Antimicrobial sulfonamides clear latent Kaposi sarcoma herpesvirus infection and impair MDM2-p53 complex formation.

Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8, is the causative agent of Kaposi sarcoma; this malignant angiosarcoma is usually treated with conventional antitumor agents that can control disease evolution, but do not clear the latent KSHV episome that binds to cellular DNA. Some commercial antibacterial sulfonamides were tested for the ability to suppress latent KSHV. Quantitative PCR (qPCR) and cytofluorometry assays were used for detecting both viral DNA and the latency factor LANA (latency-associated nuclear antigen) in BC3 cells, respectively. The capacity of sulfonamides to impair MDM2-p53 complex formation was detected by an enzyme-linked immunosorbent assay method. The analysis of variance was performed according to one-way analysis of variance with Fisher as a post hoc test. Here we show that sulfonamide antibiotics are able to suppress the KSHV latent state in permanently infected BC3 lymphoma cells and interfere with the formation of the MDM2-p53 complex that KSHV seemingly needs to support latency and to trigger tumor cell transformation. These findings detected a new molecular target for the activity of sulfonamides and offer a new potential perspective for treating KSHV-induced lymphoproliferative diseases.

Screening prescription drugs for possible carcinogenicity: eleven to fifteen years of follow-up.

Using computerized pharmacy records from 1969 to 1973 for a cohort of 143,574 members of the Kaiser Permanente Medical Care Program, we have been testing associations of 215 drugs or drug groups with subsequent incidence of cancer at 56 sites. This paper presents findings with follow-up through 1984. There were 227 statistically significant (P less than 0.05, two-tailed) associations: 170 positive, 57 negative. Some were undoubtedly chance findings; others were likely due to confounding by unmeasured covariables. However, several associations suggested hypotheses for further studies and/or the need for continued observation. Most notable among findings not previously reported were associations of several antibiotics, both oral and topical, with lung cancer. These associations could not be explained by indications for drug use or by differences in smoking habits between users and nonusers, and suggest a possible link between the occurrence of bacterial infections and risk for cancer. In general, our results continue to suggest that most medications used during that period did not affect cancer incidence substantially. However, for less frequently prescribed medications, our power to detect moderate increases in cancer risk was quite low.

Death from drug-induced hemolytic anemia.

Fatal hemolytic anemia occurred in a 71-year-old man after trimethoprim-sulfamethoxazole was given for presumed cystitis. Administration of this combination has previously caused multiple hematologic reactions by affecting folic acid metabolism. Megaloblastic anemia and neutropenia have been produced by both of these agents, while sulfamethoxazole alone has induced acute hemolytic anemia in patients with hereditary deficiency of glucose-6-phosphate dehydrogenase. Although hematologic complications of trimethoprim-sulfamethoxazole treatment usually follow long-term or high-dose therapy, acute reactions apparently may occur at lower doses as well.