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Abstract Background Metabolic syndrome is associated with formation of calcium oxalate (CaOx) uroliths in humans. Objectives To investigate the association between obesity and hyperlipidemia with CaOx lower urinary tract uroliths in client‐owned dogs. Animals Dogs with (n = 55, U [uroliths]‐dogs) and without (n = 39, UF [uroliths‐free]‐dogs) CaOx lower urinary tract uroliths. Methods Case‐control study. U‐dogs were retrospectively enrolled and compared to UF‐dogs. Body condition score (BCS; 1‐9 scoring scale), serum triglyceride (TG) and total cholesterol (CH) concentrations and glycemia (after >12‐hour food withholding) were recorded in both groups. Results On univariate logistic regression, when excluding Miniature Schnauzers, odds of having uroliths increased by a factor of 3.32 (95% CI 1.38‐11.12) for each mmol/L of TG (P = .027), of 39 (95% CI 9.27‐293.22) for each mmol/L of glycemia (P

Abstract Background Differentiation of low‐grade intestinal T‐cell lymphoma (LGITL) from lymphoplasmacytic enteritis (LPE) in cats is a diagnostic challenge for pathologists. Objective Characterize histologic, immunohistochemical, and molecular features of LGITL and LPE. Animals Forty‐four client‐owned cats, 22 diagnosed with LGITL and 22 with LPE. Methods Prospective, cohort study. Clinical suspicion of LGITL or LPE was based on persistent gastrointestinal signs, unresponsive to empirical treatments. All cats underwent a standardized diagnostic evaluation, including biopsy (preferentially full‐thickness), and were diagnosed with LGITL or LPE after review of clinical, laboratory, sonographic, histologic, immunohistochemical, and clonality results. Results A monomorphic lymphocytic population (22/22, 100%) and in‐depth mucosal infiltration (15/22, 68%) were hallmarks of LGITL. Epithelial patterns (nests and plaques) were significantly more frequent in LGITL (11/22, 50%) than in LPE (1/22, 5%) cases (P = .001). A CD3+ lymphocytic apical‐to‐basal gradient was observed in 9/22 (41%) of LGITL vs 1/22 (5%) of LPE cases (P = .004). Most LPE cases (17/18, 94%) featured marked fibrosis in the superficial part of the lamina propria. The Ki‐67 20%‐ and 30%‐thresholds discriminated between LGITL and LPE within both the epithelium (specificity >95%) and lamina propria (specificity >95%), respectively. All LGITL cases were CD3+ pSTAT3− and pSTAT5+. T‐cell receptor gamma chain gene rearrangements indicated monoclonality in 86% of LGITL cases. Surprisingly, 70% of LPE cases featured monoclonality (40%) or monoclonality on a polyclonal background (30%). Conclusions and Clinical Importance We identified new histologic, immunohistochemical, and clonality criteria to distinguish LGITL from LPE.

Although fungi produce highly structurally diverse metabolites, many of which have served as excellent sources of pharmaceuticals, no fungi-derived agent has been approved as a cancer drug so far. This is despite a tremendous amount of research being aimed at the identification of fungal metabolites with promising anticancer activities. This review discusses the results of clinical testing of fungal metabolites and their synthetic derivatives, with the goal to evaluate how far we are from an approved cancer drug of fungal origin. Also, because in vivo studies in animal models are predictive of the efficacy and toxicity of a given compound in a clinical situation, literature describing animal cancer testing of compounds of fungal origin is reviewed as well. Agents showing the potential to advance to clinical trials are also identified. Finally, the technological challenges involved in the exploitation of fungal biodiversity and procurement of sufficient quantities of clinical candidates are discussed, and potential solutions that could be pursued by researchers are highlighted., (© 2015 Wiley Periodicals, Inc.)

The anticancer activity of Amaryllidaceae isocarbostyrils is well documented. At pharmacological concentrations, that is, approximately 1 μM in vitro and approximately 10 mg/kg in vivo, narciclasine displays marked proapoptotic and cytotoxic activity, as does pancratistatin, and significant in vivo anticancer effects in various experimental models, but it is also associated with severe toxic side effects. At physiological doses, that is, approximately 50 nM in vitro and approximately 1 mg/kg in vivo, narciclasine is not cytotoxic but cytostatic and displays marked anticancer activity in vivo in experimental models of brain cancer (including gliomas and brain metastases), but it is not associated with toxic side effects. The cytostatic activity of narciclasine involves the impairment of actin cytoskeleton organization by targeting GTPases, including RhoA and the elongation factor eEF1A. We have demonstrated that chronic treatments of narciclasine (1 mg/kg) significantly increased the survival of immunodeficient mice orthotopically xenografted with highly invasive human glioblastomas and apoptosis-resistant brain metastases, including melanoma- and non-small-cell-lung cancer- (NSCLC) related brain metastases. Thus, narciclasine is a potentially promising agent for the treatment of primary brain cancers and various brain metastases. To date, efforts to develop synthetic analogs with anticancer properties superior to those of narciclasine have failed; thus, research efforts are now focused on narciclasine prodrugs., (© 2012 Wiley Periodicals, Inc.)