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Tristetraprolin (TTP) is an RNA binding protein that destabilizes mRNAs of factors involved in proliferation, invasiveness, and inflammation. Disruption of the gene that codes for TTP (Zfp36) led to severe arthritis, autoimmunity, cachexia and dermatitis in mice. It has been shown that these phenotypes were mostly due to excessive TNFα levels in the affected tissues. We have previously reported that TTP expression is required for lactation maintenance. Our results indicated that conditional MG TTP-KO female mice displayed early involution due to the untimely induction of pro-inflammatory pathways led mostly by TNFα overexpression. Here we show that reducing TTP levels not only affects the fully differentiated mammary gland, but also harms morphogenesis of this tissue by impairing the progenitor cell population. We found that Zfp36 expression is linked to mammary stemness in human and mice. In addition, diminishing TTP expression and activity induced apoptosis of stem-like mouse mammary cells, reduced its ability to form mammospheres in culture and to develop into complete glands when implanted into cleared mammary fat pads in vivo. Our results show that survival of the stem-like cells is compromised by increased levels of inflammatory cytokines and stimulation of signaling cascades involving NFκB, STAT3 and MAPK-p38 activation. Moreover, TNFα overexpression and the consequent p38 phosphorylation would be the leading cause of progenitor cell death upon TTP expression restriction. Taken together, our results reveal the relevance of TTP for the maintenance of the mammary progenitor cell compartment by maintaining local TNFα levels at bay.

Plenty of new approach methodologies (NAMs) for risk assessment have been developed but only some are included in OECD Test Guidelines (TGs) for regulatory implementation. Nevertheless, NAMs are increasingly applied, e.g. for nanomaterial (NM) risk assessments. The EFSA Guidance on NM risk assessment suggests that NAM‐derived data concerning degradation/dissolution (in relevant biofluids), intestinal uptake/crossing, genotoxicity, cytotoxicity, oxidative stress, (pro‐)inflammatory potential and barrier integrity, for many of which no OECD TGs exist, have to be evaluated first. Consequently, NM risk assessments involve data from non‐guideline studies, requiring time‐consuming and challenging case‐by‐case evaluations. Establishing an OECD TG is a formal process aiming for international use according to the Mutual Acceptance of Data (MAD). However, not every promising NAM can be prioritised for OECD TGs. A qualification, based on an expert opinion, may enable an efficient use of adequate NAMs for a specific context‐of‐use. Furthermore, it supports the optimisation of promising NAMs for regulatory applications. Existing qualification systems operate in the context of e.g., drug development tools (FDA) and research and development into pharmaceuticals (EMA). The NAMS4NANO consortium was tasked to propose a generic framework for a qualification system for chemical risk assessment in the food and feed sector to speed up the regulatory use of NAMs. Here we describe our proposal including the process and evaluation criteria. A detailed test method description, preferably as standard operating procedures (SOPs), describing the set‐up of the NAM including its application and evaluation phase is crucial. Furthermore, the scientific validity, i.e. its reliability and relevance for the context‐of‐use, needs to be demonstrated, for which we suggest a less rigorous process compared to OECD TGs. We propose to initially establish a qualification system for NM risk assessment, aligned with the EFSA framework. This document is an interim version to stipulate a broader discussion among experts and stakeholders. [ABSTRACT FROM AUTHOR]

