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The nuclear paraspeckle assembly transcript 1 (NEAT1) locus encodes two long non-coding (lnc)RNA isoforms that are upregulated in many tumours and dynamically expressed in response to stress. NEAT1 transcripts form ribonucleoprotein complexes with numerous RNA-binding proteins (RBPs) to assemble paraspeckles and modulate the localisation and activity of gene regulatory enzymes as well as a subset of messenger (m)RNA transcripts. The investigation of the dynamic composition of NEAT1-associated proteins and mRNAs is critical to understand the function of NEAT1. Interestingly, a growing number of biochemical and genetic tools to assess NEAT1 interactomes has been reported. Here, we discuss the Hybridisation Proximity (HyPro) labeling technique in the context of NEAT1. HyPro labeling is a recently developed method to detect spatially ordered interactions of RNA-containing nuclear compartments in cultured human cells. After introducing NEAT1 and paraspeckles, we describe the advantages of the HyPro technology in the context of other methods to study RNA interactomes, and review the key findings in mapping NEAT1-associated RNA transcripts and protein binding partners. We further discuss the limitations and potential improvements of HyPro labeling, and conclude by delineating its applicability in paraspeckles-related cancer research.
Cancer and heart disease are leading causes of morbidity and mortality worldwide. These diseases have common risk factors, common molecular signaling pathways that are central to their pathogenesis, and even some disease phenotypes that are interdependent. Thus, a detailed understanding of common regulators is critical for the development of new and synergistic therapeutic strategies. The Raf kinase inhibitory protein (RKIP) is a regulator of the cellular kinome that functions to maintain cellular robustness and prevent the progression of diseases including heart disease and cancer. Two of the key signaling pathways controlled by RKIP are the β-adrenergic receptor (βAR) signaling to protein kinase A (PKA), particularly in the heart, and the MAP kinase cascade Raf/MEK/ERK1/2 that regulates multiple diseases. The goal of this review is to discuss how we can leverage RKIP to suppress cancer without incurring deleterious effects on the heart. Specifically, we discuss: (1) How RKIP functions to either suppress or activate βAR (PKA) and ERK1/2 signaling; (2) How we can prevent cancer-promoting kinase signaling while at the same time avoiding cardiotoxicity.
Despite high levels of distress, family caregivers of patients with cancer rarely seek psychosocial support and Internet-based interventions (IBIs) are a promising approach to reduce some access barriers. Therefore, we developed a self-guided IBI for family caregivers of patients with cancer (OAse), which, in addition to patients' spouses, also addresses other family members (e.g., adult children, parents). This study aimed to determine the feasibility of OAse (recruitment, dropout, adherence, participant satisfaction). Secondary outcomes were caregivers’ self-efficacy, emotional state, and supportive care needs. N = 41 family caregivers participated in the study (female: 65%), mostly spouses (71%), followed by children (20%), parents (7%), and friends (2%). Recruitment (47%), retention (68%), and adherence rates (76% completed at least 4 of 6 lessons) support the feasibility of OAse. Overall, the results showed a high degree of overall participant satisfaction (96%). There were no significant pre-post differences in secondary outcome criteria, but a trend toward improvement in managing difficult interactions/emotions (p = .06) and depression/anxiety (p = .06). Although the efficacy of the intervention remains to be investigated, our results suggest that OAse can be well implemented in caregivers’ daily lives and has the potential to improve family caregivers’ coping strategies.
Personalized oncology is a rapidly evolving area and offers cancer patients therapy options that are more specific than ever. However, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Applying two unsupervised dimension reduction methods (t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP)) on three datasets of metastases (n = 682 samples) with three different data transformations (unprocessed, log10 as well as log10 + 1 transformed values), we visualized potential underlying clusters. Additionally, we analyzed two datasets (n = 616 samples) containing metastases and primary tumors of one entity, to point out potential familiarities. Using these methods, no tight link between the site of resection and cluster formation outcome could be demonstrated, or for datasets consisting of solely metastasis or mixed datasets. Instead, dimension reduction methods and data transformation significantly impacted visual clustering results. Our findings strongly suggest data transformation to be considered as another key element in the interpretation of visual clustering approaches along with initialization and different parameters. Furthermore, the results highlight the need for a more thorough examination of parameters used in the analysis of clusters.
