Restitution of lost tumor-suppressor activities may be a promising strategy to target specifically cancer cells. However, the action of ectopically expressed tumor-suppressor genes depends on genetic background of tumoral cells. Ectopic expression of p16 INK4a induces either cell cycle arrest or apoptosis in different pancreatic cancer cell lines. We examined the molecular mechanisms mediating these two different cellular responses to p16 overexpression. Ectopic expression of p16 leads to G1 arrest in NP-9 cells by redistributing p21/p27 CKIs and inhibiting cyclin-dependent kinase CDK2 activity. In contrast, in NP-18 cells cyclin E (CycE)/ CDK2 activity is significantly higher and is not downregulated by p16-mediated redistribution of p21/p27. Moreover, inhibition of CDK4 activity with fascaplysine, which does not affect CycE/ CDK2 activity, reduces pocket protein phosphorylation in both cell lines, but fails to induce growth arrest. Like overexpression of p16, fascaplysine induces apoptosis in NP-18 cells, suggesting that inhibition of D-type cyclin/CDK activity in cells with high levels of CycE/CDK2 activity activates an apoptotic pathway. Inhibition of CycE/CDK2 activity via ectopic expression of p21 in NP-18 cells overexpressing p16 induces growth arrest and prevents p16-mediated apoptosis. Accordingly, silencing of p21 expression by using small interfering RNA switches the fate of p16-expressing NP-9 cells from cell cycle arrest to apoptosis. Our data suggest that, after CDK4/6 inactivation, the fate of pancreatic tumor cells depends on the ability to modulate CDK2 activity.
(1) Background: Most common hereditary cancers in Europe have been associated with lifestyle behaviors, and people affected are lacking follow up care. However, access to education programmes to increase knowledge on cancer and genetics and promote healthy lifestyle behaviors in people at high risk of cancer is scarce. This affects the quality of care of people with a hereditary risk of cancer. This study aimed to reach a multidisciplinary consensus on topics and competencies and competencies that cancer nurses need in relation to cancer, genetics, and health promotion. (2) Methods: A two-round online Delphi study was undertaken. Experts in cancer and genetics were asked to assess the relevance of eighteen items and to suggest additional terms. Consensus was defined as an overall agreement of at least 75%. (3) Results: A total of 74 multiprofessional experts from all around the world participated in this study including healthcare professionals working in genetics (39%), researchers in cancer and genetics (31%) and healthcare professionals with cancer patients (30%). Thirteen additional items were proposed. A total of thirty-one items reached consensus. (4) Conclusions: This multidisciplinary consensus study provide the essential elements to build an educational programme to increase cancer nurses’ skills to support the complex care of people living with a higher risk of cancer including addressing lifestyle behaviors. All professionals highlighted the importance of cancer nurses increasing their skills in cancer and genetics.
The Global Power of Oncology Nursing held their 3rd annual conference on 'Celebrating Oncology Nursing: From Adversity to Opportunity'. The conference, held virtually, addressed three major nursing challenges: health workforce and migration, climate change and cancer nursing within humanitarian settings. Around the world, nurses are working in situations of adversity, whether due to the ongoing pandemic, humanitarian crises such as war or floods, shortage of nurses and other health workers, and high clinical demands leading to overwork, stress and burnout. The conference was held in two parts in order to take into account different time zones. Three hundred and fifty participants attended from 46 countries, with part of the conference being held in both English and Spanish. It was an opportunity for oncology nurses around the world to share their experiences and the realities for their patients seeking care and their families. The conference took the form of panel discussions, videos, and individual presentations from all six WHO regions and highlighted the importance of oncology nurses role in expanding beyond caring for individuals and their families, to tackle wider issues, such as nurse migration, climate change and care within humanitarian settings.
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