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Zsuzsanna Varga - One of the best experts on this subject based on the ideXlab platform.
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ny br 1 protein expression in breast carcinoma a mammary gland Differentiation Antigen as target for cancer immunotherapy
Cancer Immunology Immunotherapy, 2007Co-Authors: Jeanphilippe Theurillat, Zsuzsanna Varga, Ursina Zurrerhardi, Martina Storz, Nicole Probsthensch, Burkhardt Seifert, Mathias K Fehr, Daniel Fink, Soldano Ferrone, Bernhard C PestalozziAbstract:NY-BR-1 is a recently identified Differentiation Antigen of the mammary gland. To use NY-BR-1 for T-cell-based immunotherapy, analysis of its co-expression with HLA class I Antigens is required. In the present tissue microarray study, primary breast cancers (n = 1,444), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-BR-1 expression using a novel monoclonal antibody. NY-BR-1 expression was compared with prognosis, estrogen receptor, HER2-status, EGFR and HLA class I Antigen expression. NY-BR-1 was more frequently expressed in grade 1 (82%) than in grade 2 (69%) and grade 3 (46%) carcinomas (P < 0.0001). Moreover, NY-BR-1 expression correlated directly with estrogen receptor expression (P < 0.0001) and inversely correlated with HER2-status and EGFR expression (P < 0.0001 for both). Considering high expression level of co-expression, 198/1,321 (15%) primary breast carcinomas and 4/65 (6%) distant metastases expressed NY-BR-1 and HLA class I, suggesting that active immunotherapy can be applied to about 10% of breast cancer patients. Survival analysis showed an association of NY-BR-1 expression with better patient outcome (P = 0.015). No difference between NY-BR-1 expression of primary tumors and metastases could be found, indicating that the presence of NY-BR-1 in metastases can be deduced from their corresponding primary. Forty-three paired biopsies taken from patients before and after chemotherapy suggest that NY-BR-1 expression is not influenced by preceding chemotherapy (kappa = 0.89, P < 0.0001). In summary, the co-expression of NY-BR-1 with HLA class I Antigens and its expression in metastases without modification by chemotherapy suggest that NY-BR-1 targeted immunotherapy represents a viable strategy in addition to other targeted cancer drug therapies of breast cancer.
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Expression of the breast Differentiation Antigen NY-BR-1 in a phyllodes tumor of the vulva
Virchows Archiv, 2007Co-Authors: Olivier T. Giger, Elena Lacoste, Christoph Honegger, Barbara Padberg, Holger Moch, Zsuzsanna VargaAbstract:We describe a phyllodes tumor of borderline malignancy in the labium majus of a 49-year-old woman. The histogenetic origin of phyllodes tumors in the vulva is controversial. Strong immunoreactivity for NY-BR-1, a novel breast Differentiation Antigen, was demonstrated within the epithelial components of the phyllodes tumor. A similar expression pattern was observed in mammary-like glands of the vulva. These findings provide further evidence that phyllodes tumors of the vulva might derive from mammary-like glands in the labium majus or from ectopic breast tissue.
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preferential nuclear and cytoplasmic ny br 1 protein expression in primary breast cancer and lymph node metastases
Clinical Cancer Research, 2006Co-Authors: Zsuzsanna Varga, Jeanphilippe Theurillat, Valeriy Filonenko, Bernd Sasse, Bernhard Odermatt, Achim A Jungbluth, Yaotseng Chen, Lloyd J Old, Alexander Knuth, Dirk JagerAbstract:Purpose: NY-BR-1 is a recently isolated Differentiation Antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1 to study the protein expression of NY-BR-1. Methods: In our immunohistochemical study, NY-BR-1 was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases. Results: Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity. This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor–positive and lymph node–negative primary carcinomas ( P P Conclusion: This study supports the notion that NY-BR-1 is a Differentiation Antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.
Dean J Bacich - One of the best experts on this subject based on the ideXlab platform.
