salicylates and Leukemia--Lymphocytic--Chronic--B-Cell

Gastric pseudolymphoma is a rare disorder of unknown etiology that can undergo transformation into malignant lymphoma. This report describes the first case of a gastric pseudolymphoma associated with Helicobacter pylori infection that underwent complete clinical, endoscopic, and histologic resolution following treatment with bismuth subsalicylate, amoxicillin, and metronidazole. The eradication of Helicobacter pylori may have eliminated ongoing antigenic stimulation that has previously been postulated to be responsible for the development and subsequent progression of gastric pseudolymphoma.

Topics: Aged; Amoxicillin; Biopsy; Bismuth; Drug Therapy, Combination; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hyperplasia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytes; Male; Metronidazole; Organometallic Compounds; Ranitidine; Salicylates; Stomach; Stomach Neoplasms

Topics: Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Aspirin; Cryopreservation; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocyte Count; Mitochondria; Multienzyme Complexes; NADH, NADPH Oxidoreductases; Neoplastic Stem Cells; Salicylates

We analyzed the effect of aspirin, salicylate, and other nonsteroidal antiinflammatory drugs (NSAIDs) on the viability of B-chronic lymphocytic leukemia (B-CLL) cells. Aspirin induced a decrease in cell viability in a dose- and time-dependent manner. The mean IC50 for cells from 5 patients was 5.9 +/- 1.13 mmol/L (range, 4.4 to 7.3 mmol/L). In some cases, 2.5 mmol/L aspirin produced an important cytotoxic effect after 4 days of incubation. No effect was observed with other NSAIDs, at concentrations that inhibit cyclooxygenase, such as ketorolac (10 micromol/mL), NS-398 (100 micromol/mL), or indomethacin (20 micromol/mL), thus suggesting the involvement of cyclooxygenase-independent mechanisms in aspirin-induced cytotoxicity. Salicylate also produced dose-dependent cytotoxic effects on B-CLL cells and the mean IC50 for cells from 5 patients was 6.96 +/- 1.13 mmol/L (range, 5 to 7.8 mmol/L). Both aspirin and salicylate induced DNA fragmentation and the proteolytic cleavage of poly(ADP(adenosine 5'-diphosphate)-ribose) polymerase (PARP), demonstrating that both compounds induce apoptosis of B-CLL cells. Finally, inhibition of caspases by Z-VAD.fmk blocked proteolytic cleavage of PARP, DNA fragmentation, and cytotoxicity induced by aspirin. Mononuclear cells from normal donors showed a lower sensitivity than cells from B-CLL patients to aspirin as determined by analysis of cell viability. B and T lymphocytes from normal donors and T lymphocytes from CLL patients are more resistant to aspirin-induced apoptosis, as determined by analysis of phosphatidylserine exposure. These results indicate that aspirin and salicylate induce apoptosis of B-CLL cells by activation of caspases and that this activation involves cyclooxygenase-independent mechanisms.

Topics: Aged; Amino Acid Chloromethyl Ketones; Annexins; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Aspirin; B-Lymphocytes; Cell Survival; Cyclooxygenase Inhibitors; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; DNA Fragmentation; Enzyme Activation; Female; Humans; Indomethacin; Ketorolac; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Neoplasm Proteins; Nitrobenzenes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Proteins; Salicylates; Salicylic Acid; Sulfonamides; Tolmetin; Tumor Cells, Cultured

A population-based case-control interview study of 486 adult leukemia cases and 502 healthy controls was carried out in Shanghai, People's Republic of China during 1987-89 to evaluate the etiologic role of prior medical conditions, medications, and diagnostic X-rays. Risks were examined separately for 236 cases with acute non-lymphocytic leukemia (ANLL), 79 with chronic myeloid leukemia (CML), 81 with acute lymphocytic leukemia (ALL), and 21 with chronic lymphocytic leukemia (CLL). Little difference was found between cases and controls for prior history of diabetes, hypertension, allergic conditions, most medications, and diagnostic X-rays. A few significant associations were observed for appendectomy, tuberculosis, and for several other chronic disorders with specific leukemia cell types, but the odds ratio estimates for most of these ranged from two to three and, with the exception of the two specified above, were based generally on five or fewer exposed controls. In contrast to an association with childhood leukemia in Shanghai, prior use of chloramphenicol was not linked with ANLL or other forms of adult leukemia. Further research is needed to clarify the relation of specific medical conditions and exposures with particular subtypes of leukemia, and to examine reasons for the low incidence of CLL in China and other Asian populations.

Topics: Adolescent; Adult; Age Factors; Aged; Appendectomy; Case-Control Studies; China; Disease; Female; Humans; Hyperthyroidism; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Population Surveillance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Salicylates; Tuberculosis