Abstract: Cancer Watch August 1999

Among the highlights in this issue are: Vorozole - A new Aromatase Inhibitor to Treat Advanced Breast Cancer, p43 Positive Lymphocytes in Breast Cancer, Heparanase: An Enzyme that Helps Cancer Cells to Spread, Pregnancy and Cancer: Transplacental Transfer of Cancer Cells, Sunscreen Use Encourages Prolonged Sun Exposure, BRCA2 Mutations Linked to Many Types of Cancers, Engineered Antibodies to Enhance Antigen Delivery to Antigen-Presenting Cells, Homing in on Cancer Cells – Targeted Microradiation, Effect of Antioxidants on Hormone-Dependent Prostate Cancer, Gene Testing for Hereditary Nonpolyposis Colorectal Cancer, Designer Cancer Cell: Way to Understand Cancerogenesis, Primer on Telomere and Telomerase, NCI's Tumor Gene Index Reaches its Two-Year Mark, Dendritic Cell-Based Cancer Immunotherapy.

With permission from the Publisher Adenine Press, the abstracts below are linked to the full text versions of these articles at CW Online

News in Brief

• The growing family of multidrug resistance mechanisms in cancer.
• Visualization of multidrug resistance in vivo
• p43 positive lymphocytes in breast cancer
• Vorozole - A new aromatase inhibitor to treat advanced breast cancer

Heparanase: An Enzyme that Helps Cancer Cells to Spread

• Heparanase, an endogenous enzyme that participates in the degradation of cellular integrity has been purified from human placenta and platelet and the corresponding gene has been cloned. This enzyme, required for normal physiological functions, also plays a key role in the spread of cancer from the primary site to other organs. Availability of sufficient amount of the enzyme through cloning will facilitate research leading to the development of specific inhibitors that can be used in cancer treatment.

Pregnancy and Cancer: Transplacental Transfer of Cancer Cells.

• Cancer during pregnancy is rare and more unusual is the transfer of cancer cells to the fetus. However, cancer of the blood cells and melanoma cells are found to traverse placental barrier and invade the fetus. During the first trimester when the fetal cells divide and differentiate rapidly, aggressive therapy may harm the fetus. However, such treatment during the second, or third trimester is much safer.

Sunscreen Use Encourages Prolonged Sun Exposure

• As the SPF of sunscreen is increased its ability to delay sunburn is also increased, allowing people to remain in the sun for a longer period. This may increase the risk of skin cancer.

BRCA2 Mutations Linked to Many Types of Cancers

• Carriers of germline mutations in the BRCA2 gene are known to be at high risks of breast and ovarian cancers. Now it is found that this mutation may be associated with increased risks of several other cancers.

Engineered Antibodies to Enhance Antigen Delivery to Antigen-Presenting Cells.

• A technique has been developed for the targeted delivery of antigenic peptides to antigen-presenting cells, APCs. A bivalent antibody molecule is genetically engineered where the antigenic peptide is integrated in the constant region of the molecule and the variable region was designed to recognize a specific surface on the APCs. This technique can be used to develop new vaccines.

Homing in on Cancer Cells – Targeted Microradiation.

• Radioisotope bound to an antibody that recognizes a specific protein antigen on the surface of cancer cells can deliver radiation selectively killing the cells. For low-grade B cell non-Hodgkin’s lymphoma, an investigational treatment using iodine-131 bonded to anti-B1 antibody demonstrated safety and effectiveness in clinical trials. It has been submitted to US Food and Drug Administration (FDA) for approval.

Effect of Antioxidants on Hormone-Dependent Prostate Cancer.

• Antioxidants such as Vitamins C and E counteract the negative effect of male hormones on prostate cancer cells by modulating key molecular events on DNA that are sensitive to reactive oxygen species.

Gene Testing for Hereditary Nonpolyposis Colorectal Cancer.

• Inheritance of mutations in mismatch repair gene can increase the chance of developing hereditary nonpolyposis colorectal cancer syndrome.

IL-2, Herceptin Combo Passes Test.

• Both interleukin-2, a cytokine and Herceptin, a monoclonal antibody that binds to growth factor receptor HER2/neu of breast cancer cells, have been shown to be effective against breast cancer. A phase I study indicates that by adding Herceptin to the regimen, the required dose of interleukin-2 could be reduced thus minimizing adverse side effects from high dose of interleukin-2.

Designer Cancer Cell: Way to Understand Cancerogenesis.

• Normal cells usually have a limited life-span. After certain number of divisions, the cell stops dividing; shortening of the ends of chromosomes, the telomere, with each cell division is thought to be the responsible factor. It is now demonstrated in human kidney and fibroblast cells that elongation of the telomere in combination with expression of two well known oncoproteins can convert these cells into tumor cells.

Primer on Telomere and Telomerase

• Basic information about telomere and telomerase which imortalize cancer cells are reviewed with diagrams.

NCI's Tumor Gene Index Reaches its Two-Year Mark.

• The first comprehensive compilation of genes involved in human cancers on the Internet.

Dendritic Cell-Based Cancer Immunotherapy.

John A. Kellen, M.D., Ph.D.

• After almost two decades of largely futile efforts in harnessing the humoral and cellular arms of the immune response to fight malignant growth, the traditional concepts of recognition and subsequent destruction had to be abandoned as oversimplified, even naïve. No doubt, cancer immunotherapy has resulted in sporadic tumor regression, but the true mechanisms are still not completely understood. It took extensive research into the interplay between cytokines and immune effector cells to clarify the leading role of special "natural interferon-producing cells (IPCs)" in the production of Interferon-alpha, in response to stimuli (cancer cells, viri and bacteria). The exact role of IPCs, which comprise dendritic cells and others, is still controversial; however, successful modulation of their numbers and functional state, reflected in interferon production, may lead to an entirely novel , more rational approach to cancer immunotherapy. Eventually, the stimulation of dendritic cells aims at generating efficient cytotoxic lymphocyte responses - a potential tool for tumor prevention or rejection.

Glossary

• A glossary of the unfamiliar terms and jargons in the Aug 99 issue of CW.