Background
Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy.
Results
We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model.
Conclusion
PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
Background
Cancer patients' mental health and quality of life can be improved through professional support according to their needs. In previous analyses of the UNSAID study, we showed that a relevant proportion of cancer patients did not express their needs during the admission interview of inpatient rehabilitation. We now examine trajectories of mental health, quality of life, and utilization of professional help in cancer patients with unexpressed needs.
Methods
We enrolled 449 patients with breast, prostate, and colon cancer at beginning (T0) and end (T1) of a 3-week inpatient rehabilitation and 3 (T2) and 9 (T3) months after discharge. We explored depression (PHQ-2), anxiety (GAD-2), emotional functioning (EORTC QLQ-C30), fear of progression (FoP-Q-SF), and global quality of life (EORTC QLQ-C30) using structuring equation models. Furthermore, we evaluated self-reports about expressing needs and utilization of professional help at follow-up.
Results
Patients with unexpressed needs (24.3%, n = 107) showed decreased mental health compared to other patients (e.g., depression: d T0 = 0.32, d T1-T3 = 0.39). They showed a significant decline in global quality of life at discharge and follow-up (d = 0.28). Furthermore, they had a higher need for support (Cramer's V T2 = 0.10, T3 = 0.15), talked less about their needs (Cramer’s V T2 = 0.18), and made less use of different health care services at follow-up.
Conclusion
Unexpressed needs in cancer patients may be a risk factor for decreased mental health, quality of life, and non-utilization of professional help in the long term. Further research should clarify causal relationships and focus on this specific group of patients to improve cancer care.
Cancer-related fatigue (CRF) is a burdensome sequela of cancer treatments. Besides exercise, recommended therapies for CRF include yoga, psychosocial, and mindfulness-based interventions. However, interventions conducted vary widely, and not all show a significant effect. This meta-analysis aimed to explore intervention characteristics related to greater reductions in CRF. We included randomized controlled trials published before October 2021. Standardized mean differences were used to assess intervention efficacy for CRF and multimodel inference to explore intervention characteristics associated with higher efficacy. For the meta-analysis, we included 70 interventions (24 yoga interventions, 31 psychosocial interventions, and 15 mindfulness-based interventions) with 6387 participants. The results showed a significant effect of yoga, psychosocial, and mindfulness-based interventions on CRF but with high heterogeneity between studies. For yoga and mindfulness-based interventions, no particular intervention characteristic was identified to be advantageous for reducing CRF. Regarding psychosocial interventions, a group setting and work on cognition were related to higher intervention effects on CRF. The results of this meta-analysis suggest options to maximize the intervention effects of psychosocial interventions for CRF. The effects of yoga and mindfulness-based interventions for CRF appear to be independent of their design, although the limited number of studies points to the need for further research.
Overexpressed c-Myc sensitizes cells to TH1579, a mitotic arrest and oxidative DNA damage inducer
(2022)
Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras-expressing or -transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Several oncogenes induce replication stress, resulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment causes toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overexpressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but not by nucleoside supplementation. We conclude that the molecular toxicological mechanisms of how TH588 and TH1579 kill c-Myc overexpressing cells have several components and involve MTH1-independent proteasomal degradation of c-Myc itself, c-Myc-driven transcription and CDK activation.
Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma.
