Triple-negative breast cancers (TNBCs) are aggressive, lack targeted therapies and are enriched in cancer stem cells (CSCs). Novel therapies which target CSCs within these tumors would likely lead to improved outcomes for TNBC patients. Long non-coding RNAs (lncRNAs) are potential therapeutic targets for TNBC and CSCs. We demonstrate that lncRNA prostate androgen regulated transcript 1 (PART1) is enriched in TNBCs and in Aldefluorhigh CSCs, and is associated with worse outcomes among basal-like breast cancer patients. Although PART1 is androgen inducible in breast cancer cells, analysis of patient tumors indicates its androgen regulation has minimal clinical impact. Knockdown of PART1 in TNBC cell lines and a patient-derived xenograft decreased cell proliferation, migration, tumor growth, and mammosphere formation potential. Transcriptome analyses revealed that the lncRNA affects expression of hundreds of genes (e.g., myosin-Va, MYO5A; zinc fingers and homeoboxes protein 2, ZHX2). MiRNA 4.0 GeneChip and TaqMan assays identified multiple miRNAs that are regulated by cytoplasmic PART1, including miR-190a-3p, miR-937-5p, miR-22-5p, miR-30b-3p, and miR-6870-5p. We confirmed the novel interaction between PART1 and miR-937-5p. In general, miRNAs altered by PART1 were less abundant than PART1, potentially leading to cell line-specific effects in terms miRNA-PART1 interactions and gene regulation. Together, the altered miRNA landscape induced by PART1 explains most of the protein-coding gene regulation changes (e.g., MYO5A) induced by PART1 in TNBC.
Ancient pathways promoting unicellularity and multicellularity are associated with cancer, the former being pro‐oncogenic and the latter acting to suppress oncogenesis. However, there are only a limited number of non‐vertebrate models for studying these pathways. Here, we review Dictyostelium discoideum and describe how it can be used to understand these gene networks. D. discoideum has a unicellular and multicellular life cycle, making it possible to study orthologs of cancer‐associated genes in both phases. During development, differentiated amoebae form a fruiting body composed of a mass of spores that are supported atop a stalk. A portion of the cells sacrifice themselves to become non‐reproductive stalk cells. Cheating disrupts the principles of multicellularity, as cheater cells alter their cell fate to preferentially become spores. Importantly, D. discoideum has gene networks and several strategies for maintaining multicellularity. Therefore, D. discoideum can help us better understand how conserved genes and pathways involved in multicellularity also influence cancer development, potentially identifying new therapeutic avenues.
Over the past few years, the field of opioid research has been aimed at targeting the opioid crisis affecting communities across Canada. One way that health care workers have been contributing to this field is by identifying risk factors that predispose patients to prolonged opioid use. Given opioids have long been used for post operative pain control in orthopaedics, this article aims to address some of the more common and severe risk factors seen in orthopedic surgery patients. Included with each of the risk factors are potential mitigation strategies to reduce the risk of opioid dependence or adverse effects, including medication interactions.
Objective: To provide pharmacists and other health care professionals with the knowledge required to minimize the risk of prolonged opioid use following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Data Sources: A literature search of PubMed and Embase was performed, and included the search terms: (opioid OR opiate OR opium) AND (risk factor OR predict*) AND (arthroplasty OR replacement) NOT shoulder. Study Selection and Data Extraction: Randomized control trials, cohort studies (both prospective and retrospective), systematic reviews, and meta-analyses were included if risk ratios (RRs) or odds ratios (ORs) were reported and published within the last 5 years. Data Synthesis: ]Twenty studies met inclusion criteria, including 2 meta-analyses and 2 prospective studies. There were several risk factors that overlapped between studies and presented clinically significant risks for prolonged opioid use following THA and TKA surgery. Of these, age < 65 (RRs: 1.15-9.36), preoperative opioid use (RRs: 1.09-7.81), larger quantities of opioids prescribed at discharge (RRs: 1.26-8.81), and TKA surgery (RRs: 1.73-6.07) were the most significant. Several risk factors were recently described, including migraines (RRs: 1.14-5.11) and fibromyalgia (RRs: 1.1-2.3) that may be of interest for further research. Relevance to Patient Care and Clinical Practice: This review presents a discussion of the factors associated with prolonged opioid use following THA and TKA surgeries, which are among the most common orthopedic surgeries. Conclusions: Prescribers should carefully consider patient-specific factors when prescribing opioids as there are several factors, including age, surgery type, and medical conditions that can predispose patients to prolonged opioid use.
