Imaging techniques to evaluate the response to treatment in oncology: Current standards and perspectives

Response evaluation in solid tumours currently uses radiological imaging techniques to measure changes under treatment. Imaging requires a well-defined anatomical lesion to be viewed and relies on the measurement of a reduction in tumour size during treatment as the basis for presumed clinical benefit. However, with the development of anti-angiogenesis agents, anatomical imaging has became inappropriate as certain tumours would not reduce in size. Functional studies are therefore necessary and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), DCE-computed tomography (CT) and DCE-ultrasonography (US) are currently being evaluated for monitoring treatments. Diffusion-weighted MR imaging (DW-MRI) and magnetic resonance spectroscopy (MRS) are also capable of detecting changes in cell density and metabolite content within tumours. In this article, we review anatomical and functional criteria currently used for monitoring therapy. We review the published data on DCE-MRI, DCE-CT, DCE-US, DW-MRI and MRS. This literature review covers the following area: basic principles of the technique, clinical studies, reproducibility and repeatability, limits and perspectives in monitoring therapy.Anatomical criteria such as response evaluation criteria in solid tumours (RECIST) will require adaptation to employ not only new tools but also different complementary techniques such as functional imaging in order to monitor therapeutic effects of conventional and new anti-cancer agents.     

Distinct mechanisms of splicing regulation in vivo by the Drosophila protein Sex-lethal

The protein Sex-lethal (SXL) controls pre-mRNA splicing of two genes involved in Drosophila sex determination: transformer (tra) and the Sxl gene itself. Previous in vitro results indicated that SXL antagonizes the general splicing factor U2AF⁶⁵ to regulate splicing of tra. In this report, we have used transgenic flies expressing chimeric proteins between SXL and the effector domain of U2AF⁶⁵ to study the mechanisms of splicing regulation by SXL in vivo. Conferring U2AF activity to SXL relieves its inhibitory activity on tra splicing but not on Sxl splicing. Therefore, antagonizing U2AF⁶⁵ can explain tra splicing regulation both in vitro and in vivo, but this mechanism cannot explain splicing regulation of Sxl pre-mRNA. These results are a direct proof that Sxl, the master regulatory gene in sex determination, has multiple and separable activities in the regulation of pre-mRNA splicing.     

Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery

To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase^?/? mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase^?/? mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase^?/? tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.     

Serine protease inhibitor Serp-1 strongly impairs atherosclerotic lesion formation and induces a stable plaque phenotype in ApoE-/-mice

The myxoma virus protein Serp-1 is a member of the serine protease inhibitor superfamily. Serp-1 potently inhibits human serum proteases including plasmin, urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA). Serp-1 also displays a high antiinflammatory activity, rendering it a promising candidate for antiatherosclerotic therapy. In this study, we have thus examined the effect of Serp-1 on de novo atherosclerotic plaque formation and on advanced lesions. Perivascular collars were placed around carotid arteries of ApoE-/- mice to induce atherosclerotic plaques and Serp-1 treatment started at week 1 and week 5 after collar placement. Effects of Serp-1 on de novo atherogenesis were characterized by a significantly lower plaque size than that of control mice (18+/-5x10(3) versus 57+/-12x10(3) microm2, respectively; P=0.007). Immunostaining showed a 50% (P=0.004) decrease in the MOMA-2-stained lesion area of Serp-1-treated mice. Treatment of advanced lesions with Serp-1 resulted in a decrease in plaque size and lumen stenosis (P=0.028). Alpha-actin staining of these lesions was significantly increased compared with the control (P=0.017). In both studies, a higher cellularity of the plaque and increased collagen content was observed in Serp-1-treated mice. In vitro studies showed that Serp-1 induces proliferation and migration of vascular smooth muscle cells. In conclusion, Serp-1 inhibits carotid artery plaque growth and progression in ApoE-/- mice. Equally relevant, it enhances cellularity of the plaque core potentially leading to improved plaque stability. The above results indicate that Serp-1 constitutes a promising lead in antiatherosclerotic therapy.     

Is magnetic resonance imaging useful for the management of patients with rectal villous adenoma? A study of 45 consecutive patients treated by transanal endoscopic microsurgery

Purpose

Very few data are available about the clinical relevance of magnetic resonance (MR) imaging in preoperative evaluation of rectal villous adenoma. The aim is to evaluate the impact of MR imaging for the surgical management of rectal villous adenoma treated by transanal endoscopic microsurgery (TEM).

Methods

All patients with histologically proven rectal villous tumours operated by TEM who had a preoperative MR imaging between 2009 and 2017 were retrospectively reviewed. All patients underwent TEM because preoperative evaluation suggested systematically usT0 or usT1 tumour. Pathological stage was blindly compared to preoperative MR imaging (location according to the anal verge and the peritoneal reflection, amount of circumferential involvement, tumour size and staging) and preoperative transrectal ultrasonography (TRUS) results.

Results

Forty-five patients were included (24 men, mean age 65?±?8 years) with TRUS data available only in 37. Pathologic results were pT0-pTis in 32, pT1 in 10 and pT2 in 3. TRUS diagnosed correctly 36/37 lesions (97%) and understaged one pT2 tumour. A significant correlation between TRUS and pathologic results was noted (r?=?0.99; p?=?0.01). MR imaging diagnosed correctly 19/42 pTis-T1 and 1/3 pT2 tumours (46%). Overstaging by MR imaging was noted in 25 cases (54%). No correlation between MR imaging and pathologic results was noted (r?=?0.7; p?=?0.3).

Conclusion

Preoperative evaluation of rectal villous adenoma is overstaged by MRI in more than half of the patients. This study suggests that the indication of local excision by TEM for rectal villous adenoma should be based on TRUS rather than on MRI.