Aggressive Breast Cancer

AGGRESSIVE BREAST CANCER......Page 8
CONTENTS......Page 10
PREFACE......Page 12
RESEARCH AND REVIEW ARTICLES......Page 20
ABSTRACT......Page 22
HER PROTEIN RECEPTORS: SIGNAL TRANSDUCTION AND ONCOGENESIS......Page 23
Intracellular Signaling Pathways......Page 27
OVEREXPRESSION OF HER2 AND THE PROGNOSIS OF INVASIVE BREAST CANCER......Page 29
HER2 as A Prognostic Factor: Node-Positive Versus Node-Negative Disease......Page 30
HER2 and Progression of Early Breast Cancer Lesions to Invasive Carcinomas......Page 31
Relationship Between HER2 and Estrogen Receptor Expression......Page 32
HER2 ABNORMALITIES IN OTHER TYPES OF BREAST MALIGNANCIES......Page 33
Evaluating HER2 in Breast Tissue......Page 34
HER2 TARGETED THERAPY IN BREAST CANCER......Page 37
The Role of Trastuzumab in HER2 Overexpressing Breast Cancer......Page 39
The Role of Pertuzumab in HER2 Overexpressing Breast Cancer......Page 41
Inhibiting Several HER Receptors: The Role of Lapatinib in HER2 Overexpressing Breast Cancer......Page 42
PROPOSED RESISTANCE TO ANTI-HER2 THERAPIES......Page 45
Altered Receptor-Antibody Interaction......Page 46
Constitutive Activation of Downstream Effectors......Page 47
Anthracyclines......Page 48
Taxanes......Page 49
HER2 OVEREXPRESSION AND HORMONAL THERAPY......Page 50
CNS DISEASE IN HER2 OVEREXPRESSED BREAST CANCER......Page 52
CNS Metastases in Adjuvant Trials of Trastuzumab......Page 53
Prognosis of CNS Metastases in HER2 Overexpressing Breast Cancer......Page 54
REFERENCES......Page 55
ABSTRACT......Page 72
1) Non-Cellular MDR Mechanisms......Page 73
1b. Alteration of drug efflux......Page 74
PHYSIOLOGICAL FUNCTIONS OF P-GP......Page 77
PHARMACOLOGICAL FUNCTIONS OF P-GP......Page 78
2. Increase in Drug Detoxification......Page 79
3. Alterations of Drug Targets......Page 80
5a. Changes in genes responsible for cell cycle control......Page 81
5b. Abrogation of apoptosis......Page 82
6. Micro-Environmental Stress-Mediated Resistance of Solid Tumors......Page 84
7. Cancer Cell Dormancy and Resistant Cancer Stem Cells......Page 85
I. Circumvention of Drug Resistance Induced by P-Gp Pump Protein......Page 87
A. Chemo-sensitization by P-gp inhibitors......Page 88
B. Chemical modification or the use of anti-cancer pro-drug strategy......Page 91
II. MDR Circumvention by Steroidal Agents......Page 92
A. MDR-1 transcriptional regulators......Page 94
B. Targeting apoptosis signaling pathways......Page 96
D. Targeting angiogenic and proliferative markers of cancer drug resistance......Page 97
V. Nanotechnology for Overcoming Mdr......Page 98
VI. Stem Cell Research for Modulation of MDR......Page 99
VII. Pharmacogenomics and Screening for Molecular Signatures of MDR......Page 100
CONCLUSION......Page 101
REFERENCES......Page 102
ABSTRACT......Page 120
INTRODUCTION......Page 121
THE RKIP GENE AND PROTEIN......Page 122
1. The Raf-MEK-MAPK Signaling Pathway......Page 123
2. The G Protein-Coupled Receptor (GPCR) Signaling Pathway......Page 125
3. The NK-Κb Signaling Pathway......Page 126
1. RKIP in Cell Division and Genomic Stability......Page 127
2. RKIP in Cell Apoptosis......Page 128
4. RKIP in Cancer Metastasis......Page 129
