Applications of metabolomics in cancer research

The first discovery of metabolic changes in cancer occurred almost a century ago. While the genetic underpinnings of cancer have dominated its study since then, altered metabolism has recently been acknowledged as a key hallmark of cancer and metabolism-focused research has received renewed attention. The emerging field of metabolomics - which attempts to profile all metabolites within a cell or biological system - is now being used to analyze cancer metabolism on a system-wide scale, painting a broad picture of the altered pathways and their interactions with each other. While a large fraction of cancer metabolomics research is focused on finding diagnostic biomarkers, metabolomics is also being used to obtain more fundamental mechanistic insight into cancer and carcinogenesis. Applications of metabolomics are also emerging in areas such as tumor staging and assessment of treatment efficacy. This review summarizes contributions that metabolomics has made in cancer research and presents the current challenges and potential future directions within the field

Color pattern recognition with circular component whitening

Polychromatic object recognition based on circular whitening preprocessing of red-green-blue components and multichannel matched filtering is described. Computer simulations and experimental results are provided to facilitate recognizing a color target among objects of similar shape but with different color contents. Experimental results are obtained with an optical correlator with two spatial light modulators, one to introduce the scene and the second one to introduce the filter

The Metabolomics Society-Current State of the Membership and Future Directions.

Background: In 2017, the Metabolomics Society conducted a survey among its members to assess the degree of its current success, define opportunities for improving its service to the community and make plans to establish future goals and direction of the Society. Methods: A 32-question online survey was sent via e-mail to all Metabolomics Society members as of 19 June 2017 (n = 644). In addition to the direct e-mails, the link to access the survey was made available through social media. The survey was open until 10 August 2017. Question-specific data were reported using the summary data generated by SurveyMonkey and additional stratified analyses performed using Stata 15. Results: The number of respondents was 394 (61%) with 348 (88%) completing the multiple-choice questions in survey. Metabolomics Society annual meetings, networking and the opportunity to join the global metabolomics community were among the most important benefits expressed by the Metabolomics Society members. Conclusions: The survey collected the first data focusing on membership issues from Society members. The Society should focus on collecting and monitoring of demographic data during the membership registration process; continuing to support the early-career members of the Society; and developing initiatives that focus on member networking to retain and increase Society membership

Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: A retrospective assessment

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. METHODS: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. RESULTS: Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. CONCLUSION: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials

Influence of two pt(iv) complexes on viability, apoptosis and cell cycle of B16 mouse melanoma tumors

Several platinum(IV) complexes are showing considerable promise in initial trials, producing reactive intermediates that then interact with DNA. Aim: To perform in vitro study of two new platinum(IV) complexes cytotoxic effect on B16 mouse melanoma cells. Methods: PtCl₄ (dbtp)₂ and PtCl₂ (6mp)₂ complexes were prepared. PtCl₄ (dbtp)₂ was created as modification of PtCl₄ (dmtp) test previously.Apoptosis and necrosis were examined using flow cytometry, upon Annexin V/PI staining. Results: LC₁₀,LC₅₀ andLC₉₀ parameters established for PtCl₄ (dbtp)₂ were as following: 2.6, 17.0, 58.0 μmol/L. However LC₁₀ andLC₅₀ established for PtCl₂ (6mp)₂ were 1.2 and 14.0μmol/l respectively. The both complexes induced apoptosis. PtCl₂ (6mp)₂ induced cell cycle arrest in G0/G1, while PtCl₄ (dbtp)₂ — in S-phase. Conclusions: PtCl₄ (dbtp)₂ appeared to be more cytotoxic against B16 cells than PtCl₂ (6mp)₂ . Apoptosis was the main mechanism of cell loss in cultures incubated with both tested complexes

Treosulfan-fludarabine-thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies

Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I–IV and 26.6% for grades II–IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies

Biological and clinical significance of cancer stem cell plasticity

In the past decade, the traditional view of cancers as a homogeneous collection of malignant cells is being replaced by a model of ever increasing complexity suggesting that cancers are complex tissues composed of multiple cell types. This complex model of tumorigenesis has been well supported by a growing body of evidence indicating that most cancers including those derived from blood and solid tissues display a hierarchical organization of tumor cells with phenotypic and functional heterogeneity and at the apex of this hierarchy are cells capable of self-renewal. These “tumor imitating cells” or “cancer stem cells” drive tumorigenesis and contribute to metastasis, treatment resistance and tumor relapse. Although tumor stem cells themselves may display both genetic and phenotypic heterogeneity, recent studies have demonstrated that cancer stem cells maintain plasticity to transition between mesenchymal-like (EMT) and epithelial-like (MET) states, which may be regulated by the tumor microenvironment. These stem cell state transitions may play a fundamental role in tumor progression and treatment resistance. In this review, we discuss the emerging knowledge regarding the plasticity of cancer stem cells with an emphasis on the signaling pathways and noncoding RNAs including microRNAs (miRNA) and long non-coding RNAs (lncRNAs) in regulation of this plasticity during tumor growth and metastasis. Lastly, we point out the importance of targeting both the EMT and MET states of CSCs in order to eliminate these lethal seeds of cancers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40169-014-0032-3) contains supplementary material, which is available to authorized users

