Our work began where the greatest classical morphologists left off; their best work was the start of ours. As our work progressed, the rigidity of basic, previous embryological principles was broken down as scientific knowledge advanced. At the same time, the molecular, biological characterization of the cell surface receptor systems progressed enormously with the invention of numerous monoclonal antibodies. Thus, thymology became once again very important because the thymus is the first and central organ of the human immunological system. Then, the question of immuno-neuroendocrine regulation arose and has only been partially answered. Our book seeks to explore what has not been explored. The topic of thymic epithelial cells is a unique one and has never been explored in any previous book as it is explored in this one.

Only a handful of great thymologists remain in the world today, especially after the great loss the medical community suffered with the passing of Dr. Good, the list includes but is not limited to: Dr. Ritter and Dr. Kendall in England, Dr. Savino in Brazil, Dr. Dardenne in France, Dr. von Gaudecker in Germany, a few others in Belgium and Holland, and it is our hope that Dr. Bodey is among them. Nonetheless, a book on the thymus has not been written in the last five years and a book such as this one has never been. This book is based on a 30-year period of research and includes references from a broad range of sources spanning the globe and all sources, even those that were the beginning of thymic research. The book, thus, is uniquely well rounded, more so that previous works.

Childhood brain tumors are a diverse group of diseases characterized by the abnormal growth of tissue contained within the skull. Other than leukemia and lymphoma, brain tumors are the most common type of neoplasms that occur in children. The leading cause of death from childhood neoplasms among persons up to 19 years is brain tumors. As such, this book is a review of the most recent molecular biological research concerning brain tumors with references and comparisons to a variety of neoplastic disorders. The book then uses this information to foreshadow the direction that future anti-neoplastic therapies will take. Because of the wide spectrum of the objectives of the book, any individual involved in cancer research will greatly benefit from the work. Histopathologists, neuropathologists, clinical and research oncologists, and medical students will find this book to be an invaluable resource as a reference guide. Patients and their families will also find the book useful as it offers a comprehensive update on new, non-classical therapeutic modality options and contains a detailed description and analysis of brain tumors. Such an endeavor has yet to be undertaken by any other book and may prove to be the most comprehensive book on brain tumors thus far.

I. MOLECULAR BIOLOGY OF TUMORS.

1. Brain Tumors

1. Introduction

2. Medulloblastoma

3. Glial Tumors

2. Immunophenotypic Characterization of Infiltrating Poly- and Mononuclear Cells in Childhood Brain Tumors

1. Introduction

2. The Significance of Immunohistochemistry

3. Original Immunohistochemical Observations

4. Intermediate filaments (IFs)

5. Expression of Homeobox B3, B4, and C6 Gene Products

6. Cell proliferation

7. Epidermal growth factor (EGF) and its receptor (EGFR)

8. p53, the guardian of the integrity of the genome

9. Apoptosis in Brain Tumors

10. Survivin

11. Tumor-related Neoangiogenesis in Childhood Brain Tumors

12. Presence of Matrix Metalloproteinases (MMPs)

13. The MAGE gene family

II. ANTI-NEOPLASTIC BIOLOGICAL THERAPIES

3. Experimental Therapies in Brain Tumors

4. Biologic Anti-Neoplastic Therapies

1. Introduction

2. Active nonspecific immunomodulation of natural immunity

3. Thymic hormones

4. Interferons: basic and preclinical studies

5. Tumor Necrosis Factors

6. The discovery of interleukin-2: basic principles

5. The lymphokine activated killer (LAK) cell phenomenon

1. Administration of rIL-2 and LAK cells: preclinical trials

6. Angiogenesis Inhibition in Anti-Neoplastic Therapy

7. Antigen Presentation by Dendritic Cells and Their Significance in Anti-Neoplastic Immunotherapy

1. Active antigen specific immunotherapy (tumor vaccines)

2. Antigen Presentation within Childhood Brain Tumors

3. Immunosuppression within the Cellular Microenvironment of Childhood Brain Tumors

4. The Dendritic Cell Network

5. Antigen Presentation by DCs

6. The Significance of DCs in Anti-Neoplastic Immunotherapy

8. Genetically Engineered Antibodies for Direct Anti-Neoplastic Treatment and Systematic Delivery of Various Therapeutic Agents to Cancer Cells

1. Introduction

2. Human Cancer Cell Related Antigens

3. Oncogenes and Growth Factors in Neoplastic Cells

4. Antibodies and Neoplastic Cells

5. Anti-neoplastic Immunotherapeutical Regiments Influenced by Immunohistochemistry

6. Human Antibodies

7. Anti-Idiotypic Antibodies

8. Bispecific Antibodies

9. Radiolabeled Antibodies

10. Construction of Immunotoxins

11. Monoclonal Antibodies: Carriers of Drugs, Toxins and Cytotoxic Cells

12. Clinical Trials with Monoclonal Antibodies and their Minimal Toxicity

9. Cancer-Testis Antigens: Promising Targets for Antigen Directed Anti-neoplastic Immunotherapy

1. Introduction

2. Cancer/Testis Antigens

3. Detection of Cancer/Testis Antigens in Various Malignant Neoplasms and their Therapeutic Significance

Prologue

III. APPENDIX

10. Materials and Methods

1. Tissues and Tissue Handling

2. Libraries of Antibodies

3. Antigen Retrieval Technique

4. Immunoalkaline Phosphatase Antigen Detection Technique

5. Immunoperoxidase Antigen Detection Technique

6. Controls in Immunocytochemistry

7. Evaluation of the Immunoreactivity (immunostaining)

8. Tissue Processing for Tissue Culture Experiments

9. Preparation of Thymic, Peripheral Blood and Bone Marrow Cell Suspensions

10. Isolation of Cortical Thymocytes

11. Isolation of Thymic Nurse Cells (TNCs)

12. Thymic Stromal Cell (RE & DC) Cultures

13. Proliferation Assay (PA) for Thymocytes and Peripheral Blood Hematopoietic Cells

14. Transmission Electronmicroscopy (TEM) of Cultured Thymic Medullary Cells (RE, DC, including LC, & IDC) and Macrophages

15. Scanning Electronmicroscopic (SEM) Procedure for Tissue Samples

The processes of tumor metastasis, apoptosis and anti-tumor immune response are among the most complex yet rapidly advancing fields in the area of cancer research. This monogaph presents a comprehensive coverage of the recent advances in the various key concepts in these fundamental aspects of human cancer. It would be of particular interest to members of the cancer research community, especially those who are actively involved in the study of basic and translational aspects of human cancer. Specifically, this volume includes authentic subject reviews by leading experts on the following aspects:

• Control of tumor cell motility
• Role of tumor-cell adhesion and migration in organ-selective metastasis-formation
• Tumor heterogeneity in relation to invasion and metastasis and its clinical implications
• Tumor angiogenesis, angioprevention, anti-angiogenic therapies and response
• Role of apoptosis in the development, progression and therapy of cancer
• Role of macrophages in tumor development and metastasis
• Pathways of macrophage-mediated tumor progression
• Abnormal variation of immune response against cancer
• Immunological aspects of Marek s disease virus (MDV)-induced lymphoma progression
• A biodynamical model of human T-cell proliferative disorders
• Current methodologies for characterization of tumor directed immune response

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