Adrenocortical carcinoma (ACC) is a malignant tumor originating from the adrenal gland cortex with a heterogeneous but overall dismal prognosis in advanced stages. For more than 50 years, mitotane has remained a cornerstone for the treatment of ACC as adjuvant and palliative therapy. It has a very poor aqueous solubility of 0.1 mg/l and high partition coefficient in octanol/water (log P) value of 6. The commercially available dosage form is 500 mg tablets (Lysodren®). Even at doses up to 6 g/day (12 tablets in divided doses) for several months, > 50% patients do not achieve therapeutic plasma concentration > 14 mg/l due to poor water solubility, large volume of distribution and inter/intra-individual variability in bioavailability. This article aims to give a concise update of the clinical challenges associated with the administration of high-dose mitotane oral therapy which encompass the issues of poor bioavailability, difficult-to-predict pharmacokinetics and associated adverse events. Moreover, we present recent efforts to improve mitotane formulations. Their success has been limited, and we therefore propose an injectable mitotane formulation instead of oral administration, which could bypass many of the main issues associated with high-dose oral mitotane therapy. A parenteral administration of mitotane could not only help to alleviate the adverse effects but also circumvent the variable oral absorption, give better control over therapeutic plasma mitotane concentration and potentially shorten the time to achieve therapeutic drug plasma concentrations considerably.
Mitotane as tablet form is currently the standard treatment for adrenocortical carcinoma. It has been used for 5 decades but suffers from highly variable responses in patients, subsequent adverse effects and overall lower response rate. This can be fundamentally linked to the exceedingly poor water solubility of mitotane itself. In terms of enhancing water solubility, a few research groups have attempted to develop better formulations of mitotane to overcome the issues associated with tablet dosage form. However, the success rate was limited, and these formulations did not make it into the clinics. In this article, we have comprehensively reviewed the properties of these formulations and discuss the reasons for their limited utility. Furthermore, we discuss a recently developed mitotane nanoformulation that led us to propose a novel approach to mitotane therapy, where intravenous delivery supplements the standard oral administration. With this article, we combine the current state of knowledge as a single piece of information about the various problems associated with the use of mitotane tablets, and herein we postulate the development of a new injectable mitotane formulation, which can potentially circumvent the major problems associated to mitotane's poor water solubility.
The tropomysin receptor kinase B (TrkB), the receptor for the neurotrophin brain-derived neurotrophic factor (BDNF), plays an important role in neuronal survival, neuronal differentiation, and cellular plasticity. Conventionally, TrkB activation is induced by binding of BDNF at extracellular sites and subsequent dimerization of receptor monomers. Classical Trk signaling concepts have failed to explain ligand-independent signaling of intracellular TrkB or oncogenic NTRK-fusion proteins. The intracellular activation domain of TrkB consists of a tyrosine kinase core, with three tyrosine (Y) residues at positions 701, 705 and 706, that catalyzes the phosphorylation reaction between ATPγ and tyrosine. The release of cisautoinhibition of the kinase domain activates the kinase domain and tyrosine residues outside of the catalytic domain become phosphorylated. The aim of this study was to find out how ligand-independent activation of TrkB is brought about. With the help of phosphorylation mutants of TrkB, it has been found that a high, local abundance of the receptor is sufficient to activate TrkB in a ligand-independent manner. This self-activation of TrkB was blocked when either the ATP-binding site or Y705 in the core domain was mutated. The vast majority of this self-active TrkB was found at intracellular locations and was preferentially seen in roundish cells, lacking filopodia. Live cell imaging of actin dynamics showed that self-active TrkB changed the cellular morphology by reducing actin filopodia formation. Signaling cascade analysis confirmed that self-active TrkB is a powerful activator of focal adhesion kinase (FAK). This might be the reason why self-active TrkB is able to disrupt actin filopodia formation. The signaling axis from Y705 to FAK could be mimicked by expression of the soluble, cytosolic TrkB kinase domain. However, the signaling pathway was inactive, when the TrkB kinase domain was targeted to the plasmamembrane with the help of artificial myristoylation membrane anchors. A cancer-related intracellular NTRK2-fusion protein (SQSTM1-NTRK2) also underwent constitutive kinase activation. In glioblastoma-like U87MG cells, self-active TrkB kinase reduced cell migration. These constitutive signaling pathways could be fully blocked within minutes by clinically approved, anti-tumorigenic Trk inhibitors. Moreover, this study found evidences for constitutively active, intracellular TrkB in tissue of human grade IV glioblastoma. In conclusion, the data provide an explanation and biological function for selfactive, constitutive TrkB kinase domain signaling, in the absence of a ligand.
