Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution

Abstract

Purpose: Pseudomyxoma peritonei is an understudied cancer in which an appendiceal neoplasm invades the peritoneum and forms tumor foci on abdominal organs. Previous studies have shown that bacteria reside within pseudomyxoma peritonei tumors and mucin. Thus, we sought to analyze the effect of antibiotics on bacterial density and b-catenin expression within pseudomyxoma peritonei samples.Experimental Design: The study included 48 patients: 19 with disseminated peritoneal adenomucinosis (DPAM) and 29 with peritoneal mucinous carcinomatosis (PMCA). Fourteen patients were given antibiotics (30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin) twice a day for 14 days. One week after completion of therapy, surgery was conducted and specimens were harvested for pathology, bacterial culture, ISH, and immunohistochemistry.Results: ISH showed the presence of bacteria in 83% of the patient samples, with a higher Helicobacter pylori density observed in PMCA versus DPAM. PMCA patients treated with antibiotics had a significantly lower bacterial density and decreased b-catenin levels in the cytoplasm, the cell nuclei, and mucin-associated cells. Although not significant, similar trends were observed in DPAM patients. Cell membrane b-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics.Conclusions: Bacteria play an important role in pseudomyxoma peritonei. Antibiotic treatment improved the histopathology of tissue, particularly in PMCA patients. In PMCA, antibiotics decreased bacterial density and were associated with a significant b-catenin decrease in the cytoplasm, cell nuclei, and mucin along with a small membrane increase. These results suggest that antibiotics offer potential protection against cell detachment, cellular invasion, and metastasis.

A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei

“…Importantly, the survival rate of LN positive patients within the pilot group that received antibiotic therapy was effectively the same as those that did not receive antibiotics (data not shown). Importantly, an additional recent study from our group showed that antibiotic treatment significantly reduced the number of bacteria found in PMP tissue [28]. Thus, en masse our results support our hypothesis that eliminating bacteria from the affected peritoneal tissue prior to metastasis may improve survival of patients with PMP disease.…”

A Novel Member of Chitinophagaceae Isolated from a Human Peritoneal Tumor

“…Additionally, Gilbreath et al ( 3 ) identified a core microbiome present in PMP tumors that is conserved among examined patients. Moreover, a recent study by Semino-Mora et al ( 4 ) suggested higher bacterial density and higher expression of the MUC2 mucin associated with more malignant forms of PMP. It was further shown that the treatment of patients with antibiotics targeting H. pylori prior to cytoreductive surgery reduces the peritoneal bacterial density and decreases nuclear β-catenin, a known biomarker of carcinogenesis.…”

Repurposing Drugs in Oncology (ReDO)—clarithromycin as an anti-cancer agent

“…To the best of our knowledge, no research has been done thus far on the influence of CAM on the Wnt/β-catenin signalling pathway. In this connection, Semino-Mora et al reported that β-catenin levels were decreased in the cytoplasm, the cell nuclei, and the mucin-associated cells while β-catenin levels within membranes increased in pseudomyxoma peritonei patients after H pylori eradication treatment containing CAM, providing potential protection against cell detachment, cellular invasion, and metastasis [83]. …”