Large animal models have provided much of the descriptive data regarding the cellular and molecular events in myocardial infarction and repair. The availability of genetically altered mice may provide a valuable tool for specific cellular and molecular dissection of these processes. In this report we compare closed chest models of canine and mouse infarction/reperfusion qualitatively and quantitatively for temporal, cellular, and spatial differences. Much like the canine model, reperfused mouse hearts are associated with marked induction of endothelial adhesion molecules, cytokines, and chemokines. Reperfused mouse infarcts show accelerated replacement of cardiomyocytes by granulation tissue leading to a thin mature scar at 14 days, when the canine infarction is still cellular and evolving. Infarcted mouse hearts demonstrate a robust but transient postreperfusion inflammatory reaction, associated with a rapid up-regulation of interleukin-10 and transforming growth factor-␤. Unlike canine infarcts, infarcted mouse hearts show only transient macrophage infiltration and no significant mast cell accumulation. In correlation, the growth factor for macrophages, M-CSF, shows modest and transient up-regulation in the early days of reperfusion; and the obligate growth factor for mast cells, stem cell factor, SCF, is not induced. In summary, the postinfarction inflammatory response and resultant repair in the mouse heart shares many common characteristics with large mammalian species, but has distinct temporal and qualitative features. These important species-specific differences should be considered when interpreting findings derived from studies using genetically altered mice. For almost a century, experimental models of myocardial infarction have contributed to our understanding of the pathobiology of myocardial infarction. Large animal models have been extensively used to study the mechanisms involved in myocardial injury and repair 1,2 and have significantly contributed to our understanding of the pathological process of myocardial infarction. However, large animal studies have significant limitations in investigating the functional role of specific genes in myocardial ischemia. Recent advances in transgenic and gene targeting approaches have allowed sophisticated manipulations of genes whose functions may be important in injury and repair following myocardial infarction.3 Because of technical and economic considerations, these experiments are largely confined to the mouse. 4,5 To capitalize on these advances in gene targeting technology murine models of experimental myocardial infarction have been developed 6,7 and have been extensively used to dissect the mechanisms involved in ischemic myocardial injury. 8 -10 However, extrapolation of the findings derived from murine experiments to the human pathobiology requires similar disease mechanisms in both species. Despite the widespread use of murine models of myocardial infarction, detailed studies of the cellular and molecular events associated with repair of the mous...

Background Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. Methods NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. Results In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. Conclusions NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. Clinical trial registration NCT03494816.

Breast metastasis from primary renal cell carcinoma is a rare entity and infrequently reported in the literature. We present a case of a 65-year-old lady who presented to breast clinic with a 4-month history of rapidly growing right sided breast lump. She previously had a left mastectomy for breast cancer and a hysterectomy for endometrial cancer. Radiological evaluation with mammography and ultrasound revealed a large heterogeneous right breast lump with prominent vascularity which was biopsied. Histopathological and immunohistochemical features were not supportive of a primary breast carcinoma and favored metastasis from a renal tumor. The patient was unfortunately admitted to hospital due to increasing confusion and neurological symptoms and underwent whole-body cross-sectional CT imaging which demonstrated a giant tumor originating from the right kidney with associated intrathoracic, breast and intracranial metastasis. She was diagnosed with eosinophilic variant metastatic renal cell carcinoma. This case highlights the importance of considering alternative diagnoses to primary breast carcinoma in the context of an initial presentation of a unilateral breast lump.

No abstract