Vitamin D Status in Chronic Kidney Disease - UVB Irradiation Is Superior to Oral Supplementation

Background: In chronic kidney disease (CKD) a deficiency of 1,25-dihydroxyvitamin D is common. The aim of this review was to compare vitamin D status after oral supplementation of vitamin D₃ to that of serial suberythemal irradiation in end-stage kidney disease (ESKD) patients. Patients and Methods: Ninety-five patients, with a mean age of 62 (range=35-82) years, were treated with a mean dose of 35,000 (20,000–60,000) IU vitamin D₃ per week for a period of 18 months. Fourteen patients, with a mean age of 51 (range=41-57) years, were whole-body UVB irradiated for over 6 months. From 3 hemodialysis patients skin biopsies were performed. Results: With oral supplementation 25(OH)D₃ increased by 60%. With UV irradiation 25(OH)D₃ increased by 400%. Gene expression analysis demonstrated an improvement in the vitamin D receptor (VDR) by 0.65 fold, in 1-alpha-hydroxylase (CYP27B1) by 1.0 fold, and in 25-hydroxylase (CYP2R) by 1.2 fold. Conclusion: Serial suberythemal UVB irradiation of patients with CKD on dialysis is capable to improve serum 25(OH)D₃ and 1,25(OH)₂D₃ by enhancing the skin's ability to activate vitamin D.

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Extracorporeal Photopheresis for Non-skin GvHD

Graft versus host disease (GvHD) is one of the most feared adverse events of allogeneic hematopoietic stem cell transplantation. In severe grades of GvHD patients die from infections due to impairment of their immune defense or therapy-refractory involvement of intestines, liver and lung. Extracorporeal photopheresis is an effective treatment for acute and chronic graft versus host disease without severe impairment of the recipient's immune system. It is generally better known for its effect on skin GvHD but all other manifestations of GvHD can respond as well. Herein we report a brief review of its history and give an overview of the current knowledge of extracorporeal photopheresis in non-skin GvHD.

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Light - Instead of UV Protection: New Requirements for Skin Cancer Prevention

The requirements on sunscreens have essentially changed, since some years ago it was demonstrated that approximately 50% of free radicals, that are formed in the skin by solar radiation, originate from the visible and infrared regions of the solar spectrum. In addition, a critical radical concentration threshold could be found. If this concentration, the free radical threshold value (FRTV), is exceeded, sunburn, immunosuppression and skin cancer may develop. Application of sunscreens and lotions protects against sunburn in the UV region of the solar spectrum and therefore is frequently used to extend people's stay in the sun. However, this behaviour can enhance the concentration of free radicals formed in the visible and infrared regions of the solar spectrum, so that the critical radical threshold is exceeded and the skin may be damaged.

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Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma

Abstract

Carfilzomib (Kyprolis®) is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome (the proteolytic core particle within the 26S proteasome), inducing growth arrest and apoptosis. This intravenous drug is approved in the EU and the USA as combination therapy with oral lenalidomide and intravenous or oral dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In the multinational, phase III ASPIRE study in this patient population, carfilzomib triple combination therapy significantly prolonged progression-free survival (PFS), reflecting a clinically relevant gain in PFS of 8.7 months, compared with lenalidomide plus dexamethasone. Improvements in overall response rate and patients' global health status were also observed with carfilzomib triple combination therapy. A significant improvement in overall survival (OS) is yet to be demonstrated, with the prespecified stopping boundary not crossed at the time of the prespecified interim analysis, although OS data were not mature by the cut-off date. Carfilzomib triple combination therapy had a manageable tolerability profile. The incidences of the most frequently reported grade 3 or higher adverse events of special interest (with the exception of neutropenia, anaemia and thrombocytopenia) were low in both the carfilzomib triple combination therapy and lenalidomide plus dexamethasone groups. Although final OS data are awaited, current evidence suggests carfilzomib in combination with lenalidomide and dexamethasone is a welcome addition to the treatment options currently available for patients with relapsed multiple myeloma.

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HIV Drug to Aid Melanoma Therapies?

Publication date: 14 March 2016
Source:Cancer Cell, Volume 29, Issue 3
Author(s): Hyungsoo Kim, Ze'ev A. Ronai
The HIV1 protease inhibitor nelfinavir is being investigated as a cancer therapeutic. In this issue of Cancer Cell, Smith et al. (2016) report that nelfinavir suppresses MITF expression induced by MAPK pathway inhibition in melanoma cells and sensitizes melanoma cells with NRAS or BRAF plus NRAS mutations to MEK inhibitors.

Teaser

The HIV1 protease inhibitor nelfinavir is being investigated as a cancer therapeutic. In this issue of Cancer Cell, Smith et al. (2016) report that nelfinavir suppresses MITF expression induced by MAPK pathway inhibition in melanoma cells and sensitizes melanoma cells with NRAS or BRAF plus NRAS mutations to MEK inhibitors.


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KLF4 Initiates Acinar Cell Reprogramming and Is Essential for the Early Stages of Pancreatic Carcinogenesis

Publication date: 14 March 2016
Source:Cancer Cell, Volume 29, Issue 3
Author(s): Ravikanth Maddipati, Jonathan P. Katz
Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is minimally responsive to current chemotherapies. In this issue of Cancer Cell, Xie et al. (2016) identify the transcription factor KLF4 as essential for the early stages of pancreatic carcinogenesis, expanding the repertoire of targets for early intervention strategies.

Teaser

Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis and is minimally responsive to current chemotherapies. In this issue of Cancer Cell, Xie et al. (2016) identify the transcription factor KLF4 as essential for the early stages of pancreatic carcinogenesis, expanding the repertoire of targets for early intervention strategies.


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Mammary Ductal Environment Is Necessary for Faithful Maintenance of Estrogen Signaling in ER+ Breast Cancer

Publication date: 14 March 2016
Source:Cancer Cell, Volume 29, Issue 3
Author(s): Svasti Haricharan, Jonathan Lei, Matthew Ellis
In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER⁺ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER⁺ breast cancer cells and in driving the luminal phenotype of breast cancer.

Teaser

In this issue of Cancer Cell, Sflomos et al. (2016) describe a robust preclinical animal model of ER⁺ breast cancer. The authors identify the critical role of the breast microenvironment in determining hormone response of ER⁺ breast cancer cells and in driving the luminal phenotype of breast cancer.


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