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As the landscape of macromolecule therapeutics advances, drug developers are continuing to aim at intracellular targets. To activate, inhibit, or degrade these targets, the macromolecule must be delivered efficiently to intracellular compartments. Quite often, there is a discrepancy between binding affinity in biochemical assays and activity in cell-based assays. Identifying the bottleneck for cell-based activity requires robust assays that quantify total cellular uptake and/or cytosolic delivery. Recognizing this need, chemical biologists have designed a plethora of assays to make this measurement, each with distinct advantages and disadvantages. In this review, we describe the latest and most promising developments in the last 3 to 4 years. [Display omitted] [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.01.018 Byline: Theodore Vougiouklakis (a), Antigoni Mitselou (a), Anna Batistatou (b), Vassiliki Boumba (a), Konstantinos Charalabopoulos (c) Keywords: Peliosis; Lung; Testosterone; Steroids Abstract: Peliosis is a rare lesion characterized by the presence of blood-filled cysts, with unknown true incidence and etiology. It has been most frequently reported to the liver (peliosis hepatis) and to other organs of the mononuclear phagocytic system, such as spleen, bone marrow and lymph nodes. However, other organs may also be affected. Its occurrence has been linked to wasting conditions such as tuberculosis, cancer, immunosuppression and the use of androgenic-anabolic steroids. Herein, we report a case of pulmonary peliosis, in a 29-year-old man who was abusing testosterone as it was proved by toxicological analysis. To our knowledge this is the third reported case of pulmonary peliosis and the first one that is not associated with peliosis of any other organ. Author Affiliation: (a) Department of Forensic Medicine, Clinical Unit, Medical School, University of Ioannina, Ioannina, Greece (b) Department of Pathology, Clinical Unit, Medical School, University of Ioannina, Ioannina, Greece (c) Department of Physiology, Clinical Unit, Medical School, University of Ioannina, 13 Solomou str., 452 21 Ioannina, Greece Article History: Received 18 May 2008; Revised 23 January 2009; Accepted 25 January 2009

Dose-dense sequential (dds) chemotherapy has changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a currently widely used chemotherapeutic regimen. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. Totally, 1054 patients were prospectively enrolled in the current study with 1024 patients being eligible, while adequate tissue was available for 596 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. Importantly, the 10-year DFS and OS rates were 78.4% (95% CI 75.0–81.5) and 81.7% (95% CI 79.0–84.1), respectively. Interestingly, higher CD8+ T cells as well as TILs in the tumor microenvironment were associated with an improved long-term survival outcome. In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of TILs and infiltrating CD8+ lymphocytes in BC patients with early-stage disease. • Dose-dense sequential chemotherapy has changed the clinical outcome of patients with early breast cancer. • Its effectiveness has never been studied in conjunction with tumor microenvironment in a homogeneous population of Greek-Caucasian origin. • Long-term survival benefit in terms of DFS and OS as well as safety was confirmed. • Higher TILs and CD8-positive T cells in the tumor microenvironment were associated with an improved long-term survival outcome. [ABSTRACT FROM AUTHOR]

Flow cytometry, although indispensable for the characterization of hematologic malignancies, has not been extensively evaluated in solid tumors. To date intraoperative pathology evaluation of frozen sections of tissue obtained during surgery is the gold standard for intraoperative diagnosis. We investigated the value of a modified rapid protocol for cell cycle analysis for the intraoperative characterization of intracranial lesions and their surgical margins. We investigated patients who underwent surgery for an intracranial lesion suspicious for a tumor. DNA analysis and frozen sections were performed on tumor samples that were taken during surgery. Thirty-one patients met the inclusion criteria for the study. There was a significant difference in G0/G1 phase between high-grade and low-grade tumors. Receiver operating characteristic (ROC) analysis provided 75% of G0/G1 fraction as the optimal cutoff value thresholding the discrimination between low and high-grade tumors. There was a significant difference in S-phase and mitoses fraction between high-grade and low-grade tumors. ROC analysis indicated 6% of S-phase and 9.7% of mitoses as the optimal cutoff values thresholding the discrimination between these two groups. In the glioblastoma patients, we also analyzed the perilesional tissue and found significant differences between tumor mass and margins regarding the G0/G1 phase, the S-phase and mitoses fraction. In conclusion rapid cell cycle analysis is a method capable of differentiating low from high-grade tumors and delineating tumor margins in gliomas. Thus, the role of cell cycle analysis in brain tumors warrants further investigation. [ABSTRACT FROM AUTHOR]

