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The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.
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PURPOSE: In this study, we aimed to assess the clinical characteristics, reasons for referral, and outcomes of patients with brain metastases (BM) referred to the supportive care center. METHODS: Equal numbers of patients with melanoma, breast cancer, and lung cancer with (N = 90) and without (N = 90) BM were retrospectively identified from the supportive care database for study. Descriptive statistics were used to analyze demographic, disease, and clinical data. Kaplan Meier method was used to evaluate survival outcomes. RESULTS: While physical symptom management was the most common reason for referral to supportive care for both patients with and without BM, patients with BM had significantly lower pain scores on ESAS at time of referral (p = 0.002). They had greater interaction with acute care in the last weeks of life, with higher rates of ICU admission, emergency room visits, and hospitalizations after initial supportive care (SC) visit. The median survival time from referral to Supportive Care Center (SCC) was 0.90 years (95% CI 0.73, 1.40) for the brain metastasis group and 1.29 years (95% CI 0.91, 2.29) for the group without BM. CONCLUSIONS: Patients with BM have shorter survival and greater interaction with acute care in the last weeks of life. This population also has distinct symptom burdens from patients without BM. Strategies to optimize integration of SC for patients with BM warrant ongoing study.
Subject(s)
Brain Neoplasms , Breast Neoplasms , Lung Neoplasms , Humans , Female , Palliative Care/methods , Retrospective Studies , Brain Neoplasms/therapy , Lung Neoplasms/therapyABSTRACT
Perinatal depression (PND) screening recommendations are made by national, state-based and professional organisations; however, there is disagreement regarding screening timing, provider responsible, screening setting, screening tool as well as the follow-up and referral pathways required post-screening. This systematic review aimed to identify, describe and compare PND screening recommendations from member countries of the Organisation for Economic Co-operation and Development (OECD). Publications were identified through systematically searching PubMed, Google and the Guidelines International Network (GIN). Recommendations regarding PND screening endorsement, timing, frequency, responsible provider, tools/assessments and follow-up and referral were extracted. Twenty-one publications, including guidelines, from five countries were included. Most made recommendations in support of PND screening using the Edinburgh Postnatal Depression Scale. Details differed regarding terminology used, as well as frequency of screening, follow-up mechanisms and referral pathways. A broad range of health providers were considered to be responsible for screening. This is the first review to identify and compare PND screening recommendations from OECD member countries; however, only online publications published in English, from five countries were included. Heterogeneity of publication types and inconsistency in definitions rendered quality assessment inappropriate. While most publications generally endorsed PND screening, there are exceptions and the associated details pertaining to the actual conduct of screening vary between and within countries. Developing clear, standardised recommendations based on current evidence is necessary to ensure clarity amongst healthcare providers and a comprehensive approach for the early detection of PND.
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Depression, Postpartum , Depressive Disorder , Depression/diagnosis , Depression, Postpartum/diagnosis , Female , Humans , Mass Screening , Organisation for Economic Co-Operation and Development , PregnancyABSTRACT
BACKGROUND: Suicide is among the leading causes of death among people aged 15 to 29 worldwide. Healthcare professionals interact with people at risk of suicide regularly, yet mental health and crisis first aid training is lacking in curricula. Mental Health First Aid (MHFA) training teaches crucial communication and crisis first aid skills and is increasingly recognised as integral to healthcare education. This study aimed to explore the extent of, as well as barriers and enablers to MHFA training delivery and assessment in Australian medical, nursing and pharmacy curricula. METHODS: All accredited Australian medical, nursing and pharmacy program providers were identified through Australian Health Practitioner Regulation Agency and National Boards websites and invited to participate in a semi-structured interview. A purpose-designed interview guide explored if and how MHFA training was delivered and assessed in curricula, as well as perceptions of and barriers and enablers to MHFA training. Interview recordings were transcribed verbatim, allowing for deductive content analysis to compare MHFA training provision across programs. RESULTS: Of 75 invited program providers, 36 (48%; 13 medical, 13 nursing and 10 pharmacy) participated, of which 15 representatives (42%; six medical, two nursing and six pharmacy) reported providing MHFA training to students. Differences in mandating training, year level of students completing training, type of training delivered and source of MHFA instructors were identified. Barriers to MHFA implementation included perceived adequacy of existing curricula, lack of funding and time, while facilitators included perceived benefit and availability of funding. CONCLUSION: MHFA training is provided to more than one third of medical, nursing and pharmacy students in Australia. Increased funding may facilitate the integration of MHFA as a minimum standard of mental health training for future healthcare professionals. Further research exploring the effectiveness of MHFA in improving behaviours and its impact on patient outcomes is warranted. TRIAL REGISTRATION: This study was approved by the University of Sydney Human Research Ethics Committee [Project number: 2020/087].
