-2559.2012.04344.x -
Asian Pacific Journal of Cancer... Feb 2023Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is...
BACKGROUND AND OBJECTIVE
Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is increasingly being used as a marker of primary breast origin. This study was done to evaluate and compare GATA-3 with GCDFP-15 and Mammaglobin in invasive primary including metastatic and triple negative breast carcinomas.
METHODS
Immunohistochemistry for GATA-3, GCDFP-15 and Mammaglobin was applied on 100 cases of primary breast carcinomas, including 20 triple negative cases and 30 cases of metastatic breast carcinomas. Staining scores were given for each marker by multiplying the percentage of positive tumor cells by the intensity of staining (1+, 2+ or 3+), with scores ranging from 0 to 300. Staining score of 1 or more was considered positive.
RESULTS
GATA-3 was expressed in 92% of primary, 80% of metastatic and 60% of triple negative breast carcinomas, with an average staining score of 270. Mammaglobin was expressed in 68% of primary, 56.6% of metastatic and 25% of triple negative breast carcinomas, with an average staining score of 180. GCDFP-15 was expressed in 48% of primary, 26.6% of metastatic and 05% of breast carcinomas, with an average staining score of 60. GATA-3 demonstrated to have higher staining score (average of 270) than other two markers in maximum number of cases.
CONCLUSION
GATA-3 has a higher sensitivity and increased staining scores in primary breast carcinomas, metastatic breast carcinomas as well as in triple negative breast carcinomas.
Topics: Humans; Asian People; Breast; Staining and Labeling; Triple Negative Breast Neoplasms; Mammaglobin A; Biomarkers, Tumor
PubMed: 36853299
DOI: 10.31557/APJCP.2023.24.2.509 -
BMC Veterinary Research Jun 2018Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its...
BACKGROUND
Mammaglobin, a member of secretoglobin family has been recognized as a breast cancer associated protein. Though the exact function of the protein is not fully known, its expression has been reported to be upregulated in human breast cancer.We focused on studying the expression of mammaglobin-B gene and protein in canine mammary tumor (CMT) tissue. Expression of mammaglobin-B mRNA and protein were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), respectively.
RESULTS
High levels of mammaglobin-B mRNA expression (6.663 ± 0.841times) was observed in CMT as compared to age and breed matched healthy controls. Further, expression of mammaglobin-B protein was detected in paraffin-embedded mammary tumor tissues from the same subjects by IHC. Mammaglobin-B protein was overexpressed only in 6.67% of healthy mammary glands while, a high level of its expression was scored in 76.7% of the CMT subjects. Moreover, no significant differences in terms of IHC score and qRT-PCR score with respect to CMT histotypes or tumor grades were observed, indicating that mammaglobin-B over-expression occurred irrespective of CMT types or grades.
CONCLUSION
Overall, significantly increased expression of mammaglobin-B protein was found in CMTs with respect to healthy mammary glands, which positively correlates to its transcript. These findings suggest that overexpression of mammaglobin-B is associated with tumors of canine mammary glands.
Topics: Animals; Dog Diseases; Dogs; Female; Gene Expression; Immunohistochemistry; Mammaglobin B; Mammary Neoplasms, Animal; Neoplasm Grading; RNA, Messenger; RNA, Neoplasm; Real-Time Polymerase Chain Reaction
PubMed: 29903015
DOI: 10.1186/s12917-018-1507-z -
Journal of the Egyptian National Cancer... Dec 2015Mammaglobin A (MGA), mainly expressed in the breast epithelium, is overexpressed in breast cancer, and has been established as a tumor and promissory marker for the...
BACKGROUND
Mammaglobin A (MGA), mainly expressed in the breast epithelium, is overexpressed in breast cancer, and has been established as a tumor and promissory marker for the early detection of metastasis.
AIM
The main aim of this study was to evaluate the association between the presence of the MGA transcript in the peripheral blood of Brazilian breast cancer patients and healthy women and the development of breast cancer and tumor progression.
MATERIAL AND METHODS
The expression of the MGA transcript in peripheral blood of 102 breast cancer patients and 102 healthy women was assessed by RT-PCR.
