Magnetically Powered Chitosan Milliwheels for Rapid Translation, Barrier Function Rescue, and Delivery of Therapeutic Proteins to the Inflamed Gut Epithelium.

Inflammatory bowel disease (IBD) is mediated by an overexpression of tumor necrosis factor-α (TNF) by mononuclear cells in the intestinal mucosa. Intravenous delivery of neutralizing anti-TNF antibodies can cause systemic immunosuppression, and up to one-third of people are non-responsive to treatment. Oral delivery of anti-TNF could reduce adverse effects; however, it is hampered by antibody degradation in the harsh gut environment during transit and poor bioavailability. To overcome these shortcomings, we demonstrate magnetically powered hydrogel particles that roll along mucosal surfaces, provide protection from degradation, and sustain the local release of anti-TNF. Iron oxide particles are embedded into a cross-linked chitosan hydrogel and sieved to produce 100-200 µm particles called milliwheels (m-wheels). Once loaded with anti-TNF, these m-wheels release 10 to 80% of their payload over 1 week at a rate that depends on the cross-linking density and pH. A rotating magnetic field induces a torque on the m-wheels that results in rolling velocities greater than 500 µm/s on glass and mucus-secreting cells. The permeability of the TNF-challenged gut epithelial cell monolayers was rescued in the presence of anti-TNF carrying m-wheels, which both neutralized the TNF and created an impermeable patch over leaky cell junctions. With the ability to translate over mucosal surfaces at high speed, provide sustained release directly to the inflamed epithelium, and provide barrier rescue, m-wheels demonstrate a potential strategy to deliver therapeutic proteins for the treatment of IBD.

Coupling magnetic torque and force for colloidal microbot assembly and manipulation.

For targeted transport in the body, biomedical microbots (µbots) must move effectively in three-dimensional (3D) microenvironments. Swimming µbots translate via asymmetric or screw-like motions while rolling ones use friction with available surfaces to generate propulsive forces. We have previously shown that planar rotating magnetic fields assemble µm-scale superparamagnetic beads into circular µbots that roll along surfaces. In this, gravity is required to pull µbots near the surface; however, this is not necessarily practical in complex geometries. Here we show that rotating magnetic fields, in tandem with directional magnetic gradient forces, can be used to roll µbots on surfaces regardless of orientation. Simplifying implementation, we use a spinning permanent magnet to generate differing ratios of rotating and gradient fields, optimizing control for different environments. This use of a single magnetic actuator sidesteps the need for complex electromagnet or tandem field setups, removes requisite gravitational load forces, and enables µbot targeting in complex 3D biomimetic microenvironments.

Delivery and actuation of aerosolized microbots.

For disease of the lung, the physical key to effective inhalation-based therapy is size; too large (10's of µm) and the particles or droplets do not remain suspended in air to reach deep within the lungs, too small (subµm) and they are simply exhaled without deposition. µBots within this ideal low-µm size range however are challenging to fabricate and would lead to devices that lack the speed and power necessary for performing work throughout the pulmonary network. To uncouple size from structure and function, here we demonstrate an approach where individual building blocks are aerosolized and subsequently assembled in situ into µbots capable of translation, drug delivery, and mechanical work deep within lung mimics. With this strategy, a variety of pulmonary diseases previously difficult to treat may now be receptive to µbot-based therapies.

Impact of Sepsis Flow Chip, a novelty fast microbiology method, in the treatment of bacteremia caused by Gram-negative bacilli.