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Pharmacy , Students, Pharmacy , Australia , Curriculum , First Aid , Humans , Mental HealthABSTRACT
Brain injury in intrauterine growth restricted (IUGR) infants is a major contributing factor to morbidity and mortality worldwide. Adverse outcomes range from mild learning difficulties, to attention difficulties, neurobehavioral issues, cerebral palsy, epilepsy, and other cognitive and psychiatric disorders. While the use of medication to ameliorate neurological deficits in IUGR neonates has been identified as warranting urgent research for several years, few trials have been reported. This review summarises clinical trials focusing on brain protection in the IUGR newborn as well as therapeutic interventions trialled in animal models of IUGR. Therapeutically targeting mechanisms of brain injury in the IUGR neonate is fundamental to improving long-term neurodevelopmental outcomes. Inflammation is a key mechanism in neonatal brain injury; and therefore an appealing target. Ibuprofen, an anti-inflammatory drug currently used in the preterm neonate, may be a potential therapeutic candidate to treat brain injury in the IUGR neonate. To better understand the potential of ibuprofen and other therapeutic agents to be neuroprotective in the IUGR neonate, long-term follow-up information of neurodevelopmental outcomes must be studied. Where agents such as ibuprofen are shown to be effective, have a good safety profile and are relatively inexpensive, they can be widely adopted and lead to improved outcomes.
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Brain Injuries/drug therapy , Fetal Growth Retardation/drug therapy , Animals , Humans , Infant, NewbornABSTRACT
PURPOSE/OBJECTIVE(S): Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT). MATERIALS/METHODS: Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS. RESULTS: Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies. CONCLUSION: These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.
Subject(s)
Brain Neoplasms , Glioblastoma , Lymphopenia , Humans , Lymphopenia/etiology , Lymphopenia/mortality , Glioblastoma/mortality , Glioblastoma/therapy , Glioblastoma/radiotherapy , Glioblastoma/complications , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Brain Neoplasms/therapy , Brain Neoplasms/complications , Prognosis , Survival RateABSTRACT
INTRODUCTION: Primary healthcare workers, including doctors and pharmacists, are well-positioned to detect and support women experiencing mental health disorders in the perinatal period. However, research exploring their education and training to fulfil these roles is limited. This study aimed to examine the perspectives of medical and pharmacy educational program representatives on perinatal mental health education in medical and pharmacy curricula at Australian and New Zealand universities. METHODS: A web-based search (e.g., Australian Health Practitioner Regulation Agency) was used to identify potentially relevant medical and pharmacy educational program representatives. Eligible participants were invited to participate in audio-recorded semi-structured interviews which were transcribed verbatim. Data regarding perinatal mental health content within each program were extracted and tabulated for comparisons. Thematic analysis of participants' perspectives on perinatal mental health education was conducted. RESULTS: Fifty medical and pharmacy educational program representatives were invited to participate (December 2022-March 2023), of which 13 participated representing 14 programs. The extent and content of perinatal mental health education varied considerably across programs. Thematic analysis resulted in four themes: How much perinatal mental health content is enough?; Reflections on perinatal mental health related content; Perinatal mental health education in and beyond the classroom; Challenges associated with delivering perinatal mental health content. CONCLUSIONS: Participants acknowledged the importance of perinatal mental health content for medical and pharmacy students; however, limited time and lack of opportunities for students to complete placements were key challenges to curricular integration.