RESULTS
MGA mRNA was expressed in the peripheral blood of 39 breast cancer patients and in none of the women from the control group. The presence of MGA was significantly associated with presence of metastasis and age at onset after 60 years. The presence of MGA mRNA in peripheral blood displayed a sensitivity of 38.2%, specificity of 100.0%, positive predictive value (PPV) of 100.0%, and negative predictive value (NPV) of 61.8% as a breast cancer marker.
CONCLUSION
This study provides additional evidence of the presence of MGA in the peripheral blood of breast cancer patients, and its applicability as an efficient biomarker for breast cancer (High specificity and PPV). To our knowledge, this is the first study to assess the expression of MGA mRNA in peripheral blood obtained from the Brazilian population.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Case-Control Studies; Female; Gene Expression; Humans; Leukocytes, Mononuclear; Mammaglobin A; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; RNA, Messenger; Risk Factors
PubMed: 26490322
DOI: 10.1016/j.jnci.2015.09.003 -
Breast Cancer Research : BCR Oct 2022Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and...
BACKGROUND
Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC).
MATERIALS AND METHODS
Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs.
RESULTS
MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6-5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas.
CONCLUSIONS
Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.
Topics: Female; Humans; Triple Negative Breast Neoplasms; Breast Neoplasms; Biomarkers, Tumor; GATA3 Transcription Factor; Mammaglobin A; Calcium-Binding Proteins; Repressor Proteins; Matrix Gla Protein
PubMed: 36284362
DOI: 10.1186/s13058-022-01569-1 -
Cancer Research Feb 2011Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following...
Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following surgical excision of sentinel lymph node(s), which is an invasive, time consuming, and costly procedure with potential morbidity to the patient. Here, we describe an imaging platform for noninvasive assessment of ALN status, eliminating the need for surgical examination of patients to rule out nodal involvement. A targeted imaging probe (MamAb-680) was developed by conjugation of a mammaglobin-A-specific monoclonal antibody to a near-infrared fluorescent dye. Using DNA and tissue microarray, mammaglobin-A was validated as a cell-surface target that is expressed in ALN-positive patient samples but is not expressed in normal lymph nodes. In vivo selectivity was determined by i.v. injection of MamAb-680 into mice with mammaglobin-A-positive and -negative mammary fat pad (MFP) tumors; and by peritumoral MFP injection of the targeted imaging probe in mice with spontaneous ALN metastases. Fluorescence imaging showed that probe was only retained in positive tumors and metastases. As few as 1,000 cells that endogenously express mammaglobin-A were detected in ALN, indicating high sensitivity of this method. Translation of this approach offers considerable potential as a noninvasive clinical strategy to stage breast cancer.
Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Breast Neoplasms; Diagnostic Imaging; Female; Fluorescent Dyes; Humans; Immunoconjugates; Lymph Nodes; Lymphatic Metastasis; Mammaglobin A; Mice; Mice, Nude; Neoplasm Proteins; RNA, Messenger; Transplantation, Heterologous; Uteroglobin
PubMed: 21169406
DOI: 10.1158/0008-5472.CAN-10-3091 -
Journal of B.U.ON. : Official Journal... 2016In this study, we examined the expression of human mammaglobin (hMAM) mRNA and the protein levels in patients with breast cancer and their relationship with prognostic...
PURPOSE
In this study, we examined the expression of human mammaglobin (hMAM) mRNA and the protein levels in patients with breast cancer and their relationship with prognostic clinicopathological parameters.
METHODS
hMAM mRNA expression in leucocytes from peripheral blood samples from patients diagnosed with primary invasive breast cancer (IC), carcinoma in situ (CIS), or benign breast diseases was analyzed using RT-PCR. The hMAM protein levels and expression patterns in tissue from 3 patient groups were evaluated by immunohistochemical staining, and several non-breast neoplasms were selected as negative controls, undergoing the same examination.
RESULTS
The expression of hMAM mRNA was significantly higher in patients with IC or CIS compared to those with benign tumors (both<0.01). Immunohistochemical staining revealed similar results, where patients with IC or CIS had higher levels of hMAM protein (p<0.01 and p<0.01, respectively), while none of the negative controls expressed hMAM. Further analyses showed a strong correlation between hMAM protein/mRNA expression and clinicopathological factors, such as histological grade, clinical stage, and lymph node status, in patients with IC.
