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Timothy P. Fleming - One of the best experts on this subject based on the ideXlab platform.
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ral CANCER CELL ssBioMed Cent
2016Co-Authors: Tionalinternacancer Cell International, Timothy P. Fleming, Lian Zuo, Qian Wang, Shaojin YouAbstract:Mammaglobin as a potential molecular target for breast cancer drug deliver
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Response of Established Human Breast Tumors to
2015Co-Authors: Vaccination Mammaglobin-a Cdna, Timothy P. Fleming, Jill R. Dietz, T. MohanakumarAbstract:Background: A novel breast cancer–associated antigen, Mammaglobin-A, is expressed in 80 % of primary breast tumors. The characterization of immune responses against this highly expressed breast cancer–specific antigen would be of value in the development of new therapeutic strategies for breast cancer. Methods: We developed an in vivo model using human leukocyte antigen-A*0201/human CD8 (HLA-A2/hCD8) double-transgenic mice to define the epitopes and to study the level of protection acquired by Mammaglobin-A cDNA vaccination toward Mammaglobin-A/HLA-A2 breast cancer cell lines. Mammaglobin-A epitopes were identified using an HLA class I peptide bind-ing prediction computer program, and their activity was verified using gamma interferon ELISPOT and cytotoxicity assays. Results: We identified seven Mammaglobin-A– derived candidate epitopes that bind the HLA-A*0201 mol-ecule (Mam-A2.1–7). CD8 cytotoxic T lymphocytes (CTLs) from HLA-A2/hCD8 mice reacted to the Mam-A2.
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Mammaglobin as a potential molecular target for breast cancer drug delivery.
Cancer cell international, 2009Co-Authors: Lian Zuo, Timothy P. Fleming, Qian Wang, Shaojin YouAbstract:Background Mammaglobin (MAM) has been used as a specific molecular marker for breast cancer diagnosis. Recently, several groups of researchers proposed a number of therapeutic strategies targeting this molecule. Some of the strategies are based upon an essential but not demonstrated hypothesis – Mammaglobin is associated with the surface of breast cancer cells, which strongly disputes the therapeutic strategies.
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Mammaglobin, a breast-specific gene, and its utility as a marker for breast cancer.
Annals of the New York Academy of Sciences, 2006Co-Authors: Timothy P. Fleming, Mark A. WatsonAbstract:Abstract: The Mammaglobin gene encodes a 10-kDa glycoprotein that is distantly related to a family of proteins that includes rat estramustine binding protein (EMBP)/prostatein and human Clara cell 10-kDa protein (CC10)/uteroglobin. Among normal adult tissues, Mammaglobin mRNA expression has been detected only in the mammary gland. As an initial step to determine Mammaglobin's clinical utility as a breast tumor marker, we evaluated the frequency and specificity with which Mammaglobin expression could be detected in primary breast tumors, metastatic breast tumors, and breast tumor cells present in the peripheral circulation. Approximately 80% of all primary and metastatic breast tumors examined were strongly immunopositive for Mammaglobin protein, and staining was independent of tumor grade. Among peripheral stem cell collections from breast cancer patients, Mammaglobin mRNA could be detected in 60% of cases. Recent work has identified the secreted Mammaglobin protein in the sera of some breast cancer patients using both Western blot and ELISA. This study demonstrates that the detection of Mammaglobin protein and mRNA in clinical samples may be a useful marker for primary, metastatic, and occult breast cancer.