OBJECTIVE: The aim of this study was to assess the impact of the information provided by the new Sepsis Chip Flow system (SFC) and other fast microbiological techniques on the selection of the appropriate antimicrobial treatment by the clinical researchers of an antimicrobial stewardship team. METHODS: Two experienced clinical researchers performed the theoretical exercise of independently selecting the treatment for patients diagnosed by bacteremia due to bacilli gram negative (BGN). At first, the clinicians had only available the clinical characteristics of 74 real patients. Sequentially, information regarding the Gram stain, MALDI-TOF, and SFC from Vitro were provided. Initially, the researchers prescribed an antimicrobial therapy based on the clinical data, later these data were complementing with information from microbiological techniques, and the clinicians made their decisions again. RESULTS: The data provided by the Gram stain reduced the number of patients prescribed with combined treatments (for clinician 1, from 23 to 7, and for clinician 2, from 28 to 12), but the use of carbapenems remained constant. In line with this, the data obtained by the MALDI-TOF also decreased the combined treatment, and the use of carbapenems remained unchanged. By contrast, the data on antimicrobial resistance provided by the SFC reduced the carbapenems treatment. CONCLUSIONS: From the theoretical model the Gram stain and the MALDI-TOF results achieved a reduction in the combined treatment. However, the new system tested (SFC), due to the resistance mechanism data provided, not only reduced the combined treatment, it also decreased the prescription of the carbapenems.

Estimulación eléctrica nerviosa transcutánea como tratamiento de la espasticidad: una revisión sistemática / Transcutaneous electrical nerve stimulation for spasticity: A systematic review

Introducción: Aunque tradicionalmente la estimulación eléctrica nerviosa transcutánea (TENS) se ha utilizado como tratamiento del dolor, algunos estudios han evidenciado una reducción de la espasticidad tras la aplicación de TENS. Sin embargo, su uso en la clínica aún está muy poco extendido. El objetivo de este estudio consiste en determinar si la estimulación TENS aplicada en pacientes con afectación neurológica resulta efectiva para tratar la espasticidad o alguno de sus síntomas asociados. Además, se pretende determinar los parámetros de estimulación que mayor efecto producen sobre las diferentes variables asociadas a la espasticidad. Desarrollo: Se buscaron ensayos clínicos aleatorizados relacionados con TENS y espasticidad encontrados en las bases de datos PubMed, PEDro y Cochrane con anterioridad al 12 de mayo del 2015. Dos revisores independientes realizaron las búsquedas y seleccionaron los estudios en función de los criterios de inclusión previamente establecidos. En la búsqueda inicial se encontraron un total de 96 artículos, de los cuales 86 fueron excluidos y 10 fueron seleccionados para analizar en esta revisión. Se presentan resultados en 207 sujetos con accidente cerebrovascular, 84 con esclerosis múltiple y 39 con lesión medular. Conclusiones: Debido a los resultados observados, su bajo coste, facilidad de aplicación y ausencia de efectos adversos, se recomienda la estimulación mediante TENS como tratamiento de la espasticidad. Sin embargo, la gran variabilidad existente entre las formas de estimulación, los parámetros utilizados y las variables analizadas, dificultan el análisis y la comparación de resultados que puedan determinar la eficacia objetiva de la técnica y la optimización de parámetros

Introduction: Although transcutaneous electrical nerve stimulation (TENS) has traditionally been used to treat pain, some studies have observed decreased spasticity after use of this technique. However, its use in clinical practice is still limited. Our purpose was twofold: to determine whether TENS is effective for treating spasticity or associated symptoms in patients with neurological involvement, and to determine which stimulation parameters exert the greatest effect on variables associated with spasticity. Development: Two independent reviewers used PubMed, PEDro, and Cochrane databases to search for randomised clinical trials addressing TENS and spasticity published before 12 May 2015, and selected the articles that met the inclusion criteria. Of the initial 96 articles, 86 were excluded. The remaining 10 articles present results from 207 patients with a cerebrovascular accident, 84 with multiple sclerosis, and 39 with spinal cord lesions. Conclusions: In light of our results, we recommend TENS as a treatment for spasticity due to its low cost, ease of use, and absence of adverse reactions. However, the great variability in the types of stimulation used in the studies, and the differences in parameters and variables, make it difficult to assess and compare any results that might objectively determine the effectiveness of this technique and show how to optimise parameters

Transcutaneous electrical nerve stimulation for spasticity: A systematic review. / Estimulación eléctrica nerviosa transcutánea como tratamiento de la espasticidad: una revisión sistemática.

