Acetate drives ovarian cancer quiescence via ACSS2-mediated acetyl-CoA production.

Quiescence is a reversible cell cycle exit traditionally thought to be associated with a metabolically inactive state. Recent work in muscle cells indicates that metabolic reprogramming is associated with quiescence. Whether metabolic changes occur in cancer to drive quiescence is unclear. Using a multi-omics approach, we found that the metabolic enzyme ACSS2, which converts acetate into acetyl-CoA, is both highly upregulated in quiescent ovarian cancer cells and required for their survival. Indeed, quiescent ovarian cancer cells have increased levels of acetate-derived acetyl-CoA, confirming increased ACSS2 activity in these cells. Furthermore, either inducing ACSS2 expression or supplementing cells with acetate was sufficient to induce a reversible quiescent cell cycle exit. RNA-Seq of acetate treated cells confirmed negative enrichment in multiple cell cycle pathways as well as enrichment of genes in a published G0 gene signature. Finally, analysis of patient data showed that ACSS2 expression is upregulated in tumor cells from ascites, which are thought to be more quiescent, compared to matched primary tumors. Additionally, high ACSS2 expression is associated with platinum resistance and worse outcomes. Together, this study points to a previously unrecognized ACSS2-mediated metabolic reprogramming that drives quiescence in ovarian cancer. As chemotherapies to treat ovarian cancer, such as platinum, have increased efficacy in highly proliferative cells, our data give rise to the intriguing question that metabolically-driven quiescence may affect therapeutic response.

New section and species in Talaromyces.

Talaromyces is a monophyletic genus containing seven sections. The number of species in Talaromyces grows rapidly due to reliable and complete sequence data contributed from all over the world. In this study agricultural soil samples from Fujiang, Guangdong, Jiangxi, Shandong, Tibet and Zhejiang provinces of China were collected and analyzed for fungal diversity. Based on a polyphasic approach including phylogenetic analysis of partial ITS, BenA, CaM and RPB2 gene sequences, macro- and micro-morphological analyses, six of them could not be assigned to any described species, and one cannot be assigned to any known sections. Morphological characters as well as their phylogenetic relationship with other Talaromyces species are presented for these putative new species. Penicillium resedanum is combined in Talaromyces section Subinflati as T. resedanus.

Early referral for endoscopy is the most appropriate management strategy in cases of food bolus obstruction.

OBJECTIVE: To investigate the characteristics of patients presenting with oesophageal food bolus obstruction (FBO) who achieve early resolution of symptoms, and to assess the impact of medical therapies on the overall time course of FBO. METHODS: A retrospective observational study was performed in a university teaching hospital with regional acute endoscopy services. Patients presenting with symptoms of FBO were identified through clinical coding and demographic, clinical and endoscopic data extracted from the electronic medical record. The primary outcome was the time to resolution defined as the earliest of symptom resolution, endoscopic or surgical intervention or discharge. RESULTS: A total of 116 patients presented with symptoms of FBO. Twenty-seven (23.3%) had early resolution of symptoms and were discharged from the ED without acute endoscopy, the remainder were admitted for further management. Patients discharged from the ED presented to hospital sooner after the onset of symptoms (137 vs 288 min, P < 0.05), but did not differ from those admitted in any other characteristic. Seventy-one (61.2%) patients received medical therapy. There was no statistical difference in the time to resolution between those who received medical therapy and those who did not. Furthermore, the use of medical therapy was associated with a delay in referral for endoscopy (140 vs 100 min, P < 0.05). CONCLUSIONS: Time from symptom onset to presentation is the only predictor of early resolution from FBO, while medical therapy is ineffective in relieving obstruction and may delay definitive therapy. We recommend the use of an institutional management plan to facilitate early access to endoscopy in cases of FBO.