Tumor-specific colonization, tissue distribution, and gene induction by probiotic Escherichia coli Nissle 1917 in live mice.

Systemic administration of microorganisms into tumor-bearing mice revealed preferential accumulation in tumors in comparison to clearance in organs such as spleen and liver. Here we compared the efficiency of tumor-specific colonization of pathogenic Salmonella typhimurium strains 14028 and SL1344 to the enteroinvasive Escherichia coli 4608-58 strain and to the attenuated Salmonella flexneri 2a SC602 strain, as well as to the uropathogenic E. coli CFT073, the non-pathogenic E. coli Top10, and the probiotic E. coli Nissle 1917 strain. All strains colonized and replicated in tumors efficiently each resulting in more than 1 x 10(8) colony-forming units per gram tumor tissue. Colonization of spleen and liver were significantly lower when E. coli strains were used in comparison to S. typhimurium and the non-pathogenic strains did not colonize those organs at all. Further investigation of E. coli Nissle 1917 showed that no drastic differences in colonization and amplification were seen when immunocompetent and immunocompromised animals were used, and we were able to show that E. coli Nissle 1917 replicates at the border of live and necrotic tumor tissue. We also demonstrated exogenously applied L-arabinose-dependent gene activation in colonized tumors in live mice. These findings will prepare the way for bacterium-mediated controlled protein delivery to solid tumors.

Multiple primary gynecologic neoplasms in a young HIV-positive patient.

Immune suppression from human immunodeficiency virus (HIV) infection is frequently associated with the development of certain neoplasms, including Kaposi's sarcoma and non-Hodgkin's lymphoma. A young patient with a 5-year history of HIV infection was found simultaneously to have invasive carcinoma of the breast, microinvasive carcinoma of the cervix, and intraepithelial neoplasia of the vulva. In view of the early nature of these neoplasms, conservative therapy was utilized; lumpectomy and adjuvant radiation therapy, conservative hysterectomy, and local therapy for the breast carcinoma, cervical carcinoma and vulvar intraepithelial neoplasia, respectively. Epithelial malignancies appear to be more common in the HIV-positive population than previously appreciated. To our knowledge this is the first report of multiple primary gynecologic neoplasms in association with HIV infection.

Etiology of breast carcinoma: no apparent role for papillomavirus types 6/11/16/18.

A recent study has shown that human papillomavirus (HPV) types 16 and 18 can immortalize normal breast epithelium, and raised the possibility that HPV may be etiologically related to some cases of breast cancer. In order to investigate this possibility, we performed polymerase chain reaction (PCR) assays for HPV types 6, 11, 16 and 18 in 15 papillomas, 15 papillary carcinomas, and 13 infiltrating ductal carcinomas of the breast. No HPV-related DNA sequences were identified by Southern blotting of the PCR products. It therefore seems unlikely that a significant percentage of human breast carcinomas is etiologically related to infection with one of these HPV types.

Immunohistochemical evaluation of reverse transcriptase in breast carcinoma with polyclonal antibodies raised in rabbit.

In this study, the presence of reverse transcriptase in breast tumours was examined with immunoperoxidase staining using antibodies raised in rabbit against reverse transcriptase of Moloney murine leukemia virus and against reverse transcriptase of avian myeloblastosis virus. The specificity of such antibodies was investigated with ELISA and Western blotting techniques. Five cases of infiltrating ductal carcinomas were found positive with the immune serum anti-reverse transcriptase of Moloney murine leukemia virus on 28 studied infiltrating ductal carcinomas, 2 infiltrating lobular carcinomas and 2 fibroadenomas.

A human breast tumor cell line (BT-474) that supports mouse mammary tumor virus replication.

A human breast tumor cell line BT-474 derived from an invasive ductal carcinoma was experimentally infected in vitro with a mouse mammary tumor virus from the TIII strain (RIII-MuMTV). The virus that replicated in the human cells was characterized as a mouse virus by immunofluorescence, electron microscopy and the presence of a specific RNA-directed DNA polymerase. The cells themselves were human as per the karyotype and isoenzyme migration patterns. It is concluded that human cells are susceptible to the mouse mammary tumor virus and can, eventually, support its replication.