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Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer
Clinical cancer research : an official journal of the American Association for Cancer Research, 2005Co-Authors: Jonine L. Bernstein, Mark A. Watson, James Godbold, George Raptis, Brooke Levinson, Stuart A. Aaronson, Timothy P. FlemingAbstract:Purpose: Early detection of breast cancer has implications for the management and treatment of patients with this disease. Currently, there exist no highly sensitive and specific serologic biomarkers for detection of breast cancer. Mammaglobin is predicted to be a secreted protein, and expression of this gene seems to be highly specific in breast cancer. The present studies were undertaken to develop the Mammaglobin protein as a serum biomarker for detection of breast cancer. Experimental Design: We characterized the Mammaglobin protein as a secreted, 14- to 21-kDa species, which is likely post-translationally processed based on its predicted 7-kDa size. Immunostaining for Mammaglobin was conducted. An ELISA was developed for the detection of the Mammaglobin protein in serum, and levels were compared between women with and without breast cancer. A receiver operating characteristic curve was used to show sensitivity and specificity for cut points on the continuous Mammaglobin scale. Results: The protein was detectable by immunostaining in 72% of breast tumors and not in other tumor types. The ELISA was highly sensitive and specific for detection of Mammaglobin protein in tissue culture fluids of breast cancer cells and sera of breast cancer patients. The ELISA differentiated healthy women from those with breast cancer with accurate, repeatable results across time and under varying storage conditions. Conclusion: Our results indicate that Mammaglobin, as measured by the ELISA, holds significant promise for breast cancer screening with the realistic potential to impact management of this disease.
Mark A. Watson - One of the best experts on this subject based on the ideXlab platform.
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Mammaglobin, a breast-specific gene, and its utility as a marker for breast cancer.
Annals of the New York Academy of Sciences, 2006Co-Authors: Timothy P. Fleming, Mark A. WatsonAbstract:Abstract: The Mammaglobin gene encodes a 10-kDa glycoprotein that is distantly related to a family of proteins that includes rat estramustine binding protein (EMBP)/prostatein and human Clara cell 10-kDa protein (CC10)/uteroglobin. Among normal adult tissues, Mammaglobin mRNA expression has been detected only in the mammary gland. As an initial step to determine Mammaglobin's clinical utility as a breast tumor marker, we evaluated the frequency and specificity with which Mammaglobin expression could be detected in primary breast tumors, metastatic breast tumors, and breast tumor cells present in the peripheral circulation. Approximately 80% of all primary and metastatic breast tumors examined were strongly immunopositive for Mammaglobin protein, and staining was independent of tumor grade. Among peripheral stem cell collections from breast cancer patients, Mammaglobin mRNA could be detected in 60% of cases. Recent work has identified the secreted Mammaglobin protein in the sera of some breast cancer patients using both Western blot and ELISA. This study demonstrates that the detection of Mammaglobin protein and mRNA in clinical samples may be a useful marker for primary, metastatic, and occult breast cancer.
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Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer
Clinical cancer research : an official journal of the American Association for Cancer Research, 2005Co-Authors: Jonine L. Bernstein, Mark A. Watson, James Godbold, George Raptis, Brooke Levinson, Stuart A. Aaronson, Timothy P. FlemingAbstract:Purpose: Early detection of breast cancer has implications for the management and treatment of patients with this disease. Currently, there exist no highly sensitive and specific serologic biomarkers for detection of breast cancer. Mammaglobin is predicted to be a secreted protein, and expression of this gene seems to be highly specific in breast cancer. The present studies were undertaken to develop the Mammaglobin protein as a serum biomarker for detection of breast cancer. Experimental Design: We characterized the Mammaglobin protein as a secreted, 14- to 21-kDa species, which is likely post-translationally processed based on its predicted 7-kDa size. Immunostaining for Mammaglobin was conducted. An ELISA was developed for the detection of the Mammaglobin protein in serum, and levels were compared between women with and without breast cancer. A receiver operating characteristic curve was used to show sensitivity and specificity for cut points on the continuous Mammaglobin scale. Results: The protein was detectable by immunostaining in 72% of breast tumors and not in other tumor types. The ELISA was highly sensitive and specific for detection of Mammaglobin protein in tissue culture fluids of breast cancer cells and sera of breast cancer patients. The ELISA differentiated healthy women from those with breast cancer with accurate, repeatable results across time and under varying storage conditions. Conclusion: Our results indicate that Mammaglobin, as measured by the ELISA, holds significant promise for breast cancer screening with the realistic potential to impact management of this disease.
