Among the highlights in the April 1999 Cancer Watch issue are: Exercise in the Treatment of Patients with Cancer, Invasive Breast Cancer and Cadherin-11 Expression, Steroid Sulfatase (STS) in Breast Cancer, Survival in Epithelial Ovarian Cancer, New Drug for Ovarian Cancer, Medical Therapy Holds Promise For Basal Cell Carcinoma, Sunscreens Suppress Mole Formation Among Children, Plasma Prolactin Level and Risk of Breast Cancer in Postmenopausal Women, Organ Transplant Patients Have High Skin Cancer Risk, Thalidomide in Phase II Pilot Cancer Trial, Molecular Technique Measures Early Age Smoking Damage in the Lung, The CD105 Antibody: A New Tool in the Determination of Tumor Vascularization, Angiostatin - A New Angle, Tea-Drinking Inhibits Angiogenesis, A New Method for the Determination of Telomerase Activity, Adjuvant Therapy for Liver Cancer, Heartburn - A Risk Factor for Esophageal Cancer, Interim Results of Breast Cancer Treatment Trials and The NCI Launches a New Project to Study Minority Populations.

• Exercise in the Treatment of Patients with Cancer
• Invasive Breast Cancer and Cadherin-11 Expression
• Steroid Sulfatase (STS) in Breast Cancer
• Survival in Epithelial Ovarian Cancer

• A synthetic agent, carboxyamido-triazole, is found to prevent ovarian cancer growth by inhibting calcium influx in cancer cells. Angiogenesis, a process that produces new blood vessels to sustain tumors, requires calcium at various phases. This agent does not kill the cancer cells, but prevents it from growing further.

• Imiquimod, a cream that uses body's own immune system to fight disease by stimulating production of cytokines such as interferon-alpha, is found to be effective against basal cell carcinoma, the most common form of skin cancer.

• Children who use sunscreens regularly can prevent the formation of moles, a known risk factor for the development of melanoma, according to one of the first prospective, randomized trials of mole formation.

• Higher level of the hormone prolactin was found in the blood of postmenopausal women who developed breast cancer compared to those who did not.

• Poor immune system increases the risk of cancer. It is observed that organ transplant patients who are given high dose of an immunesuppressant to prevent rejection are susceptible to develop skin cancer.

• A phase II trial using the controversial drug thalidomide in patients with recurrent and metastatic squamous cell carcinoma of the head and neck is initiated by the National Cancer Institute (NCI) in collaboration with Celgene. Celgene Corporation will provide Thalomid TM (thalidomide).

• Exposure to cigarette smoke can produce cancer-causing DNA adducts and their presence may indicate a high risk of lung cancer. These adducts produced during adulthood seem to last as long as 12 years after cessation of smoking, though the levels are reduced.

• Tumor growth requires the formation of new blood vessels (neo-angiogenesis) to meet the increasing demands of rapidly proliferating cells for oxygen and nutrients. This is a complex process, involving the remodelling of extracellular matrix, multiplication and eventual migration of endothelial cells, their differentiation and finally anastomosis. All this is the result of a complex interplay between many angiogenic factors, which recently have come to attention of the media and public in a haphazard, irresponsible way. The lay press, which is scientifically close to being illiterate, has lead the way in raising false hopes for many. Truly, there is an ongoing persistent search for a realistic therapeutical interference with undesirable angiogenesis in cancer, but useful treatment protocols are still remote. However, there are other interesting fall-outs from research in this field. The presence or levels of endothelial cell markers, a reflection of their active participation in neo-vascularization, is one such novel indicator of tumor angiogenesis with possibly prognostic significance.

• The excitement about a potential "cancer cure" by preventing blood vessel growth in tumors has cooled of; research has been going on in this field for some twenty years and it was only media hype which had blown (otherwise excellent) experiments on mice out of proportion and generated false hopes. In several notes, CW has touched upon this topic in a critical manner. In February 99, one of the major pharmaceutical companies involved in angiostatin (Bristol-Myers Squibb) announced that they had stopped working on the development of a commercially available preparation: since angiostatin is a relatively large protein, it is fragile and very difficult to produce or synthesize in large quantities. The obvious solution to this would be a simpler, small molecules able to mimic the effects of angiostatin, if only we would understand its mechanism(s) of action. It appears that recently progress has been achieved in that direction: for angiostatin to exert its antigrowth effect, it must bind to and inactivate an enzyme (adenosine triphosphate synthase), which is essential in normal cells to synthesize ATP for survival.

• Tumor growth inhibiting effect associated with tea-drinking may be due to the antiangiogenic effect of its components. Epigallocatechin-3-gallate (EGCG) present in tea is shown to prevent new blood vessel formation in culture system as well as in animal models.

• Telomeres are highly specialized DNA/protein structures located at the end of chromosomes in higher species. They are essential to the maintenance and stability of the chromosome within the cell. With each replicative cycle of cellular DNA, the telomere shortens, the cell cannot divide and ultimately it dies (apoptosis). An enzyme telomerase can add nucleotides to the telomere thus preventing it from shortening. In normal somatic cells this enzyme activity is negligible. But a large number of tumors studied was found to have telomerase activity. A sensitive assay to measure telomerase activity could be used to determine presence of cancerous cells. A new telomerase PCR-ELISA test has become commercially available, in which telomerase elongates a specific, biotin-labeled primer; the elongation products are amplified by an optimized PCR hybridized to a telomerase repeat-specific detection probe and subsequently visualized in streptavidin-coated microtiter plates. The results are available in six hours.

• Adjuvant therapy using radioactive iodine directly in liver artery after removal of cancerous tumor of the liver significantly reduces local recurrence.

• Heartburn caused by reflux from stomach through esophagus, if continues for a long period with great severity, could lead to one type of esophageal cancer.

• Preliminary results from four large randomized, controlled phase III clinical trials indicate that high-dose chemotherapy with supportive bone marrow transplant is not superior to lower-dose chemotherapy. However, one trial from South Africa shows a significant difference in favor of high-dose chemotherapy with transplant.

• To determine better ways to address cancer prevention and control needs of minority and under served populations the National Cancer Institute (NCI) launches new projects. These projects will be carried out in three phases. In the first phase the community groups will work with government and non government organizations to develop project plans. In the second phase the NCI-designated cancer centers and other institutions to enhance minority participation in clinical trials and to improve training opportunities for minority scientists. The last phase will be devoted to carrying out pilot projects developed in the second phase, as well as maintaining the infrastructure developed in the first and second phase.

Glossary

• A glossary of unfamiliar words and jargons in Cancer Watch, April 1999.