Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers and the 3rd leading cause of cancer-related mortality. The emergence of drug resistance poses a major challenge in CRC care or treatment. This can be addressed by determining cancer mechanisms, discovery of druggable targets, and development of new drugs. In search for novel agents, aquatic microorganisms offer a vastly untapped pharmacological source that can be developed for cancer therapeutics. In this study, we characterized the anti-colorectal cancer potential of euglenophycin, a microalgal toxin from Euglena sanguinea. The toxin (49.1-114.6 μM) demonstrated cytotoxic, anti-proliferative, anti-clonogenic, and anti-migration effects against HCT116, HT29, and SW620 CRC cells. We identified G1 cell cycle arrest and cell type - dependent modulation of autophagy as mechanisms of growth inhibition. We validated euglenophycin’s anti-tumorigenic activity in vivo using CRL:Nu(NCr)Foxn1nu athymic nude mouse CRC xenograft models. Intraperitoneal toxin administration (100 mg/kg; 5 days) decreased HCT116 and HT29 xenograft tumor volumes (n=10 each). Tumor inhibition was associated with reduced expression of autophagy negative regulator mechanistic target of rapamycin (mTOR) and decreased trend of serum pro-inflammatory cytokines. Together, these results provide compelling evidence that euglenophycin can be a promising anti-colorectal cancer agent targeting multiple cancer-promoting processes. Furthermore, this study supports expanding natural products drug discovery to freshwater niches as prospective sources of anti-cancer compounds.

Addison disease is chronic primary adrenal insufficiency, which, in developed countries, is most commonly due to autoimmune destruction of the cortex (termed autoimmune or idiopathic Addison disease). Although the disease process has some classic features, such as increased pigmentation, salt craving, and signs and symptoms related to decreased blood pressure, the initial clinical presentation may be vague and/or insidious. Following an acute stressor such as a gastrointestinal (GI) infection, the patient may experience an adrenal crisis, which can cause sudden death. As such, knowledge of this disease process and the diagnostic criteria in the postmortem period is essential for the practicing forensic pathologist. The diagnosis of autoimmune Addison disease at autopsy is aided by several factors including 1) history, including salt craving, features consistent with orthostatic hypotension, and GI complaints including nausea, vomiting and pain, 2) physical examination findings of increased pigmentation and small or unidentifiable adrenal glands, 3) serologic testing for 21-hydroxylase antibodies, 4) serum cortisol concentrations, and 5) vitreous electrolyte testing. While the listed historical information, the increased pigmentation, decreased serum cortisol concentrations, and evidence of hyponatremia may be found in all forms of Addison disease, small or unidentifiable adrenal glands and 21-hydroxylase antibodies are found exclusively in the autoimmune form of Addison disease. While other causes of Addison disease, such as tuberculosis, metastatic tumor, or other infiltrative processes would have enlarged adrenal glands, these diseases would lack 21-hydroxylase antibodies. The purpose of this paper is to focus on the diagnosis of autoimmune Addison disease.

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In this case report, we describe a case of imatinib leading to a false-positive amphetamine result on urine drug testing. A 21-year-old female with chronic myelocytic leukemia and in recovery from opioid use disorder reinitiated imatinib maintenance therapy in her third trimester, after previous discontinuation at the beginning of pregnancy. Subsequently, she had multiple presumptive immunoassay-based urine drug tests that resulted positive for amphetamines. The infant's meconium testing was negative for amphetamines, as was maternal definitive testing using urine gas chromatography-mass spectrometry. She had no history of stimulant use and denied any substance use during her pregnancy. Imatinib and/or its metabolites may be responsible for cross-reactivity with urine drug immunoassays leading to a false-positive result for amphetamine.