Subject(s)
Antineoplastic Agents/adverse effects , Cladribine/adverse effects , Immunosuppressive Agents/adverse effects , Leukemia, Hairy Cell/drug therapy , Meningitis, Cryptococcal/etiology , Antineoplastic Agents/therapeutic use , Cladribine/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Male , Meningitis, Cryptococcal/physiopathology , Middle AgedABSTRACT
The expression of prostaglandin H synthases can be induced by many stimuli and is likely to be important in control of the cell cycle. The analysis of prostaglandin H synthase-1 and -2 expression in colon adenocarcinoma cell lines is a useful model system for studying the function of the prostaglandin H synthases, especially with regard to proliferation and adhesion. Prostaglandin H synthase-1 protein is not found in any of eight human colon adenocarcinoma cell lines. Expression of prostaglandin H synthase-2 is variable for the eight cell lines: three constitutively expressed active protein, four did not express this gene at all, and one had mRNA but no active protein. Thus, five colorectal adenocarcinoma cell lines exhibit "null" expression of prostaglandin synthase-2. The three cell lines with constitutive expression of prostaglandin H synthase-2 produce PGE2. Prostaglandin E2 production could be inhibited by aspirin and NS398 without inhibiting proliferation, while direct addition of prostaglandin E2 inhibits proliferation. Adhesion to collagen IV and fibronectin was stronger in those cell lines that expressed prostaglandin H synthase-2. The constitutive expression of prostaglandin H synthase-2 is associated with increased adhesion to extracellular matrix components and a potential inhibition of proliferation through the production of prostaglandin E2. The absence of PGH synthase-2 expression in some cell lines may result from the original tumor's need to inactivate these associated functions. Our evidence suggests that PGH synthase-2 is a possible candidate for a tumor suppressor gene at 1q23-qter.
Subject(s)
Caco-2 Cells/enzymology , HT29 Cells/enzymology , Prostaglandin-Endoperoxide Synthases/genetics , Adult , Aged , Aspirin/pharmacology , Blotting, Southern , Caco-2 Cells/cytology , Cell Adhesion/physiology , Cell Division/physiology , Cyclooxygenase Inhibitors/pharmacology , DNA, Neoplasm/analysis , Extracellular Matrix Proteins/metabolism , Female , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Enzymologic/physiology , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/physiology , HT29 Cells/cytology , Humans , Male , Middle Aged , Nitrobenzenes/pharmacology , Prostaglandin-Endoperoxide Synthases/metabolism , Prostaglandins/biosynthesis , RNA, Messenger/metabolism , Sulfonamides/pharmacologySubject(s)
Acquired Immunodeficiency Syndrome/complications , Herpesvirus 4, Human , Lymphoma, AIDS-Related/diagnosis , Lymphoma, Large-Cell, Immunoblastic/diagnosis , Multiple Myeloma/diagnosis , Multiple Myeloma/virology , Muscle Proteins , Myeloma Proteins/analysis , Acquired Immunodeficiency Syndrome/blood , Adult , Connectin , Diagnosis, Differential , Humans , Lymphoma, AIDS-Related/blood , Lymphoma, Large-Cell, Immunoblastic/blood , Multiple Myeloma/bloodABSTRACT
In a murine model system, folinic acid demonstrated host-protective properties during administration of repetitive and lethal doses of vincristine (VCR). Subsequently, folinic acid was evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 18 patients receiving folinic acid have been compared with those observed in 70 patients who previously received VCR without folinic acid in the same chemotherapy program. All patients ideally were intended to receive VCR 1.0 mg/m2 weekly for 6 weeks, with dose modification for neurotoxicity. Treatment patients received folinic acid 800 mg PO daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 7 (39%) treatment patients and 17 (24%) comparison patients (P = 0.21). The mean percentage of the ideal dosage of VCR was 73.7 +/- 28.7 in patients receiving folinic acid and 76.1 +/- 20.5 in those given only VCR (P = 0.69). Hematologic toxicities were similar in both groups, but nausea occurred more frequently in the folinic acid group. Folinic acid in this dose and schedule afforded no protection from the neurotoxic side effects of VCR.
