Carcinoma in the porcelain gallbladder: a relationship revisited.

BACKGROUND: Gallbladder cancer is the most common biliary tract malignancy. Calcification of the gallbladder wall is reported to be associated with gallbladder cancer. In the literature, the incidence is quoted to be between 12% and 61%. This study aims to clarify the risk of cancer in a calcified gallbladder. METHODS: The charts and pathology reports at the Massachusetts General Hospital were reviewed, and patients with either gallbladder cancer or a calcified gallbladder were included in the study. The Fisher exact test was used to test for the association between cancer and gallbladder wall calcifications. RESULTS: From 1962 to 1999, there were approximately 25,900 gallbladder specimens analyzed at the Massachusetts General Hospital. There were 150 patients with gallbladder cancer and 44 patients with calcified gallbladders. Two types of calcified gallbladders were noted: those with complete intramural calcification (n = 17) and those with selective mucosal calcification (n = 27). The incidence of cancer arising in a gallbladder with selective mucosal wall calcification was approximately 7%. There was a significant association between gallbladder cancer and selective mucosal calcification with an odds ratio of 13.89 (P =.01). There were no patients with diffuse intramural calcification and cancer. CONCLUSIONS: A calcified gallbladder is associated with an increased risk of gallbladder cancer, but at a much lower rate than previously estimated. The incidence of cancer depends on the pattern of calcification; selective mucosal calcification poses a significant risk of cancer whereas diffuse intramural calcification does not.

Mullerian inhibiting substance regulates NFkappaB signaling and growth of mammary epithelial cells in vivo.

Müllerian inhibiting substance (MIS) inhibits breast cancer cell growth in vitro through interference with cell cycle progression and induction of apoptosis, a process associated with NFkappaB activation and up-regulation of one of its important target genes, IEX-1S (Segev, D. L., Ha, T., Tran, T. T., Kenneally, M., Harkin, P., Jung, M., MacLaughlin, D. T., Donahoe, P. K., and Maheswaran, S. (2000) J. Biol. Chem. 275, 28371-28379). Here we demonstrate that MIS activates the NFkappaB signaling cascade, induces IEX-1S mRNA, and inhibits the growth of MCF10A, an immortalized human breast epithelial cell line with characteristics of normal cells. In vivo, an inverse correlation was found to exist between various stages of mammary growth and MIS type II receptor expression. Receptor mRNA significantly diminished during puberty, when the ductal system branches and invades the adipose stroma and during the expansive growth at lactation, but it was up-regulated during involution, a time of regression and apoptosis. Peripartum variations in MIS type II receptor expression correlated with NFkappaB activation and IEX-1S mRNA expression. Administration of MIS to female mice induced NFkappaB DNA binding and IEX-1S mRNA expression in the breast. Furthermore, exposure to MIS in vivo increased apoptosis in the mouse mammary ductal epithelium. Thus, MIS may function as an endogenous hormonal regulator of NFkappaB signaling and growth in the breast.

Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo.

Techniques of tissue engineering and cell and molecular biology were used to create a biodegradable scaffold for transfected cells to produce complex proteins. Mullerian Inhibiting Substance (MIS) causes regression of Mullerian ducts in the mammalian embryo. MIS also causes regression in vitro of ovarian tumor cell lines and primary cells from ovarian carcinomas, which derive from Mullerian structures. In a strategy to circumvent the complicated purification protocols for MIS, Chinese hamster ovary cells transfected with the human MIS gene were seeded onto biodegradable polymers of polyglycolic acid fibers and secretion of MIS confirmed. The polymer-cell graft was implanted into the right ovarian pedicle of severe combined immunodeficient mice. Serum MIS in the mice rose to supraphysiologic levels over time. One week after implantation of the polymer-cell graft, IGROV-1 human tumors were implanted under the renal capsule of the left kidney. Growth of the IGROV-1 tumors was significantly inhibited in the animals with a polymer-cell graft of MIS-producing cells, compared with controls. This novel MIS delivery system could have broader applications for other inhibitory agents not amenable to efficient purification and provides in vivo evidence for a role of MIS in the treatment of ovarian cancer.