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Background: First Nations populations have poorer colorectal cancer (CRC) survival compared to non-First Nations populations. Whilst First Nations populations across the world are distinct, shared experiences of discrimination and oppression contribute to persistent health inequities. CRC screening improves survival, however screening rates in First Nations populations are poorly described. This study seeks to define participation rates in CRC screening in First Nations populations worldwide. Methods: A systematic literature search was conducted of PubMed, Embase, Cochrane Library, CINAHL, MEDLINE, grey literature, national registries and ClinicalTrials.gov. All sources were searched from their inception date to 18 February 2024. Studies were included if they reported CRC screening rates in adult (≥18 years) First Nations populations. We aimed to undertake a meta-analysis if there were sufficient data. Quality of papers were assessed using the Joanna Briggs Institute (JBI) appraisal tool. The study was registered with PROSPERO, CRD42020210181. Findings: The literature search identified 1723 potentially eligible published studies. After review, 57 studies were included, 50 from the United States (US), with the remaining studies from Australia, Aotearoa New Zealand (NZ), Canada, Dominica and Guatemala. Additionally, eleven non-indexed reports from national programs in Australia and NZ were included. There were insufficient data to undertake meta-analysis, therefore a systematic review and narrative synthesis were conducted. CRC screening definitions varied, and included stool-based screening, sigmoidoscopy and colonoscopy. US First Nations screening rates ranged between 4.0 and 79.2%, Australia reported 10.6-35.2%, NZ 18.4-49%, Canada 22.4-53.4%, Guatemala 2.2% and Dominica 4.2%. Fifty-five studies were assessed as moderate or high quality and two as low quality. Interpretation: Our findings suggested that there is wide variation in CRC screening participation rates across First Nations populations. Screening data are lacking in direct comparator groups and longitudinal outcomes. Disaggregation of screening data are required to better understand and address First Nations CRC outcome inequities. Funding: None.
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BACKGROUND: While pharmacists' roles in mental healthcare are expanding, research exploring pharmacists' acceptability and willingness to provide mental health services is limited. This study developed and validated theory-driven measures of pharmacists' acceptability and willingness to screen for perinatal depression in community pharmacy settings. MATERIALS/METHODS: Items were developed using published literature and the Theoretical Framework of Acceptability (TFA), then content validated using consensus methods with experts who completed the content validity index (CVI). The revised items were disseminated to pharmacists in Australia. Responses were analysed descriptively. Exploratory factor analyses (EFA) were used to explore the factorial structure and generate scales. Multivariate regression analysis was conducted to explore predictors of willingness. RESULTS: A 58-item questionnaire was developed, encompassing the 7 domains of the TFA and an eighth domain (willingness). The average CVI was 0.92, domain range (0.88-0.96). The universal CVI was 56/58. Expert feedback informed item revision, creation and deletion. Pharmacists' responses (n = 157) to the final 42-item questionnaire indicated overall acceptance and willingness to conduct PND screening. However, perceived knowledge was lacking. The EFA resulted a two-factor solution (1 = acceptance; 2 = self-efficacy). The measurement scales created had good internal consistency. In multivariate regression analysis, 'Acceptance' (Beta = 0.949 (0.760-1.103)) and 'Self-Efficacy' (Beta = 0.107 (0.036-0.174)) were significant predictors of 'Willingness' and the model predicted 77 % of the variation in 'Willingness'. CONCLUSIONS: Psychometrically-sound measures of pharmacists' acceptability and willingness to screen for PND have been developed with stakeholder input. The questionnaire can be used for standardised measurement of these constructs across studies.