ABSTRACT Frequent recombination is a hallmark of retrovirus replication. In rare cases, recombination occurs between distantly related retroviruses, generating novel viruses that may significantly impact viral evolution and public health. These recombinants may initially have substantial replication defects due to impaired interactions between proteins and/or nucleic acids from the two parental viruses. However, given the high mutation rates of retroviruses, these recombinants may be able to evolve improved compatibility of these viral elements. To test this hypothesis, we examined the adaptation of chimeras between two distantly related human pathogens: HIV-1 and HIV-2. We constructed HIV-1-based chimeras containing the HIV-2 nucleocapsid (NC) domain of Gag or the two zinc fingers of HIV-2 NC, which are critical for specific recognition of viral RNA. These chimeras exhibited significant defects in RNA genome packaging and replication kinetics in T cells. However, in some experiments, the chimeric viruses replicated with faster kinetics when repassaged, indicating that viral adaptation had occurred. Sequence analysis revealed the acquisition of a single amino acid substitution, S18L, in the first zinc finger of HIV-2 NC. This substitution, which represents a switch from a conserved HIV-2 residue to a conserved HIV-1 residue at this position, partially rescued RNA packaging and replication kinetics. Further analysis revealed that the combination of two substitutions in HIV-2 NC, W10F and S18L, almost completely restored RNA packaging and replication kinetics. Our study demonstrates that chimeras of distantly related retroviruses can adapt and significantly enhance their replication by acquiring a single substitution. IMPORTANCE Novel retroviruses can emerge from recombination between distantly related retroviruses. Most notably, HIV-1 originated from zoonotic transmission of a novel recombinant (SIVcpz) into humans. Newly generated recombinants may initially have significant replication defects due to impaired interactions between viral proteins and/or nucleic acids, such as between cis- and trans-acting elements from the two parental viruses. However, provided that the recombinants retain some ability to replicate, they may be able to adapt and repair the defective interactions. Here, we used HIV-1 and HIV-2 Gag chimeras as a model system for studying the adaptation of recombinant viruses. We found that only two substitutions in the HIV-2 NC domain, W10F and S18L, were required to almost fully restore RNA genome packaging and replication kinetics. These results illustrate the extremely flexible nature of retroviruses and highlight the possible emergence of novel recombinants in the future that could pose a significant threat to public health.

The interaction of semiconductor nanoparticles with bio-molecules attracts increasing interest of researchers, considering the reactivity of nanoparticles and the possibility to control their properties remotely giving mechanical, thermal, or electrical stimulus to the surrounding bio-environment. This work reports on a systematic comparative study of the protein-corona formation on aluminum doped zinc oxide and gallium nitride nanoparticles. Bovine serum albumin was chosen as a protein model. Dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy techniques have been used to demonstrate the formation of protein-corona as well as the stability of the colloidal suspension given by BSA, which also works as a surfactant. The protein adsorption on the NPs surface studied by Bradford Assay showed the dependence on the quantity of proteins adsorbed to the available sites on the NPs surface, thus the saturation was observed at ratio higher than 5:1 (NPs:Proteins) in case of ZnO, these correlating with DLS results. Moreover, the kinetics of the proteins showed a relatively fast adsorption on the NPs surface with a saturation curve after about 25 min. GaN NPs, however, showed a very small amount of proteins adsorbed on the surface, a change in the hydrodynamic size being not observable with DLS technique or differential centrifugal sedimentation. The Circular Dichroism analysis suggests a drastic structural change in the secondary structure of the BSA after attaching on the NPs surface. The ZnO nanoparticles adsorb a protein-corona, which does not protect them against dissolution, and in consequence, the material proved to be highly toxic for Human keratinocyte cell line (HaCaT) at concentration above 25 µg/mL. In contrast, the GaN nanoparticles which do not adsorb a protein-corona, show no toxicity signs for HaCaT cells at concentration as high as 50 µg/mL, exhibiting much lower concentration of ions leakage in the culture medium as compared to ZnO nanoparticles.

The economic evaluation of mastitis control is challenging. The objective of this study was to perform the economic evaluation of mastitis control, under different intervention scenarios, quantifying the total cost of mastitis caused by S. aureus in Holstein cows in Argentina. A model was set for a dairy herd of Holstein cows endemically infected with S. aureus. A basic mastitis control plan including proper milking procedures, milking machine test, dry cow therapy, and treatment for clinical mastitis, was compared against other more complex and costly interventions, such as segregation and culling of chronically infected cows. Sensitivity analysis was performed by modifying the intramammary infection transition probabilities, economic parameters, and efficacy of treatment strategies. The basic mastitis control plan showed a median total cost of USD88.6/cow per year, which was close to the infected cows culling scenarios outputs. However, the segregation scenario was the most efficient, in which the total cost was reduced by about 50%. Such cost was more sensitive to probabilities and efficacy than the economic parameters. The model is flexible and can be customized by producers and veterinarians according to different control and herd settings.

