Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression.

Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late-stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted HGF facilitates HNSCC progression; however, very little is known about the role of CAFs in HNSCC metabolism. Here, we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis. CAF-secreted HGF induced basic FGF (bFGF) secretion from HNSCC. CAFs were more efficient than HNSCC in using lactate as a carbon source. HNSCC-secreted bFGF increased mitochondrial oxidative phosphorylation and HGF secretion from CAFs. Combined inhibition of c-Met and FGFR significantly inhibited CAF-induced HNSCC growth in vitro and in vivo (P < 0.001). Our cumulative findings underscore reciprocal signaling between CAF and HNSCC involving bFGF and HGF. This contributes to metabolic symbiosis and a targetable therapeutic axis involving c-Met and FGFR.Significance: HNSCC cancer cells and CAFs have a metabolic relationship where CAFs secrete HGF to induce a glycolytic switch in HNSCC cells and HNSCC cells secrete bFGF to promote lactate consumption by CAFs. Cancer Res; 78(14); 3769-82. ©2018 AACR.

Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has had little improvement in mortality rates in decades. A clearer understanding of the HNSCC tumor microenvironment will aid in finding more effective targeted therapies for this disease. Tumor-associated fibroblasts (TAFs) are the largest stromal cellular components of the tumor microenvironment in HNSCC. METHODS: We isolated TAFs from clinical HNSCC cases and propagated in vitro. The effects of TAF-secreted paracrine factors on in vitro HNSCC migration, invasion, and proliferation was assessed. The effect of TAFs on HNSCC growth and metastases was determined in an orthotopic floor-of-the-mouth tumor model. RESULTS: TAF-conditioned media increased HNSCC cell migration, invasion, and proliferation. TAFs increased HNSCC tumor growth and metastases in vivo. CONCLUSION: TAFs play a major role in increasing tumor growth and metastasis in HNSCC. Targeting the tumor stroma may be important to reduce the rate of HNSCC metastasis.

Hazardous workplace review program in Taiwan.

In Taiwan, relevant mid-term plans and projects of mitigating occupational hazards have been launched in recent years in the hopes of lowering the incidence of occupational hazards. In light of the lack of objective methodologies for researches on issues pertaining occupational safety and health, this research aims to explore the priorities of safety and health issues through focal groups, expert questionnaires and interviews on relevant issues such as hazard installations identified in R181 Prevention of Major Industrial Accidents Recommendation, 1993 proposed during the 18th World Congress on Safety and Health at work in Seoul 2008. Results revealed that distribute reports of major domestic/foreign occupational disasters to relevant sectors for the prevention of major accidents is needed, both from the importance and feasibility analysis. It is the only topic that scored over 4 points in average for expert and focal group consensus. Furthermore, the experts and focal groups came to consensus in the ranking of priority for 4 items, namely: 1) Installations containing/using large quantities of hazardous materials should be prioritized for inspection, 2) Incorporation of hazard installation review/inspection into OSH management system accreditation, 3) Impose operation shutdown as a means of penalty) and 4) Prioritize the promotion of preliminary PHA.

Organisational support, organisational identification and organisational citizenship behaviour among male nurses.

AIMS: The purpose of this study was to explore the relationship between organisational support, organisational identification, and organisational citizenship behaviour and the predictors of organisational citizenship behaviour in Taiwanese male nurses. BACKGROUND: The turnover rate among male nurses is twice that of female nurses. Organisational citizenship behaviour is the predictor of turnover intention. Little information is available on the relationship between organisational support, organisational identification and organisational citizenship behaviour, particularly for male nurses. METHODS: Data were collected in 2010 from a questionnaire mailed to 167 male nurses in Taiwan. A cross-sectional survey with simple sampling was used in this study. RESULTS: The results showed that organisational identification and organisational support were correlated with organisational citizenship behaviour. Organisational distinctiveness, organisational support of work conditions and the type of organisation were the main predictors of organisational citizenship behaviour. Together they accounted for 40.7% of the total variation in organisational citizenship behaviour. Organisational distinctiveness was the most critical predictor, accounting for 29.6% of the variation. CONCLUSION: Organisational support and organisational identification have positive relationships with organisational behaviour. Organisational distinctiveness is an important factor in explaining organisational citizenship behaviour in male nurses. IMPLICATIONS FOR NURSING MANAGEMENT: This finding provides concrete directions for managers to follow when providing organisational identification, in particular, the organisational distinctiveness will help male nurses to display increasingly more organisational citizenship behaviour.