ABSTRACT
Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 10(7) MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2-treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally.
Subject(s)
Anus Neoplasms/therapy , Genetic Therapy , Uterine Cervical Neoplasms/therapy , Viral Vaccines/administration & dosage , Adult , Animals , Anus Neoplasms/immunology , Anus Neoplasms/pathology , Chick Embryo , Female , Humans , Male , Middle Aged , Papillomaviridae/immunology , Papillomaviridae/pathogenicity , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Vaccines, DNA , Viral Vaccines/adverse effectsABSTRACT
This investigation sought to assess the biological responses to Pb along a simplified four-level food chain, from the primary producer, the microalgae Tetraselmis suecica, grown in a control medium with < 1 µg/L of Pb and exposed to a sublethal dose (20 µg/L of Pb) and used as the base of a simulated food chain, through the primary-, secondary-, and tertiary-level consumers, namely, the brine shrimp, Artemia franciscana; the white-leg shrimp, Litopenaeus vannamei; and the grunt fish, Haemulon scudderi, respectively. Growth of Pb-exposed T. suecica was 40% lower than that of the control cultures, and survival of A. franciscana fed this diet was 25 to 30% lower than the control. No differences in the growth rates of Pb-exposed and control shrimp and fish and no gross morphological changes were evident in the exposed specimens. However, the exposed shrimp and fish had 20 and 15% higher mortalities than their controls, respectively. In addition, behavioral alterations were observed in exposed shrimp and fish, including reduction in food consumption or cessation of feeding, breathing air out of the water, reduction of motility, and erratic swimming. The negative correlation between Pb concentration in whole body of shrimp and fish and Fulton's condition factor suggested also that the exposed organisms were stressed because of Pb accumulation.
