Bone Pain Assessment and Relationship with Parathyroid Hormone and Health-Related Quality of Life in Hemodialysis

WOS: 000318951100011PubMed: 23560898Renal osteodystrophy is a common problem in renal failure patients. Bone pain is a common manifestation of renal osteodystrophy. The aim of the study was to assess the intensity of chronic bone pain via visual analog scale (VAS) and its relationship with parathyroid hormone, health-related quality of life (HRQoL), and depression in hemodialysis patients. Ninety-five patients recruited were asked to rate chronic bone pain via VAS. Depressive symptoms and HRQoL were assessed by Beck Depression Inventory (BDI) and Short-Form 36, respectively. VAS was positively correlated with intact parathyroid hormone (r (_) +0.322, p (-) 0.001), phosphorus (r- +0.300, p -0.003), alkaline phosphatase (r- +0.275, p = 0.009), and negatively correlated with physical component (r= - 0.320, p 0.002) and mental component summary scores (r = -0.247, p = 0.016). In multivariate linear regression analysis, logVAS was independently associated with serum phosphorus (beta = 0.072, 95% confidence interval: 0.020-0.123, p = 0.007), log intact parathyroid hormone (beta = 0.176, 95% confidence interval: 0.041-0.310, p = 0.011), and physical component summary score (beta = -0.018, 95% confidence interval: -0.031-(-0.005), p - 0.008). VAS is correlated with bone metabolism markers, namely, intact parathyroid hormone, and may be used to assess the intensity of chronic bone pain. The intensity of chronic bone pain is related with HRQoL in hemodialysis patients

Mouse models of spontaneous liver and lung metastasis for colorectal cancer

Summary: To investigate underlying mechanisms for cancer metastasis and promising therapies in animal models, spontaneous metastasis models can be used to recreate metastasis development. Here, we present three mouse models of spontaneous lung and/or liver metastasis induction. We describe steps for cancer cell preparation, mouse analgesia, and three injection techniques (subcutaneous, intracecal, and intramucosal). We then detail procedures for evaluating metastasis. Most of these models generate metastasis in a time span of 4 weeks in the majority of injected mice.For complete details on the use and execution of this protocol, please refer to Giannou et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

A Critical Role of the IL-22–IL-22 Binding Protein Axis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) ranks among the five most common cancer entities worldwide and leads to hundred-thousands of deaths every year. Despite some groundbreaking therapeutical revelations during the last years, the overall prognosis remains poor. Although the immune system fights malignant transformations with a robust anti-tumor response, certain immune mediators have also been shown to promote cancer development. For example, interleukin (IL)-22 has been associated with HCC progression and worsened prognosis in multiple studies. However, the underlying mechanisms of the pathological role of IL-22-signaling as well as the role of its natural antagonist IL-22 binding protein (IL-22BP) in HCC remain elusive. Here, we corroborate the pathogenic role of IL-22 in HCC by taking advantage of two mouse models. Moreover, we observed a protective role of IL-22BP during liver carcinogenesis. While IL-22 was mainly produced by CD4+ T cells in HCC, IL-22BP was abundantly expressed by neutrophils during liver carcinogenesis. Hepatocytes could be identified as a major target of this pathological IL-22-signaling. Moreover, abrogation of IL-22 signaling in hepatocytes in IL22ra1flox/flox × AlbCre+ mice reduced STEAP4 expression-a known oncogene-in HCC in vivo. Likewise, STEAP4 expression correlated with IL22 levels in human HCC samples, but not in healthy liver specimens. In conclusion, these data encourage the development of therapeutical approaches that target the IL-22–IL-22BP axis in HCC

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis

ABSTRACTMetastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis