Targeting MYC induces lipid droplet accumulation by upregulation of HILPDA in clear cell renal cell carcinoma.

Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.

Bedtime to the brain: how infants' sleep behaviours intertwine with non-rapid eye movement sleep electroencephalography features.

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioural function. Observational research has associated early life sleep problems with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep behaviours (e.g., duration, regularity) in early life relate to non-rapid eye movement (NREM) neurophysiology-acutely and the long-term-remains to be studied. We measured sleep behaviours in 32 healthy 6-month-olds assessed with actimetry and neurophysiology with high-density electroencephalography (EEG) to investigate the association between NREM sleep and habitual sleep behaviours. Our study revealed four findings: first, daytime sleep behaviours are related to EEG slow-wave activity (SWA). Second, night-time movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as delta coherence. And lastly, delta coherence at 6 months predicts night-time sleep duration at 12 months. These novel findings widen our understanding that infants' sleep behaviours are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). The crucial next step is to extend this concept to clinical groups to objectively characterise infants' sleep behaviours 'at risk' that foster later neurodevelopmental problems.

Not simply a matter of parents-Infants' sleep-wake patterns are associated with their regularity of eating.

In adults there are indications that regular eating patterns are related to better sleep quality. During early development, sleep and eating habits experience major maturational transitions. Further, the bacterial landscape of the gut microbiota undergoes a rapid increase in complexity. Yet little is known about the association between sleep, eating patterns and the gut microbiota. We first hypothesized that higher eating regularity is associated with more mature sleep patterns, and second, that this association is mediated by the maturational status of the gut microbiota. To test this hypothesis, we performed a longitudinal study in 162 infants to assess actigraphy, diaries of sleep and eating times, and stool microbiota composition at ages 3, 6 and 12 months. To comprehensively capture infants' habitual sleep-wake patterns, 5 sleep composites that characterize infants' sleep habits across multiple days in their home environment were computed. To assess timing of eating habits, we developed an Eating Regularity Index (ERI). Gut microbial composition was assessed by 16S rRNA gene amplicon sequencing, and its maturation was assessed based on alpha diversity, bacterial maturation index, and enterotype. First, our results demonstrate that increased eating regularity (higher ERI) in infants is associated with less time spent awake during the night (sleep fragmentation) and more regular sleep patterns. Second, the associations of ERI with sleep evolve with age. Third, the link between infant sleep and ERI remains significant when controlling for parents' subjectively rated importance of structuring their infant's eating and sleeping times. Finally, the gut microbial maturational markers did not account for the link between infant's sleep patterns and ERI. Thus, infants who eat more regularly have more mature sleep patterns, which is independent of the maturational status of their gut microbiota. Interventions targeting infant eating rhythm thus constitute a simple, ready-to-use anchor to improve sleep quality.

Learning during sleep in humans - A historical review.

Sleep helps to consolidate previously acquired memories. Whether new information such as languages and other useful skills can also be learned during sleep has been debated for over a century, however, the sporadic studies' different objectives and varied methodologies make it difficult to draw definitive conclusions. This review provides a comprehensive overview of the history of sleep learning research conducted in humans, from its empirical beginnings in the 1940s to the present day. Synthesizing the findings from 51 research papers, we show that several studies support the notion that simpler forms of learning, such as habituation and conditioning, are possible during sleep. In contrast, the findings for more complex, applied learning (e.g., learning a new language during sleep) are more divergent. While there is often an indication of processing and learning during sleep when looking at neural markers, behavioral evidence for the transfer of new knowledge to wake remains inconclusive. We close by critically examining the limitations and assumptions that have contributed to the discrepancies in the literature and highlight promising new directions in the field.

Lack of association between behavioral development and simplified topographical markers of the sleep EEG in infancy.

The sleep EEG mirrors neuronal connectivity, especially during development when the brain undergoes substantial rewiring. As children grow, the slow-wave activity (SWA; 0.75-4.25 Hz) spatial distribution in their sleep EEG changes along a posterior-to-anterior gradient. Topographical SWA markers have been linked to critical neurobehavioral functions, such as motor skills, in school-aged children. However, the relationship between topographical markers in infancy and later behavioral outcomes is still unclear. This study aims to explore reliable indicators of neurodevelopment in infants by analyzing their sleep EEG patterns. Thirty-one 6-month-old infants (15 female) underwent high-density EEG recordings during nighttime sleep. We defined markers based on the topographical distribution of SWA and theta activity, including central/occipital and frontal/occipital ratios and an index derived from local EEG power variability. Linear models were applied to test whether markers relate to concurrent, later, or retrospective behavioral scores, assessed by the parent-reported Ages & Stages Questionnaire at ages 3, 6, 12, and 24 months. Results indicate that the topographical markers of the sleep EEG power in infants were not significantly linked to behavioral development at any age. Further research, such as longitudinal sleep EEG in newborns, is needed to better understand the relationship between these markers and behavioral development and assess their predictive value for individual differences.

Identification and validation of NFIA as a novel prognostic marker in renal cell carcinoma.

Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression and malignancy, as a blueprint. Through transcriptomic analyses, we show that the nuclear factor I A (NFIA)-driven transcription network is active in primary RCC and that higher levels of NFIA confer a survival benefit. We validate our findings using immunohistochemical staining and analysis of a 363-patient tissue microarray (TMA), showing for the first time that NFIA can independently predict poor cancer-specific survival in clear cell RCC (ccRCC) patients (hazard ratio = 0.46, 95% CI = 0.24-0.85, p value = 0.014). Furthermore, we confirm the association of HNF4A with higher grades and stages in ccRCC in our TMA cohort. We present novel data that show HNF4A protein expression does not confer favourable prognosis in papillary RCC, confirming our survival analysis with publicly available HNF4A RNA expression data. Further work is required to elucidate the functional role of NFIA in RCC as well as the testing of these markers on patient material from diverse multi-centre cohorts, to establish their value for the prognostication of RCC.

Memory reactivations during sleep: a neural basis of dream experiences?

Newly encoded memory traces are spontaneously reactivated during sleep. Since their discovery in the 1990s, these memory reactivations have been discussed as a potential neural basis for dream experiences. New results from animal and human research, as well as from the rapidly growing field of sleep and dream engineering, provide essential insights into this question, and reveal both strong parallels and disparities between the two phenomena. We suggest that, although memory reactivations may contribute to subjective experiences across different states of consciousness, they are not likely to be the primary neural basis of dreaming. We identify important limitations in current research paradigms and suggest novel strategies to address this question empirically.

Neural correlates of sleep-induced benefits on traumatic memory processing.

Recent findings indicate that sleep after trauma compared to sleep loss inhibits intrusive memory development, possibly by promoting adequate memory consolidation and integration. However, the underlying neural mechanisms are still unknown. Here, we examined the neural correlates underlying the effects of sleep on traumatic memory development in 110 healthy participants using a trauma film paradigm and an implicit memory task with fMRI recordings in a between-subjects design. To further facilitate memory integration, we used targeted memory reactivation (TMR) to reactivate traumatic memories during sleep. We found that sleep (i.e., nap) compared to wakefulness reduced the number of intrusive traumatic memories for the experimental trauma groups. TMR during sleep only descriptively reduced the intrusions further. On the level of brain activity, increased activity in the anterior and posterior cingulate cortex, retrosplenial cortex and precuneus was found in the experimental trauma group compared to the control group after wakefulness. After sleep, on the other hand, these findings could not be found in the experimental trauma groups compared to the control group. Sleep compared to wakefulness increased activity in the cerebellum, fusiform gyrus, inferior temporal lobe, hippocampus, and amygdala during implicit retrieval of trauma memories in the experimental trauma groups. Activity in the hippocampus and the amygdala predicted subsequent intrusions. Results demonstrate the beneficial behavioral and neural effects of sleep after experimental trauma and provide indications for early neural predictor factors. This study has implications for understanding the important role of sleep for personalized treatment and prevention in posttraumatic stress disorder.

An infant sleep electroencephalographic marker of thalamocortical connectivity predicts behavioral outcome in late infancy.

Infancy represents a critical period during which thalamocortical brain connections develop and mature. Deviations in the maturation of thalamocortical connectivity are linked to neurodevelopmental disorders. There is a lack of early biomarkers to detect and localize neuromaturational deviations, which can be overcome with mapping through high-density electroencephalography (hdEEG) assessed in sleep. Specifically, slow waves and spindles in non-rapid eye movement (NREM) sleep are generated by the thalamocortical system, and their characteristics, slow wave slope and spindle density, are closely related to neuroplasticity and learning. Spindles are often subdivided into slow (11.0-13.0 Hz) and fast (13.5-16.0 Hz) frequencies, for which not only different functions have been proposed, but for which also distinctive developmental trajectories have been reported across the first years of life. Recent studies further suggest that information processing during sleep underlying sleep-dependent learning is promoted by the temporal coupling of slow waves and spindles, yet slow wave-spindle coupling remains unexplored in infancy. Thus, we evaluated three potential biomarkers: 1) slow wave slope, 2) spindle density, and 3) the temporal coupling of slow waves with spindles. We use hdEEG to first examine the occurrence and spatial distribution of these three EEG features in healthy infants and second to evaluate a predictive relationship with later behavioral outcomes. We report four key findings: First, infants' EEG features appear locally: slow wave slope is maximal in occipital and frontal areas, whereas slow and fast spindle density is most pronounced frontocentrally. Second, slow waves and spindles are temporally coupled in infancy, with maximal coupling strength in the occipital areas of the brain. Third, slow wave slope, fast spindle density, and slow wave-spindle coupling are not associated with concurrent behavioral status (6 months). Fourth, fast spindle density in central and frontocentral regions at age 6 months predicts overall developmental status at age 12 months, and motor skills at age 12 and 24 months. Neither slow wave slope nor slow wave-spindle coupling predict later behavioral development. We further identified spindle frequency as a determinant of slow and fast spindle density, which accordingly, also predicts motor skills at 24 months. Our results propose fast spindle density, or alternatively spindle frequency, as early EEG biomarker for identifying thalamocortical maturation, which can potentially be used for early diagnosis of neurodevelopmental disorders in infants. These findings are in support of a role of sleep spindles in sensorimotor microcircuitry development. A crucial next step will be to evaluate whether early therapeutic interventions may be effective to reverse deviations in identified individuals at risk.

The sleeping brain's connectivity and family environment: characterizing sleep EEG coherence in an infant cohort.

Brain connectivity closely reflects brain function and behavior. Sleep EEG coherence, a measure of brain's connectivity during sleep, undergoes pronounced changes across development under the influence of environmental factors. Yet, the determinants of the developing brain's sleep EEG coherence from the child's family environment remain unknown. After characterizing high-density sleep EEG coherence in 31 healthy 6-month-old infants by detecting strongly synchronized clusters through a data-driven approach, we examined the association of sleep EEG coherence from these clusters with factors from the infant's family environment. Clusters with greatest coherence were observed over the frontal lobe. Higher delta coherence over the left frontal cortex was found in infants sleeping in their parents' room, while infants sleeping in a room shared with their sibling(s) showed greater delta coherence over the central parts of the frontal cortex, suggesting a link between local brain connectivity and co-sleeping. Finally, lower occipital delta coherence was associated with maternal anxiety regarding their infant's sleep. These interesting links between sleep EEG coherence and family factors have the potential to serve in early health interventions as a new set of targets from the child's immediate environment.

Functional lateralization of the medial temporal lobe in novel associative processing during creativity evaluation.

Although hemispheric lateralization of creativity has been a longstanding topic of debate, the underlying neurocognitive mechanism remains poorly understood. Here we designed 2 types of novel stimuli-"novel useful and novel useless," adapted from "familiar useful" designs taken from daily life-to demonstrate how the left and right medial temporal lobe (MTL) respond to novel designs of different usefulness. Taking the "familiar useful" design as a baseline, we found that the right MTL showed increased activation in response to "novel useful" designs, followed by "novel useless" ones, while the left MTL only showed increased activation in response to "novel useful" designs. Calculating an asymmetry index suggests that usefulness processing is predominant in the left MTL, whereas the right MTL is predominantly involved in novelty processing. Moreover, the left parahippocampal gyrus (PHG) showed stronger functional connectivity with the anterior cingulate cortex when responding to "novel useless" designs. In contrast, the right PHG showed stronger connectivity with the amygdala, midbrain, and hippocampus. Critically, multivoxel representational similarity analyses revealed that the left MTL was more effective than the right MTL at distinguishing the usefulness differences in novel stimuli, while representational patterns in the left PHG positively predicted the post-behavior evaluation of "truly creative" products. These findings suggest an apparent dissociation of the left and right MTL in integrating the novelty and usefulness information and novel associative processing during creativity evaluation, respectively. Our results provide novel insights into a longstanding and controversial question in creativity research by demonstrating functional lateralization of the MTL in processing novel associations.

Size-based isolation and detection of renal carcinoma cells from whole blood.

Renal cell carcinoma (RCC) is a tumour type with an indolent growth pattern and rather vague symptoms. The present study developed a platform for liquid biopsy of RCC based upon the isolation of circulating tumour cells (CTCs). Founded on the observation that RCC tumour cells are considerably larger than leucocytes, the present study employed a microfluidics-based system for isolation of RCC CTCs from whole blood. Using this system, it was revealed that 66% of spiked-in RCC tumour cells could be retrieved using this approach. Furthermore, it was demonstrated that these cells could be molecularly detected with digital PCR using RCC-specific genes down to one tumour cell, whilst avoiding detection in samples lacking tumour cells. Finally, subtype specific transcripts were identified to distinguish the different subtypes of RCC, which were then validated in patient tumours. The present study established a novel workflow for the isolation of RCC CTCs from whole blood, with the potential to detect these cells irrespective of subtype.

Association of transportation noise with sleep during the first year of life: A longitudinal study.

STUDY OBJECTIVES: During infancy, adequate sleep is crucial for physical and neurocognitive development. In adults and children, night-time noise exposure is associated with sleep disturbances. However, whether and to what extent infants' sleep is affected, is unknown. Thus, this study investigated the relationship between nocturnal transportation noise and actimetry-derived habitual sleep behavior across the first year of life. METHODS: In 144 healthy infants (63 girls), nocturnal (23:00-7:00) transportation noise (i.e., road, railway, and aircraft) was modelled at the infants' individual places of residence. Using actimetry, we recorded movement patterns for 11 days in a longitudinal design at 3, 6, and 12 months of age and derived the recently proposed core sleep composites of night-time sleep duration, activity, and variability. Using linear mixed-effects models, we determined associations between noise exposure and sleep composites. Sex, gestational age, parents' highest educational level, infants' age, and the existence of siblings served as control variables. RESULTS: In models without interactions, night-time transportation noise was unrelated to sleep composites across the first year of life (p > .16). Exploratory analyses of an interaction between noise and the existence of siblings yielded an association between night-time transportation noise and sleep duration in infants without siblings only (p = .004). CONCLUSION: In our study, sleep in infants during the first year of life was relatively robust against external perturbation by night-time transportation noise. However, particularly in children without siblings increasing night-time transportation noise reduced sleep duration. This suggests that the habitual noise environment may modulate individual susceptibility to adverse effects of noise on sleep.

In Vitro Nephrotoxicity Studies of Established and Experimental Platinum-Based Compounds.

Cisplatin is one of the most commonly used drugs for the treatment of various solid cancers. However, its efficacy is restricted by severe side effects, especially dose-limiting nephrotoxicity. New platinum-based compounds are designed to overcome this limitation. Previous investigations showed that the platinum(IV)-nitroxyl complex PN149 is highly cytotoxic in various tumor cell lines. In the present study, investigations with PN149 were extended to normal human kidney tubule epithelia. Coincident with higher intracellular platinum accumulation, the cytotoxicity of PN149 in the proximal tubule epithelial cell line ciPTEC was more pronounced compared to the established platinum chemotherapeutics cisplatin, carboplatin and oxaliplatin. Quantitative gene expression profiling revealed the induction of ROS-inducible and anti-oxidative genes, suggesting an oxidative stress response by PN149. However, in contrast to cisplatin, no pro-inflammatory response was observed. Genes coding for distinct DNA damage response factors and genes related to apoptosis were up-regulated, indicating the activation of the DNA damage response system and induction of the apoptotic cascade by PN149. Altogether, a comparable transcriptional response was observed for PN149 and the platinum chemotherapeutics. However, the lack of inflammatory activity, which is a possible cause contributing to toxicity in human renal proximal tubule epithelia, might indicate the reduced nephrotoxic potential of PN149.

Sleep behavior of infants with infantile hemangioma treated with propranolol-a cohort study.

Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7-10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted.Conclusion: Propranolol exerts a measurable yet mild impact on objectively assessed infants' sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas. What is Known: • Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation. • Investigations of the sleep pattern in this patient group using objective measures are lacking. What is New: • The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls. • Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.

Platinum Complexes in Colorectal Cancer and Other Solid Tumors.

Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.

Actigraphy in sleep research with infants and young children: Current practices and future benefits of standardized reporting.

Actigraphy is a cost-efficient method to estimate sleep-wake patterns over long periods in natural settings. However, the lack of methodological standards in actigraphy research complicates the generalization of outcomes. A rapidly growing methodological diversity is visible in the field, which increasingly necessitates the detailed reporting of methodology. We address this problem and evaluate the current state of the art and recent methodological developments in actigraphy reporting with a special focus on infants and young children. Through a systematic literature search on PubMed (keywords: sleep, actigraphy, child *, preschool, children, infant), we identified 126 recent articles (published since 2012), which were classified and evaluated for reporting of actigraphy. Results show that all studies report on the number of days/nights the actigraph was worn. Reporting was good with respect to device model, placement and sleep diary, whereas reporting was worse for epoch length, algorithm, artefact identification, data loss and definition of variables. In the studies with infants only (n = 58), the majority of articles (62.1%) reported a recording of actigraphy that was continuous across 24 hr. Of these, 23 articles (63.9%) analysed the continuous 24-hr data and merely a fifth used actigraphy to quantify daytime sleep. In comparison with an evaluation in 2012, we observed small improvements in reporting of actigraphy methodology. We propose stricter adherence to standards in reporting methodology in order to streamline actigraphy research with infants and young children, to improve comparability and to facilitate big data ventures in the sleep community.

Which are the Central Aspects of Infant Sleep? The Dynamics of Sleep Composites across Infancy.

Sleep during infancy is important for the well-being of both infant and parent. Therefore, there is large interest in characterizing infant sleep with reliable tools, for example by combining actigraphy with 24-h-diaries. However, it is critical to select the right variables to characterize sleep. In a longitudinal investigation, we collected sleep data of 152 infants at ages 3, 6, and 12 months. Using principal component analysis, we identified five underlying sleep composites from 48 commonly-used sleep variables: Sleep Night, Sleep Day, Sleep Activity, Sleep Timing, and Sleep Variability. These composites accurately reflect known sleep dynamics throughout infancy as Sleep Day (representing naps), Sleep Activity (representing sleep efficiency and consolidation), and Sleep Variability (representing day-to-day stability) decrease across infancy, while Sleep Night (representing nighttime sleep) slightly increases, and Sleep Timing becomes earlier as one ages. We uncover interesting dynamics between the sleep composites and demonstrate that infant sleep is not only highly variable between infants but also dynamic within infants across time. Interestingly, Sleep Day is associated with behavioral development and therefore a potential marker for maturation. We recommend either the use of sleep composites or the core representative variables within each sleep composite for more reliable research.

Comparative Study of the Mode of Action of Clinically Approved Platinum-Based Chemotherapeutics.

Platinum drugs are among the most effective anticancer agents, but their mode of action is still not fully understood. We therefore carried out a systematic investigation on the cellular activities of cisplatin, carboplatin and oxaliplatin in A498 kidney cancer cells. Cytotoxicity was higher for cisplatin and oxaliplatin compared to carboplatin, with induction of apoptosis as the preferred mode of cell death. Gene expression profiling displayed modulation of genes related to DNA damage response/repair, cell cycle regulation and apoptosis which was more pronounced upon oxaliplatin treatment. Furthermore, repression of specific DNA repair genes was restricted to oxaliplatin. Transcriptional level observations were further analyzed on the functional level. Uptake studies revealed low intracellular platinum accumulation and DNA platination upon carboplatin treatment. Removal of overall DNA platination was comparable for the three drugs. However, no processing of oxaliplatin-induced interstrand crosslinks was observed. Cisplatin and carboplatin influenced cell cycle distribution comparably, while oxaliplatin had no effect. Altogether, we found a similar mode of action for cisplatin and carboplatin, while the activity of oxaliplatin appeared to differ. This might be clinically relevant as due to the difference in mode of action oxaliplatin could be active in tumors which show resistance towards cisplatin and carboplatin.