The incidence of cancer cases is rising steadily, while improved early detection and new cancer-specific therapies are reducing the mortality rate. In addition to curing cancer or prolonging life, increasing the quality of life is thus an important goal of oncology, which is why the burdens of cancer and treatment are becoming more important. A common side effect of cancer and its therapy is cancer-related fatigue, a tiredness that manifests itself on physical, emotional and cognitive levels and is not in proportion to previous physical efforts. Since the etiology of fatigue has not yet been fully clarified, symptom-oriented therapy is preferable to cause-specific therapy. In addition to activity management, sleep hygiene, and cognitive behavioral therapy, mind-body interventions such as yoga are recommended for reducing fatigue.
Previous studies with small sample sizes were able to examine the efficacy of yoga regarding fatigue predominantly in patients with breast cancer. Long-term effects of yoga have rarely been studied and there have been no attempts to increase long-term effects through interventions such as reminder e-mails. This dissertation takes a closer look at these mentioned aspects of the study sample and long-term effects. An 8-week randomized controlled yoga intervention was conducted, including patients with different cancer types reporting mild to severe fatigue. Following the 8-week yoga therapy, a randomized group of participants received weekly reminder e-mails for 6 months for regular yoga practice, whereas the control group did not receive reminder e-mails.
The first paper is a protocol article, which addresses the design and planned implementation of the research project this dissertation is based upon. This serves to ensure better replicability and comparability with other yoga studies. Due to a very low consent rate of patients in the pilot phase, it was necessary to deviate from the protocol article in the actual implementation and the planned inclusion criterion of fatigue >5 was reduced to fatigue >1.
The second paper examines the efficacy of the eight-week yoga intervention. Patients in the intervention group who participated in the yoga classes seven times or more showed a significantly greater reduction in general and physical fatigue than those who participated less often. The efficacy of yoga was related to the number of attended yoga sessions. Women with breast cancer who participated in yoga reported greater reductions in fatigue than women with other cancer types. There was also an improvement for depression and quality of life after eight weeks of yoga therapy compared to no yoga therapy. These results imply that yoga is helpful in reducing depression and cancer-related fatigue, especially in terms of physical aspects and improving quality of life.
The third paper focuses on the efficacy of reminder e-mails in terms of fatigue and practice frequency. Patients who received reminder e-mails reported greater reductions in general and emotional fatigue, as well as significant increases in practice frequency, compared to patients who did not receive reminder e-mails. Compared to fatigue scores before yoga, significantly lower fatigue and depression scores and higher quality of life were reported after yoga therapy and at follow-up six months later. Weekly e-mail reminders after yoga therapy may have positive effects on general and emotional fatigue and help cancer patients with fatigue establish a regular yoga practice at home. However, higher practice frequency did not lead to higher improvement in physical fatigue as found in Paper 2. This may indicate other factors that influence the efficacy of yoga practice on physical fatigue, such as mindfulness or side effects of therapy.
This research project provides insight into the efficacy of yoga therapy for oncology patients with fatigue. It is important that such interventions be offered early, while fatigue symptoms are not too severe. Regular guided yoga practice can reduce physical fatigue, but subsequent yoga practice at home does not further reduce physical fatigue. Reminder emails after completed yoga therapy could only reduce patients' emotional fatigue. It may be that physical fatigue was reduced as much as possible by the previous yoga therapy and that there was a floor effect, or it may be that reminder emails are not suitable as an intervention to reduce physical fatigue at all. Further research is needed to examine the mechanisms of the different interventions in more detail and to find appropriate interventions that reduce all levels of fatigue equally.
