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Through intersubjective theory it is possible define perversions as behaviors characterized by the negation of the subjectivity of the Other. In the paper it is observed that perversions are a mode of affective regulation; especially the perverse individual tries to deny the reality of the Other to avoid the anxiety associated to an intersubjective relationship. According to Jessica Benjamin's intersubjective theory, perversions are a behavioral mode of avoiding intimate development with the Other. In the relations that the perverse establishes there is no mutual recognition of subjectivity. Sexuality is therefore observed from a relational and intersubjective point of view. In the final part, some reflections are proposed on the therapeutic relationship of perverse individuals [ABSTRACT FROM AUTHOR]

Context: In France, preimplantation genetic diagnosis (PGD) has been regulated by the 2004 bioethics law. According to this law, a PGD is done only for couples with a high risk of transmitting a serious and incurable inherited disease. Each PGD indication has to be authorized by the local multidisciplinary centre for prenatal diagnosis to which the PGD centre is attached. The Posters, Topic: ART, lab, biopsy Agence de la biomedicine (ABM) authorized three PGD centres: Paris/Clamart, Strasbourg and Montpellier. The aim of the ABM and the health ministry is to increase the activity according to the population needs in respect of safety and quality, ethics and transparency. The main objective of this study was to describe the French PDG activity, these specificities and the evolution in the last three years. Method: Annual reports of the three PGD centres activities are collected by the ABM. The exhaustive national data from 2006 to 2008 are analysed in a descriptive fashion and presented here. Results: PGD activity has been growing since 2006. The three PGD centres examined 342 requests in 2006, 361 in 2007 and 416 in 2008. This growth is mainly due to the increase of requests for autosomic dominant pathology. Among these examined requests, 310 were accepted, 69 in Paris/Clamart, 119 in Strasbourg and 122 in Montpellier. Most of the rejected cases (47%) were related to difficulties or impossibility to practice assisted reproduction treatment. In 2008, a very large panel of genetic disease (103 different diseases) was examined in 2008. All activity indicators have increased since 2006 and most notably in 2008: 278 couples had an in vitro fertilization treatment in 2008 (89 in Paris/Clamart, 92 in Strasbourg, 97 in Montpellier). Furthermore, 391 treatment cycles (138 in Paris/Clamart, 117 in Strasbourg, 136 in Montpellier) and 320 ovocytes aspirations were done. Indeed, 73 ultrasound diagnosis of early pregnancy (27 in Paris/Clamart, 26 in Strasbourg, 20 in Montpellier), 62 deliveries (20 in Paris/Clamart, 23 in Strasbourg, 19 in Montpellier) and 71 children born alive (22 in Paris/Clamart, 27 in Strasbourg, 22 in Montpellier) were reported. Conclusion: The three French PGD centres cover a large panel of diseases and manage to assist an important number of couples. Even with constant resources, their activities have increased in France this last three years. However, some couples still wait for a very long time before being taken care of. Allocations of new resources from the health ministry should decrease this waiting list in the next few years. [ABSTRACT FROM AUTHOR]