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BACKGROUND: Psychosis is a mental disorder that, despite its low prevalence, causes high disease and economic burden. Inadequate knowledge, lack of confidence and stigmatising attitudes of healthcare professionals (HCPs) may lead to suboptimal care. AIM: To review the literature exploring HCPs' knowledge, confidence and attitudes in relation to psychosis care. METHOD: A systematic search was undertaken across three databases (MEDLINE, Embase, PsycINFO) using a search strategy encompassing the concepts: 'healthcare professionals', 'knowledge, attitude, and confidence in care' and 'psychotic illnesses and symptoms' to identify relevant records published from 1st January 2002 to 18th March 2022. Results were screened against predetermined inclusion and exclusion criteria by title and abstract, followed by full text. Data were extracted into tables and synthesised narratively. RESULTS: Initially, 7,397 studies were identified. Following two-stage screening, 24 studies were eligible for inclusion. Of these studies, 16 explored attitudes, four explored knowledge and attitudes, one explored knowledge, one explored confidence, one explored attitudes and confidence in care and one explored all three constructs. Most HCPs in the included studies demonstrated stigmatising attitudes towards people with psychosis. Furthermore, certain HCPs, including nurses and general practitioners, demonstrated low levels of knowledge, while psychiatrists, occupational therapists, psychologists and nurses had low levels of confidence in caring for people with psychosis. Conversely, positive attitudes were also observed in some HCPs resulting from having acquaintances with lived experience of psychosis. The need for additional education and training to improve HCPs' knowledge and confidence in relation to caring for people living with psychosis was identified. CONCLUSIONS: Most attitudes identified were negative and stemmed from stigma, while some were positive due to HCPs' compassion and familiarity with psychosis. The level of knowledge and confidence identified were mostly suboptimal, and so further research is required to develop and evaluate tailored interventions to address this gap.
Subject(s)
General Practitioners , Psychotic Disorders , Humans , Health Personnel , Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Psychotic Disorders/therapy , Social StigmaABSTRACT
BACKGROUND: Total hip and knee arthroplasties are common surgeries performed worldwide, but the management of pain during the subacute period (defined as hospital discharge to 3 months postoperatively) is poorly understood. This study aimed to determine patients' experiences, facilitators and barriers to subacute pain management following total hip or knee arthroplasty. METHODS: Semi-structured interviews with a purposive sample of patients following total hip or knee arthroplasty were conducted between June and August 2022. Participants were recruited from two tertiary metropolitan hospitals. Interviews were audio-recorded and transcribed verbatim. Data were analysed using an inductive thematic approach to identify common themes. RESULTS: In total, 30 interviews were conducted with patients following hip or knee arthroplasty. Four main themes were identified: (i) Physical constitution before surgery (joint condition, analgesic use, age, and hearing); (ii) Attitude and knowledge (motivation, outlook on life, attitude towards taking medications, individual benchmarking, and knowledge); (iii) Socio-ethno-cultural factors (family and community connection, language, and religion), and (iv) Health-system support (health-professional delivered education, medications, services, staff, and costs). CONCLUSIONS: Participants' experiences of subacute pain following hip or knee arthroplasty were shaped by multidimensional factors. Strategies to empower patients through increased education and support during postoperative opioid tapering as well as a shift to a biopsychosocial approach to pain management during the subacute period may improve patient and health-system outcomes.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Humans , Pain Management , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/psychology , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/psychology , Pain , AnalgesicsABSTRACT
BACKGROUND: Perinatal depression (PND) screening is often recommended in primary care settings, which includes the community pharmacy setting. However, there is limited research exploring pharmacists' perspectives on their roles in screening for perinatal mental illness. AIM: This study aimed to explore pharmacists' views of pharmacists' roles in PND screening, as well as training and resource needs for PND screening in community pharmacy settings. METHOD: A questionnaire including three open-ended questions focusing on pharmacists' perspectives of their role in PND screening, their training, and resource needs in this area, was disseminated to pharmacists across Australia via professional organisations and social media. Each open-ended question was separately analysed by inductive content analysis. Subcategories were deductively mapped to the Theoretical Framework of Acceptability. RESULTS: Responses (N = 149) from the first open-ended question about pharmacists' roles in PND screening resulted in three categories (PND screening in primary care settings will support the community, community pharmacy environment, and system and policy changes) and ten subcategories. Responses to question two on training needs (n = 148) were categorised as: training content, training length, and training delivery while responses about resource needs (n = 147) fell into three categories: adapting community pharmacy operating structures, pharmacist-specific resources, and consumer-specific resources. CONCLUSION: While some pharmacists were accepting of a role in PND screening due to pharmacists' accessibility and positive relationships with consumers, others had concerns regarding whether PND screening was within pharmacists' scope of practice. Further training and resources are needed to facilitate pharmacists' roles in PND screening, referral and care.
