Int J Technol Assess Health Care
May 2022
Objectives: To clarify the concept of disruptive technologies in health care, provide examples and consider implications of potentially disruptive technologies for health technology assessment (HTA).
Methods: We conducted a systematic review of conceptual and empirical papers on healthcare technologies that are described as "" We searched MEDLINE and Embase from 2013 to April 2019 (updated in December 2021). Data extraction was done in duplicate by pairs of reviewers utilizing a data extraction form.
Significant investments in regenerative medicine necessitate discussion to align evidentiary requirements and decision-making considerations from regulatory, health system payer and developer perspectives. Only with coordinated efforts will the potential of regenerative medicine be realized. We report on discussions from two workshops sponsored by NICE, University of Alberta, Cell Therapy Catapult and Centre for Commercialization of Regenerative Medicine.
View Article and Find Full Text PDFBioactivation of precursor proteins by members of the proprotein convertase (PC) family is essential for normal reproduction. The Pcsk6 gene is a member of the PC family that is expressed in numerous ovarian cell types including granulosa cells and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in the mouse ovary.
View Article and Find Full Text PDFBackground: Activation of bone morphogenetic protein (BMP)4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer.
Methods: To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, ALK3QD, and administered these cells to immunocompromised mice.
Tumour-associated antigen L6 (L6-Ag, also known as TM4SF1) regulates tumour cell motility and invasiveness. We found that L6-Ag is abundant on the plasma membrane and on intracellular vesicles, on which it is co-localised with the markers for late endosomal/lysosomal compartments, including Lamp1/Lamp2 proteins and LBPA. Antibody internalisation and live-imaging experiments suggested that L6-Ag is targeted to late endocytic organelles (LEO) predominantly via a biosynthetic pathway.
View Article and Find Full Text PDFWe identified previously an autocrine bone morphogenetic protein-4 (BMP4) signalling pathway in primary human normal ovarian surface epithelial (OSE) and epithelial ovarian cancer (OvCa) cells. Herein we show that treatment of OvCa cells with BMP4 produced morphological alterations and increased cellular adhesion, motility and invasion. The BMP4 inhibitor noggin blocked the BMP4-induced phenotype, and decreased autocrine BMP4-mediated OvCa cell motility and adherence.
View Article and Find Full Text PDFThe purine nucleoside adenosine is produced at increased levels in the tissues of solid cancers as a result of local hypoxia. Adenosine inhibits the cell-mediated anti-tumor immune response, promotes tumor cell migration and angiogenesis, and stimulates the proliferation of tumor cells. We examined the stimulatory effect of adenosine on DNA synthesis, cell cycle progression, and cell proliferation in MCF7 and T-47D breast carcinoma cell lines in culture, and identified factors that modulate the growth response.
View Article and Find Full Text PDFDipeptidyl peptidase IV (DPPIV) is a multifunctional cell-surface protein that, as well as having dipeptidase activity, is the major binding protein for adenosine deaminase (ADA) and also binds extracellular matrix proteins such as fibronectin and collagen. It typically reduces the activity of chemokines and other peptide mediators as a result of its enzymatic activity. DPPIV is aberrantly expressed in many cancers, and decreased expression has been linked to increases in invasion and metastasis.
View Article and Find Full Text PDFAdenosine is a purine nucleoside which is present at micromolar concentrations in the extracellular fluid of solid cancers as a result of tissue hypoxia. Adenosine acts to promote tumor survival by inhibiting the cell-mediated anti-tumor immune response. However, its role in modulating proliferation of the tumor cell population is unclear.
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