Background: Endometrial Cancer (EC) is strongly linked to obesity. Bariatric surgery is recognized as a long-term solution for weight loss in severely obese patients. This pilot study investigates the feasibility, intraoperative and 30-day morbidity outcomes of integrating gynecological surgical staging and bariatric robotic surgery in class II and III obese patients affected by early EC or Endometrial Intraepithelial Neoplasia (EIN)., Methods: Patients aged over 18 years old with early EC or EIN and class II and III obesity (Body mass index (BMI) ≥ 35 kg/m 2 ) who are surgical and anesthesiologic candidates. Standard robotic surgery for early EC staging performed alone (THBSO group) or in conjunction with sleeve gastrectomy (THBSO + SG group) for obesity management was proposed., Results: Of the 13 patients who met the inclusion criteria, 5 (38.46%) opted for combined surgery. The groups showed a significant difference in preoperative BMI (49.68 kg/m 2 vs. 40.24 kg/m 2 p = 0.017 with and without SG), preoperative weight (143.92 kg vs. 105.62 kg p = 0.004 with and without SG), preoperative (p = 0.01) and postoperative (p = 0.005) aspartate transaminase (AST). The THBSO + SG group had higher anesthesia induction end-tidal carbon dioxide (ETCO2) (p = 0.05), final Partial pressure of carbon dioxide (PaCO2) (p = 0.044), anesthesia induction lactate (p = 0.001) and final lactate (p = 0.011) without a significant difference in final pH (p = 0.31). Operative time was longer in the THBSO + SG group (p < 0.001), but this did not result in longer ICU (p = 0.351), total hospital stays (p = 0.208), nor increased blood loss and transfusion. The simultaneous combined approach had an 80% success rate. At 6 months, the THBSO + SG group achieved significantly greater weight loss than the THBSO group (ΔBMI - 11.81 kg/m 2 vs - 1.72 kg/m 2 , p = 0.003, with and without SG)., Conclusion: Integrating robotic EC staging with SG in obese women with early EC increased the operative time without increasing intraoperative risks, early and 30 days post-surgery complication and offering a promising approach to simultaneously treating both conditions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to investigate the efficacy and duration of multiple non-ablative intravaginal CO2 laser (V-lase ® ) cycles in breast cancer patients, gynecological and other pelvic cancers previously subjected to multiple oncological treatments. This prospective study enrolled women under the age of 65 years who reported vaginal symptoms. Data on the Vaginal Health Index (VHI), vaginal length (VL), vaginal pain measured using a Visual Analog Scale (VAS), and the Female Sexual Function Index (FSFI) were collected at baseline and before each laser application, and at subsequent follow-up visits. A total of 170 laser applications were performed on 113 women with various types of cancer. Most patients (57.5%) had received radiotherapy-based treatments before receiving laser treatment. Vaginal health parameters and sexual function improved significantly with each laser application. However, a temporary decline in these improvements occurred during the intervals between cycles. Such worsening was reversed with the subsequent cycle in all groups of patients, irrespective of the type of oncological treatments they had undergone. Multiple course vaginal laser therapy showed promising results as a potential treatment for vaginal atrophy in heavily treated gynecological and breast cancer patients, necessitating further research to determine the optimal time interval between cycles to ensure sustained positive effects.

Background: The accurate discrimination of uterine leiomyosarcomas and leiomyomas in a pre-operative setting remains a current challenge. To date, the diagnosis is made by a pathologist on the excised tumor. The aim of this study was to develop a machine learning algorithm using radiomic data extracted from contrast-enhanced computed tomography (CECT) images that could accurately distinguish leiomyosarcomas from leiomyomas., Methods: Pre-operative CECT images from patients submitted to surgery with a histological diagnosis of leiomyoma or leiomyosarcoma were used for the region of interest identification and radiomic feature extraction. Feature extraction was conducted using the PyRadiomics library, and three feature selection methods combined with the general linear model (GLM), random forest (RF), and support vector machine (SVM) classifiers were built, trained, and tested for the binary classification task (malignant vs. benign). In parallel, radiologists assessed the diagnosis with or without clinical data., Results: A total of 30 patients with leiomyosarcoma (mean age 59 years) and 35 patients with leiomyoma (mean age 48 years) were included in the study, comprising 30 and 51 lesions, respectively. Out of nine machine learning models, the three feature selection methods combined with the GLM and RF classifiers showed good performances, with predicted area under the curve (AUC), sensitivity, and specificity ranging from 0.78 to 0.97, from 0.78 to 1.00, and from 0.67 to 0.93, respectively, when compared to the results obtained from experienced radiologists when blinded to the clinical profile (AUC = 0.73 95%CI = 0.62-0.84), as well as when the clinical data were consulted (AUC = 0.75 95%CI = 0.65-0.85)., Conclusions: CECT images integrated with radiomics have great potential in differentiating uterine leiomyomas from leiomyosarcomas. Such a tool can be used to mitigate the risks of eventual surgical spread in the case of leiomyosarcoma and allow for safer fertility-sparing treatment in patients with benign uterine lesions.

