Corrupting Capitalism: Michael Ende’s Momo and “Cathedral Station”

Michael Ende, the well-known author of The Neverending Story, foresaw dramatic changes in the fabric of society resulting from a turn toward neoliberal policies. One such far-reaching and dangerous change has to do with a diminishing of temporal autonomy, the ability to freely determine the use and meaning of our time. This article explores how neoliberalism is shaping our concept of time and our experience of it. In an effort to demonstrate the process and the line of reasoning behind the monetization of time, and to connect time to more qualitative considerations of the human condition, I shall demonstrate how Ende conceptualizes time as an integral part of the accumulation process of capitalism. I also discuss a fairly cryptic short story, “Cathedral Station,” that envisions “the mystery of money.” Utilizing Walter Benjamin’s critique issued in his 1921 fragment “Capitalism as Religion,” I outline Ende’s dystopian vision of the uncontested, unquestioned reign of capitalism as a religious cult. Read together, the novel and the short story offer a way of contrasting two extreme byproducts of capitalism’s colonization of time, namely what I would call an “ideology of work” and an “ideology of growth.” The first of these is a result of capitalism’s commodification of time according to liberal ideals such as choice, freedom, and self-interest. The second is a decidedly neoliberal phenomenon in that the “financialization of everything,” to use David Harvey’s phrase, results in the ever-present expectation of unlimited, exponential growth. By drawing out these two interconnected ideologies through close readings, the subtle processes of capitalism’s colonization of time are revealed

Extravesicular TIMP-1 is a non-invasive independent prognostic marker and potential therapeutic target in colorectal liver metastases

Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role of extravesicular tissue inhibitor of matrix metalloproteinase-1 (TIMP1EV) in pro-invasive extracellular matrix (ECM) remodelling of the liver microenvironment to aid tumour progression in colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression of stromal TIMP1 in the invasion front that was associated with poor progression-free survival in patients with colorectal liver metastases. Molecular analysis identified TIMP1EV enrichment in CRC-EVs as a major factor in the induction of TIMP1 upregulation in recipient fibroblasts. Mechanistically, we proved that EV-mediated TIMP1 upregulation in recipient fibroblasts induced ECM remodelling. This effect was recapitulated by human serum-derived EVs providing strong evidence that CRC release active EVs into the blood circulation of patients for the horizontal transfer of malignant traits to recipient cells. Moreover, EV-associated TIMP1 binds to HSP90AA, a heat-shock protein, and the inhibition of HSP90AA on human-derived serum EVs attenuates TIMP1EV-mediated ECM remodelling, rendering EV-associated TIMP1 a potential therapeutic target. Eventually, in accordance with REMARK guidelines, we demonstrated in three independent cohorts that EV-bound TIMP1 is a robust circulating biomarker for a non-invasive, preoperative risk stratification in patients with colorectal liver metastases

Evaluation of response using FDG-PET/CT and diffusion weighted MRI after radiochemotherapy of pancreatic cancer: a non-randomized, monocentric phase II clinical trial—PaCa-DD-041 (Eudra-CT 2009-011968-11)

Abstract Background Pancreatic cancer is a devastating disease with a 5-year survival rate of 20–25%. As approximately only 20% of patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence, neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor. The aim of this non-randomized, monocentric, prospective, phase II clinical study was to assess the prognostic value of functional imaging techniques, i.e., [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) and diffusion weighted magnetic resonance imaging (DW-MRI), prior to and during neoadjuvant radiochemotherapy. Methods Patients with histologically proven resectable, borderline resectable or unresectable non-metastatic pancreatic adenocarcinoma received induction chemotherapy followed by neoadjuvant radiochemotherapy. Patients underwent FDG-PET/CT and DW-MRI including T1- and T2-weighted sequences prior to and after neoadjuvant chemotherapy as well as following induction radiochemotherapy. The primary endpoint was the evaluation of the response as quantified by the standardized uptake value (SUV) measured with FDG-PET. Response to treatment was evaluated by FDG-PET and DW-MRI during and after the neoadjuvant course. Morphologic staging was performed using contrast-enhanced CT and contrast-enhanced MRI to decide inclusion of patients and resectability after neoadjuvant therapy. In those patients undergoing subsequent surgery, imaging findings were correlated with those of the pathologic resection specimen. Results A total of 25 patients were enrolled in the study. The response rate measured by FDG-PET was 85% with a statistically significant decrease of the maximal SUV (SUVmax) during therapy (p < 0.001). Using the mean apparent diffusion coefficient (ADC), response was not detectable with DW-MRI. After neoadjuvant treatment 16 patients underwent surgery. In 12 (48%) patients tumor resection could be performed. The median overall survival of all patients was 25 months (range: 7–38 months). Conclusion Based on these limited patient numbers, it was possible to show that this trial design is feasible and that the neoadjuvant therapy regime was well tolerated. FDG-PET/CT may be a reliable method to evaluate response to the combined therapy. In contrast, when evaluating the response using mean ADC, DW-MRI did not show conclusive results

