Translational Research Institute

About: Translational Research Institute is a facility organization based out in Woolloongabba, Queensland, Australia. It is known for research contribution in the topics: Population & Cancer. The organization has 817 authors who have published 1163 publications receiving 25513 citations.

Functional Balance between TCF21-Slug defines phenotypic plasticity and sub-classes in high-grade serous ovarian cancer

Abstract: Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis initiated by single cell epithelial to mesenchymal transition or cooperative cell migration (CCM). We identified novel regulatory cross-talks between Tcf21 and Slug in mediating phenotypic and migration plasticity in high-grade serous ovarian adenocarcinoma. Live imaging discerned CCM as being achieved either through rapid cell proliferation or sheet migration. Transitional states were enriched over the rigid epithelial or mesenchymal phenotypes under conditions of environmental stresses. The Tcf21-Slug interplay identified in HGSC tumors through effective stratification of subtypes also contributed to class-switching in response to disease progression or therapy. Our study effectively provides a framework for understanding the relevance of cellular plasticity in situ as a function of two transcription factors.

Assessment of the use of the Internet and social media among people with bladder cancer and their carers, and the quality of available patient-centric online resources: a systematic review

Abstract: Objective: To conduct a systematic synthesis of the literature evaluating the use of the Internet and social media by people with bladder cancer (BCa) and their carers, and to synthesize the evidence on the quality of available online resources for patients with BCa. Methods: We selected studies published between January 2000 and September 2018, written in the English language and meeting the inclusion criteria. Data sources included PubMed, PsycINFO, EMBASE, Web of Science and Scopus. Results: A total of 15 studies were included in the review. Four studies explored patterns of Internet use among patients with BCa, five studies investigated social media use related to BCa and six studies evaluated the quality of online resources available for patients with BCa. Evidence in all these three dimensions was limited in its ability to establish rigorously if use of the Internet, social media and online resources for BCa is effective in improving the care outcomes for patients with BCa. Conclusion: Our review emphasizes the forgotten status of BCa by establishing that, despite its high global incidence, it remains underrepresented in the building of evidence on patient information needs and the possible role of online spaces. Our synthesis establishes that further research is needed to examine the full impact of online information and social media use on the health management of people with BCa.

Enabling Technologies for Homing and Engraftment of Cells for Therapeutic Applications

Abstract: Application of cells to restore damaged myocardium or reduce further functional deterioration represents an important therapeutic modality for the treatment of patients with myocardial infarction and heart failure. In pre-clinical models of myocardial infarction, delivery of bone marrow–derived

Patterns of oral disease in adults with chronic kidney disease treated with hemodialysis

Abstract: Background Oral disease is a potentially treatable determinant of mortality and quality of life. No comprehensive multinational study to quantify oral disease burden and to identify candidate preventative strategies has been performed in the dialysis setting. Methods The ORAL disease in hemoDialysis (ORALD) study was a prospective study in adults treated with hemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Oral disease was assessed using standardized WHO methods. Participants self-reported oral health practices and symptoms. Sociodemographic and clinical factors associated with oral diseases were determined and assessed within nation states. Results Of 4726 eligible adults, 4205 (88.9%) participated. Overall, 20.6% were edentulous [95% confidence interval (CI), 19.4-21.8]. Participants had on average 22 (95% CI 21.7-22.2) decayed, missing or filled teeth, while moderate to severe periodontitis affected 40.6% (95% CI 38.9-42.3). Oral disease patterns varied markedly across countries, independent of participant demographics, comorbidity and health practices. Participants in Spain, Poland, Italy and Hungary had the highest mean adjusted odds of edentulousness (2.31, 1.90, 1.90 and 1.54, respectively), while those in Poland, Hungary, Spain and Argentina had the highest odds of ≥14 decayed, missing or filled teeth (23.2, 12.5, 8.14 and 5.23, respectively). Compared with Argentina, adjusted odds ratios for periodontitis were 58.8, 58.3, 27.7, 12.1 and 6.30 for Portugal, Italy, Hungary, France and Poland, respectively. National levels of tobacco consumption, diabetes and child poverty were associated with edentulousness within countries. Conclusions Oral disease in adults on hemodialysis is very common, frequently severe and highly variable among countries, with much of the variability unexplained by participant characteristics or healthcare. Given the national variation and high burden of disease, strategies to improve oral health in hemodialysis patients will require implementation at a country level rather than at the level of individuals.

Synthetic lethality of TNK2 inhibition in PTPN11-mutant leukemia.

Abstract: The protein tyrosine phosphatase PTPN11 is implicated in the pathogenesis of juvenile myelomonocytic leukemia (JMML), acute myeloid leukemia (AML), and other malignancies. Activating mutations in PTPN11 increase downstream proliferative signaling and cell survival. We investigated the signaling upstream of PTPN11 in JMML and AML cells and found that PTPN11 was activated by the nonreceptor tyrosine/serine/threonine kinase TNK2 and that PTPN11-mutant JMML and AML cells were sensitive to TNK2 inhibition. In cultured human cell-based assays, PTPN11 and TNK2 interacted directly, enabling TNK2 to phosphorylate PTPN11, which subsequently dephosphorylated TNK2 in a negative feedback loop. Mutations in PTPN11 did not affect this physical interaction but increased the basal activity of PTPN11 such that TNK2-mediated activation was additive. Consequently, coexpression of TNK2 and mutant PTPN11 synergistically increased mitogen-activated protein kinase (MAPK) signaling and enhanced colony formation in bone marrow cells from mice. Chemical inhibition of TNK2 blocked MAPK signaling and colony formation in vitro and decreased disease burden in a patient with PTPN11-mutant JMML who was treated with the multikinase (including TNK2) inhibitor dasatinib. Together, these data suggest that TNK2 is a promising therapeutic target for PTPN11-mutant leukemias.