Endometrial cancer (EC) is the most prevalent gynecological cancer in high-income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity-related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; ≥30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI ≥30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI ≥30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR-199a-5p, miR-449a, miR-449b-5p) in normal-weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity-related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity-related pathways and that may provide novel implications for the clinical management of obese EC patients., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objective: Neoadjuvant chemotherapy (NACT) represents a treatment option in patients with advanced epithelial ovarian cancer (AEOC) who are not good candidates for primary debulking surgery. Usually, 3 cycles of chemotherapy before surgery have been considered the best option for patient survival, although quite often some patients receive more than 3 cycles. The aim of this systematic review and meta-analysis was to identify the optimal number of NACT cycles reporting better survival in AEOC patients., Methods: PubMed, Cochrane Library, and Scopus were searched for original articles that analyzed the relationship between the number of chemotherapy cycles and clinical outcomes in AEOC patients before interval debulking surgery (IDS). The main outcomes were progression-free survival (PFS) and overall survival (OS)., Results: A total of 22 studies comprising 7,005 patients diagnosed with AEOC were included in our analysis. In terms of survival, the reviewed studies dividing the patients in ≤3 NACT cycles vs. >3, showed a trend for a decrease in PFS and a significant reduction in OS with an increasing number of cycles, while a difference in both PFS and OS was revealed if early IDS included patients with 4 NACT cycles. These results should be interpreted with caution due to the complex characteristics of AEOC patients., Conclusion: In conclusion, our review and meta-analysis revealed that there is not enough evidence to determine the optimal number of NACT treatments before surgery. Further research in the form of well-designed randomized controlled trials is necessary to address this issue., Trial Registration: PROSPERO Identifier: CRD42022334959., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2023. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Current prognostic models lack the use of pre-operative CT images to predict recurrence in endometrial cancer (EC) patients. Our study aimed to investigate the potential of radiomic features extracted from pre-surgical CT scans to accurately predict disease-free survival (DFS) among EC patients., Methods: Contrast-Enhanced CT (CE-CT) scans from 81 EC cases were used to extract the radiomic features from semi-automatically contoured volumes of interest. We employed a 10-fold cross-validation approach with a 6:4 training to test set and utilized data augmentation and balancing techniques. Univariate analysis was applied for feature reduction leading to the development of three distinct machine learning (ML) models for the prediction of DFS: LASSO-Cox, CoxBoost and Random Forest (RFsrc)., Results: In the training set, the ML models demonstrated AUCs ranging from 0.92 to 0.93, sensitivities from 0.96 to 1.00 and specificities from 0.77 to 0.89. In the test set, AUCs ranged from 0.86 to 0.90, sensitivities from 0.89 to 1.00 and specificities from 0.73 to 0.90. Patients classified as having a high recurrence risk prediction by ML models exhibited significantly worse DSF ( p -value < 0.001) across all models., Conclusions: Our findings demonstrate the potential of radiomics in predicting EC recurrence. While further validation studies are needed, our results underscore the promising role of radiomics in forecasting EC outcomes.