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Community Pharmacy Services , Pharmacies , Pregnancy , Female , Humans , Pharmacists , Depression , Australia , Professional Role , Attitude of Health PersonnelABSTRACT
Public health orders were introduced in many countries, including Australia, during the COVID-19 pandemic to reduce the spread of the virus. However, for many people this led to an exacerbation of mental health symptoms, particularly those living with severe or persistent mental illness (SPMI). Additionally, the conduct of clinical research was severely impacted during the pandemic, with many difficulties encountered in the conduct of clinical trials. This paper describes the COVID-related impacts experienced during the implementation of a randomised controlled trial (RCT) testing the effectiveness of a community pharmacist-led support service for people living with SPMI in Australia (the PharMIbridge RCT), and the strategies used to successfully implement the RCT. Australian public health orders led to interstate border closures, stay-at-home orders and work-from-home requirements, resulting in necessary changes to allow for the continuation of the RCT including; changes to trial regions, transferring some training materials online while delaying face-to-face (F2F) training components, delays in pharmacy and consumer recruitment, encouraging telehealth service delivery and extensions to timelines with existing funding. Having a solution-focussed and flexible approach, while still ensuring critical trial protocol elements were adhered to, such as providing opportunities for F2F skills-based training for pharmacists, as well as F2F site visits from researchers and mentors to support trial implementation, resulted in high pharmacy and consumer participant retention through to trial conclusion. Future planning for RCTs should consider possible pandemic-related risks and rapid responses from approval bodies to ensure researchers can be agile and adapt to ensure successful trial completion.
Subject(s)
COVID-19 , Mental Disorders , Pharmacies , Humans , COVID-19/prevention & control , Australia , Mental Disorders/epidemiology , Mental Disorders/therapy , Mental HealthABSTRACT
Background: Giant cell myocarditis (GCM) is a rare and rapidly progressive disease associated with significant morbidity and mortality. Whilst patients more frequently present with acute heart failure, diagnosis is difficult due to heterogeneity in clinical presentations. Case summary: This case report presents a previously healthy 59-year-old Vietnamese woman who initially presented with syncope and a motor vehicle accident who developed rapid decline in left ventricular function. Her initial echocardiogram was suggestive of an infiltrative cardiomyopathy. GCM was confirmed on biopsy, and she received combined immunosuppression. Twenty-seven days following her initial presentation to hospital, she was unable to recover from severe multi-organ dysfunction, and the patient was palliated and passed away. Discussion: This case highlights the varied manner in which GCM may present. Even in the absence of cardiogenic shock at presentation, giant cell myocarditis should be considered in the evaluation of new cardiomyopathy of uncertainty aetiology. Diagnosis of this condition has distinct clinical implications on management and prognosis.
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Internationally, 20% of women experience perinatal depression (PND). Healthcare providers including general practitioners and midwives are critical in providing PND screening and support; however, the current workforce is unable to meet growing demands for PND care. As accessible and trusted primary healthcare professionals, pharmacists could provide PND care to complement existing services, thereby contributing to early detection and intervention. This study aimed to explore perinatal women's views of community pharmacist-delivered PND screening and care, with a focus on their attitudes towards and acceptability of PND screening implementation in community pharmacy. Semi-structured interviews with women (n = 41) were undertaken, whereby interview data were transcribed verbatim and then inductively and thematically analysed. Five overarching themes emerged; "patient experience with existing PND support and screening services"; "familiarity with pharmacists' roles"; "pharmacist visibility in PND screening care"; "patient-pharmacist relationships" and "factors influencing service accessibility". Themes and subthemes were mapped to the Consolidated Framework for Implementation Research. Findings highlight participants' generally positive attitudes towards community pharmacist-delivered PND screening and care, and the potential acceptability of such services provided pharmacists are trained and referral pathways are established. Addressing perceived barriers and facilitators would allow community pharmacist-delivered PND screening and care to support existing PND care models.
