Cancer relapse occurs with substantial frequency even after treatment with curative intent. Here we studied drug-tolerant colonies (DTCs), which are subpopulations of cancer cells that survive in the presence of drugs. Proteomic characterization of DTCs identified stemness- and epithelial-dominant subpopulations, but functional screening suggested that DTC formation was regulated at the transcriptional level independent from protein expression patterns. We consistently found that α-amanitin, an RNA polymerase II (RNAPII) inhibitor, effectively inhibited DTCs by suppressing TAF15 expression, which binds to RNA to modulate transcription and RNA processing. Sequential administration of α-amanitin and cisplatin extended overall survival in a cancer-relapse mouse model, namely peritonitis carcinomatosa. Therefore, post-treatment cancer relapse may occur through non-distinct subpopulations and may be effectively prevented by α-amanitin to disrupt transcriptional machinery, including TAF15.

The favorable outcome of H. pylori-positive patients implies that the host immune system is modulated by H. pylori enhancing the chemotherapeutic efficacy.

Drug-tolerant cancer cell subpopulations are responsible for relapse after chemotherapy. By continuously exposing the gastric cancer cell line MKN45 to 5-FU for >100 passages, we established a 5-fluorouracil (5-FU)-tolerant line, MKN45/5FU. Orthotopic xenografts of MKN45/5FU cells in the stomach of nude mice revealed that these cells had a high potential to metastasize to sites such as the liver. Levels of phosphorylated phosphatidylinositide 3-kinase (PI3K) increased both in 5-FU-tolerant subpopulations according to the 5-FU dose, and in gastric submucosal orthotopic xenografts of MKN45/5FU cells. Sequential administration of 5-FU and a PI3K inhibitor, GDC-0941, targeted the downstream ribosomal S6 kinase phosphorylation to significantly suppress 5-FU-tolerant subpopulations and tumor propagation of orthotopic MKN45/5FU xenografts. These results suggest that administration of 5-FU followed by GDC-0941 may suppress disease relapse after 5-FU-based gastric cancer chemotherapy.

Background: Postoperative adjuvant chemotherapy is not indicated for T1N1M0/ T2N0M0/T3N0M0 gastric cancer. However, approximately 10% to 30% of these patients experience recurrence and metastasis.Methods: Among 658 patients with gastric cancer who received gastrectomy with curative intent, 130 T1N1M0/T2N0M0 and 73 T3N0M0 patients were enrolled.Overall survival (OS) and relapse-free survival (RFS) were analyzed based on TP53 codon 72 polymorphisms Arg/Arg, Arg/Pro, and Pro/Pro. The hazard ratio (HR) for each subgroup was compared by TP53 codon 72 polymorphisms.Results: Of the 189 patients for whom polymorphism analysis results were available, the 5-and 10-year OS was 84.9% and 65.1%, respectively. The 5-and 10-year RFS was 81.8% and 65.4%, respectively. When the study cohort was divided into two groups according to polymorphism status (ie, "Arg/Arg and Arg/Pro" vs Pro/Pro), both the OS (HR, 2.799; 95% confidence interval [CI], 1.071-7.315; P = .036) and RFS (HR, 2.639; 95% CI, 1.025-6.794; P = .044) of the Pro/Pro group were significantly lower than those for the Arg/Arg and Arg/Pro groups across the entire observation period. Conclusions:The TP53 codon 72 Pro/Pro polymorphism may isolate a relatively high-risk patient group in T1N1M0/T2N0M0/T3N0M0 gastric cancer. K E Y W O R D S gastric cancer, postoperative adjuvant chemotherapy, T1N1M0/T2N0M0/T3N0M0, TP53 codon 72 polymorphism Members of Northern Gastric Cancer Study Consortium:

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematological malignancy with aggressive clinical course and poor prognosis. 1 The incidence of BPDCN is higher in elderly people, but therapeutic approaches for this population have not been fully established. We report the case of an elderly patient with progressive BPDCN successfully controlled by local electron beam therapy (EBT) and medium-dose systemic prednisolone, and present a review of the literature.An 87-year-old Japanese woman presented with a 3-week history of rapidly growing nodules on her face.Physical examination revealed multiple, dark reddish-purple nodules on her right temporal area, and haemorrhagic and indurated plaques spreading from her right temporal area to her mandible (Fig. 1a). Both the nodules and plaques were ulcerated and severely painful, with the pain uncontrolled by nonsteroidal anti-inflammatory drugs.Laboratory investigation detected elevation of monocytes (20%; normal range 2-8%) and atypical lymphocytes (12%; normal range 0%) with normal white blood count. Normocytic anaemia was observed (haemoglobin 8.5 g/dL, mean corpuscular volume 84.0 fL). Chest radiography and enhanced computed tomography scans were unremarkable.