Low level of exosomal long non-coding RNA HOTTIP is a prognostic biomarker in colorectal cancer

Molecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs (H19, HOTTIP, HULC and MALAT1) derived from serum exosomes of patients with non-metastatic CRC and healthy donors was analyzed. Exosomes from healthy donors carried significantly more H19, HULC and HOTTIP transcripts in comparison to CRC patients. Correlation analysis between lncRNAs and clinical data revealed a statistical significance between low levels of exosomal HOTTIP and poor overall survival. This was confirmed by multivariate analysis that HOTTIP is an independent prognostic marker for overall survival (HR: 4.5, CI: 1.69–11.98, p = 0.0027). Here, HOTTIP poses to be a valid biomarker for patients with a CRC to predict post-surgical survival time. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group

Plasma extracellular vesicle messenger RNA profiling identifies prognostic EV signature for non-invasive risk stratification for survival prediction of patients with pancreatic ductal adenocarcinoma

Background The prognosis of pancreatic ductal adenocarcinoma (PDAC) is one of the most dismal of all cancers and the median survival of PDAC patients is only 6–8 months after diagnosis. While decades of research effort have been focused on early diagnosis and understanding of molecular mechanisms, few clinically useful markers have been universally applied. To improve the treatment and management of PDAC, it is equally relevant to identify prognostic factors for optimal therapeutic decision-making and patient survival. Compelling evidence have suggested the potential use of extracellular vesicles (EVs) as non-invasive biomarkers for PDAC. The aim of this study was thus to identify non-invasive plasma-based EV biomarkers for the prediction of PDAC patient survival after surgery. Methods Plasma EVs were isolated from a total of 258 PDAC patients divided into three independent cohorts (discovery, training and validation). RNA sequencing was first employed to identify differentially-expressed EV mRNA candidates from the discovery cohort (n = 65) by DESeq2 tool. The candidates were tested in a training cohort (n = 91) by digital droplet polymerase chain reaction (ddPCR). Cox regression models and Kaplan–Meier analyses were used to build an EV signature which was subsequently validated on a multicenter cohort (n = 83) by ddPCR. Results Transcriptomic profiling of plasma EVs revealed differentially-expressed mRNAs between long-term and short-term PDAC survivors, which led to 10 of the top-ranked candidate EV mRNAs being tested on an independent training cohort with ddPCR. The results of ddPCR enabled an establishment of a novel prognostic EV mRNA signature consisting of PPP1R12A, SCN7A and SGCD for risk stratification of PDAC patients. Based on the EV mRNA signature, PDAC patients with high risk displayed reduced overall survival (OS) rates compared to those with low risk in the training cohort (p = 0.014), which was successfully validated on another independent cohort (p = 0.024). Interestingly, the combination of our signature and tumour stage yielded a superior prognostic performance (p = 0.008) over the signature (p = 0.022) or tumour stage (p = 0.016) alone. It is noteworthy that the EV mRNA signature was demonstrated to be an independent unfavourable predictor for PDAC prognosis. Conclusion This study provides a novel and non-invasive prognostic EV mRNA signature for risk stratification and survival prediction of PDAC patients

Corrupting Capitalism: Michael Ende’s Momo and “Cathedral Station”

Michael Ende, the well-known author of The Neverending Story , foresaw dramatic changes in the fabric of society resulting from a turn toward neoliberal policies. One such far-reaching and dangerous change has to do with a diminishing of temporal autonomy, the ability to freely determine the use and meaning of our time. This article explores how neoliberalism is shaping our concept of time and our experience of it. In an effort to demonstrate the process and the line of reasoning behind the monetization of time, and to connect time to more qualitative considerations of the human condition, I shall demonstrate how Ende conceptualizes time as an integral part of the accumulation process of capitalism. I also discuss a fairly cryptic short story, “Cathedral Station,” that envisions “the mystery of money.” Utilizing Walter Benjamin’s critique issued in his 1921 fragment “Capitalism as Religion,” I outline Ende’s dystopian vision of the uncontested, unquestioned reign of capitalism as a religious cult. Read together, the novel and the short story offer a way of contrasting two extreme byproducts of capitalism’s colonization of time, namely what I would call an “ideology of work” and an “ideology of growth.” The first of these is a result of capitalism’s commodification of time according to liberal ideals such as choice, freedom, and self-interest. The second is a decidedly neoliberal phenomenon in that the “financialization of everything,” to use David Harvey’s phrase, results in the ever-present expectation of unlimited, exponential growth. By drawing out these two interconnected ideologies through close readings, the subtle processes of capitalism’s colonization of time are revealed