INTRODUCTION: Although transcutaneous electrical nerve stimulation (TENS) has traditionally been used to treat pain, some studies have observed decreased spasticity after use of this technique. However, its use in clinical practice is still limited. Our purpose was twofold: to determine whether TENS is effective for treating spasticity or associated symptoms in patients with neurological involvement, and to determine which stimulation parameters exert the greatest effect on variables associated with spasticity. DEVELOPMENT: Two independent reviewers used PubMed, PEDro, and Cochrane databases to search for randomised clinical trials addressing TENS and spasticity published before 12 May 2015, and selected the articles that met the inclusion criteria. Of the initial 96 articles, 86 were excluded. The remaining 10 articles present results from 207 patients with a cerebrovascular accident, 84 with multiple sclerosis, and 39 with spinal cord lesions. CONCLUSIONS: In light of our results, we recommend TENS as a treatment for spasticity due to its low cost, ease of use, and absence of adverse reactions. However, the great variability in the types of stimulation used in the studies, and the differences in parameters and variables, make it difficult to assess and compare any results that might objectively determine the effectiveness of this technique and show how to optimise parameters.

Conversion of Sugars and Biomass to Furans Using Heterogeneous Catalysts in Biphasic Solvent Systems.

Within the last decade, interest in using biphasic systems for producing furans from biomass has grown significantly. Biphasic systems continuously extract furans into the organic phase, which prevents degradation reactions and potentially allows for easier separations of the products. Several heterogeneous catalyst types, including zeolites, ion exchange resins, niobium-based, and others, have been used with various organic solvents to increase furan yields from sugar dehydration reactions. In this minireview, we summarized the use of heterogeneous catalysts in biphasic systems for furfural and 5-hydroxymethylfurfural production from the past five years, highlighting trends in chemical and physical properties that effect catalytic activity. Additionally, the selection of an organic solvent for a biphasic system is extremely important and we review and discuss properties of the most commonly used organic solvents.

Prospective evaluation of toceranib phosphate in metastatic canine osteosarcoma.

Efficacious therapies for measurable metastatic canine osteosarcoma (OSA) are generally lacking. Preliminary retrospective studies suggested that approximately 50% of dogs with measurable metastatic OSA experienced clinical benefit (objective response or clinically meaningful disease stabilisation) following toceranib (TOC) treatment. The purpose of this clinical trial was to prospectively evaluate the clinical outcome following TOC treatment in dogs with measurable pulmonary metastatic OSA. A secondary goal was to identify potential biomarkers of clinical benefit by measuring changes in plasma vascular endothelial growth factor (VEGF) and circulating regulatory T-cell (Treg) percentage. Twenty-two dogs with pulmonary metastasis from appendicular OSA having undergone previous amputation were treated prospectively with TOC. Adverse events (AEs) were common but predominantly low grade. Nine patients were withdrawn from the study prior to the week 8 assessment of response either due to progressive disease (PD), decreased quality of life or owner perceived unacceptable AEs. Of the patients evaluable for disease progression at week 8 (or earlier), 3/17 (17.6 %) had stable disease with the remainder having PD. The median progression-free survival time for all patients was 57 days (range 7-176 days) with a median overall survival time of 89 days (range 7-574 days). Plasma VEGF concentrations were significantly elevated in patients after 4 weeks of TOC treatment, but no changes were observed in percentage of Treg in peripheral blood. Overall, the results of this clinical trial do not support the use of TOC as single agent therapy for canine metastatic OSA.

Cuantificación de la espasticidad autopercibida. Revisión de escalas y cuestionarios / Quantification of self-perceived spasticty. Review of scales and questionnaires

A pesar de la gran cantidad de herramientas disponibles para evaluar la espasticidad, su fluctuación durante el día, la interferencia en la vida diaria y la falta de correlación entre los diferentes síntomas, fundamentan la cuantificación de la percepción del paciente de su propia espasticidad. Esta revisión pretende analizar los principales métodos de valoración de la espasticidad autopercibida por el paciente con enfermedad neurológica, descritos en la literatura científica, y realizar una descripción y análisis crítico de sus ventajas y limitaciones. Tras analizar las principales escalas de valoración de la espasticidad percibida, se concluye que existen pocas herramientas de cuantificación de la espasticidad que contemplen la percepción del paciente y, comparadas con las escalas de evaluación clínica tradicionales, han sido poco utilizadas en la literatura científica. Sin embargo, para su correcta valoración, es fundamental incluir al menos una medición que valore la autopercepción de espasticidad (AU)