Abstract: The Androgen Receptor (AR) is a potential prognostic marker and therapeutic target in breast cancer. We evaluated AR protein expression in high-risk breast cancer treated in the adjuvant setting. Tumors were subtyped into luminal (ER+/PgR±/AR±), molecular apocrine (MAC, [ER−/PgR−/AR+]) and hormone receptor negative carcinomas (HR-negative, [ER−/PgR−/AR−]). Subtyping was evaluated with respect to prognosis and to taxane therapy. High histologic grade (p < 0.001) and increased proliferation (p = 0.001) more often appeared in MAC and HR-negative than in luminal tumors. Patients with MAC had outcome comparable to the luminal group, while patients with HR-negative disease had increased risk for relapse and death. MAC outcome was favorable upon taxane-containing treatment; this remained significant upon multivariate analysis for overall survival (HR 0.31, 95%CI 0.13–0.74, interaction p = 0.035) and as a trend for time to relapse (p = 0.15). In conclusion, AR-related subtyping of breast cancer may be prognostic and serve for selecting optimal treatment combinations. [Copyright &y& Elsevier]

Purpose: To investigate the different types of innervation and the presence of mechanoreceptors in relation to the structural composition of the scapholunate interosseous ligament and to correlate the findings with the known mechanical properties of the ligament subregions. Methods: Six fresh cadaveric scapholunate interosseous ligaments were divided into their 3 subregions: dorsal, palmar, and proximal. The microscopic features were investigated with use of a standard hematoxylin-eosin stain and immunostains for S-100, neurofilaments, neuron-specific enolase, protein gene product 9.5, CD31, and smooth muscle actin. The connective tissue structural composition and the presence of blood vessels and neural structures (myelinated and unmyelinated nerve fibers and mechanoreceptors) were investigated. The macroscopic anatomic details were also noted. Results: The palmar subregion consists of structured, densely collagenized tissue at the core, surrounded by looser connective tissue. Myelinated nerve fibers forming fascicles accompany the interspersed blood vessels inside the ligament substance. Their concentration is greater in the proximal part of the palmar subregion, reaching a distance of approximately 150 μm from the ligament free surface. The dorsal subregion has similar structure to the palmar one, but the fibrous tissue ratio and density are higher. The proximal subregion consists of chondroid matrix and of loose connective tissue at its core. The radio-scapholunate ligament insertion is noted at the palmar aspect of the proximal subregion. Pacinian and other sensory corpuscles were found mostly at the palmar and proximal subregions. Conclusions: The scapholunate interosseous ligament is a richly innervated ligament that contributes to carpal proprioception, a fundamental element of dynamic wrist stability. The palmar subregion, apart from its major mechanical role, contains the greatest amount of the neural structures and mechanoreceptors. The dorsal subregion, with densely packed collagen fibers and limited innervation, functions mainly to constrain the scaphoid-lunate relative motion. [Copyright &y& Elsevier]

Summary: Common melanocytic nevi are ubiquitous lesions which in some cases constitute a risk factor for the development of melanoma. To date, despite long term research there are no known molecular hallmarks for nevus development. We have observed that common acquired nevi excised from the same individual share remarkable similarity in their microscopic appearance and in the immunohistochemical expression of E-cadherin. Based on these observations, we hypothesize that all melanocytes are genetically similar in the same individual and changes predisposing to neoplasia are a global melanocytic event characteristic for each person and propose a microgenomics/proteomics approach to test this hypothesis. [Copyright &y& Elsevier]

