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 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 Frizzled class receptor 7 is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Signal Transduction ◽  
Embryonic Stem ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Epidermal Growth

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 Wnt pathway receptor frizzled-7, FZD7, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at significantly higher 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 signal transduction receptor that can support proliferation of triple negative breast cancer cells (5) and is required for the maintenance of pluripotency of human embryonic stem cells (6).

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).

scholarly journals Six homeobox 6 (SIX6) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Visual Processing ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Optic Stalk ◽  
The Central Nervous System ◽  
Epidermal Growth

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 six homeobox 6, SIX6, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at higher levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with activation of a gene important for maintenance of multipotent retinal progenitors and expressed in regions of the central nervous system involved in visual processing including the optic stalk and retina (5-8).

scholarly journals TNFSF8 (CD153 / CD30L) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Trastuzumab Treatment ◽  
Epidermal Growth

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 TNFSF8, also known as CD153 and CD30 ligand (CD30L) was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. TNFSF8 messenger RNA expression was significantly enhanced in the primary tumors of patients treated with trastuzumab. Thus, trastuzumab treatment in patients with breast cancer is associated with increased expression, in primary tumors of the breast, of a marker with broad expression in multiple human cancers of the hematopoietic system (5, 6), and with the capacity to regulate immunoglobulin class switching (7).

scholarly journals TNFAIP1 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 Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Necrosis Factor Alpha ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
Factor Alpha ◽  
Necrosis Factor

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 tumor necrosis factor alpha-induced protein 1, TNFAIP1, 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 decreased expression of a gene (5) that can induce apoptosis of cancer cells (6).

scholarly journals Differential expression of Notch4 in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Transcriptional Responses ◽  
Primary Tumors ◽  
Over Expression ◽  
Epidermal Growth

The mechanism of action underlying trastuzumab (Herceptin) function is ascribed to binding of the Fab region of trastuzumab to the extracellular domain of the human epidermal growth factor receptor (HER2) (1). The transcriptional responses that follow signals transduced after trastuzumab binding of HER2 are less well understood. We mined published microarray and multiplexed gene expression data (2, 3) to understand in an unbiased fashion genes most differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab. We found significant differential and over-expression of Notch4 (4, 5), described as a mammary proto-oncogene (4), in the primary 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 Platelet-derived growth factors α and β are differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Epidermal Growth

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 platelet-derived growth factors α and β , PDGF-α and PDGF-β, are among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at significantly higher levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression growth factors important for development of the neural crest and neural tube (5,6).

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