Background: Adequate pain management is important in patients’ recovery from total hip arthroplasty (THA) and total knee arthroplasty (TKA). Objective: To determine whether risk factors for prolonged opioid use are considered when discharge prescriptions for postoperative pain are written following THA and TKA. Methods: Opioid prescriptions written between June 14 and July 9, 2021, for patients who underwent THA or TKA were analyzed. Data were also collected on the patients’ age, sex, type of surgery, type of anesthesia (regional or general), preoperative use of opioids, and preoperative use of antidepressants. Results: Among the 59 patients included in the study, the most common prescriptions were for hydromorphone 2 mg (n = 15, 25%) and hydromorphone 1 mg (n = 15, 25%). At discharge, patients received a median of 400 morphine milligram equivalents (MMEs). There was no significant difference in the quantity of opioids (MMEs) prescribed at discharge in relation to surgery type (p = 0.63), sex (p = 0.44), preoperative antidepressant use (p = 0.22), or preoperative opioid use (p = 0.97). There also appeared to be no correlation between a patient’s age and MMEs at discharge (p = 0.21; r2 = 0.028). None of these variables could be used to predict which patients would receive more than 400 MMEs. Conclusions: Patient-specific factors appeared not to be taken into consideration when opioids were prescribed for postoperative pain among patients who underwent THA or TKA. RÉSUMÉ Contexte : Une gestion adéquate de la douleur est importante pour le rétablissement des patients après une arthroplastie totale de la hanche (ATH) et une arthroplastie totale du genou (ATG). Objectif : Déterminer si les facteurs de risque relatifs à l’utilisation prolongée d’opioïdes sont pris en compte lors de la rédaction d’ordonnances de congé pour douleurs postopératoires après une ATH et une ATG. Méthodes : Les prescriptions d’opioïdes rédigées entre le 14 juin et le 9 juillet 2021 pour les patients ayant subi une ATH ou une ATG ont été analysées. Des données ont également été recueillies sur l’âge, le sexe, le type de chirurgie, le type d’anesthésie (locale ou générale), l’utilisation préopératoire d’opioïdes et l’utilisation préopératoire d’antidépresseurs. Résultats : Parmi les 59 patients compris dans l’étude, les prescriptions les plus fréquentes étaient l’hydromorphone 2 mg (n = 15; 25 %) et l’hydromorphone 1 mg (n = 15; 25 %). Les patients recevaient une médiane de 400 équivalents milligrammes de morphine (MME) au moment du congé. Aucune différence significative quant à la quantité d’opioïdes (mesurée en MME) prescrits au moment du congé en fonction du type de chirurgie (p = 0,63), du sexe (p = 0,44), de l’utilisation préopératoire d’antidépresseurs (p = 0,22) ou de l’utilisation préopératoire d’opioïdes (p = 0,97) n’a été observée. Il ne semblait pas non plus y avoir de corrélation entre l’âge d’un patient et les MME au moment du congé (p = 0,21; r2 = 0,028). Aucune de ces variables ne pouvait être utilisée pour prédire quels patients recevraient plus de 400 MME. Conclusions : Les facteurs spécifiques au patient ne semblaient pas être pris en compte lors de la prescription d’opioïdes pour la douleur postopératoire chez les patients ayant subi une ATH ou une ATG.
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