Recent progress in nanotechnology has attracted interest to a biomedical application of the carbon nanoparticle C60 fullerene (C60) due to its unique structure and versatile biological activity. In the current study the dual functionality of C60 as a photosensitizer and a drug nanocarrier was exploited to improve the efficiency of chemotherapeutic drugs towards human leukemic cells.
Pristine C60 demonstrated time-dependent accumulation with predominant mitochondrial localization in leukemic cells. C60’s effects on leukemic cells irradiated with high power single chip LEDs of different wavelengths were assessed to find out the most effective photoexcitation conditions. A C60-based noncovalent nanosized system as a carrier for an optimized drug delivery to the cells was evaluated in accordance to its physicochemical properties and toxic effects. Finally, nanomolar amounts of C60-drug nanocomplexes in 1:1 and 2:1 molar ratios were explored to improve the efficiency of cell treatment, complementing it with photodynamic approach.
A proposed treatment strategy was developed for C60 nanocomplexes with the common chemotherapeutic drug Doxorubicin, whose intracellular accumulation and localization, cytotoxicity and mechanism of action were investigated. The developed strategy was revealed to be transferable to an alternative potent anticancer drug – the herbal alkaloid Berberine.
Hereafter, a strong synergy of treatments arising from the combination of C60-mediated drug delivery and C60 photoexcitation was revealed. Presented data indicate that a combination of chemo- and photodynamic treatments with C60-drug nanoformulations could provide a promising synergetic approach for cancer treatment.
Squamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damage repair, apoptosis and oncogenesis. In squamous cell carcinoma, USP28 is strongly expressed and stabilizes the essential squamous transcription factor ΔNp63, together with important oncogenic factors, such as NOTCH1, c-MYC and c-JUN. It is presumed that USP28 is an oncoprotein; however, recent data suggest that the deubiquitinase also has an antineoplastic effect regulating important tumor suppressor proteins, such as p53 and CHK2. In this review, we discuss: (1) The emerging role of USP28 in cancer. (2) The complexity and mutational landscape of squamous tumors. (3) The genetic alterations and cellular pathways that determine the function of USP28 in squamous cancer. (4) The development and current state of novel USP28 inhibitors.
Simple Summary
Despite significant strides in multimodal therapy, cancers still rank within the first three causes of death especially in industrial nations. A lack of individualized approaches and accurate preclinical models are amongst the major barriers that limit the development of novel therapeutic options and drugs. Recently, the 3D culture system of organoids was developed which stably retains the genetic and phenotypic characteristics of the original tissue, healthy as well as diseased. In this review, we summarize current data and evidence on the relevance and reliability of such organoid culture systems in cancer research, focusing on their role in drug investigations (in a personalized manner).
Abstract
Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.
Purpose
The subclassification of adrenal cancers according to the WHO classification in ordinary, myxoid, oncocytic, and sarcomatoid as well as pediatric types is well established, but the criteria for each subtype are not sufficiently determined and the relative frequency of the different types of adrenal cancers has not been studied in large cohorts. Therefore, our large collection of surgically removed adrenal cancers should be reviewed o establish the criteria for the subtypes and to find out the frequency of the various types.
Methods
In our series of 521 adrenal cancers the scoring systems of Weiss et al., Hough et al., van Slooten et al. and the new Helsinki score system were used for the ordinary type of cancer (97% of our series) and the myxoid type (0.8%). For oncocytic carcinomas (2%), the scoring system of Bisceglia et al. was applied.