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PEA3, AP-1, and a unique repetitive sequence all are involved in transcriptional regulation of the breast cancer-associated gene, Mammaglobin
Breast cancer research and treatment, 2005Co-Authors: Diane R. Hesselbrock, Mark A. Watson, Natasza A. Kurpios, John A. Hassell, Timothy P. FlemingAbstract:The breast cancer-associated gene Mammaglobin is a member of the secretoglobin protein family and has demonstrated its utility as a breast cancer marker. However, the transcriptional regulation of Mammaglobin has not been well-characterized. In this report, we used luciferase reporter assays to identify the 200 bp directly 5' of the transcriptional start site as the minimal promoter region of Mammaglobin. Sequence scanning indicated that two PEA3 transcription sites were possibly involved in Mammaglobin transcription. By transfecting a PEA3 expression vector into breast cancer cell lines MDA-MB-415 and MCF-7, we determined that exogenous PEA3 was able to drive transcription. Mutational analysis indicated that each PEA3 site was functional. Our reporter system and electrophorectic mobility shift assays (EMSAs) also identified the involvement of a unique repetitive element in Mammaglobin transcription. Finally, AP-1 was determined via luciferase assays to be involved in regulating non-PEA3 dependent transcription. Elucidating these cis-acting elements will impact our understanding of transcription of normal breast and breast cancer-associated genes.
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Mammaglobin-based strategies for treatment of breast cancer.
Current cancer drug targets, 2004Co-Authors: Peter S. Goedegebuure, Mark A. Watson, Carsten T. Viehl, Timothy P. FlemingAbstract:Mammaglobin is a gene that is expressed almost exclusively in the normal breast epithelium and human breast cancer. It is a member of the secretoglobin gene family and forms a heterodimer with lipophilin B. We have focused on the tissue-specificity of Mammaglobin as a potential mechanism for the specific killing of breast cancer cells. By elucidating the promoter region of Mammaglobin, we hope to utilize this site as a method for turning on the apoptosis inducer gene, Bax, in breast cancer cells. The Bax gene will only be expressed at levels necessary to induce apoptosis in Mammaglobin positive cells. This would include > 80% of all breast cancer cells and some normal breast epithelium. This type of targeted killing could be conceptualized as a biochemical mastectomy; that is, genetic ablation of breast tumor cells and perhaps non-malignant breast epithelium while preserving the adipose and stromal components of the breast. Work is also being done to address the binding specificity of the secreted Mammaglobin protein. There is early evidence that the Mammaglobin heterodimer may in fact bind to breast and breast cancer cells. If this finding is validated, this creates the possibility that Mammaglobin can be tagged with a radioisotope or a toxin, so that binding of the tagged-Mammaglobin complex results in the specific killing of that breast cancer cell. Finally, Mammaglobin is being explored as a target for immune-based interventions. In vitro studies have demonstrated that T cellmediated immune responses can be induced against Mammaglobin-derived peptides expressed by MHC molecules on tumor cells and antigen-presenting cells. In summary, Mammaglobin displays several unique features that make it a promising target for intervention.
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Mammaglobin is associated with low grade steroid receptor positive breast tumors from postmenopausal patients and has independent prognostic value for relapse free survival time
Journal of Clinical Oncology, 2004Co-Authors: Paul N. Span, Mark A. Watson, Esme Waanders, Peggy Manders, J J T M Heuvel, John A Foekens, L V A M Beex, Fred C.g.j. SweepAbstract:Purpose The tumor mRNA expression levels of Mammaglobin, a novel breast-specific and breast cancer-associated marker, were correlated with disease outcome in 280 patients with primary breast cancer. Patients and Methods Mammaglobin expression levels were assessed by quantitative reverse transcriptase polymerase chain reaction in frozen tumor tissue from breast cancer patients with a median age of 60 years (range, 30 to 88 years) and a median follow-up of 85 months (range, 2 to 169 months). Results High expression levels were associated with low-grade tumors (P = .018), with positive estrogen and progesterone receptor status (P < .001), and postmenopausal status (P = .010). In the analysis of all patients, low tumor Mammaglobin expression levels predicted an early relapse both in Cox univariate (hazard ratio [HR], 0.52; 95% CI, 0.34 to 0.79; P = .002) and multivariate regression analyses corrected for the traditional prognostic factors (HR, 0.55; 95% CI, 0.35 to 0.88; P = .012). The association of mammaglo...