Osteosarcomas represent the most common primary malignant bone tumors; however, comprehension of the molecular mechanisms underlying their pathogenesis is far from thorough. Studies in cultured cells have demonstrated that the c-Jun N-terminal kinase (JNK) signal transduction pathway participates in the proliferation, differentiation, and apoptosis of osteoblasts. Phosphorylated JNKs activate the oncoprotein c-Jun, which is known to form the activator protein-1 (AP-1) transcription factor as a homo- or heterodimer. c-Jun’s principal dimerization partner is c-Fos, which participates in the differentiation and function of osteoblasts and in the pathogenesis of osteosarcomas. A similar role for the JNK cascade in the malignant transformation of human osteoblasts and in the generation of osteosarcomas has not been documented. Our study addressed the possibility that a functional upregulation of the JNK pathway is implicated in the pathogenesis of osteosarcomas. To this end, we employed immunohistochemistry to examine normal bone and osteosarcoma cells in paraffin-embedded sections from 56 patients with high-grade tumors and 15 patients with low-grade tumors. We assessed the protein levels of the two major JNK isoforms (JNK1 and JNK2); their phosphorylated—hence activated—species, p-JNK; their substrate, c- Jun; its phosphorylated (activated) form, pc-Jun; and c-Jun’s heterodimeric partner, c-Fos. We also examined the immunohistochemical profile of the α chain of the nascent polypeptide-associated complex (α-NAC), an osteoblast-specific AP-1 coactivator that potentiates the transcriptional activity of the c-Jun/c-Jun homodimer. Positive immunostaining for JNK1, JNK2, p-JNK, c-Jun, pc-Jun, c-Fos, and α-NAC was observed in 86, 93, 94, 99, 97, 99, and 97.5% of the samples, respectively, whereas normal bone was devoid of these immunoreactivities. The cellular levels of all proteins were significantly correlated to each other (P < 0.001 for each correlation). Moreover, significantly higher expression levels of all proteins were detected in high-grade tumors compared to levels in low-grade ones. The observed expression profile of α-NAC implies that the active AP-1 in human osteosarcomas most likely comprises c-Jun/c-Jun homodimers. When cellular levels of the JNK pathway components and c-Fos were evaluated as possible biological markers of tumor grade, high expression of c-Jun and abundant pc-Jun predicted a high-grade tumor. Our findings provide novel evidence that the JNK signaling pathway is functionally operative in the malignant transformation of osteoblasts and the subsequent development and progression of human osteosarcomas. Evaluation of c-Jun expression and JNK-dependent activation may facilitate an improved prediction of the tumor’s clinical behavior and potentially be exploited in designing patient-tailored treatment regimens. [Copyright &y& Elsevier]

Abstract: We present the case of a 63-year-old Caucasian woman with early gastric adenocarcinoma, suffering from extensive metastases at the time of initial presentation. Microscopic examination of the gastrectomy specimen revealed an invasive adenocarcinoma with oncocytic features. Interestingly, despite the fact that the carcinoma was pT1, it also was found to be N2, stage IV. The biologic behavior of oncocytic adenocarcinoma of the stomach is still unclear. We would like to present this case, so that its clinicopathological characteristics can be added to the few cases already published. [Copyright &y& Elsevier]

A 22-year-old woman presented with pain on the dorsum of her left big toe. The patient had had an accident 1 year previously, when a heavy object fell on her left big toe. She experienced no pain in the hallux before the injury. Radiographic evaluation revealed a well-circumscribed osseous mass, in close relationship to the underlying dorsal cortex of the proximal phalanx. A 2 × 1.5 × 0.7 cm mass was resected. No communication was found between the undersurface of the bony mass and the medullar space of the phalanx. The histology report confirmed diagnosis of acquired osteochondroma. Removal of the bony mass resulted in disappearance of symptoms without any sign of recurrence 10 months later. [Copyright &y& Elsevier]

Neonatal brachial plexus palsy remains a problem, even in light of current advances in perinatal care. While many cases resolve spontaneously, the concern remains on the best means of surgical management for restoration of elbow flexion and shoulder reanimation. The present experimental study in an animal model examines the evidence that supports that neonatal brachial plexus injuries result in structural changes in the affected bone. The study suggests that if the microsurgical reinnervation takes place early enough, these changes may be diminished. On the other hand there is no way to identify at birth, which injuries will be permanent and will need surgical repair and which will spontaneously improve. [ABSTRACT FROM AUTHOR]

Abstract: The present study investigates the histological alterations and expression of matrix metalloproteinase 9 (MMP-9) in disc specimens of 43 patients who underwent surgery for lumbar disc herniation. The immunostaining for MMP-9 was evaluated semi-quantitatively. Histologic degeneration was scored between 0 and 12 depending on the degree of chondrocyte proliferation and presence of tears and clefts, granular changes and mucous degeneration. Herniation was graded as grade 1 (protrusion), grade 2 (extrusion) or grade 3 (sequestration) on MRI. Although there was no significant statistical difference between the histologic degeneration score and age, degenerative changes were more pronounced in higher grade of herniation (p <0.0001). MMP-9 expression was related to histologic degenerative score in all age groups (p =0.0065). MMP-9 was also related to herniation grade in patients younger than 30 years of age (p =0.0037). No significant association was found between MMP-9 expression and herniation grade in patients who were 30–60 years or over 60 years of age. [Copyright &y& Elsevier]

