Mastocytic Enterocolitis: An Overlooked Diagnosis for Unexplained Chronic Diarrhea in a Patient With Colon Polyps and a Family History of Colon Cancer.

Chronic intractable diarrhea is a common presenting complaint that is often clinically worked up for a wide variety of diseases including inflammatory bowel disease, celiac disease, and hyperthyroidism. When lab results come back normal, patients are often diagnosed with irritable bowel disease-diarrheal subtype, overlooking the potential diagnosis of mastocytic enterocolitis. Mastocytic enterocolitis is an uncommon diagnosis where patients can benefit from mast cell stabilizers that directly target the underlying pathology. Given the broad differential diagnosis of nonspecific diarrhea presentation, a histopathological examination is warranted for definitive diagnosis. We hope to raise awareness of this potentially treatable disease that can be effectively managed with antihistamines. We describe the case of a 63-year-old male patient with a family history significant for colon cancer who presented with intractable diarrhea and was ultimately diagnosed with mastocytic enterocolitis by histopathology. His symptoms were relieved by antihistamine treatment.

Mitochondrial copper depletion suppresses triple-negative breast cancer in mice.

Depletion of mitochondrial copper, which shifts metabolism from respiration to glycolysis and reduces energy production, is known to be effective against cancer types that depend on oxidative phosphorylation. However, existing copper chelators are too toxic or ineffective for cancer treatment. Here we develop a safe, mitochondria-targeted, copper-depleting nanoparticle (CDN) and test it against triple-negative breast cancer (TNBC). We show that CDNs decrease oxygen consumption and oxidative phosphorylation, cause a metabolic switch to glycolysis and reduce ATP production in TNBC cells. This energy deficiency, together with compromised mitochondrial membrane potential and elevated oxidative stress, results in apoptosis. CDNs should be less toxic than existing copper chelators because they favorably deprive copper in the mitochondria in cancer cells instead of systemic depletion. Indeed, we demonstrate low toxicity of CDNs in healthy mice. In three mouse models of TNBC, CDN administration inhibits tumor growth and substantially improves survival. The efficacy and safety of CDNs suggest the potential clinical relevance of this approach.