The cytotoxicity and synergistic potential of aspirin and aspirin analogues towards oesophageal and colorectal cancer

Background: Oesophageal cancer (OC) is a deadly cancer because of its aggressive nature with survival rates that have barely improved in decades. Epidemiologic studies have shown that low-dose daily intake of aspirin can decrease the incidence of OC. Methods: The toxicity of aspirin and aspirin derivatives to OC and a colorectal cancer (CRC) cell line were investigated in the presence and absence of platins. Results: The data in this study show the effects of a number of aspirin analogues and aspirin on OC cell lines that originally presented as squamous cell carcinoma (SSC) and adenocarcinoma (ADC). The aspirin analogues fumaryldiaspirin (PN517) and the benzoylsalicylates (PN524, PN528 and PN529), were observed to be more toxic against the OC cell lines than aspirin. Both quantitative and qualitative apoptosis experiments reveal that these compounds largely induce apoptosis, although some necrosis was evident with PN528 and PN529. Failure to recover following the treatment with these analogues emphasized that these drugs are largely cytotoxic in nature. The OE21 (SSC) and OE33 (ADC) cell lines were more sensitive to the aspirin analogues compared to the Flo-1 cell line (ADC). A non-cancerous oesophageal primary cells NOK2101, was used to determine the specificity of the aspirin analogues and cytotoxicity assays revealed that analogues PN528 and PN529 were selectively toxic to cancer cell lines, whereas PN508, PN517 and PN524 also induced cell death in NOK2101. In combination index testing synergistic interactions of the most promising compounds, including aspirin, with cisplatin, oxaliplatin and carboplatin against the OE33 cell line and the SW480 CRC cell line were investigated. Compounds PN517 and PN524, and to a lesser extent PN528, synergised with cisplatin against OE33 cells. Cisplatin and oxaliplatin synergised with aspirin and PN517 when tested against the SW480 cell line. Conclusion: These findings indicate the potential and limitations of aspirin and aspirin analogues as chemotherapeutic agents against OC and CRC when combined with platins

Motivating factors towards willingness to contribute in collaborative tasks: A crisis cooperation perspective

The interaction among various stakeholder organizations in modern crisis response is very similar to negotiation where each organization has its own goal in addition to a common goal. Decision makers in stakeholder organizations most often have to settle for win-win situations to attain higher joint benefit. In such cases willingness to contribute in joint tasks becomes a prerequisite. In our present study performed with 111 crisis management professionals from various stakeholder organizations in decision making roles, we study familiarity and expectation to future cooperation as constructs that can motivate decision makers to be more willing to contribute to joint tasks in crisis response

Temporal differences in the expression of messenger-RNA for IL-10 and IFN-gamma in the brains and spleens of C57BL/10 mice infected with Toxoplasma gondii

C57BL/10 Sc Sn (B10) mice infected orally with Toxoplasma gondii tissue cysts were killed at regular intervals up to day 116 post infection (p.i.) and their brains excised. These were used either to count the total number of cysts in the brain, for RNA purification or histopathological studies. Mortality levels in a parallel group of T. gondii infected B10 mice were also monitored and regular plasma samples taken to measure specific antibody production. Seventy per cent of mice died within the first 35 days of infection. Thereafter deaths were infrequent. Inflammation in the brain was apparent from day 10 onwards and by day 25 there was widespread astrocyte activation, perivascular cuffing, meningitis and extensive encephalitis. Total cyst numbers increased rapidly from day 15 to day 35 when they peaked. By day 60, however, cyst numbers had dropped dramatically and this decrease continued through to day 116. Using the polymerase chain reaction mRNA transcripts for IFN-gamma were detected from the first time point sampled, day 25 p.i., until the end of the study. Transcripts for IL-10, an inhibitor of IFN-gamma production, release and activity, were not detected until day 70. The predominant antibody detected against T. gondii was IgG2a but not IgG1. Significantly transcripts for IFN-gamma were found in the spleens of infected but not non-infected animals. Our results suggest that an inflammatory response associated with IFN-gamma production in B10 mice eventually controls T. gondii infection. After the cyst burden has dropped dramatically transcripts for IL-10 are detected in the brain, perhaps to suppress inflammation, and limit pathology