Pancreatic cancer is characterized by an intense stromal reaction. Reproducible three-dimensional in vitro systems for exploring interactions of the stroma with pancreatic cancer cells have not previously been available, prompting us to develop such a model. Cancer cells were grown on collagen/Matrigel and embedded with or without stromal cells (hTERT-immortalized human PS-1 stellate cells or MRC-5 fibroblasts) for 7 days. Proliferation and apoptosis, as well as important cell-cell adhesion and cytoskeleton-regulating proteins, were studied. PS-1 cells were confirmed as stellate based on the expression of key cytoskeletal proteins and lipid vesicles. Capan-1, and to a lesser extent PaCa-3, cells differentiated into luminal structures, exhibiting a central apoptotic core with a proliferating peripheral rim and an apico-basal polarity. Presence of either stromal cell type translocated Ezrin from apical (when stromal cells were absent) to basal aspects of cancer cells, where it was associated with invasive activity. Interestingly, the presence of 'normal' (not tumor-derived) stromal cells induced total tumor cell number reduction (P < 0.005) associated with a significant decrease in Ecadherin expression (P < 0.005). Conversely, ␤-catenin expression was up-regulated (P < 0.01) in the presence of stromal cells with predominant cytoplasmic expression. Moreover , patient samples confirmed that these data recapitulated the clinical situation. In conclusion , pancreatic organotypic culture offers a reproducible, bio-mimetic, three-dimensional in vitro model that allows examination of the interactions between stromal elements and pancreatic cancer cells.

Podosomes and their rosettes are driven by ezrin-cortactin interaction and this plays a role in pancreatic cancer invasion.

No abstract

Retinoic acid has the ability to induce differentiation in some myeloid leukaemia cell lines and has been used to induce remission in acute promyelocytic leukaemia patients. We have analysed changes in gene expression, by differential display, in HL60 cells exposed to all-trans retinoic acid (ATRA) for only 1 h. Only about 0.4% of the genes examined by this technique showed changes in expression level, and all four of the gene fragments identified were downregulated during the short 1 h exposure. Two of the fragments were novel, a third was MYC and the fourth was the FUS proto-oncogene. Northern analysis showed that FUS was downregulated within 1 h only during induced neutrophil differentiation but not at all during induced monocyte differentiation. Unlike the sensitive cell lines, ATRA-resistant cell lines did not show a downregulation of FUS over a 24 h period of exposure to ATRA. Using a semiquantitative PCR analysis, no difference in FUS levels was observed between ATRA-sensitive and -resistant cell lines. A similar analysis was carried out on primary acute myeloid leukaemia (AML), peripheral stem cell harvests (PBSC) and cord blood samples. The PBSC and cord blood samples had FUS levels that were similar or generally less than the cell lines. However, much higher levels were seen in 63% of the AML samples examined. The data presented are consistent with previous reports for a role for FUS in the promotion and maintenance of cellular proliferation.

Introduction Asthma is the most common respiratory disease worldwide. In Saudi Arabia, asthma is considered as a major public health concern and has a negative impact in the life of patients, their families, and the community, including lost days of work, absence from school, and poor quality of life, which can eventually lead to frequent emergency department visits, hospitalizations, and sometimes, to death. Thus, the objectives of this study were to evaluate asthma control status among asthmatic patients in primary health care centers (PHCCs) in Makkah, Saudi Arabia and to identify factors associated with poor asthma control. Methods This was a cross-sectional study conducted from March to May 2016 in selected PHCCs in Makkah, Saudi Arabia. Data was collected from five PHCCs which were selected using a stratified random sample technique from a total of 47 PHCCs to represent the different geographic regions of the city. The 167 asthmatic patients, aged four years and above, presented during the study period were included. Each respondent completed two tools: the first is a self-administrated questionnaire and the second is the asthma control test. Statistical analyses were performed with SPSS version 21 software (IBM Corp, Armonk, USA). Qualitative variables were analyzed with the Chi-square test or Fisher's exact test as appropriate. Results Around one-third (34.1%) of all asthmatic patients were categorized as having uncontrolled asthma and about one-quarter (24.6%) were partially controlled asthma. Dust (91.6%), exposure to incense, detergent and essence (86.8%), common cold (82%) and cold weather (79.6%) were the factors that trigger or exacerbate asthma attacks. Physical activity/exercise and cold weather were the commonest factors that significantly exacerbate asthma attacks particularly among children and were mostly uncontrolled. More than one-third (36.5%) of the asthmatic patients in the PHCCs were cared for by general practitioners. Conclusion Poor asthma control was observed in a high proportion of asthmatic children, adolescents and adults in the Makkah region and they were mostly from non-specialized PHCCs. The poor asthma control among the respondents affects their quality of sleep (i.e., frequent awakening at night), recurrent absences from work and school, increased hospitalizations, emergency and unscheduled visits to the hospital.