Several tools are available to evaluate spasticity. However, because of factors such as fluctuation within the day, interference with daily activities and the absence of correlation among spasticity symptoms, there is a need for tools that measure self-perceived spasticity. This review aims to analyse the main methods for the evaluation of self-perceived spasticity by individuals with neurologic disorders and to discuss their advantages and disadvantages. Analysis of the main scales of self-perceived spasticity revealed that there are few spasticity measurement tools that include the patient's subjective point of view and that very few are used in the scientific literature compared with traditional clinical spasticity scales. However, for a comprehensive evaluation of spasticity, it is crucial to include at least one scale that assesses self-perceived spasticity (AU)

PD-1 expression by canine T cells and functional effects of PD-1 blockade.

The co-inhibitory checkpoint molecule programmed death receptor 1 (PD-1) can trigger T cell functional exhaustion upon binding to its ligand PD-L1 expressed on tumour cells or macrophages. PD-1 blocking antibodies have generated remarkable results in human cancer patients, including inducing durable responses in a number of advanced cancers. Therefore, monoclonal antibodies specific for canine PD-1 were assessed for T cell binding and induction of functional activation. A total of 5-10% of CD4 T cells and 20-25% of CD8 T cells from healthy dogs expressed PD-1, and PD-1 expression was upregulated on T cells from dogs with cancer. Functionally, PD-1 antibodies significantly enhanced T-cell activation, as assessed by proliferation and interferon-gamma (IFN-γ) production. PD-1 antibodies also reversed T-cell suppression induced by canine soluble PD-L1 and by tumour cells and tumour explant fragments. These findings indicate that PD-1 antibodies have potential for use in cancer immunotherapy in dogs.

Immune regulation of canine tumour and macrophage PD-L1 expression.

Expression of programmed cell death receptor ligand 1 (PD-L1) on tumor cells has been associated with immune escape in human and murine cancers, but little is known regarding the immune regulation of PD-L1 expression by tumor cells and tumor-infiltrating macrophages in dogs. Therefore, 14 canine tumor cell lines, as well as primary cultures of canine monocytes and macrophages, were evaluated for constitutive PD-L1 expression and for responsiveness to immune stimuli. We found that PD-L1 was expressed constitutively on all canine tumor cell lines evaluated, although the levels of basal expression were very variable. Significant upregulation of PD-L1 expression by all tumor cell lines was observed following IFN-γ exposure and by exposure to a TLR3 ligand. Canine monocytes and monocyte-derived macrophages did not express PD-L1 constitutively, but did significantly upregulate expression following treatment with IFN-γ. These findings suggest that most canine tumors express PD-L1 constitutively and that both innate and adaptive immune stimuli can further upregulate PD-L1 expression. Therefore the upregulation of PD-L1 expression by tumor cells and by tumor-infiltrating macrophages in response to cytokines such as IFN-γ may represent an important mechanism of tumor-mediated T-cell suppression in dogs as well as in humans.

Role of monocyte recruitment in hemangiosarcoma metastasis in dogs.

Canine hemangiosarcoma (HSA) is a highly malignant tumour associated with short survival times because of early and widespread metastasis. In humans and rodents, monocytes play key roles in promoting tumour metastasis through stimulating tumour cell extravasation, seeding, growth and angiogenesis. Therefore, we investigated the potential association between monocyte infiltration and tumour metastasis in HSA and other common canine tumours. Immunohistochemistry was used to quantify CD18+ monocytes within metastases. We found that HSA metastases had significantly greater numbers of CD18+ monocytes compared with metastases from other tumour types. HSA cells were the highest producers of the monocyte chemokine CCL2, and stimulated canine monocyte migration in a CCL2 dependent manner. These results are consistent with the hypothesis that overexpression of CCL2 and recruitment of large numbers of monocytes may explain in part the aggressive metastatic nature of canine HSA. Thus, therapies designed to block monocyte recruitment may be an effective adjuvant strategy for suppressing HSA metastasis in dogs.

