Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma

Introduction

Malignant pleural mesothelioma (MPM) has limited treatment options and a poor outcome. Programmed death 1/programmed death ligand 1 (PD-L1) checkpoint inhibitors have proven efficacious in several cancer types. Nivolumab is a fully humanized monoclonal antibody against programmed death 1 with a favorable toxicity profile. In MPM, the immune system is considered to play an important role. We therefore tested nivolumab in recurrent MPM.

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1

Abstract: The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K₁ prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K₁, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K₁. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K₁ were to have a longer duration of effect than intravenous vitamin K₁. This may be because intramuscular vitamin K₁ acts as a depot preparation. The findings suggest that intravenous vitamin K₁ is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K₁ should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.     

Cisplatin rapidly down-regulates its own influx transporter hCTR1 in cultured human ovarian carcinoma cells.

PURPOSE: Cisplatin (DDP)-resistant cells commonly exhibit reduced drug accumulation. Previous studies have shown that the major copper (Cu) influx transporter CTR1 controls the uptake of DDP in yeast and mammalian cells. The goal of this study was to examine the effect of Cu and DDP on the level and subcellular localization of hCTR1 protein in human ovarian carcinoma cells. EXPERIMENTAL DESIGN: Cultured human ovarian carcinoma A2780 cells were exposed to DDP and Cu, and the effect on hCTR1 was determined using Western blot analysis and confocal digital deconvolution microscopy. RESULTS: Loss of hCTR1 was triggered by DDP exposure in a concentration and time-dependent manner. Exposure to 0.5 micromol/L DDP for 5 minutes reduced hCTR1 levels and exposure to DDP concentrations > or =2 micromol/L caused almost complete disappearance. The loss of hCTR1 was observed within 1 minute of the start of exposure to 2 micromol/L DDP. Treatment of cells with 100 micromol/L Cu for 5 minutes produced a smaller effect. Pretreatment of cells with 2 micromol/L DDP for 5 minutes resulted in a 50% decrease in 64Cu uptake, demonstrating that the DDP-induced loss of hCTR1 detected by Western blot analysis and imaging was functionally significant. CONCLUSIONS: DDP down-regulated the amount of its major influx transporter in cultured human ovarian carcinoma cells in a concentration- and time-dependent manner. The effect was observed at DDP concentrations within the range found in the plasma of patients being treated with DDP, and it occurred very quickly relative to the half-life of the drug.     

Fast acquisition-weighted three-dimensional proton MR spectroscopic imaging of the human prostate.

The clinical application of 3D proton spectroscopic imaging (3D SI) of the human prostate requires a robust suppression of periprostatic lipid signal contamination, minimal intervoxel signal contamination, and the shortest possible measurement time. In this work, a weighted elliptical sampling of k-space, combined with k-space filtering and pulse repetition time (TR) reduction minimized lipid signals, intervoxel contamination, and measurement time. At 1.5 T, the MR-visible prostate metabolites citrate, creatine, and choline can now be mapped over the entire human prostate with uncontaminated spherical voxels, with a volume down to 0.37 cm3, in measurement times of 7-15 min.     

Optimal timing for in vivo 1H-MR spectroscopic imaging of the human prostate at 3T.

Proton MR spectroscopic imaging ((1)H-MRSI) of the human prostate, which has an interesting clinical potential, may be improved by increasing the magnetic field strength from 1.5T to 3T. Both theoretical and practical considerations are necessary to optimize the pulse timing for spectroscopic imaging of the human prostate at 3T. For in vivo detection of the strongly coupled spin system of citrate, not only should the spectral shape of the signal be easy to identify, but the timing used should produce MR signals at reasonably short echo times (TEs). In this study the spectral shape of the methylene protons of citrate was simulated with density matrix calculations and checked with phantom measurements. Different calculated optimal spectral shapes were measured in patients with prostate cancer with a 2D spectroscopic imaging sequence. T(1) and T(2) relaxation times were calculated for citrate and choline, the two major metabolites of interest in the prostate. We conclude that the optimum timing for in vivo point-resolved spectroscopy (PRESS) imaging at 3T is an interpulse timing sequence of 90 degrees-25 ms-180 degrees- 37.5 ms-180 degrees-12.5 ms-echo. A short repetition time (TR) of 750 ms partially saturates choline signals, but increases the SNR per unit time for citrate, and accommodates a maximum number of weighted averages of an elliptically sampled k-space for accurate localization and minimal contamination of the individual spectra. This is illustrated by means of a 3D spectroscopic imaging experiment in a complete prostate in vivo.     

表现为Krukenberg瘤的胰腺癌卵巢转移1例

继发于胃肠道癌的卵巢转移性癌称作Krukenberg瘤,而表现为Krukenberg瘤的胰腺癌卵巢转移病例尚属罕见,本文报道1例表现为Krukenberg瘤的胰腺癌卵巢转移病例.