sirolimus and Helicobacter-Infections

Helicobacter pylori has developed several mechanisms to evade the intracellular killing after phagocytosis. In this study, we reported that some Taiwanese clinical isolated H. pylori can multiply in human monocytic cells, such as THP-1 or U937 cells, but not in murine macrophage Raw264.7 cells. After internalization, there was a 5- to 10-fold increment of re-cultivable H. pylori from the infected THP-1 cells at 12 hrs post infection. The dividing H. pylori was found in a double-layer vesicle, which is characteristic of autophagosome. The formation of autophagosomes is associated with the multiplication of H. pylori in THP-1 cells. Its modulation with rapamycin or 3-MA affects the level of H. pylori replication. Furthermore, the VacA or CagA mutants of H. pylori have lower levels of multiplication in macrophages. We conclude that H. pylori infection induces autophagosome formation, and these autophagic vesicles were adapted for the multiplication of H. pylori in the host.

Topics: Adenine; Animals; Autophagy; Bacterial Proteins; Cell Line; Cell Proliferation; Helicobacter Infections; Helicobacter pylori; Humans; Macrophages; Mice; Microbial Viability; Microtubule-Associated Proteins; Monocytes; Mutation; Sirolimus; Vacuoles

The treatment of B-cell non-Hodgkin lymphoma, the most common posttransplant lymphoproliferative disorder, is not well defined. Herein we have reported a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with rapid, persistent, and complete remission after conversion of the immunosuppression from cyclosporine (CsA) to sirolimus (SRL). A 42-year-old woman underwent renal transplantation in 1992 with no major abnormalities until 2006 when a gastroscopy performed to investigate dyspeptic symptoms showed a mixed MALT gastric lymphoma (with low- and high-grade components) associated with the presence of Helicobacter pylori infection. Two therapeutic interventions in a 1-week interval were performed: treatment of the H. pylori infection (omeprazole, amoxicillin, and clarithromycin for 14 days) and modification of the immunosuppression by substitution of CsA and azathioprine (AZA) with SRL. Control endoscopy performed 1 month later showed persistence of H. pylori infection and absence of the gastric tumor. New endoscopies performed at 2 and 7 months after therapy confirmed the absence of neoplasia and H. pylori eradication. Currently, the patient has no complaints, displaying a creatinine value of 1.8 mg/dL and a hemoglobin of 9.4 mg/dL using SRL and ibersatan. SRL has been studied extensively as an anticancer drug, acting as a mammalian target for rapamycin (mTOR) inhibitor. Accumulating data support the role of mTOR in lymphomagenesis. In conclusion, our case of gastric MALT lymphoma in a renal transplant patient displayed a complete remission after alteration of the immunosuppressive scheme with the introduction of SRL.

Topics: Adult; Azathioprine; Cyclosporine; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Lymphoma, B-Cell, Marginal Zone; Sirolimus; Stomach Neoplasms