To explore the mechanism by which long non-coding RNA (lncRNA) TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the microRNA miR-134-5p/malignant brain tumour domain containing 1 ...(MBTD1) axis.
The lncRNA TTN-AS1 was highly expressed in osteosarcoma and was associated with poor prognosis. The lncRNA TTN-AS1 promoted cell viability and inhibited apoptosis. MiR-134-5p targeted MBTD1, which was regulated by lncRNA TTN-AS1. MBTD1 was highly expressed in osteosarcoma and was associated with poor prognosis. MBTD1 promoted cell viability and inhibited apoptosis, and knockdown of MBTD1 reversed the cancer-promoting effects of lncRNA TTN-AS1. Downregulation of lncRNA TTN-AS1 reduced drug resistance.
In osteosarcoma, lncRNA TTN-AS1 promoted the expression of MBTD1 by targeting miR-134-5p and regulated cell growth, apoptosis and drug resistance.
The expression characteristics of genes in osteosarcoma patients were analysed using bioinformatics. Plasmid transfection technology was applied to silence or overexpress lncRNA TTN-AS1, miR-134-5p and MBTD1. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect protein and RNA, respectively. A cell counting kit 8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis. The effects of lncRNA TTN-AS1 and MBTD1 on osteosarcoma in vivo were studied by using a tumour burden assay.
Background
Patients receiving a brain cancer diagnosis may face cognitive decline and a poor prognosis. In addition, they suffer from a high symptom burden in a complex cancer pathway. The aim of ...this study was to investigate the early hospital experiences of brain tumour patients during the diagnostic and surgical treatment phase.
Methods
A descriptive longitudinal single‐case study design was used, and data were analysed via systematic text condensation.
Results
The patients' experiences of being diagnosed with and treated for brain cancer were interpreted in terms of the central theme: a fast transition into an unknown journey. This theme consisted of the following subthemes: emotionally overwhelmed, putting life on hold and an unfamiliar dependency.
Conclusions
Patients diagnosed with brain cancer struggle with overwhelming emotions due to this sudden life‐threatening diagnosis, their fear of brain surgery and their progressing dependence. Patients did not voice their feelings, fears or needs, so these may easily be overlooked and unmet. A proactive and continuous care approach throughout the diagnostic phase is needed to support these patients.
Purpose
Psychological distress in primary malignant brain tumour (PMBT) patients is associated with poorer outcomes. Radiotherapy (RT) often induces side effects that significantly influence ...patients’ quality of life (QoL), with potential impact on survival. We evaluated distress, anxiety, depression, and QoL over time to identify patients with difficulties in these areas who required more intense psychological support.
Methods
Psychological questionnaires—Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy (FACT-G and FACT-Br)—were completed at the beginning (T0), in the middle (T1), directly after RT (T2), and 3 months after RT (T3). We personalised the psychological support provided for each patient with a minimum of three sessions (‘typical’ schedule) and a maximum of eight sessions (‘intensive’ schedule), depending on the patients’ psychological profiles, clinical evaluations, and requests. Patients’ survival was evaluated in the glioblastoma multiforme (GBM) patients, with an explorative intent.
Results
Fifty-nine consecutive PMBT patients receiving post-operative RT were included. For patients who were reported as ‘not distressed’ at T0, no statistically significant changes were noted. In contrast, patients who were ‘distressed’ at T0 showed statistically significant improvements in DT, HADS, FACT-G, and FACT-Br scores over time. ‘Not distressed’ patients required less psychological sessions over the study duration than ‘distressed’ patients. Interestingly, ‘not distressed’ GBM patients survived longer than ‘distressed’ GBM patients.
Conclusions
Increased psychological support improved distress, mood, and QoL for patients identified as ‘distressed’, whereas psychological well-being was maintained with typical psychological support in patients who were identified as being ‘not distressed’. These results encourage a standardisation of psychological support for all RT patients.
Research on the impact of caring for patients with an acoustic neuroma is scarce. Findings from 12 interviews with primary carers of this patient population highlight six key themes: life disruption, ...support, well-being, the carer role, lessons learned and the impact of COVID-19. Carers need more practical information and emotional support, starting from the diagnosis stage through to recovery. Recommendations include routine carer assessments, early signposting to auxiliary services and information materials about recovery. This study contributes to the UK literature gap of this under-studied population and demonstrates the importance of carer assessments, as set out in the Carers Act 2014.
Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the ...administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time.
BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 μM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 μm with a center-to-center distance of ≈400 μm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31.
After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain.
In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time.
Background:
Caring for a partner with primary malignant brain tumour can be a dramatic life-changing event. Primary malignant brain tumour is known to give poor life expectancy and severe ...neurological and cognitive symptoms, such as changed behaviour and personality, which demand greater caring responsibilities from spouses.