Ivo Vieira de Sousa Neto,1 João Luiz Quaglioti Durigan,1,2 Gonçalo Carreiro de Farias Junior,2 Fabio Henrique Bogni,3 Amanda Lima Ruivo,1 Juliana Oliveira de Araújo,1 Keico Okino Nonaka,3 Heloísa Selistre-de-Araújo,3 Rita de Cássia Marqueti1,2 1Laboratory of Molecular Analysis, Graduate Program of Sciences and Technology of Health, Universidade de Brasília, Distrito Federal, Brazil; 2Graduate Program in Rehabilitation Sciences, Universidade de Brasília, Distrito Federal, Brazil; 3Department of Physiological Sciences, Universidade Federal de São Carlos, São Paulo, BrazilCorrespondence: Ivo Vieira de Sousa Neto; Rita de Cássia MarquetiLaboratory of Molecular Analysis, Graduate Program of Sciences and Technology of Health, Universidade de Brasília, Distrito Federal, BrazilEmail ivoneto04@hotmail.com; marqueti@gmail.comBackground: Aging decreases osteogenic ability, inducing harmful effects on the bone extracellular matrix (ECM), while exercise training has been indicated as a tool to counteract bone disorders related to advancing age. The modulation of bone ECM is regulated by several types of matrix metalloproteinase (MMP); however, MMP-2 activity in different trabecular bones in response to resistance training (RT) has been neglected. Remodeling differs in different bones under the application of the same mechanical loading. Thus, we investigated the effects of 12 weeks of RT on MMP-2 activity in the lumbar vertebra (L6), tibia, and femur of young (3 months) and older rats (21 months).Methods: Twenty Wistar rats were divided into four groups (five animals per group): young sedentary or trained and older sedentary or trained. The 12-week RT consisted of climbing a 1.1-m vertical ladder three times per week with progressive weights secured to the animals’ tails. The animals were killed 48 h after the end of the experimental period. The MMP-2 activity was assessed by the zymography method.Results: The aging process induced lower MMP-2 activity in the lumbar vertebrae and tibia (p=0.01). RT upregulated pro, intermediate, and active MMP-2 activity in the tibia of young rats (p=0.001). RT also upregulated pro and active MMP-2 activity in the lumbar vertebrae and tibia with advancing age (p=0.01). There was no significant difference (p> 0.05) between groups for MMP-2 of the femur, regardless of age and RT.Conclusion: The aging process impairs MMP-2 activity, but RT is a potential therapeutic approach to minimize the deleterious effects of ECM degeneration in different aged bones. Distinct MMP-2 responses to exercise training may result in specific remodeling processes.Keywords: senescent, skeletal system, remodeling, matrix metalloproteinase, exercise

Abstract Background Clonal chromosome changes are often found in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS). The most frequent ones include an isochromosome of the long arm of chromosome 7, i (7)(q10), and an interstitial deletion of the long arm of chromosome 20, del (20)(q). These two imbalances are mechanisms of somatic genetic rescue. The literature offers few expression studies on SDS. Results We report the expression analysis of bone marrow (BM) cells of patients with SDS in relation to normal karyotype or to the presence of clonal chromosome anomalies: del (20)(q) (five cases), i (7)(q10) (one case), and other anomalies (two cases). The study was performed using the microarray technique considering the whole transcriptome (WT) and three gene subsets selected as relevant in BM functions. The expression patterns of nine healthy controls and SDS patients with or without chromosome anomalies in the bone marrow showed clear differences. Conclusions There is a significant difference between gene expression in the BM of SDS patients and healthy subjects, both at the WT level and in the selected gene sets. The deletion del (20)(q), with the EIF6 gene consistently lost, even in patients with the smallest losses of material, changes the transcription pattern: a low proportion of abnormal cells led to a pattern similar to SDS patients without acquired anomalies, whereas a high proportion yields a pattern similar to healthy subjects. Hence, the benign prognostic value of del (20)(q). The case of i (7)(q10) showed a transcription pattern similar to healthy subjects, paralleling the positive prognostic role of this anomaly as well.