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moderate expression of prostate specific membrane Antigen a tissue Differentiation Antigen and folate hydrolase facilitates prostate carcinogenesis
Cancer Research, 2008Co-Authors: Veronica Yao, Anil V Parwani, Christoph Maier, Warren D W Heston, Dean J BacichAbstract:Increased expression of PSMA, a Differentiation Antigen with folate hydrolase activity, is an independent marker of prostate cancer progression. Mice expressing moderate levels of human PSMA in their prostate develop PIN-like lesions by 9 months. The aim of this study was to determine whether PSMA is involved in prostate carcinogenesis and progression and, if so, the possible mechanism by which PSMA may exert its effects. Using prostates from PSMA-transgenic mice, we developed a tissue recombinant model that exhibits small atypical glands with features of adenocarcinoma. This was not observed in tissue recombinants that were composed of prostate tissues from the wild-type siblings. Cells from PSMA-transgenic tissue recombinants have the ability to form colonies in semisolid agar. PSMA may facilitate this phenotype by increasing the invasive ability of cells. Ectopic PSMA expression on PC-3 cells increased the invasive capacity of cells in in vitro invasion assays, which could be competed out by folic acid. These results suggest PSMA facilitates the development of prostate cancer, and the invasive ability of these cells may be modulated by folate levels. These findings show a novel mechanism that may contribute to the known role of folate in cancer prevention, and may lead to the use of PSMA inhibitors as novel chemopreventive agents for prostate cancer. Moreover, our model should prove useful for further dissecting pathways involved in prostate carcinogenesis and progression.
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moderate expression of prostate specific membrane Antigen a tissue Differentiation Antigen and folate hydrolase facilitates prostate carcinogenesis
Cancer Research, 2008Co-Authors: Veronica Yao, Anil V Parwani, Christoph Maier, Warren D W Heston, Dean J BacichAbstract:Increased expression of PSMA, a Differentiation Antigen with folate hydrolase activity, is an independent marker of prostate cancer progression. Mice expressing moderate levels of human PSMA in their prostate develop PIN-like lesions by 9 months. The aim of this study was to determine whether PSMA is involved in prostate carcinogenesis and progression and, if so, the possible mechanism by which PSMA may exert its effects. Using prostates from PSMA-transgenic mice, we developed a tissue recombinant model that exhibits small atypical glands with features of adenocarcinoma. This was not observed in tissue recombinants that were composed of prostate tissues from the wild-type siblings. Cells from PSMA-transgenic tissue recombinants have the ability to form colonies in semisolid agar. PSMA may facilitate this phenotype by increasing the invasive ability of cells. Ectopic PSMA expression on PC-3 cells increased the invasive capacity of cells in in vitro invasion assays, which could be competed out by folic acid. These results suggest PSMA facilitates the development of prostate cancer, and the invasive ability of these cells may be modulated by folate levels. These findings show a novel mechanism that may contribute to the known role of folate in cancer prevention, and may lead to the use of PSMA inhibitors as novel chemopreventive agents for prostate cancer. Moreover, our model should prove useful for further dissecting pathways involved in prostate carcinogenesis and progression. [Cancer Res 2008;68(21):9070–7]
Dirk Jager - One of the best experts on this subject based on the ideXlab platform.
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preferential nuclear and cytoplasmic ny br 1 protein expression in primary breast cancer and lymph node metastases
Clinical Cancer Research, 2006Co-Authors: Zsuzsanna Varga, Jeanphilippe Theurillat, Valeriy Filonenko, Bernd Sasse, Bernhard Odermatt, Achim A Jungbluth, Yaotseng Chen, Lloyd J Old, Alexander Knuth, Dirk JagerAbstract:Purpose: NY-BR-1 is a recently isolated Differentiation Antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1 to study the protein expression of NY-BR-1. Methods: In our immunohistochemical study, NY-BR-1 was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases. Results: Among normal tissues, NY-BR-1 was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1 positive, displaying cytoplasmic and/or nuclear immunoreactivity. This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor–positive and lymph node–negative primary carcinomas ( P P Conclusion: This study supports the notion that NY-BR-1 is a Differentiation Antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1 and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.
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immunoselection in vivo independent loss of mhc class i and melanocyte Differentiation Antigen expression in metastatic melanoma
International Journal of Cancer, 1997Co-Authors: Elke Jager, Dirk Jager, Mark Ringhoffer, Michael Altmannsberger, Michael Arand, Julia Karbach, Franz Oesch, Alexander KnuthAbstract:Peptides derived from melanocyte Differentiation Antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of Antigen-expressing tumors as well as selection of Antigen-loss variants in the presence of Antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte Differentiation Antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of Antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of Antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing Antigen-positive tumors in the presence of Antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated Antigens need to be considered in attempts at making vaccination more effective.