Normalizing Community Mask-Wearing: A Cluster Randomized Trial in Bangladesh

Background: A growing body of scientific evidence suggests that face masks can slow the spread of COVID-19 and save lives, but mask usage remains low across many parts of the world, and strategies to increase mask usage remain untested and unclear. Methods: We conducted a cluster-randomized trial of community-level mask promotion in rural Bangladesh involving 341,830 adults in 600 villages. We employed a series of strategies to promote mask usage, including free household distribution of surgical or cloth masks, distribution and promotion at markets and mosques, mask advocacy by Imams during Friday prayers, role modeling by local leaders, promoters periodically monitoring passers-by and reminding people to put on masks, village police accompanying those mask promoters, providing monetary rewards or certificates to villages if mask-wearing rate improves, public signaling of mask-wearing via signage, text message reminders, messaging emphasizing either altruistic or self-protection motives for mask-wearing, and extracting verbal commitments from households. The primary objective was to assess which of these interventions would increase proper (covering nose and mouth) wearing of face masks, and secondarily, whether mask promotion unintentionally creates moral hazard and decreases social distancing. This analysis is part of larger study evaluating the effect of mask-wearing on transmission of SARS-CoV-2. Results: There were 64,937 households in the intervention group and 64,183 households in the control group; study recruitment has ended. In the control group, proper mask-wearing was practiced by 13% of those observed across the study period. Free distribution of masks along with role modeling by community leaders produced only small increases in mask usage during pilot interventions. Adding periodic monitoring by mask promoters to remind people in streets and public places to put on the masks we provided increased proper mask-wearing by 29.0 percentage points (95% CI: 26.7% - 31.3%). This tripling of mask usage was sustained over all 10 weeks of surveillance, which includes a period after intervention activities ended. Physical distancing, measured as the fraction of individuals at least one arm’s length apart, also increased by 5.2 percentage points (95% CI: 4.2%-6.3%). Beyond the core intervention package comprised of free distribution and promotion at households/mosques/markets, leader endorsements plus periodic monitoring and reminders, several elements had no additional effect on mask wearing, including: text reminders, public signage commitments, monetary or non-monetary incentives, altruistic messaging or verbal commitments, or village police accompanying the mask promoters (the last not cross-randomized, but assessed in panel data). No adverse events were reported during the study period. Conclusions: Our intervention demonstrates a scalable and cost-effective method to promote mask adoption and save lives, and identifies a precise combination of intervention activities that were necessary. Comparisons between pilots shows that free mask distribution alone is not sufficient to increase mask-wearing, but adding periodic monitoring in public places to remind people to wear the distributed masks had large effects on behavior. The absence of any further effect of the village police suggests that the operative mechanism is not any threat of formal legal sanctions, but shame and people’s aversion to a light informal social sanction. The persistence of effects for 10 weeks and after the end of the active intervention period, as well as increases in physical distancing, all point to changes in social norms as a key driver of behavior change. Our cross-randomizations suggest that improved mask-wearing norms can be achieved without incentives that require costly monitoring, that aesthetic design choices and colors can influence mask-wearing, and that surgical masks with a substantially higher filtration efficiency can be a cost-effective alternative to cloth masks (1/3 the cost) and are equally or more likely to be worn. Implementing these interventions – including distribution of free masks, and the information campaign, reminders, encouragement – cost $2.30-$3.75 per villager, or between $8 and$13 per person adopting a mask. Combined with existing estimates of the efficacy of masks in preventing COVID-19 deaths, this implies that the intervention cost $28,000-$66,000 per life saved. Beyond reducing the transmission of COVID-19, mask distribution is likely to be a cost-effective strategy to prevent future respiratory disease outbreaks

Correction: Long-term outcome after allogeneic hematopoietic stem cell transplantation for Shwachman–Diamond syndrome: a retrospective analysis and a review of the literature by the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation (SAAWP-EBMT)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorder in Children Treated with Rituximab: The Impact of Viral Load and Non-Lymphoid Tissue Involvement

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