A tumour-resident Lgr5+ stem-cell-like pool drives the establishment and progression of advanced gastric cancers.

Gastric cancer is among the most prevalent and deadliest of cancers globally. To derive mechanistic insight into the pathways governing this disease, we generated a Claudin18-IRES-CreERT2 allele to selectively drive conditional dysregulation of the Wnt, Receptor Tyrosine Kinase and Trp53 pathways within the gastric epithelium. This resulted in highly reproducible metastatic, chromosomal-instable-type gastric cancer. In parallel, we developed orthotopic cancer organoid transplantation models to evaluate tumour-resident Lgr5+ populations as functional cancer stem cells via in vivo ablation. We show that Cldn18 tumours accurately recapitulate advanced human gastric cancer in terms of disease morphology, aberrant gene expression, molecular markers and sites of distant metastases. Importantly, we establish that tumour-resident Lgr5+ stem-like cells are critical to the initiation and maintenance of tumour burden and are obligatory for the establishment of metastases. These models will be invaluable for deriving clinically relevant mechanistic insights into cancer progression and as preclinical models for evaluating therapeutic targets.

A 10-year journey in sustaining fall reduction in an academic medical center in Singapore.

BACKGROUND: The incidence rate of falls at 1.3 falls/1000 patient-days at a tertiary hospital in 2004 was found to be high when benchmarked against other hospitals' fall rates in Singapore. This marked the starting point of a journey of reducing fall incidence by successfully combining evidence-based healthcare measures with quality-improvement strategies. AIM: The aim of this project was to implement fall-reduction strategies in the inpatient care areas in an acute care tertiary hospital. METHODS: Two action research studies commissioned for ascertaining an appropriate fall-risk assessment and effectiveness of targeted individualized interventions formed the foundation of fall-reduction strategies. Evidence-based healthcare measures were combined with quality-improvement strategies that addressed fall risks to prevent falls and mitigate injuries. The process of managing fall-related incidents was standardized as the fall rate continues to be a key nursing performance indicator. RESULTS: The overall fall trend decreased from 1.09/1000 patient-days in 2008 to 0.82/1000 patient-days in 2012. The decreasing trends were sustained in 2013 and 2014 at 0.91/100 and 0.85/1000, respectively. The fall injury rate reduced from 0.31/1000 patient-days in 2008 and was maintained at a rate of 0.20-0.24 during 2009-2012. CONCLUSION: The implementation of fall-reduction strategies reduced the fall incidence rate in this acute care setting. However, more work is required to ensure the changes made to the fall assessment, interventions, and processes are sustained and incorporated in patient care.

[Effect of liu wei di huang or jin gui shen qi decoction as on adjuvant treatment in small cell lung cancer].

Eighty-three patients with small cell lung cancer were randomized with or without using a traditional Chinese Kidney-tonifying decoction (Liu Wei Di Huang or Jin Gui Shen Qi medicinal decoction) in chemotherapy or radiotherapy courses. 74 patients were availble to be analysis. The two treatment groups were well-matched in age, sex, stage and performance status. There was a statistically significant difference in response rate and the median survival between two groups. The overall response rate (CR+PR) was 91.5% for Chinese herb group and 46.9% for control group (P less than 0.001). The median survival was 16 months for the traditional Chinese Kidney-tonifying decoction group, and 10 months for the control group (P less than 0.05). Survival curve (Kaplan-meire's) of the Chinese herb group was better than that of the control group. 10 patients of Chinese herb group was alive beyond more than 2 years. Until now, 4 patients in the Chinese herb group, one in the control group are still enjoying their disease-free life for more than 7 years. Hematologic toxicities were observed much frequently in the patients of the control group (P less than 0.005 and 0.01/WBC and BPC). Results of animal experiments with the same traditional medicinal decoctions as used in clinic have showed immuno-enhancement activities. These results have showed that the traditional Chinese Kidney-tonifying decoction may enhance non-specific immunology activities and may be much useful for solid cancer patients as an adjuvant treatment.