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immunoselection in vivo independent loss of mhc class i and melanocyte Differentiation Antigen expression in metastatic melanoma
International Journal of Cancer, 1997Co-Authors: Elke Jager, Dirk Jager, Mark Ringhoffer, Michael Altmannsberger, Michael Arand, Julia Karbach, Franz Oesch, Alexander KnuthAbstract:Peptides derived from melanocyte Differentiation Antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma. Regression of Antigen-expressing tumors as well as selection of Antigen-loss variants in the presence of Antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte Differentiation Antigens Melan A/MART-I and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-I and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of Antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of Antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-I expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing Antigen-positive tumors in the presence of Antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated Antigens need to be considered in attempts at making vaccination more effective. Int. J. Cancer, 71:142–147, 1997. © 1997 Wiley-Liss, Inc.
Eugene Lukanidin - One of the best experts on this subject based on the ideXlab platform.
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the Differentiation Antigen ly 6e 1 is expressed in mouse metastatic tumor cell lines
FEBS Letters, 1997Co-Authors: Martin A Cohn, Dmitri A Kramerov, Egil F Hulgaard, Eugene LukanidinAbstract:Abstract We report the cloning of the mouse surface GPI-anchored Ly-6E.1 protein from a highly metastatic mouse adenocarcinoma cell line CSML-100 by differential display. The expression is specific for the metastatic cell line as the closely related, non-metastatic mouse adenocarcinoma cell line CSML-0 does not express Ly-6E.1. Northern blot analysis reveals expression in a number of mouse tumour cell lines, exclusively metastatic ones. To date, active Ly-6A/E has only been described in lymphoid cells. The correlation between Ly-6E.1 expression, and the ability to metastasize, is discussed. © Federation of European Biochemical Societies.
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the Differentiation Antigen ly 6e 1 is expressed in mouse metastatic tumor cell lines
FEBS Letters, 1997Co-Authors: Martin A Cohn, Dmitri A Kramerov, Egil F Hulgaard, Eugene LukanidinAbstract:We report the cloning of the mouse surface GPI-anchored Ly-6E.1 protein from a highly metastatic mouse adenocarcinoma cell line CSML-100 by differential display. The expression is specific for the metastatic cell line as the closely related, non-metastatic mouse adenocarcinoma cell line CSML-0 does not express Ly-6E.1. Northern blot analysis reveals expression in a number of mouse tumour cell lines, exclusively metastatic ones. To date, active Ly-6A/E has only been described in lymphoid cells. The correlation between Ly-6E.1 expression, and the ability to metastasize, is discussed.
Roland B Walter - One of the best experts on this subject based on the ideXlab platform.
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investigational cd33 targeted therapeutics for acute myeloid leukemia
Expert Opinion on Investigational Drugs, 2018Co-Authors: Roland B WalterAbstract:Introduction: There is long-standing interest in drugs targeting the myeloid Differentiation Antigen CD33 in acute myeloid leukemia (AML). Positive results from randomized trials with the antibody-...
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the past and future of cd33 as therapeutic target in acute myeloid leukemia
Blood Reviews, 2014Co-Authors: George S Laszlo, Roland B Walter, Elihu H EsteyAbstract:CD33 is a myeloid Differentiation Antigen with endocytic properties. It is broadly expressed on acute myeloid leukemia (AML) blasts and, possibly, some leukemic stem cells and has therefore been exploited as target for therapeutic antibodies for many years. The improved survival seen in many patients when the antibody-drug conjugate, gemtuzumab ozogamicin, is added to conventional chemotherapy validates this approach. However, many attempts with unconjugated or conjugated antibodies have been unsuccessful, highlighting the challenges of targeting CD33 in AML. With the development of improved immunoconjugates and CD33-directed strategies that harness immune effector cells, therapeutics with enhanced efficacy may soon become available. Toxic effects on normal hematopoietic cells may increase in parallel with this increased efficacy and demand new supportive care measures, including possibly rescue with donor cells, to minimize morbidity and mortality from drug-induced cytopenias and to optimize treatment outcomes with these agents in patients with AML.