Optimization and regeneration kinetics of lymphatic-specific photodynamic therapy in the mouse dermis.

Lymphatic vessels transport fluid, antigens, and immune cells to the lymph nodes to orchestrate adaptive immunity and maintain peripheral tolerance. Lymphangiogenesis has been associated with inflammation, cancer metastasis, autoimmunity, tolerance and transplant rejection, and thus, targeted lymphatic ablation is a potential therapeutic strategy for treating or preventing such events. Here we define conditions that lead to specific and local closure of the lymphatic vasculature using photodynamic therapy (PDT). Lymphatic-specific PDT was performed by irradiation of the photosensitizer verteporfin that effectively accumulates within collecting lymphatic vessels after local intradermal injection. We found that anti-lymphatic PDT induced necrosis of endothelial cells and pericytes, which preceded the functional occlusion of lymphatic collectors. This was specific to lymphatic vessels at low verteporfin dose, while higher doses also affected local blood vessels. In contrast, light dose (fluence) did not affect blood vessel perfusion, but did affect regeneration time of occluded lymphatic vessels. Lymphatic vessels eventually regenerated by recanalization of blocked collectors, with a characteristic hyperplasia of peri-lymphatic smooth muscle cells. The restoration of lymphatic function occurred with minimal remodeling of non-lymphatic tissue. Thus, anti-lymphatic PDT allows control of lymphatic ablation and regeneration by alteration of light fluence and photosensitizer dose

Corpo-Affective Politics of Anxious Breathing: On the Agential Force of Bodies and Affects in Vulnerable Protest

Analysing SIA’s music video Big Girls Cry (2015), this chapter argues for a recognition of corpomaterial and affective agency amongst forms of political resistance beyond forms of protest, in which engagement can be restricted by bodily and affective vulnerability. It signals the agential significance of quotidian corpomaterial and affective actions in enacting political resistance by focusing on anxious breathing diffused throughout SIA’s music video. Although breathing and anxiety are not usually associated with politics, this chapter shows how quotidian corpomaterial and affective practices are intra-actively enacted through social power relations, and how they enact transformations, breaks, and re-directions of the ways social power relations are lived. It argues that striving for breath and for breathable lives needs a recognition of differential forms of political practices and resistance needs to focus not only on how bodies and affects act in politics but also how they enact politics in a quotidian manner

Corpo-Affective Politics of Anxious Breathing: On the Agential Force of Bodies and Affects in Vulnerable Protest

Analysing SIA’s music video Big Girls Cry (2015), this chapter argues for a recognition of corpomaterial and affective agency amongst forms of political resistance beyond forms of protest, in which engagement can be restricted by bodily and affective vulnerability. It signals the agential significance of quotidian corpomaterial and affective actions in enacting political resistance by focusing on anxious breathing diffused throughout SIA’s music video. Although breathing and anxiety are not usually associated with politics, this chapter shows how quotidian corpomaterial and affective practices are intra-actively enacted through social power relations, and how they enact transformations, breaks, and re-directions of the ways social power relations are lived. It argues that striving for breath and for breathable lives needs a recognition of differential forms of political practices and resistance needs to focus not only on how bodies and affects act in politics but also how they enact politics in a quotidian manner

Rapid Angiogenesis Onset after Discontinuation of Sunitinib Treatment of Renal Cell Carcinoma Patients

Item does not contain fulltextPURPOSE: To investigate the angiogenic changes in primary tumor tissue of renal cell carcinoma (RCC) patients treated with VEGF-targeted therapy. EXPERIMENTAL DESIGN: Phase II trials of VEGF pathway-targeted therapy given before cytoreductive surgery were carried out with metastatic RCC patients with the primary tumor in situ to investigate the necessity of nephrectomy. Primary tumor tissues were obtained and assessed for angiogenesis parameters. Results were compared with similar analyses on untreated tumors. RESULTS: Sunitinib or bevacizumab pretreatment resulted in a significant reduction of microvessel density in the primary tumor. Also, an increase in vascular pericyte coverage was found in sunitinib-pretreated tumors, consistent with efficient angiogenesis inhibition. Expression of several key regulators of angiogenesis was found to be suppressed in pretreated tissues, among which VEGFR-1 and VEGFR-2, angiopoietin-1 and angiopoietin-2 and platelet-derived growth factor-B. In addition, apoptosis in tumor and endothelial cells was induced. Interestingly, in sunitinib-pretreated tissues a dramatic increase of the number of proliferating endothelial cells was observed, which was not the case in bevacizumab-pretreated tumors. A positive correlation with the interval between halting the therapy and surgery was found, suggesting a compensatory angiogenic response caused by the discontinuation of sunitinib treatment. CONCLUSION: This study describes, for the first time, the angiostatic response in human primary renal cancers at the tissue level upon treatment with VEGF-targeted therapy. Discontinuation of treatment with tyrosine kinase inhibitors leads to accelerated endothelial cell proliferation. The results of this study contribute important data to the ongoing discussion on the discontinuation of treatment with kinase inhibitors