A Novel Murine Model of a High Dose Brachytherapy-Induced Actinic Proctitis.

Background: Radiation proctitis affects 1-20% of cancer patients undergoing radiation exposure due to pelvic malignancies, including prostate, gynecological and rectum cancers. The patients manifest rectal discomfort, pain, discharge, and bleeding. Notably, the efficacy of prophylactic measures remains controversial due to the lack of adequate animal models that mimic this condition.

SN-38, the active metabolite of irinotecan, inhibits the acute inflammatory response by targeting toll-like receptor 4.

Purpose: Anticancer-drug efficacy seems to involve the direct interaction with host immune cells. Although topoisomerase I (Top I) inhibitors have been suggested to block LPS-evoked inflammation, the interaction between these drugs and toll-like receptor 4 (TLR4) is unaddressed.

Methods: SN-38, the active metabolite of the Top I inhibitor irinotecan, and TLR4 interaction was assessed using the in vitro luciferase nuclear factor-κB reporter assay, neutrophil migration to murine air-pouch, in silico simulation, and the thermal shift assay (TSA).

Irinotecan- and 5-fluorouracil-induced intestinal mucositis: insights into pathogenesis and therapeutic perspectives.

Purpose: Intestinal mucositis and diarrhea are common manifestations of anticancer regimens that include irinotecan, 5-fluorouracil (5-FU), and other cytotoxic drugs. These side effects negatively impact therapeutic outcomes and delay subsequent cycles of chemotherapy, resulting in dose reductions and treatment discontinuation. Here, we aimed to review the experimental evidence regarding possible new targets for the management of irinotecan- and 5-FU-related intestinal mucositis.

Paradoxical Roles of the Neutrophil in Sepsis: Protective and Deleterious.

Sepsis, an overwhelming inflammatory response syndrome secondary to infection, is one of the costliest and deadliest medical conditions worldwide. Neutrophils are classically considered to be essential players in the host defense against invading pathogens. However, several investigations have shown that impairment of neutrophil migration to the site of infection, also referred to as neutrophil paralysis, occurs during severe sepsis, resulting in an inability of the host to contain and eliminate the infection.

The Adaptor Protein Myd88 Is a Key Signaling Molecule in the Pathogenesis of Irinotecan-Induced Intestinal Mucositis.

Intestinal mucositis is a common side effect of irinotecan-based anticancer regimens. Mucositis causes cell damage, bacterial/endotoxin translocation and production of cytokines including IL-1 and IL-18. These molecules and toll-like receptors (TLRs) activate a common signaling pathway that involves the Myeloid Differentiation adaptor protein, MyD88, whose role in intestinal mucositis is unknown.

Target Inhibition of IL-1 Receptor Prevents Ifosfamide Induced Hemorrhagic Cystitis in Mice.

Purpose: Hemorrhagic cystitis is an important dose limiting side effect of ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can still be found in cystoscopy guided biopsies. Previous studies confirmed the role of TNF-α and IL-1β.

Involvement of nitric oxide on the pathogenesis of irinotecan-induced intestinal mucositis: role of cytokines on inducible nitric oxide synthase activation.

Purpose: Intestinal mucositis and the closely associated diarrhea are common costly side effects of irinotecan. Cytokine modulators, such as thalidomide and pentoxifylline, are found capable of attenuating intestinal mucositis progression. Nitric oxide (NO) seems to be a key mediator of the antineoplastic drug toxicity.