Purpose: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a firstin-class small activating RNA oligonucleotide drug which up-regulates C/EBP-α. Experimental Design:We conducted a phase I, open label, dose escalation trial of MTL-CEBPA in adults with advanced HCC with cirrhosis, or resulting from non-alcoholic steatohepatitis (NASH) or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose escalation phase (3+3 design).Results: 38 participants have been treated across 6 dose levels (28-160 mg/m2) and 3 dosing schedules. 34 patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatmentrelated adverse events were not associated with dose and no maximum dose was reached across the 3 schedules evaluated. Grade 3 treatment related adverse events occurred in 9 (24%) patients. In 24 HCC patients evaluable for efficacy, an objective tumour response was achieved in 1 patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKI); 3 patients had a complete response with one further PR and two with SD.Conclusions: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging Phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.Funding: This study was funded by MiNA Therapeutics. ClinicalTrials.gov ID: NCT02716012 Statement of translational relevancePreclinical data have emerged suggesting C/EBP-a effects on the tumour microenvironment through myeloid derived suppressor cells could enhance response to sorafenib. The data from this trial provide preliminary validation for targeting C/EBP-a in patients with advanced HCC, particularly in context of sequential administration with TKIs and provide a rationale for combining MTL-CEBPA with TKIs.

Ex situ conservation of threatened terrestrial orchids requires the simultaneous conservation of their mycorrhizal associations. A method for encapsulating both seed and fungi in alginate beads (known as encapsulation–dehydration) was applied to the storage and propagation of two endangered orchid species in NSW, Australia—Pterostylis saxicola D.L.Jones & M.A.Clem. and Diuris arenaria D.L.Jones. We tested the effect of storage duration and temperature on fungal recovery and germination potential in vitro, and recorded survival for seedlings subsequently transferred to potting mix. Storage at 23°C significantly reduced fungal recovery and germination for both species after only 3 months (P < 0.05), whereas storage at 4°C significantly reduced fungal recovery for P. saxicola after 6 months (P < 0.05). Storage for 6 months at −18 and −196°C had no significant effect on the fungal recovery and germination percentages of either species. All beads transferred directly from in vitro culture to potting mix resulted in the establishment of at least one seedling, and production of a healthy tuberoid, when transferred near the commencement of the natural growing season. The encapsulation–dehydration method may have a practical application for use in ex situ conservation of other terrestrial orchids, as well as their mycorrhizal fungi.

Patients with moderate to severe asthma who receive intravenous methylprednisolone in the prehospital setting have significantly fewer hospital admissions.

Antisera to a number of synthetic peptides predicted from nucleic acid sequences of oncogenes have been used to screen 483 urine samples of cancer patients, pregnant women, and normal controls for the presence of immunologically related proteins. Increased levels of oncogene-related proteins are found during neoplasia and pregnancy. The differential detection of these oncogene-related proteins indicates that panels of monoclonal antibodies may provide a convenient noninvasive means of detecting, classifying, and staging a wide variety of malignancies and may be useful in following fetal development during pregnancy.