Epithelial-to-mesenchymal transition (EMT) in intraductal papillary mucinous neoplasm (IPMN) is associated with high tumor grade and adverse outcomes.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is generally associated with increased tumor aggressiveness and poor prognosis. We evaluated EMT characteristics in intraductal papillary mucinous neoplasm (IPMN) tumor specimens and their potential role as biomarkers for malignancy, metastasis, and adverse patient outcomes. METHODS: IPMN surgical specimens were identified and reviewed by two gastrointestinal pathologists. Immunohistochemical analysis of E-cadherin, vimentin, and ZEB-1 was performed. Samples were linked to clinicopathologic and outcome data for these patients. Western blot test was used to evaluate ZEB-1 expression in IPMN samples; 846 human miRNAs were profiled, and EMT-related differentially expressed miRNAs were validated using quantitative real-time polymerase chain reaction. RESULTS: Fifty-eight IPMN specimens and five normal pancreatic tissue samples were immunohistochemically stained and scored. E-cadherin expression was significantly lower in malignant versus low-grade IPMN (p < 0.05). Vimentin expression was increased in malignant IPMN tumor samples (p < 0.05). EMT was associated with increased lymph node metastasis and decreased survival of malignant IPMN patients (p < 0.05). ZEB-1, an imperative EMT regulator, was exclusively expressed by malignant IPMN tumors. miRNA hierarchical clustering demonstrated grouping of two main IPMN subgroups: low-grade IPMN versus high-grade IPMN and carcinoma. Twenty-four miRNAs were differentially expressed (14 up-regulated, 10 down-regulated). The EMT-regulatory miRNAs, miR-200c and miR-141, were down-regulated (twofold and 1.8-fold decrease, respectively) in malignant versus low-grade IPMN (p < 0.05). CONCLUSIONS: EMT may play a role in IPMN tumorigenesis and metastasis. EMT molecular deregulations could be utilized as potential novel biomarkers for the identification of high-risk IPMN patients.

Operationalising Regional Cooperation for Infectious Disease Control: A Scoping Review of Regional Disease Control Bodies and Networks.

BACKGROUND: The rapid spread of the coronavirus disease 2019 (COVID-19) pandemic demonstrates the value of regional cooperation in infectious disease prevention and control. We explored the literature on regional infectious disease control bodies, to identify lessons, barriers and enablers to inform operationalisation of a regional infectious disease control body or network in southeast Asia. METHODS: We conducted a scoping review to examine existing literature on regional infectious disease control bodies and networks, and to identify lessons that can be learned that will be useful for operationalisation of a regional infectious disease control body such as the Association of Southeast Asian Nations (ASEAN) Center for Public Health Emergency and Emerging Diseases. RESULTS: Of the 57 articles included, 53 (93%) were in English, with two (3%) in Spanish and one (2%) each in Dutch and French. Most were commentaries or review articles describing programme initiatives. Sixteen (28%) publications focused on organisations in the Asian continent, with 14 (25%) focused on Africa, and 14 (25%) primarily focused on the European region. Key lessons focused on organisational factors, diagnosis and detection, human resources, communication, accreditation, funding, and sustainability. Enablers and constraints were consistent across regions/ organisations. A clear understanding of the regional context, budgets, cultural or language issues, staffing capacity and governmental priorities, is pivotal. An initial workshop inclusive of the various bodies involved in the design, implementation, monitoring or evaluation of programmes is essential. Clear governance structure, with individual responsibilities clear from the beginning, will reduce friction. Secure, long-term funding is also a key aspect of the success of any programme. CONCLUSION: Operationalisation of regional infectious disease bodies and networks is complicated, but with extensive groundwork, and focus on organisational factors, diagnosis and detection, human resources, communication, accreditation, funding, and sustainability, it is achievable. Ways to promote success are to include as many stakeholders as possible from the beginning, to ensure that context-specific factors are considered, and to encourage employees through capacity building and mentoring, to ensure they feel valued and reduce staff turnover.

The anti-leukemic and lipid lowering effects of imatinib are not hindered by statins in CML: a retrospective clinical study and in vitro assessment of lipid-genes transcription.

Imatinib, which has revolutionized chronic myeloid leukemia (CML) treatment, was suggested to improve lipid profile. Statins, a dyslipidemia drug, were reported to potentiate imatinib's antileukemic effect. However, analysis of imatinib combined with statins is lacking. We have retrospectively analyzed the normalization period of bcr-abl, blood counts, and lipids in 40 CML patients, 19 of which co-treated with statins, during short (<12 months) and prolonged (>12 months) imatinib treatment. Prior statins treatment did not hinder nor sensitized imatinib's anti-leukemic and lipid-lowering effects. CML cells (K562) treated with 1µM imatinib (24-96 h) were further assessed for the expression of central lipid-related genes by real-time PCR. HMGCoAR, LDL-R, and apobec1 expressions were significantly increased while CETP declined after 48-96 h. To conclude, imatinib produces an independent favorable lipid profile, which is not hindered by statins and is partly mediated via transcription regulation of genes involved in the clearance of plasma lipids.