CONCLUSION
The hMAM mRNA and protein expression profiles validate the potential of hMAM as a specific marker for breast cancer diagnosis and target treatment delivery.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Female; Humans; Immunohistochemistry; Mammaglobin A; Prognosis; RNA, Messenger
PubMed: 27061528
DOI: No ID Found -
Cancers May 2019Mammaglobin-A (MamA) is overexpressed in 40-80% of all human breast cancers. Recent phase I clinical trials of the MamA DNA vaccine showed encouraging safety outcomes....
Oligodeoxynucleotides ODN 2006 and M362 Exert Potent Adjuvant Effect through TLR-9/-6 Synergy to Exaggerate Mammaglobin-A Peptide Specific Cytotoxic CD8+T Lymphocyte Responses against Breast Cancer Cells.
Mammaglobin-A (MamA) is overexpressed in 40-80% of all human breast cancers. Recent phase I clinical trials of the MamA DNA vaccine showed encouraging safety outcomes. However, this vaccine elicited only a modest increase in MamA specific CD8+T lymphocyte (CTL) activation. As vaccine adjuvants play a critical role in enhancing the immunotherapeutic efficiency of vaccines, we tested the potential role of three synthetic CpG oligodeoxynucleotides (ODN2216-class A ODN, ODN2006-class B ODN, and ODN M362-class C ODN) to further enhance MamA specific CTL responses. Towards this, naïve CD8+T cells were obtained from healthy HLA-A2+ human donors. The HLA-A2 specific immunodominant epitope of MamA, MamA2.1 (LIYDSSLCDL), was utilized to activate naïve CD8+T cells. The THP-1 (HLA-A2+) cells were used as antigen presenting cells to stimulate naïve CD8+T cells along with (or without) co-treatment of various ODNs mentioned above. Activation of naïve CD8+T cells with the MamA2.1 peptide along with ODNs demonstrated enhanced MamA specific CTL mediated cytotoxicity on AU565 (HLA-A/MamA) breast cancer cells following co-treatment with ODN2006 and M362 compared to ODN2216 or MamA2.1 peptide alone. However, no significant cytotoxicity was noted upon treatment of MamA2.1 activated CTLs on MCF7 (HLA-A/MamA) cells, suggesting that the activation of CTLs is specific to the MamA antigen. Functional characterization studies demonstrated specific IL-12 mediated cross-talk between TLR-6 and -9 in THP-1 cells following stimulation with ODN2006 and M362, which was critical for the final cytotoxic activation of CD8+T lymphocytes. Based on these data, we conclude that ODN2006 and ODN M362 exerted a strong adjuvant effect through induction of the initial innate immune response through TLR9 upregulation followed by enhanced MamA specific CTL dependent adaptive immune responses. Our current data provide evidence for the application of Class-B/-C-CpG-ODNs as potential vaccine adjuvants towards enhancing the success of MamA based breast cancer vaccination.
PubMed: 31091800
DOI: 10.3390/cancers11050672 -
Cancer Biology & Therapy Apr 2013Among the different types of tests used for cancer diagnosis, molecular tests have been increrasingly incorporated because of their ability to detect either expression...
Among the different types of tests used for cancer diagnosis, molecular tests have been increrasingly incorporated because of their ability to detect either expression or functional changes in the molecules associated with the disease. Mammaglobin is a protein found in mammary tissue and can be detected in serum. This protein has been proposed as a biomarker to diagnose breast cancer, given that patients exhibit an increased amount of the protein in serum and tumor tissue, in comparison to healthy individuals. The ELISA test was used in the present study to detect mammaglobin in blood samples from 51 breast cancer patients and 51 control individuals. Antibodies against mamaglobin were generated in rabbits by using the following synthetic peptides: A (amino acids 13 to 21), B (amino acids 31 to 39), C (amino acids 56 to 64) and a D peptide, corresponding to the protein isoform without three amino acids (59, 60 and 61 amino acids) from peptide C. All peptides were immunogenic and allowed generation of antibodies that were able to discriminate patients from controls. The best results were obtained for antiserum B, achieving the best sensitivity (86.3%) and specificity (96%).
Topics: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Animals; Biomarkers, Tumor; Breast Neoplasms; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immune Sera; Mammaglobin A; Middle Aged; Peptide Fragments; Rabbits
PubMed: 23358476
DOI: 10.4161/cbt.23614