Background: The optimal number of neoadjuvant chemotherapy cycles in patients with advanced ovarian cancer is still disputed., Objective: To evaluate the impact of the number of neoadjuvant chemotherapy cycles and role of optimal cytoreduction on the prognosis of patients with advanced ovarian cancer., Methods: Clinical and pathological details were examined. Patients were evaluated combining the number of cycles of neoadjuvant chemotherapy-namely, 'interval debulking surgery' after up to four neoadjuvant chemotherapy cycles, and 'delayed debulking surgery' after more than four cycles of therapy., Results: A total of 286 patients were included in the study. Complete cytoreduction with no residual peritoneal disease (CC0) was achieved in 74 (74%) patients with interval debulking surgery and 124 (66.7%) patients with delayed interval debulking. Of those with residual disease, there were 26/88 (29.5%) patients in the interval debulking surgery group and 62/88 (70.5%) patients in the delayed debulking surgery group. Comparison of patients with delayed debulking-CC0 and interval debulking-CC0 showed no difference in progression-free survival (p=0.3) or overall survival (p=0.4), while significantly worse outcomes were observed in patients with interval debulking-CC1 (p=0.02 and p=0.04, respectively). Specifically, patients with interval debulking-CC1 had an approximately 67% increased risk of disease progression (p=0.04; HR=2.01 (95% CI 1.04 to 4.18)) and a 69% higher risk of death than patients with delayed debulking-CC0 (p=0.03; HR=2.34 (95% CI 1.11 to 4.67))., Conclusion: Increasing the number of neoadjuvant chemotherapy cycles does not worsen patient outcomes if complete resection is achieved. Nevertheless, additional prospective trials are necessary to establish the optimum number of neoadjuvant chemotherapy cycles., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: The management of vulvar cancer recurrences is complicated by patients' advanced age and comorbidities. Bleomycin-based electrochemotherapy is a potential treatment option in this setting. However, no data on long-term outcomes are available. Therefore, a multicenter observational study was designed to evaluate the 5-year results in these patients., Methods: Data about patients and tumor characteristics, electrochemotherapy cycles, clinical response, and follow-up were recorded. Treatment procedures were performed according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines. Response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria., Results: Fifty-one patients (mean age 82.31±7.28 years) with squamous cell vulvar cancer underwent electrochemotherapy (median number of sessions 1; range 1-4). 20 patients had complete response and 32% of these were disease-free after 2 years (median progression-free survival 16.8 months). In 13 patients with partial response the median progression-free survival was 15.36 months, while patients with stable or progressive disease showed tumor relapse after 6.95 and 3.26 months, respectively (p<0.001). Median overall survival was 18.77, 13.07, 6.73, and 11.13 months in patients with complete response, partial response, stable disease, and progressive disease, respectively (p=0.001)., Conclusion: Long-term follow-up of vulvar cancer patients showed reasonable tumor control after electrochemotherapy and improved progression-free survival and overall survival in responder subjects compared with non-responders. Further studies aimed at improving local response after electrochemotherapy are warranted. Thus, this approach represents a potential alternative for these patients., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Cutaneous somatosensory modalities play pivotal roles in generating a wide range of sensorimotor behaviors, including protective and corrective reflexes that dynamically adapt ongoing movement and posture. How interneurons (INs) in the dorsal horn encode these modalities and transform them into stimulus-appropriate motor behaviors is not known. Here, we use an intersectional genetic approach to functionally assess the contribution that eight classes of dorsal excitatory INs make to sensorimotor reflex responses. We demonstrate that the dorsal horn is organized into spatially restricted excitatory modules composed of molecularly heterogeneous cell types. Laminae I/II INs drive chemical itch-induced scratching, laminae II/III INs generate paw withdrawal movements, and laminae III/IV INs modulate dynamic corrective reflexes. These data reveal a key principle in spinal somatosensory processing, namely, sensorimotor reflexes are driven by the differential spatial recruitment of excitatory neurons., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Analysis of the genome sequence of Yersinia mollaretii ATCC 43969 identified the bla YEM gene, encoding YEM-1, a putative subclass B2 metallo-β-lactamase. The objectives of our work were to produce and purify YEM-1 and to complete its kinetic characterization. YEM-1 displayed the narrowest substrate range among known subclass B2 metallo-β-lactamases, since it can hydrolyze imipenem, but not other carbapenems, such as biapenem, meropenem, doripenem, and ertapenem, with high catalytic efficiency. A possible explanation of this activity profile is the presence of tyrosine at residue 67 (loop L1), threonine at residue 156 (loop L2), and serine at residue 236 (loop L3). We showed that replacement of Y67 broadened the activity profile of the enzyme for all carbapenems but still resulted in poor activity toward the other β-lactam classes., (Copyright © 2020 American Society for Microbiology.)

Acute itch can be generated by either chemical or mechanical stimuli, which activate separate pathways in the periphery and spinal cord. While substantial progress has been made in mapping the transmission pathway for chemical itch, the central pathway for mechanical itch remains obscure. Using complementary genetic and pharmacological manipulations, we show that excitatory neurons marked by the expression of the neuropeptide Y1 receptor (Y1 Cre neurons) form an essential pathway in the dorsal spinal cord for the transmission of mechanical but not chemical itch. Ablating or silencing the Y1 Cre neurons abrogates mechanical itch, while chemogenetic activation induces scratching. Moreover, using Y1 conditional knockout mice, we demonstrate that endogenous neuropeptide Y (NPY) acts via dorsal-horn Y1-expressing neurons to suppress light punctate touch and mechanical itch stimuli. NPY-Y1 signaling thus regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Loss-of-function (LOF) mutations in CC2D1A cause a spectrum of neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and seizures, identifying a critical role for this gene in cognitive and social development. CC2D1A regulates intracellular signaling processes that are critical for neuronal function, but previous attempts to model the human LOF phenotypes have been prevented by perinatal lethality in Cc2d1a-deficient mice. To overcome this challenge, we generated a floxed Cc2d1a allele for conditional removal of Cc2d1a in the brain using Cre recombinase. While removal of Cc2d1a in neuronal progenitors using Cre expressed from the Nestin promoter still causes death at birth, conditional postnatal removal of Cc2d1a in the forebrain via calcium/calmodulin-dependent protein kinase II-alpha (CamKIIa) promoter-driven Cre generates animals that are viable and fertile with grossly normal anatomy. Analysis of neuronal morphology identified abnormal cortical dendrite organization and a reduction in dendritic spine density. These animals display deficits in neuronal plasticity and in spatial learning and memory that are accompanied by reduced sociability, hyperactivity, anxiety, and excessive grooming. Cc2d1a conditional knockout mice therefore recapitulate features of both cognitive and social impairment caused by human CC2D1A mutation, and represent a model that could provide much needed insights into the developmental mechanisms underlying nonsyndromic neurodevelopmental disorders., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Dystroglycan is a transmembrane glycoprotein whose interactions with the extracellular matrix (ECM) are necessary for normal muscle and brain development, and disruptions of its function lead to dystroglycanopathies, a group of congenital muscular dystrophies showing extreme genetic and clinical heterogeneity. Specific glycans bound to the extracellular portion of dystroglycan, α-dystroglycan, mediate ECM interactions and most known dystroglycanopathy genes encode glycosyltransferases involved in glycan synthesis. POMK, which was found mutated in two dystroglycanopathy cases, is instead involved in a glycan phosphorylation reaction critical for ECM binding, but little is known about the clinical presentation of POMK mutations or of the function of this protein in the muscle. Here, we describe two families carrying different truncating alleles, both removing the kinase domain in POMK, with different clinical manifestations ranging from Walker-Warburg syndrome, the most severe form of dystroglycanopathy, to limb-girdle muscular dystrophy with cognitive defects. We explored POMK expression in fetal and adult human muscle and identified widespread expression primarily during fetal development in myocytes and interstitial cells suggesting a role for this protein during early muscle differentiation. Analysis of loss of function in the zebrafish embryo and larva showed that pomk function is necessary for normal muscle development, leading to locomotor dysfuction in the embryo and signs of muscular dystrophy in the larva. In summary, we defined diverse clinical presentations following POMK mutations and showed that this gene is necessary for early muscle development., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