Empirical monotherapy with meropenem or combination therapy: the microbiological point of view.

The increase in the number of clinical isolates of multiresistant Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making on empirical treatments for severe Gram-negative bacilli-associated infections. The aim of our study is to determine the resistance of meropenem in our setting and the co-resistance of a combination of this compound with two antibiotics from different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of 81,310 clinical isolates belonging to the main species of Enterobacteriaceae and 39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the Valencian Community on the South East Mediterranean Coast of Spain were analyzed using data provided by RedMiva (microbiological surveillance network of the Valencian Community). Meropenem resistance in Enterobacteriaceae increased from 0.16 % in 2009 to 1.25 % in 2013. Very few Enterobacteriaceae strains resistant to meropenem were sensitive to ciprofloxacin; in contrast, the combination of meropenem and amikacin led to a marked decrease in the risk of the microorganisms being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa, meropenem resistance also increased (from 14.32 % in 2009 to 24.52 % in 2013). Most meropenem-resistant P. aeruginosa isolates were also resistant to fluoroquinolones. However, the addition of amikacin led to a more than three-fold decrease in the risk of resistance. In our setting, empirical treatment with meropenem is adequate in enterobacterial infections, but poses difficulties when infection due to P. aeruginosa is suspected, in which case a combination of meropenem and amikacin has been shown to have a higher microbiological success rate.

Source investigation of two outbreaks of skin and soft tissue infection by Mycobacterium abscessus subsp. abscessus in Venezuela.

Outbreaks of soft tissue or skin infection due to non-tuberculous mycobacteria are reported frequently in scientific journals but in general the infection source in these outbreaks remains unknown. In Venezuela, in two distinct outbreaks, one after breast augmentation surgery and another after hydrolipoclasy therapy, 16 patients contracted a soft tissue infection due to Mycobacterium abscessus subsp. abscessus. Searching for the possible environmental infection sources in these outbreaks, initially the tap water (in the hydrolipoclasy therapy outbreak) and a surgical skin marker (in the breast implant surgery outbreak), were identified as the infection sources. Molecular typing of the strains with a variable number tandem repeat typing assay confirmed the tap water as the infection source but the molecular typing technique excluded the skin marker. We discuss the results and make a call for the implementation of stringent hygiene and disinfection guidelines for cosmetic procedures in Venezuela.

Hypoxia induces the expression of transketolase-like 1 in human colorectal cancer.

BACKGROUND AND AIMS: Transketolase-like (TKTL) 1 is one of the key enzymes for anaerobic sugar degradation even in the presence of oxygen (aerobic glycolysis). Transketolase-dependent reactions supply malignant tumors with ribose and NADPH. Therefore, TKTL1 activity could be crucial for tumor proliferation and survival. The aim of the study was to evaluate the expression of TKTL1 in colorectal cancer (CRC) and its regulation under hypoxic conditions. METHODS: We studied TKTL1 mRNA and protein expression in CRC cell lines and human CRC biopsies by quantitative real-time PCR, Western blotting and immunohistochemistry. Regulation of TKTL1 under oxygen depletion was analyzed by cultivating cells either in a three-dimensional spheroid model or in a hypoxia incubator chamber. RESULTS: TKTL1 mRNA was heterogeneously expressed in monolayers of cells with high levels in HT-29 and SW480. TKTL1 protein was also clearly detectable in HT-29 and SW480. Hypoxia-inducible factor (HIF)-1α protein expression correlated with TKTL1 protein expression in SW480 spheroids over time. On the one hand, induction of hypoxia in T84 spheroids did not induce TKTL1; on the other hand, hypoxia by incubation at 1% O2 in a hypoxia incubator chamber clearly showed an upregulation of TKTL1. In 50% of CRC patients, TKTL1 protein expression was upregulated in tumor compared to non-tumor tissue. The immunohistochemical staining of TKTL1 in CRC patient samples resulted in 14 positive and 30 negative samples. CONCLUSIONS: TKTL1 expression correlated with HIF-1α protein expression and was induced upon hypoxic conditions which could facilitate energy supply to tumors under these circumstances.

Laboratory test of Newton's second law for small accelerations.