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Community Pharmacy Services , General Practitioners , Pregnancy , Female , Humans , Pharmacists , Professional Role , Attitude of Health Personnel , Qualitative ResearchABSTRACT
BACKGROUND: Infective endocarditis (IE) is a rare entity in children associated with significant morbidity and mortality. To optimize management, it is important to understand local epidemiology, risk factors, clinical features and outcome. These are investigated in this retrospective 10-year study of endocarditis in children in Queensland. METHODS: Children <18 years with IE were identified from the state-wide pediatric cardiology center (Mater Children's Hospital, 2009-2014; Queensland Children's Hospital, 2014-2018) through International Classification of Diseases codes and local cardiology database. Clinical records were assessed by a clinician and echocardiograms by a cardiologist. Incidence was calculated using Australian Bureau of Statistics Queensland Estimated Resident Population data, 2019. RESULTS: Fifty-one children were identified, with an overall estimated incidence of 0.84 per 100,000 per year; 0.69 per 100,000 in 2009-2013 and 0.99 per 100,000 in 2014-2018, respectively. Twenty-four (47.1%) children were male and 10 (19.6%) were identified as Aboriginal or Torres Strait Islander peoples. Underlying cardiac conditions were present in 29 (56.9%): 25 congenital heart disease, 3 rheumatic heart disease and 1 cardiomyopathy. A causative pathogen was identified in 46 (90.2%) children with Staphylococcus aureus most common. Thirty-six (70.6%) met criteria for "Definite IE" as per modified Duke criteria, with the remainder "Possible IE." Surgery was required in 26 (51%). Median duration of antibiotics was 42 (interquartile range = 32-51) days and hospitalization 49 (interquartile range = 34-75) days. One child died due to IE. CONCLUSIONS: IE in children in Queensland is increasing in incidence and is higher than the reported incidence in New Zealand and the United States. Congenital heart disease is the most common risk factor and S. aureus is the commonest responsible organism. Aboriginal or Torres Strait Islander children are over-represented. Mortality remains low.
Subject(s)
Endocarditis, Bacterial/epidemiology , Endocarditis/epidemiology , Endocarditis/microbiology , Hospitalization/statistics & numerical data , Adolescent , Bacteria/classification , Bacteria/isolation & purification , Bacteria/pathogenicity , Bacterial Infections/epidemiology , Child , Child, Preschool , Endocarditis/complications , Endocarditis/physiopathology , Female , Humans , Incidence , Infant , Male , Queensland/epidemiology , Retrospective Studies , Risk Factors , Staphylococcal Infections/complications , Staphylococcal Infections/epidemiology , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/pathogenicityABSTRACT
Glioblastoma is the most common malignant brain cancer with a dismal prognosis. The difficulty in treating glioblastoma is largely attributed to the lack of effective therapeutic targets. In our previous work, we identified casein kinase 1 ε (CK1ε, also known as CSNK1E) as a potential survival factor in glioblastoma. However, how CK1ε controls cell survival remains elusive and whether targeting CK1ε is a possible treatment for glioblastoma requires further investigation. Here we report that CK1ε was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma, but not glia cells. Depletion of CK1ε remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells, while having limited effect on astrocytes. CK1ε deprivation activated ß-catenin and induced apoptosis, which was further counteracted by knockdown of ß-catenin. The CK1ε inhibitor IC261, but not PF-4800567, activated ß-catenin and blocked the growth of glioblastoma cells and glioblastoma stem cells. Congruently, IC261 elicited a robust growth inhibition of human glioblastoma xenografts in mice. Together, our results demonstrate that CK1ε regulates the survival of glioblastoma cells and glioblastoma stem cells through ß-catenin signaling, underscoring the importance of targeting CK1ε as an effective treatment for glioblastoma.