Aim:
The aim of the study is to explore ethical dilemmas spouses experience in the everyday care of a partner in treatment for primary malignant brain tumour.
Research design, participants and research context:
A phenomenological and hermeneutic qualitative descriptive design was adopted as a method for collecting and analysing data. Ten spouses were interviewed twice using an in-depth, semi-structured interview guide. The interviews took place at the spouses’ homes or at the hospital.
Ethical consideration:
Ethical matters were considered throughout the research process. Permission from The National Committee on Health Research Ethics and the Danish Data Protection Agency was obtained.
Findings:
The analysis showed that the spouses perceived daily ethical dilemmas in caring for a partner with primary malignant brain tumour. Their life as well as their partner’s life had changed considerably. The main theme that emerged therefore was ‘oscillating in a changing relationship’. This theme was further elaborated in three subthemes that in more detail demonstrated the dilemmas: ‘doing the right thing in unpredictable daily situations’; ‘torn between patience and guilt’; and ‘living in a time of uncertainty, hope and despair’.
Conclusion:
Caring for a partner with changed behaviour and personality due to primary malignant brain tumour may involve exhausting ethical caring dilemmas. Spouses’ married life may change to a semi-professional asymmetrical relationship, which is challenged by the oscillation between acting responsibly for their partners’ well-being and caring dilemmas with no answer for what the right thing to do is. Mixed feelings of right and wrong, patience and guilt, hope and despair seem to be spousal companions through their partners’ progressing illness.
Background
Primary malignant brain tumours (PMBT) constitute less than 2% of all malignancies and carry a dismal prognosis. Treatment options at relapse are limited. First-in-human solid tumour ...studies have historically excluded patients with PMBT due to the poor prognosis, concomitant drug interactions and concerns regarding toxicities.
Methods
Retrospective data were collected on clinical and tumour characteristics of patients referred for consideration of Ph1 trials in the Royal Marsden Hospital between June 2004 and August 2016. Survival analyses were performed using the Kaplan–Meier method, Cox proportional hazards model. Chi squared test was used to measure bivariate associations between categorical variables.
Results
100pts with advanced PMBT were referred. At initial consultation, patients had a median ECOG PS 1, median age 48 years (range 18–70); 69% were men, 76% had glioblastoma; 68% were on AEDs, 63% required steroid therapy; median number of prior treatments was two. Median OS for patients treated on a Ph1 trials was 9.3 months (95% CI 5.9–12.9) versus 5.3 months (95% CI 4.1–6.1) for patients that did not proceed with a Ph1 trial, p = 0.0094. Steroid use, poor PS, neutrophil-to-lymphocyte ratio and treatment on a Ph1 trial were shown to independently influence OS.
Conclusions
We report a survival benefit for patients with PMBT treated on Ph1 trials. Toxicity and efficacy outcomes were comparable to the general Ph1 population. In the absence of an internationally recognized standard second line treatment for patients with recurrent PMBT, more Ph1 trials should allow enrolment of patients with refractory PMBT and Ph1 trial participation should be considered at an earlier stage.
The number of patients with malignant brain tumours is on the rise, but due to the novel treatment methods the survival rates are higher. Despite increased survival the consequences of tumour ...properties and treatment can have a significant negative effect on the patients' quality of life. Providing timely and appropriate rehabilitation interventions is an important aspect of patient treatment and should be started immediately after surgery. The most important goal of rehabilitation is to prevent complications that could have a negative effect on the patients' ability to function.
By using individually tailored early rehabilitation it is often possible to achieve the patients' independence in mobility as well as in performing daily tasks before leaving the hospital. A more precise evaluation of the patients' functional state after completing additional oncologic therapy should be performed to stratify the patients who should be directed to complex rehabilitation treatment. The chances of a good functional outcome in patients with malignant brain tumours could be increased with good early medical rehabilitation treatment.
Abstract Purpose Caring for someone with a primary malignant brain tumour is very demanding due to the dynamic situation involving changes to personality, short term memory loss and changes in family ...relationships. The purpose of this qualitative study is to examine the support needs of carers of those with a primary malignant brain tumour. Methods & sample 22 Carers who were currently caring for someone with a primary malignant brain tumour were recruited from one specialist cancer centre in the south east of England. The study took a grounded theory approach and data were analysed using the constant comparative method generating categories and themes that are grounded in the data. Key results A key concept that emerged from the data was: ‘Connecting on the caring journey’. The themes that emerged from the key concept were: building helpful relationships; safe places and comfort zones; and threats to connecting. Conclusions Many carers do find a great deal of support within the family and from their relationships with friends as well as from cancer and carer support groups. However this is by no means universal and many carers experience a lack of timely access to good quality supportive care services. For some carers supportive care services do not meet their expectations so they spend valuable time searching for the connections they need to continue to care combined with feeling frustrated and under pressure.
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