Benefits and opportunities of the transgenic Oncopig cancer model.

Cancer remains a leading cause of morbidity and mortality, and a paradigm shift is needed to fundamentally revisit drug development efforts. Pigs share close similarities to humans and may serve as an alternative model. Recently, a transgenic 'Oncopig' line has been generated to induce solid tumors with organ specificity, opening the potential of Oncopigs as a platform for developing novel therapeutic regimens.

Pigs: Large Animal Preclinical Cancer Models.

Pigs are playing an increasingly vital role as translational biomedical models for studying human pathophysiology. The annotation of the pig genome was a huge step forward in translatability of pigs as a biomedical model for various human diseases. Similarities between humans and pigs in terms of anatomy, physiology, genetics, and immunology have allowed pigs to become a comprehensive preclinical model for human diseases. With a diverse range, from craniofacial and ophthalmology to reproduction, wound healing, musculoskeletal, and cancer, pigs have provided a seminal understanding of human pathophysiology. This review focuses on the current research using pigs as preclinical models for cancer research and highlights the strengths and opportunities for studying various human cancers.

Reliability of Magnetic Resonance Spectroscopy and Positron Emission Tomography Computed Tomography in Differentiating Metastatic Brain Tumor Recurrence from Radiation Necrosis.

BACKGROUND: Clinical and/or neuroimaging changes after whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for metastatic brain tumor(s) present the clinical dilemma of differentiating tumor recurrence from radiation necrosis. Several imaging modalities attempt to answer this clinical question, including magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) computed tomography (CT). We evaluated our experience regarding the ability of MRS and PET CT to differentiate tumor recurrence from radiation necrosis in patients who have received WBRT or SRS. METHODS: We retrospectively reviewed records of 242 patients with previous WBRT or SRS to identify those who had MRS and/or PET CT to differentiate tumor recurrence from radiation necrosis. Patients were sorted into true-positive, false-positive, false-negative, and true-negative groups on the basis of imaging interpretation and clinical course combined with surgical pathology results or reaction to nonsurgical treatments including SRS, dexamethasone, or observation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were then calculated. RESULTS: Of 25 patients presenting such diagnostic questions, 19 were evaluated with MRS and 13 with PET CT. MRS sensitivity was 100%, specificity was 50%, and accuracy was 81.8%, whereas PET CT sensitivity was 36.4%, specificity was 66.7%, and accuracy was 42.9%. CONCLUSIONS: MRS has better accuracy than PET CT and a high negative predictive value, therefore making it more useful in distinguishing recurrent tumor from radiation necrosis. We encourage correlation with symptoms at imaging to aid in clinical decision making.

Toxicology studies of aqueous-alcohol extracts of Harpagophytum procumbens subsp. procumbens (Burch.) DC.Ex Meisn. (Pedaliaceae) in female and male rats.

BACKGROUND: A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil's Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil's Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil's Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS. METHODS: Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7-10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett's test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis. RESULTS: Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected. CONCLUSION: Toxicologic analysis of Devil's Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.