Andrés Jaramillo - One of the best experts on this subject based on the ideXlab platform.
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Adoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumors.
PloS one, 2012Co-Authors: Nadine M. Lerret, Andrés Jaramillo, Magdalena Rogozinska, A L. MarzoAbstract:Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.
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response of established human breast tumors to vaccination with Mammaglobin a cdna
Journal of the National Cancer Institute, 2004Co-Authors: Kishore Narayanan, Andrés Jaramillo, N. Benshoff, Lacey G. Campbell, Timothy P. Fleming, Jill R. Dietz, T. MohanakumarAbstract:Background: A novel breast cancer‐associated antigen, Mammaglobin-A, is expressed in 80% of primary breast tumors. The characterization of immune responses against this highly expressed breast cancer‐specific antigen would be of value in the development of new therapeutic strategies for breast cancer. Methods: We developed an in vivo model using human leukocyte antigen-A*0201/human CD8 (HLA-A2/hCD8) double-transgenic mice to define the epitopes and to study the level of protection acquired by Mammaglobin-A cDNA vaccination toward MammaglobinA/HLA-A2 breast cancer cell lines. Mammaglobin-A epitopes were identified using an HLA class I peptide binding prediction computer program, and their activity was verified using gamma interferon ELISPOT and cytotoxicity assays. Results: We identified seven Mammaglobin-A‐ derived candidate epitopes that bind the HLA-A*0201 molecule (Mam-A2.1‐7). CD8 cytotoxic T lymphocytes (CTLs) from HLA-A2/hCD8 mice reacted to the Mam-A2.1 (amino acids [aa] 83‐92, LIYDSSLCDL), Mam-A2.2 (aa 2‐10, KLLMVLMLA), Mam-A2.4 (aa 66‐74, FLNQTDETL), and Mam-A2.6 (aa 32‐40, MQLIYDSSL) epitopes. CD8 CTLs from breast cancer patients also recognized a similar epitope pattern as did those in the HLA-A2/hCD8 mice and reacted to the Mam-A2.1, Mam-A2.2, Mam-A2.3, Mam-A2.4, and Mam-A2.7 epitopes. Passive transfer of Mammaglobin-A‐reactive CTLs into SCID (severe combined immunodeficient) beige mice with actively growing Mammaglobin-A tumors resulted in statistically significant regression (P<.001) in the growth of the tumors. Conclusions: The HLA-A2/hCD8 mouse represents a valuable animal model to characterize the HLA-A*0201‐restricted CD8 CTL immune response to Mammaglobin-A in vivo, and the data reported here demonstrate the immunotherapeutic potential of Mammaglobin-A for the treatment and/or prevention of breast cancer. [J Natl Cancer Inst 2004;96: 1388 ‐96]
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Response of Established Human Breast Tumors to Vaccination with Mammaglobin-A cDNA
Journal of the National Cancer Institute, 2004Co-Authors: Kishore Narayanan, Andrés Jaramillo, N. Benshoff, Lacey G. Campbell, Timothy P. Fleming, Jill R. Dietz, T. MohanakumarAbstract:Background: A novel breast cancer‐associated antigen, Mammaglobin-A, is expressed in 80% of primary breast tumors. The characterization of immune responses against this highly expressed breast cancer‐specific antigen would be of value in the development of new therapeutic strategies for breast cancer. Methods: We developed an in vivo model using human leukocyte antigen-A*0201/human CD8 (HLA-A2/hCD8) double-transgenic mice to define the epitopes and to study the level