scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of Wnt2 and Wnt10b.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Wnt Pathway ◽  
Nuclear Translocation ◽  
Growth Factor Receptor ◽  
Primary Tumors ◽  
Wnt Ligands ◽  
Frizzled Receptors ◽  
Casein Kinases ◽  
Tumor Expression ◽  
Intracellular Mediators

The Wnt pathway transduces signals through a series of intracellular mediators including Axin, dishevelled proteins, and through regulation of an Axin destruction complex by casein kinases to effect nuclear translocation of β-catenin and β-catenin cooperation with TCF/LEF proteins at nuclear transactivation targets following binding of Wnt ligands to Frizzled receptors which in concert with LRP co-receptors at the plasma membrane (1-3). Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (4), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (5-7) from the primary tumors of patients treated with trastuzumab, we found that the Wnt ligands Wnt2 and Wnt10b, molecules with the capacity to support proliferation of ventral midbrain progenitors (8) and to induce transformation of the mammary gland (9), were among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. Increased expression of Wnt2 and Wnt10b implies that the Wnt pathway may be activated in primary tumors of patients treated with trastuzumab.

scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of SH3BP2.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Binding Partner ◽  
Syk Kinase ◽  
Src Homology ◽  
Epidermal Growth ◽  
Tumor Expression

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the cell signaling intermediate and Src homology domain binding protein SH3BP2, also known as 3BP2, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. 3BP2 is a binding partner of the Syk kinase (5, 6); we recently described differential and increased expression of Syk in the tumors of breast cancer patients treated with trastuzumab (7); thus, trastuzumab may likely be associated with activation of Syk kinase signal transduction in primary tumors of patients with breast cancer.

scholarly journals ITGβ1 (CD29) is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Tumor Expression

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the cell adhesion molecule integrin β1 (5-9) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed significantly higher levels of ITGβ1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of ITGβ1 in primary tumors of the breast, suggesting that increased primary tumor expression of ITGβ1 in the primary tumors of patients with breast cancer, a molecule whose increased expression in human breast cancer is correlated with overall survival, metastasis and significantly decreased time from diagnosis to death (10, 11), is a direct transcriptional result of treatment with trastuzumab.

scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of STAT3.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Constitutive Expression ◽  
Growth Factor Receptor ◽  
Signal Transduction Pathway ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
Tumor Expression

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the cell signaling intermediate signal transducer and activator of transcription STAT3 was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. STAT3 was expressed at significantly higher levels in the tumors of patients treated with trastuzumab, indicating that trastuzumab is potentially associated with activation of a signal transduction pathway important for survival of breast cancer cells, and demonstrating that a molecule described as an oncogene (5) with constitutive expression in all cell lines transformed by the Src proto-oncogene (6) is present at significantly higher quantities in the tumors of breast cancer patients treated with trastuzumab.

scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of CEACAM1.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion Molecule ◽  
Growth Factor Receptor ◽  
Expression Data ◽  
Human Breast ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Trastuzumab Treatment ◽  
Epidermal Growth ◽  
Tumor Expression

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the cell adhesion molecule CEACAM1 was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. Thus, a molecule whose expression is predictive of metastatic disease in patients with malignant melanoma (5) and whose expression in melanoma cell lines can support invasive properties (6) is expressed at significantly higher levels in the primary tumors of patients treated with trastuzumab for breast cancer.

scholarly journals Trastuzumab administration in patients with breast cancer is associated with increased primary tumor expression of IL-1β.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Growth Factor Receptor ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Gene Encoding ◽  
Primary Tumors ◽  
Cancer Models ◽  
Epidermal Growth ◽  
Tumor Expression

A complete understanding of how tumor signal transduction in human breast cancer is modulated by trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) (1, 2), is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the gene encoding interleukin-1β (5), IL1β, was among those most differentially expressed in the primary tumors of patients treated with trastuzumab. IL1β was expressed at significantly higher levels in the tumors of patients treated with trastuzumab, indicating that a cytokine associated with metastasis to the bones in cancer models (6-9) and correlated with relapse of disease to the bones in human breast cancer (8) is produced at significantly higher quantities in the tumors of breast cancer patients treated with trastuzumab.

scholarly journals Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer

2012 ◽  
Vol 30 (6) ◽  
pp. 587-592 ◽  
Author(s):  
Eitan Amir ◽  
Naomi Miller ◽  
William Geddie ◽  
Orit Freedman ◽  
Farrah Kassam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Treatment Plan ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Primary Tumors ◽  
Receptor Status ◽  
Metastatic Recurrence ◽  
The Impact

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

scholarly journals DVL3 is over-expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Breast Cancer Patients ◽  
Gene Encoding ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Unbiased Manner

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published and public microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified significant differential expression of the gene encoding the Wnt pathway molecule dishevelled-3, DVL3 (5-7), in the primary tumors of breast cancer patients treated with trastuzumab. DVL3 expression in primary tumors of the breast in patients treated with trastuzumab was significantly higher than in patients not treated with trastuzumab.

scholarly journals DCC is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
The United States ◽  
Differentially Expressed ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Deleted In Colorectal Cancer

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the deleted in colorectal cancer locus DCC (5, 6) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of DCC messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DCC in primary tumors of the breast, demonstrating that a gene encoding for a netrin receptor, cellular machinery utilized for axon guidance in the central nervous system (5-9), is transcriptionally induced in primary tumors of the breast following treatment with trastuzumab.

scholarly journals The placental growth factor (PGF) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
The Brain

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the placental growth factor, encoded by PGF was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a growth factor that is chemotactic, angiogenic (5) and important for growth of blood vessels in the brain (6).

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