Bortezomib therapy-related lung disease in Japanese patients with multiple myeloma: incidence, mortality and clinical characterization.

Because of the potentially high mortality rate (6.5%) associated with bortezomib-induced lung disease (BILD) in Japanese patients with relapsed or refractory multiple myeloma, we evaluated the incidence, mortality and clinical features of BILD in a Japanese population. This study was conducted under the Risk Minimization Action Plan (RMAP), which was collaboratively developed by the pharmaceutical industry and public health authority. The RMAP consisted of an intensive dissemination of risk information and a recommended countermeasure to health-care professionals. All patients treated with bortezomib were consecutively registered in the study within 1 year and monitored for emerging BILD. Of the 1010 patients registered, 45 (4.5%) developed BILD, 5 (0.50%) of whom had fatal cases. The median time to BILD onset from the first bortezomib dose was 14.5 days, and most of the patients responded well to corticosteroid therapy. A retrospective review by the Lung Injury Medical Expert Panel revealed that the types with capillary leak syndrome and hypoxia without infiltrative shadows were uniquely and frequently observed in patients with BILD compared with those with conditions associated with other molecular-targeted anticancer drugs. The incidence rate of BILD in Japan remains high compared with that reported in other countries, but the incidence and mortality rates are lower than expected before the introduction of bortezomib in Japan. This study describes the radiographic pattern and clinical characterization of BILD in the Japanese population. The RMAP seemed clinically effective in minimizing the BILD risk among our Japanese population.

Molecular cloning and expression analysis of the aryl hydrocarbon receptor of Xenopus laevis.

The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors. Although this receptor has been known to mediate the toxic effects of environmental pollutants, its physiological functions remain elusive. Here, we describe the isolation and expression pattern of the Xenopus AHR gene. The predicted amino acid sequence contained regions characteristic of other vertebrate AHRs. However, in line with previously described fish AHR genes, no distinct Q-rich domain was found. Phylogenetic analysis demonstrated that Xenopus AHR was clustered within the AHR1 clade. As in the case of mammalian AHR genes, the Xenopus AHR gene was expressed in all the adult tissues tested. Xenopus AHR was also expressed during early development, in parallel with expression of the CYP1A7 gene, which is thought to be regulated by AHR. These results suggest that while frogs are relatively tolerant to TCDD toxicity, the AHR of frogs has characteristics similar to those of other vertebrate AHRs.