Results
Discrepancies between benign and malignant diagnoses from the first thee classical scoring systems are not rare (22% in our series) and could be resolved by the Helsinki score especially by Ki-67 index (more than 8% unequivocally malignant). Since all our cancer cases are positive in the Helsinki score, this system can replace the three elder systems. For identification of sarcomatoid cancer as rarest type in our series (0.2%), the scoring systems are not practical but additional immunostainings used for soft tissue tumors and in special cases molecular pathology are necessary to differentiate these cancers from adrenal sarcomas. According to the relative frequencies of the different subtypes of adrenal cancers the main type is the far most frequent (97%) followed by the oncocytic type (2%), the myxoid type (0.8%) and the very rare sarcomatoid type (0.2%).
Conclusions
The Helsinki score is the best for differentiating adrenal carcinomas of the main, the oncocytic, and the myxoid type in routine work. Additional scoring systems for these carcinomas are generally not any longer necessary. Signs of proliferation (mitoses and Ki-67 index) and necroses are the most important criteria for diagnosis of malignancy.
Objective
In order to optimize psycho‐oncological care, studies that quantify the extent of distress and identify certain risk groups are needed. Among patients with prostate cancer (PCa), findings on depression and anxiety are limited.
Methods
We analyzed data of PCa patients selected from a German multi‐center study. Depression and anxiety were assessed with the PHQ‐9 and the GAD‐7 (cut‐off ≥7). We provided physical symptom burden, calculated absolute and relative risk (AR and RR) of depression and anxiety across patient subsets and between patients and the general population (GP) and tested age as a moderator within the relationship of disease‐specific symptoms with depression and anxiety.
Results
Among 636 participants, the majority reported disease‐specific problems (sexuality: 60%; urination: 52%). AR for depression and anxiety was 23% and 22%, respectively. Significant RR were small, with higher risks of distress in patients who are younger (eg, RR\(_{depression}\) = 1.15; 95%‐CI: 1.06‐1.26), treated with chemotherapy (RR\(_{depression}\)n = 1.46; 95%‐CI: 1.09‐1.96) or having metastases (RR\(_{depression}\) = 1.30; 95%‐CI: 1.02‐1.65). Risk of distress was slightly elevated compared to GP (eg, RR\(_{depression}\) = 1.13; 95%‐CI: 1.07‐1.19). Age moderated the relationship between symptoms and anxiety (B\(_{urination}\) = −0.10, P = .02; B\(_{sexuality}\) = −0.11, P = .01).
Conclusions
Younger patients, those with metastases or treatment with chemotherapy seem to be at elevated risk for distress and should be closely monitored. Many patients suffer from disease‐specific symptom burden, by which younger patients seem to be particularly distressed. Support of coping mechanisms associated with disease‐specific symptom burden seems warranted.
Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I–III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers.
Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a “Trojan horse” for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors.
Objective
The admission interview in oncological inpatient rehabilitation might be a good opportunity to identify cancer patients' needs present after acute treatment. However, a relevant number of patients may not express their needs. In this study, we examined (a) the proportion of cancer patients with unexpressed needs, (b) topics of unexpressed needs and reasons for not expressing needs, (c) correlations of not expressing needs with several patient characteristics, and (d) predictors of not expressing needs.
Methods
We enrolled 449 patients with breast, prostate, and colon cancer at beginning and end of inpatient rehabilitation. We obtained self‐reports about unexpressed needs and health‐related variables (quality of life, depression, anxiety, adjustment disorder, and health literacy). We estimated frequencies and conducted correlation and ordinal logistic regression analyses.
Results
A quarter of patients stated they had “rather not” or “not at all” expressed all relevant needs. Patients mostly omitted fear of cancer recurrence. Most frequent reasons for not expressing needs were being focused on physical consequences of cancer, concerns emerging only later, and not knowing about the possibility of talking about distress. Not expressing needs was associated with several health‐related outcomes, for example, emotional functioning, adjustment disorder, fear of progression, and health literacy. Depression measured at the beginning of rehabilitation showed only small correlations and is therefore not sufficient to identify patients with unexpressed needs.
Conclusions
A relevant proportion of cancer patients reported unexpressed needs in the admission interview. This was associated with decreased mental health. Therefore, it seems necessary to support patients in expressing needs.