The effects of platelet-derived growth factor and receptor on normal and neoplastic human ovarian surface epithelium.

UNLABELLED: Several growth factors have been shown to stimulate or inhibit the growth of human ovarian surface epithelial (HOSE) cells. Platelet-derived growth factor (PDGF) is likely to be released onto the ovarian surface epithelium during follicular wound repair. We undertook the evaluation of this factor and its receptor in normal and malignant ovarian cells. OBJECTIVES: The goal of this study was to evaluate the response of HOSE cells to PDGF in vitro and identify PDGF receptors on normal and malignant ovarian epithelial cells. In addition, we wanted to examine the prognostic value of the PDGF receptors in clinical specimens. METHODS: Normal HOSE cells were cultured and growth response to PDGF assayed by 3H uptake. PDGF receptor status on HOSE cells, established ovarian carcinoma cell lines, and paraffin tissue was performed by immunohistologic techniques. Data on ovarian cancer patients relapse-free survival (RFS) were abstracted from the Lankenau Hospital Tumor Registry and RFS was plotted using the Kaplan-Meier method. RESULTS: HOSE cells increased 3H uptake in a dose-dependent manner in response to PDGF. HOSE cells stain positively for both alpha and beta receptors, as does the chemotherapy naive cell line A2780. The platinum-resistant CP30 cell line loses PDGF alpha staining. Of 21 ovarian cancer specimens, only 1 retained PDGF alpha receptors while 8 retained PDGF beta receptors. Those patients positive for PDGF receptor beta had a significantly longer relapse-free survival than PDGF beta receptor-negative patients. CONCLUSIONS: PDGF enhances the growth of HOSE cells in vitro and may play a role in ovarian cancer development. Patients whose tumors retain PDGF receptor beta staining positivity have a prolonged relapse-free survival.

Splenic hypofunction in systemic lupus erythematosus.

Systemic lupus erythematosus is a relatively common autoimmune disease in the United States. Hyposplenism is infrequently described in patients with systemic lupus erythematosus. It is seen in up to 5% of patients and is thought to be caused by vasculitic changes within the spleen. The diagnosis of hyposplenism can be made easily by identifying Howell-Jolly bodies on a peripheral blood smear. The authors describe a patient with systemic lupus erythematosus associated with hyposplenism and discuss possible diagnostic and treatment implications.

Hematologic emergencies. Management of transfusion reactions and crises in sickle cell disease.

Two hematologic emergencies are reviewed in this article: transfusion reactions and crises in patients who have sickle cell disease. Transfusion reactions may be due to incompatibility, IgA deficiency, allergy or, rarely, bacterial contamination of the blood product. A major hemolytic reaction due to incompatibility may progress to hypotension and shock. To prevent this type of reaction, blood products should be given only when necessary and attention should be given to eliminating clerical errors, which are responsible for many hemolytic reactions. In patients with sickle cell disease, a painful crisis due to vascular occlusion is the most common emergency. Rehydration is essential, and narcotics may be needed to relieve pain. Aplastic crisis is managed by transfusion of packed red blood cells and supportive care. Sickle cell crisis may affect major organ systems. The acute chest syndrome can be complicated by pneumonia; rapid respiratory failure may occur if multiple lobes are involved. Splenic or hepatic sequestration requires aggressive rehydration and transfusion. In patients who have had stroke or subarachnoid hemorrhage, a long-term exchange transfusion program is needed to keep hemoglobin S levels below 30%.

Hematologic emergencies. Management of hyperleukocytic syndrome, DIC, and thrombotic thrombocytopenic purpura.

Three hematologic emergencies are reviewed in this article: the hyperleukocytic syndrome, disseminated intravascular coagulopathy (DIC), and thrombotic thrombocytopenic purpura (TTP). The hyperleukocytic syndrome most commonly occurs in patients with acute myelogenous leukemia. It commonly affects the lungs and may cause intracranial hemorrhage. Long-term control is accomplished only by inducing a remission of the leukemia. Patients with DIC may have excessive clotting, uncontrolled bleeding, or both. Infections are the most common cause; cases in obstetric patients are usually due to abruptio placentae or retained dead fetus. Any acute leukemia can cause DIC. The underlying disorder is the usual cause of death. TTP is thought to be due to a substance or substances in the plasma that initiate marked platelet aggregation in the microcirculation. It affects persons of any age and either sex. Plasmapheresis is the preferred treatment.

Molecular dimensions and properties of N-[1-(2-hydroxyethyl)-2-nitro-1H-imidazol-1-yl]acetamide (SR2508).

Hypoxic cells in tumors are resistant to radiation and chemotherapy treatment. To decrease this resistance, 2-nitroimidazoles are used as radiation and chemical sensitizers in the treatment of tumors. Their use is marred by their toxicity. Therefore, the compound SR2508, a new 2-nitroimidazole derivative, was introduced in an attempt to obtain a less toxic nitroimidazole than those used thus far. The molecular structure and conformation of SR2508, determined from X-ray diffraction studies, is reported. The compound, formula C7H10N4O4, molecular weight 214.18, crystallizes in the monoclinic system, space group P2(1)/c, unit cell dimensions a = 12.052(3), b = 11.116(4), c = 7.330(2) A, beta = 106.94(2) degrees, V = 939.4(5) A3, Z = 4. The crystal structure was refined to Robs = 0.041. The imidazole and C-NO2 groups are each planar and inclined at 6.6 degrees to each other. The side chain, which contains an amide group, is also planar. There are hydrogen bonds between different molecules and they involve O(11) and O(15), as well as N(12) and O(15). When compared to other 2-nitroimidazoles that have been clinically tested, the hydrogen bonds in SR2508 account for the increased hydrophilic character of the compound. Based on the crystal structure data, models for a possible interaction between SR2508 and DNA have been proposed.

Multidrug resistance to alkylating agents and platinum compounds: state of our knowledge.

Resistance to platinum-containing drugs and alkylating agents is multifactorial. Relapsed patients and those who have an incomplete response to induction chemotherapy are unlikely to achieve a complete response to other treatments. This pattern of resistance to therapy is very broad in that patients not only fail to respond to drugs from the same pharmacologic classes as used in primary treatment, but also do not respond to other available drugs or irradiation. Using ovarian cancer as a prototype tumor, researchers have initiated laboratory studies to determine the mechanisms responsible for this drug-resistance phenotype. Insights into this action may promote development of therapeutic strategies to prevent the onset of resistance or reverse resistance when it occurs.