PED/PEA-15 is a death effector domain (DED) family member with a variety of effects on cell growth and metabolism. To get further insight into the role of PED in cancer, we aimed to find new PED interactors. Using tandem affinity purification, we identified HSC70 (Heat Shock Cognate Protein of 70 kDa)-which, among other processes, is involved in chaperone-mediated autophagy (CMA)-as a PED-interacting protein. We found that PED has two CMA-like motifs (i.e., KFERQ), one of which is located within a phosphorylation site, and demonstrate that PED is a bona fide CMA substrate and the first example in which phosphorylation modifies the ability of HSC70 to access KFERQ-like motifs and target the protein for lysosomal degradation. Phosphorylation of PED switches its function from tumor suppression to tumor promotion, and we show that HSC70 preferentially targets the unphosphorylated form of PED to CMA. Therefore, we propose that the up-regulated CMA activity characteristic of most types of cancer cell enhances oncogenesis by shifting the balance of PED function toward tumor promotion. This mechanism is consistent with the notion of a therapeutic potential for targeting CMA in cancer, as inhibition of this autophagic pathway may help restore a physiological ratio of PED forms., (© 2014 Wiley Periodicals, Inc.)

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons reduces dendritic complexity and increases NF-κB activity, and the effects of Cc2d1a depletion can be rescued by inhibiting NF-κB activity. Homeostatic regulation of neuronal signaling pathways provides a mechanism whereby common founder mutations could manifest diverse symptoms in different patients., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Although many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neuronal degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional and functional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered subcellular transport, and activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that these pathways were perturbed in a manner dependent on the SOD1 mutation. Finally, interrogation of stem-cell-derived motor neurons produced from ALS patients harboring a repeat expansion in C9orf72 indicates that at least a subset of these changes are more broadly conserved in ALS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

PED (phosphoprotein enriched in diabetes) is a 15 kDa protein involved in many cellular pathways and human diseases including type II diabetes and cancer. We recently reported that PED is overexpressed in human cancers and mediates resistance to induced apoptosis. To better understand its role in cancer, we investigated on PED interactome in non-small cell lung cancer (NSCLC). By the Tandem Affinity Purification (TAP), we identified and characterized among others, Rac1, a member of mammalian Rho GTPase protein family, as PED-interacting protein. In this study we show that PED coadiuvates Rac1 activation by regulating AKT mediated Rac1-Ser(71) phosphorylation. Furthermore, we show that the expression of a constitutively active Rac, affected PED-Ser(104) phosphorylation, which is important for PED-regulated ERK 1/2 nuclear localization. Through specific Rac1-siRNA or its pharmacological inhibition, we demonstrate that PED augments migration and invasion in a Rac1-dependent manner in NSCLC. In conclusion, we show for the first time that PED and Rac1 interact and that this interaction modulates cell migration/invasion processes in cancer cells through ERK1/2 pathway., ((c) 2010 Wiley-Liss, Inc.)