RKIP SUPPRESSES BREAST CANCER METASTASIS......Page 131
CONCLUSION......Page 132
REFERENCES......Page 133
ABSTRACT......Page 140
INTRODUCTION......Page 141
RADIATION THERAPY FOR BREAST CANCER......Page 142
BRCA1 IN RESISTANCE TO BREAST CANCER  RADIATION THERAPY......Page 144
BRCA1-Associated Proteins: Functional Modifiers of BRCA1 Activity......Page 145
BRCA1-Associated Proteins as Potential Targets of Breast Cancer Therapies......Page 149
SUMMARY......Page 152
REFERENCES......Page 154
ABSTRACT......Page 162
WHAT IS PBR?......Page 163
ROLE OF PBR IN CANCER......Page 164
IMPACT OF DIET ON PBR MEDIATED CANCER......Page 167
THERAPEUTIC APPROACH TO PREVENT BY TARGETING PBR......Page 168
REFERENCES......Page 169
ABSTRACT......Page 178
INTRODUCTION......Page 179
Phospholipid Biosynthesis Pathway......Page 180
Function of Phospholipids in the Cell......Page 181
Altered Membrane Choline Phospholipid Metabolism of Human Mammary Epithelial Cells......Page 182
Altered Membrane Choline Phospholipid Metabolism in Breast Cancer Animal Models......Page 184
CONCLUSION......Page 185
REFERENCES......Page 186
ABSTRACT......Page 192
INTRODUCTION......Page 193
GENERATION OF HUMAN T LYMPHOCYTES ARMED WITH AN HER2/NEU -SPECIFIC TRIPARTITE CHIMERIC RECEPTOR......Page 195
Therapeutic Potential of T-Bodies in Murine Models......Page 197
CONCLUSION......Page 201
REFERENCES......Page 202
ABSTRACT......Page 206
INTRODUCTION......Page 207
1). Inability of the Antibody to Bind to its Target......Page 208
2). Activation of other HER Family Receptors......Page 209
3). Increased Signaling of IGF-1R......Page 210
4). Dysregulation of Downsteam Signaling......Page 211
REFERENCES......Page 212
LYMPHATIC SPREADING PROPENSITY AND ABERRANT MUC1 BEARING TN/TN-LIKE CARBOHYDRATE OF AGGRESSIVE BREAST CANCER CELLS......Page 218
ABSTRACT......Page 219
INTRODUCTION......Page 220
I. EXPRESSION OF VICIA VILLOSA AGGLUTININ (VVA)-BINDING CARBOHYDRATE OF BREAST CANCER CELLS IN RELATION TO THE LYMPHATIC SPREAD......Page 221
I-2. Frequency of Positive Staining of all the Cases and Changes by T Factor and Histological Subtype......Page 224
I-3. Relationship between Lymph Node Metastasis and Reactivity with Lectin or Monoclonal Antibodies......Page 226
I-4. Carbohydrate Network Associated with Lymph Node Metastasis......Page 227
I-6. Significance of Combination Analysis of Carbohydrate Antigen Expression on Lymph Node Metastasis Status of Primary Breast Cancer Cells......Page 230
II-1. Localization of Carbohydrate Antigen by Staining With VVA and HB-Tn1 Mab in Primary Breast Cancer......Page 231
II-2. Correlation of Breast Cancer Aggressiveness with Expression of VVA-Binding Protein, HB-Tn1-Binding Protein, and MUC1......Page 233
II-3. Partial Characterization of VVA-Binding Carbohydrates in Relation to Tn Antigen......Page 237
II-4. MUC1 as a Possible Carrier Protein of VVA-Binding Carbohydrate(S) and HB-Tn1-Reactive Tn Antigen......Page 239
III. ABERRANT MUC1 BEARING TN/TN-LIKE ANTIGEN IN RAT ASCITES HEPATOMA CELLS WITH STRONG......Page 242
CONCLUSION......Page 243
REFERENCES......Page 244
EXPERT COMMENTARY......Page 248
INTRODUCTION......Page 250
REFERENCES......Page 254
INDEX......Page 256