of protection acquired by Mammaglobin-A cDNA vaccination toward MammaglobinA/HLA-A2 breast cancer cell lines. Mammaglobin-A epitopes were identified using an HLA class I peptide binding prediction computer program, and their activity was verified using gamma interferon ELISPOT and cytotoxicity assays. Results: We identified seven Mammaglobin-A‐ derived candidate epitopes that bind the HLA-A*0201 molecule (Mam-A2.1‐7). CD8 cytotoxic T lymphocytes (CTLs) from HLA-A2/hCD8 mice reacted to the Mam-A2.1 (amino acids [aa] 83‐92, LIYDSSLCDL), Mam-A2.2 (aa 2‐10, KLLMVLMLA), Mam-A2.4 (aa 66‐74, FLNQTDETL), and Mam-A2.6 (aa 32‐40, MQLIYDSSL) epitopes. CD8 CTLs from breast cancer patients also recognized a similar epitope pattern as did those in the HLA-A2/hCD8 mice and reacted to the Mam-A2.1, Mam-A2.2, Mam-A2.3, Mam-A2.4, and Mam-A2.7 epitopes. Passive transfer of Mammaglobin-A‐reactive CTLs into SCID (severe combined immunodeficient) beige mice with actively growing Mammaglobin-A tumors resulted in statistically significant regression (P
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Recognition of HLA-A2-restricted Mammaglobin-A-derived epitopes by CD8+ cytotoxic T lymphocytes from breast cancer patients.
Breast cancer research and treatment, 2004Co-Authors: Andrés Jaramillo, Kishore Narayanan, N. Benshoff, Lacey G. Campbell, Timothy P. Fleming, Jill R. Dietz, Lonnie Lybarger, Ted H. Hansen, T. MohanakumarAbstract:A breast cancer-associated antigen, Mammaglobin-A, is specifically expressed in 80% of primary breast tumors. The definition of immune responses against this highly expressed breast cancer-specific antigen should be of great value in the development of new therapeutic strategies for breast cancer. Thus, the purpose of this study was to identify HLA-A2-restricted Mammaglobin-A-derived epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL). We identified seven Mammaglobin-A-derived candidate epitopes that bind the HLA-A2 molecule (Mam-A2.1-7) by means of a HLA class I-peptide binding computer algorithm from the Bioinformatics & Molecular Analysis Section of the National Institutes of Health. Subsequently, we determined that CD8+ CTLs from breast cancer patients reacted to the Mam-A2.1 (83–92, LIYDSSLCDL), Mam-A2.2 (2–10, KLLMVLMLA), Mam-A2.3 (4–12, LMVLMLAAL), Mam-A2.4 (66–74, FLNQTDETL), and Mam-A2.7 (32–40, TINPQVSKT) epitopes using an IFN-c ELISPOT assay. Interestingly, healthy individuals also showed high reactivity to the Mam-A2.2 epitope. Two CD8+ CTL lines generated in vitro against TAP-deficient T2 cells loaded with the candidate epitopes showed significant cytotoxic activity against the Mam-A2.1-4 epitopes. These CD8+CTL lines recognized a HLA-A2+breast cancer cell line expressing the Mam-A2.1 epitope. In addition, DNA vaccination of HLA-A2+/human CD8+ double-transgenic mice with a DNA construct encoding the Mam-A2.1 epitope and the HLA-A2 molecule induced a significant expansion of epitope-specific CD8+ CTLs that recognize the same HLA- A2+/Mam-A2.1+ breast cancer cell line. In conclusion, these results demonstrate the immunotherapeutic potential of Mammaglobin-A for the treatment and prevention of breast cancer.
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Generation of CD8+ cytotoxic T lymphocytes against breast cancer cells by stimulation with Mammaglobin-A-pulsed dendritic cells.