The uncertainty of potential risks associated with micro- and nanoplastics (MNPs) are of growing public concern. However, the diversity of MNPs in the environment makes a systematic analysis of potential health effects challenging. New tools and approaches are necessary to investigate biological effects of MNPs. With this quick scoping review, we aim to analyse the suitability of in vitro models for assessing the interaction of MNPs with intestinal cells. Our analysis revealed that currently the majority of in vitro tests are based on the three cell lines Caco-2, HT-29, and HCT-116. They have particularly been used to assess endpoints related to basal cytotoxicity, the internalisation of MNPs and effects on the intestinal barrier. When co-cultured with various cell lines, they also allow to investigate additional effects such as inflammation, metabolic actions and the relevance of the intestinal mucus. However, methodological gaps remain regarding the assessment of a potential accumulation of MNPs, leaching of additives/impurities and in resulting long-term effects as well as cell-type specific toxicities. In addition, only few in vitro studies investigated effects of MNPs on the microbiome. Stem cell-based assays using, for example, the emerging organoid technology are promising for analysing MNP effects on tissue-like structures, while avoiding the particular characteristics of the currently used cancer derived cell lines. The various cell lines and culture techniques can be combined in testing strategies, to better elucidate potential biological interaction of MNPs with biological systems. We suggest to implement a tiered testing strategy, in which monocultures can serve as a tool for high-throughput testing of MNPs. In the next steps co-cultures can be used to assess the potential of a systemic uptake of MNPs and organ-on-a-chip models will provide more reliable insights into relevant doses triggering biological effects. Finally, organoids can help to discover new and more complex reactions initiated by MNPs.

A synthetic route to producing gold-doped environmentally relevant nanoplastics and a method for the rapid and high-throughput qualitative investigation of their cellular interactions have been developed. Polyethylene (PE) and polyvinyl chloride (PVC) nanoparticles, doped with ultrasmall gold nanoparticles, were synthesized via an oil-in-water emulsion technique as models for floating and sedimenting nanoplastics, respectively. Gold nanoparticles were chosen as a dopant as they are considered to be chemically stable, relatively easy to obtain, interference-free for elemental analysis, and suitable for bio-applications. The suitability of the doped particles for quick detection via inductively coupled plasma mass spectrometry (ICP-MS), operating in single-cell mode (scICP-MS), was demonstrated. Specifically, the method was applied to the analysis of nanoplastics in sizes ranging from 50 to 350 nm, taking advantage of the low limit of detection of single-cell ICP-MS for gold nanoparticles. As an initial proof of concept, gold-doped PVC and PE nanoplastics were employed to quantify the interaction and uptake of nanoplastics by the RAW 264.7 mouse macrophage cell line, using scICP-MS and electron microscopy. Macrophages were chosen because their natural biological functions would make them likely to internalize nanoplastics and, thus, would produce samples to verify the test methodology. Finally, the method was applied to assess the uptake by CaCo-2 human intestinal cells, this being a more relevant model for humanexposure to those nanoplastics that are potentially available in the food chain. For both case studies, two concentrations of nanoplastics were employed to simulate both standard environmental conditions and exceptional circumstances, such as pollution hotspot areas.

Abstract Background Prostate cancer (PCa) is the second leading cause of cancer-related death in the Western population. The use in oncology of positron emission tomography/computed tomography (PET/CT) with emerging radiopharmaceuticals promises accurate staging of primary disease, restaging of recurrent disease and detection of metastatic lesions. Prostate-specific membrane antigen (PSMA) expression, directly related to androgen-independence, metastasis and progression, renders this tumour associate antigen a good target for the development of new radiopharmaceuticals for PET. Aim of this study was to demonstrate in a preclinical in vivo model (PSMA-positive versus PSMA-negative tumours) the targeting specificity and sensitivity of the anti-PSMA single-chain variable fragment (scFv) labelled with 124I. Methods The 124I-labeling conditions of the antibody fragment scFvD2B were optimized and assessed for purity and immunoreactivity. The specificity of 124I-scFvD2B was tested in mice bearing PSMA-positive and PSMA-negative tumours to assess both ex-vivo biodistribution and immune-PET. Results The uptake fraction of 124I-scFvD2B was very high on PSMA positive cells (range 75–91%) and highly specific and immuno-PET at the optimal time point, defined between 15 h and 24 h, provides a specific localization of lesions bearing the target antigen of interest (PSMA positive vs PSMA negative tumors %ID/g: p = 0.0198 and p = 0.0176 respectively) yielding a median target/background ratio around 30–40. Conclusions Preclinical in vivo results of our immuno-PET reagent are highly promising. The target to background ratio is improved notably using PET compared to SPECT previously performed. These data suggest that, upon clinical confirmation of sensitivity and specificity, our anti-PSMA 124I-scFvD2B may be superior to other diagnostic modalities for PCa. The possibility to combine in patients our 124I-scFvD2B in multi-modal systems, such as PET/CT, PET/MR and PET/SPECT/CT, will provide quantitative 3D tomographic images improving the knowledge of cancer biology and treatment.