We have tested the proportionality of force and acceleration in Newton's second law, F=ma, in the limit of small forces and accelerations. Our tests reach well below the acceleration scales relevant to understanding several current astrophysical puzzles such as the flatness of galactic rotation curves, the Pioneer anomaly, and the Hubble acceleration. We find good agreement with Newton's second law at accelerations as small as 5 x 10(-14) m/s(2).

Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases.

Tumorbiology of ovarian cancer remains unclear. However, it is known that ovarian tumors, especially carcinomas, show elevated expression of glucose membrane transporters for facilitated glucose uptake. It can be assumed that increased glucose uptake leads to higher glucose metabolism. The energy resources of fully malignant transformed carcinomas are mainly supplied by aerobic glycolysis, for which several pathways are known. A key role in aerobic glycolysis is described for the transketolase enzymes. Recently, a novel transketolase-like enzyme called transketolase-like 1 (TKTL1) has been described that links aerobic glycolysis to the synthesis of fatty acids via production of acetyl-CoA. In order to investigate the role of TKTL1 for the progression of ovarian carcinomas, we examined paraffin sections of normal ovarian tissues, ovarian borderline tumors, and mucinous or serous papillary ovarian adenocarcinomas with respect to their expression of TKTL1. We identified a significantly elevated expression of TKTL1 in serous papillary ovarian adenocarcinomas, which correlates with poor prognostic parameters in the examined study group. Therefore, it can be assumed that TKTL1 plays a crucial role in ovarian cancer metabolism and that its expression predicts poor prognosis. Further investigations should be performed in order to evaluate whether this new enzyme is important for ovarian cancer tumorbiology and to analyze the potential role of TKTL1 as new target for specific antitumoral therapy.

Indicadores de calidad: estudio estructura personal académico en escuelas universitarias públicas de fisioterapia / Quality assurance indicators: research of academic staff in public universities where there is physiotherapy career

El objetivo del estudio es analizar la dotación de personal docente de las universidades públicas españolas que imparten el título de fisioterapia así como la ratio alumnos-profesor como indicador de calidad. Material y método. Se envió por correo electrónico un cuestionario a los directores de las 23 Escuelas Universitarias públicas que imparten la titulación de fisioterapia en el año 2004, siendo el número de cuestionarios válidos (n = 15). Resultados. La media de profesores que imparten docencia teórico-práctica en la titulación es de 38,13 (DS 15,11) con un coeficiente de variación de 39,6 %. La media de profesores que imparten docencia clínica es de 20,07 (DS 10,99) y el coeficiente de variación 54,7 %. La ratio alumnos-profesor en docencia teórico-práctica tiene un valor medio de 6,68 (DS 2,80) un coeficiente de variación de 41,9 %. Mientras que la media de la ratio en docencia clínica es 8,36 alumnos por profesor (DS 3,3) con un coeficiente de variación del 39,7 %. Conclusiones. Se observan diferencias marcadas entre universidades tanto en número como en estructura del personal docente. Estas diferencias también se producen en las ratios de alumnos por profesor tanto en docencia teórica como clínica

The goal of this research is to analyse the staff of professors in the spanish public universities where there is Physiotherapy career, besides the rate student-professor as a sign of quality. Setting and apparatus. One questionnaire was sent by e-mail to the Deans of the 23 public Universities teaching Physiotherapy studies during the year 2004. The number of valid questionnaires was n = 15. Results. The mean of professors who teach both theoretical and practical lesson in the Physiotherapy career is 38.13 (DS 15.11), with a variation quotient of 39,6 %. The mean of professors teaching clinical trainning is 20.07 (DS 10.99), and the variation quotient is 54.7 %. The rate student-professor in the theoretical and practical lessons is 6.68 on average (DS 2.8), and the variation quotient is about 41.9 %. However, the rate mean of clinical training is 8.36 students per each professor (DS 3.3), and the variation quotient is about 39.7 %. Conclusions. Several importants differences were found between the Universities, not only in the number but also in the structure of the professors staff. There were also those differences between the rates student-professor both in theoretical and in clinical training lessons

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted.

Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactate-based matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.