Breast cancer research and treatment, 2003Co-Authors: Partha Pratim Manna, Andrés Jaramillo, Lacey G. Campbell, Timothy P. Fleming, Jill R. Dietz, John F. Dipersio, Kanchana Majumder, T. MohanakumarAbstract:Mammaglobin-A is exclusively expressed by breast cancer cells. Thus, Mammaglobin-A-specific T cell immune responses may be useful for the design of new breast cancer-specific immunotherapies. We show herein that CD8+ T cells generated against recombinant Mammaglobin-A-pulsed dendritic cells display a marked cytotoxic activity against Mammaglobin-A-positive breast cancer cell lines. This study indicates the immunotherapeutic potential of this novel antigen for the treatment of breast cancer.
A L. Marzo - One of the best experts on this subject based on the ideXlab platform.
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Adoptive Transfer of Mammaglobin-A Epitope Specific CD8 T Cells Combined with a Single Low Dose of Total Body Irradiation Eradicates Breast Tumors
2016Co-Authors: Nadine M. Lerret, Magdalena Rogozinska, A L. MarzoAbstract:Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80 % of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for th
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Adoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumors.
PloS one, 2012Co-Authors: Nadine M. Lerret, Andrés Jaramillo, Magdalena Rogozinska, A L. MarzoAbstract:Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.
Fred C.g.j. Sweep - One of the best experts on this subject based on the ideXlab platform.
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Mammaglobin RT-qPCR for breast cancer metastasis detection in sentinel lymph nodes
Cancer science, 2010Co-Authors: Paul N. Span, Hanneke W.m. Van Laarhoven, Fred C.g.j. SweepAbstract:They report on the use of the Gene-Search Breast Lymph Node (BLN) Assay in detecting sentinellymph node metastases in a substantial cohort of breast cancerpatients. This RT-qPCR-based assay detects cytokeratin 19 (anepithelial cell-specific marker) and Mammaglobin (a breast cell-specific marker) transcripts. Their results show that the BLNassay is specific and more sensitive than intraoperative imprintcytology.We would like to point out that Mammaglobin is notuniformly expressed by all breast cells. In fact, we found thatdifferences in Mammaglobin expression can amount to 10 000-fold between different subtypes of breast cancer,
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Concerns about Mammaglobin Assays
Clinical chemistry, 2005Co-Authors: Paul N. Span, Nicolai Grebenchtchikov, Anneke Geurts-moespot, Fred C.g.j. SweepAbstract:Mammaglobin is a protein with a strong association with breast tissue. As such, many reports have been published on the use of reverse transcription-PCR of Mammaglobin mRNA for the detection of circulating breast tumor cells. In a recent article in Clinical Chemistry , Zehentner et al. (1) reported on the use of an ELISA to detect Mammaglobin protein in blood from breast cancer patients. This strategy has much potential, as the only currently useful biomarker for breast cancer, CA15-3, has very limited specificity and sensitivity (2). Given the importance of having a breast cancer-specific serum biomarker assay, it is a regret …
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Mammaglobin is associated with low grade steroid receptor positive breast tumors from postmenopausal patients and has independent prognostic value for relapse free survival time
Journal of Clinical Oncology, 2004Co-Authors: Paul N. Span, Mark A. Watson, Esme Waanders, Peggy Manders, J J T M Heuvel, John A Foekens, L V A M Beex, Fred C.g.j. SweepAbstract:Purpose The tumor mRNA expression levels of Mammaglobin, a novel breast-specific and breast cancer-associated marker, were correlated with disease outcome in 280 patients with primary breast cancer. Patients and Methods Mammaglobin expression levels were assessed by quantitative reverse transcriptase polymerase chain reaction in frozen tumor tissue from breast cancer patients with a median age of 60 years (range, 30 to 88 years) and a median follow-up of 85 months (range, 2 to 169 months). Results High expression levels were associated with low-grade tumors (P = .018), with positive estrogen and progesterone receptor status (P < .001), and postmenopausal status (P = .010). In the analysis of all patients, low tumor Mammaglobin expression levels predicted an early relapse both in Cox univariate (hazard ratio [HR], 0.52; 95% CI, 0.34 to 0.79; P = .002) and multivariate regression analyses corrected for the traditional prognostic factors (HR, 0.55; 95% CI, 0.35 to 0.88; P = .012). The association of mammaglo...