The JRC COVID-19 In Vitro Diagnostic Devices and Test Methods Database, aimed to collect in a single place all publicly available information on performance of CE-marked in vitro diagnostic medical devices (IVDs) as well as in house laboratory-developed devices and related test methods for COVID-19, is here presented. The database, manually curated and regularly updated, has been developed as a follow-up to the Communication from the European Commission “Guidelines on in vitro diagnostic tests and their performance” of 15 April 2020 and is freely accessible at https://covid-19-diagnostics.jrc.ec.europa.eu/.

The development of powerful sequencing techniques has allowed, albeit with some biases, the identification and inventory of complex microbial communities that inhabit different body sites or body fluids, some of which were previously considered sterile. Notably, milk is now considered to host a complex microbial community with great diversity. Milk microbiota is now well documented in various hosts. Based on the growing literature on this microbial community, we address here the question of what milk microbiota is. We summarize and compare the microbial composition of milk in humans and in ruminants and address the existence of a putative core milk microbiota. We discuss the factors that contribute to shape the milk microbiota or affect its composition, including host and environmental factors as well as methodological factors, such as the sampling and sequencing techniques, which likely introduce distortion in milk microbiota analysis. The roles that milk microbiota are likely to play in the mother and offspring physiology and health are presented together with recent data on the hypothesis of an enteromammary pathway. At last, this fascinating field raises a series of questions, which are listed and commented here and which open new research avenues.

Tristetraprolin (TTP) is an RNA binding protein that destabilizes mRNAs of factors involved in proliferation, invasiveness, and inflammation. Disruption of the gene that codes for TTP (Zfp36) led to severe arthritis, autoimmunity, cachexia and dermatitis in mice. It has been shown that these phenotypes were mostly due to excessive TNFα levels in the affected tissues. We have previously reported that TTP expression is required for lactation maintenance. Our results indicated that conditionalMGTTPKO female mice displayed early involution due to the untimely induction of proinflammatory pathways led mostly by TNFα overexpression. Here we show that reducing TTP levels not only affects the fully differentiatedmammary gland, but also harms morphogenesis of this tissue by impairing the progenitor cell population. We found that Zfp36 expression is linked to mammary stemness in human and mice. In addition, diminishing TTP expression and activity induced apoptosis of stem-like mousemammary cells, reduced its ability to formmammospheres in culture and to develop into complete glands when implanted into cleared mammary fat pads in vivo. Our results show that survival of the stem-like cells is compromised by increased levels of inflammatory cytokines and stimulation of signaling cascades involving NFκB, STAT3 and MAPK-p38 activation. Moreover, TNFα overexpression and the consequent p38 phosphorylation would be the leading cause of progenitor cell death upon TTP expression restriction. Taken together, our results reveal the relevance of TTP for the maintenance of themammary progenitor cellcompartment by maintaining local TNFα levels at bay. [ABSTRACT FROM AUTHOR]

Drugs targeting myostatin reverse muscle wasting in animal models, but have limited efficacy in patients. The authors show that the myostatin pathway is downregulated in patients, possibly explaining the poor outcome of anti-myostatin approaches, and that it can be reactivated by correcting disease-causing mutations in mice.

Abstract Background Significant progress of nanotechnology, including in particular biomedical and pharmaceutical applications, has resulted in a high number of studies describing the biological effects of nanomaterials. Moreover, a determination of so-called “critical quality attributes”, that is specific physicochemical properties of nanomaterials triggering the observed biological response, has been recognised as crucial for the evaluation and design of novel safe and efficacious therapeutics. In the context of in vitro studies, a thorough physicochemical characterisation of nanoparticles (NPs), also in the biological medium, is necessary to allow a correlation with a cellular response. Following this concept, we examined whether the main and frequently reported characteristics of NPs such as size and the agglomeration state can influence the level and the mechanism of NP cellular internalization. Results We employed fluorescently-labelled 30 and 80 nm silicon dioxide NPs, both in agglomerated and non-agglomerated form. Using flow cytometry, transmission electron microscopy, the inhibitors of endocytosis and gene silencing we determined the most probable routes of cellular uptake for each form of tested silica NPs. We observed differences in cellular uptake depending on the size and the agglomeration state of NPs. Caveolae-mediated endocytosis was implicated particularly in the internalisation of well dispersed silica NPs but with an increase of the agglomeration state of NPs a combination of endocytic pathways with a predominant role of macropinocytosis was noted. Conclusions We demonstrated that the agglomeration state of NPs is an important factor influencing the level of cell uptake and the mechanism of endocytosis of silica NPs.

pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 (Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the physical-chemical characterization of vesicles (mean size, size distribution, zeta potential, vesicle morphology, bilayer properties and stability) dynamic light scattering (DLS), small angle X-ray scattering and fluorescence studies were performed. Potential cytotoxicity was evaluated on immortalized human keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3. In vivo antinociceptive activity (formalin test) and anti-inflammatory activity tests (paw edema induced by zymosan) in murine models were performed on drug-loaded niosomes. pH-sensitive niosomes were stable in the presence of 0 and 10% fetal bovine serum, non-cytotoxic and able to modify IBU or LID pharmacological activity in vivo. The synthesis of stimuli responsive surfactant, as an alternative to add pH-sensitive molecules to niosomes, could represent a promising delivery strategy for anesthetic and anti-inflammatory drugs.

Abstract INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomial pathogen in community settings. MRSA colonized individuals may contribute to its dissemination; the risk of MRSA infection is increased in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients, although the prevalence of colonization in this group is not well established. The present study addressed this issue by characterizing MRSA isolates from HIV/AIDS patients and their healthcare providers (HCPs) to determine whether transmission occurred between these two populations. METHODS: A total of 24 MRSA isolates from HIV-infected patients and five from HCPs were collected between August 2011 and May 2013. Susceptibility to currently available antimicrobials was determined. Epidemiological typing was carried out by pulsed-field gel electrophoresis, multilocus sequence typing, and Staphylococcus cassette chromosome (SCCmec) typing. The presence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and heterogeneous daptomycin-resistant Staphylococcus aureus (hDRSA) was confirmed by population analysis profile. Isolates characterized in this study were also compared to isolates from 2009 obtained from patients at the same hospital. RESULTS: A variety of lineages were found among patients, including ST5-SCCmecII and ST30-SCCmecIV. Two isolates were Panton-Valentine leukocidin-positive, and hVISA and hDRSA were detected. MRSA isolates from two HCPs were not related to those from HIV/AIDS patients, but clustered with archived MRSA from 2009 with no known relationship to the current study population. CONCLUSIONS: ST105-SCCmecII clones that colonized professionals in 2011 and 2012 were already circulating among patients in 2009, but there is no evidence that these clones spread to or between HIV/AIDS patients up to the 7th day of their hospitalization.

RATIONALE:Pathological response to neo-adjuvant chemotherapy (NAC) represents a commonly used predictor of survival in triple negative breast cancer (TNBC) and the need to identify markers that predict response to NAC is constantly increasing. Aim of this study was to evaluate the potential usefulness of PET imaging with [18F]FDG and [18F]FLT for the discrimination of TNBC responders to Paclitaxel (PTX) therapy compared to the response assessed by an adapted Response Evaluation Criteria In Solid Tumors (RECIST) criteria based on tumor volume (Tumor Volume Response). METHODS:Nu/nu mice bearing TNBC lesions of different size were evaluated with [18F]FDG and [18F]FLT PET before and after PTX treatment. SUVmax, Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) and Proliferation (TLP) were assessed using a graph-based random walk algorithm. RESULTS:We found that in our TNBC model the variation of [18F]FDG and [18F]FLT SUVmax similarly defined tumor response to therapy and that SUVmax variation represented the most accurate parameter. Response evaluation using Tumor Volume Response (TVR) showed that the effectiveness of NAC with PTX was completely independent from lesions size at baseline. CONCLUSIONS:Our study provided interesting results in terms of sensitivity and specificity of PET in TNBC, revealing the similar performances of [18F]FDG and [18F]FLT in the identification of responders to Paclitaxel.