Summary: Science and art are, surprisingly, intimately linked to each other. Over the centuries, artists used their talent in order to depict with the greatest detail possible the human anatomy and later the histology of tissues, helping scientists comprehend better the world and human nature. From the opposite perspective, scientific images coming from observation or experimentation can constitute art since they can have form and beauty. An example is mitotic figures, particularly the atypical ones observed in cancer. The affinity between art and science is demonstrated herein, by their harmonic coexistence in one figure, and also by the ease and naturalness by which the phrases used by Magritte in order to describe one of his paintings, the famous “Golconda” can be paraphrased to describe a neoplasm, a transitional cell carcinoma of the bladder. [Copyright &y& Elsevier]

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody–drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement. • Targeting HER2-low expression with novel antibody-drug conjugates has reshaped the treatment of metastatic breast cancer. • This advancement raised relevant questions pertaining to the definition, diagnosis and management of HER2-low breast cancer. • We gathered 32 international experts to build consensus regarding key controversial topics pertaining HER2-low breast cancer. • A modified Delphi voting methodology was deployed, leading to 20 consensus statements, each with at least 90% consensus among experts. • Ongoing studies may lead to further refinement in our understanding of HER2-low breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Intra-articular ganglia are rare and mostly incidental findings on magnetic resonance imaging (MRI) and arthroscopy. We present 4 cases of intra-articular ganglion cysts associated with the anterior cruciate ligament (ACL) in 3 patients. The most commonly occurring symptoms were pain aggravated after stressing activities and limited knee range of motion. In 1 patient, ganglion cysts appeared in both knees with a time difference of 1 year. An MRI revealed typical signs of ganglion cysts in the substance of the ACL. Arthroscopy was performed for further evaluation and treatment. Histologic examination of the tissue removed revealed the presence of features consistent with ganglion cysts. Therefore, in the case of chronic knee discomfort with nonspecific clinical signs and symptoms and without a clear cause, an intra-articular ganglion cyst should be considered as causing pathology. An MRI is the most sensitive and specific method for diagnosis. However, the relatively slow progression of symptoms may delay the patient’s decision to seek medical attention. Delayed diagnosis makes arthroscopic total resection of the ganglion technically demanding or not possible at all, and extensive debridement of the ACL may be required. [Copyright &y& Elsevier]

Abstract: Numerous studies indicate the importance of hypoxia-induced pathway in tumor angiogenesis, but in vivo studies examining the importance of this mechanism in prognosis of patients with head and neck squamous cell carcinoma present conflicting results. We performed a retrospective analysis of 81 patients with head and neck squamous cell carcinoma in order to investigate whether hypoxia-inducible factor 1a (HIF-1a) immunohistochemical expression correlates with vascular endothelial growth factor (VEGF) expression and clinicopathologic parameters or prognosis. Our results showed a statistically significant association between HIF-1a and VEGF expression in tumors located in the lower lip and in larynx, but not in those located in the oral cavity. HIF-1a expression had no impact on prognosis, while VEGF expression correlated significantly with adverse prognosis. These findings support the hypothesis that tumor angiogenesis is close related, but not strictly dependent, on the hypoxic conditions of tumor''s microenvironment. [Copyright &y& Elsevier]

Background: The ubiquitin–proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients. Methods: Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose-dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one-step quantitative RT-PCR for assessment of mRNA expression of UBE2C. Results: High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05). Conclusions: High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts. [ABSTRACT FROM PUBLISHER]

• SARS-CoV-2 demonstrates a continuous tendency for new variants emergence. • Differences in those variants regarding their mutations/deletions/insertions in spike genomic sequence leads to altered transmissibility/infectivity/re-infection/morbidity/mortality rates. • Omicron variant is characterized by an ''exotic" genomic profile due to the increased number of host mutations and the combination of deletions/insertion in S1-RBD/S2 domains. • Delta to Omicron transition is the next step for SARS-CoV-2 adjustment regarding its effort to survive in human affected cells. Coronavirus-related Severe Acute Respiratory Syndrome (SARS-CoV) in 2002/2003, Middle-East Respiratory Syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) affected negatively the national health systems' endurance worldwide. SARS-Cov-2 virus belongs to lineage b of beta-CoVs demonstrating a strong phylogenetic similarity with BatCoVRaTG13 type. Spike (S) glycoprotein projections -consisting of two subunits S1/S2- provide a unique crown-like formation (corona) on virion's surface. Concerning their functional role, S1 represents the main receptor-binding domain (RBD), whereas S2 is involved in the virus-cell membrane fusion mechanism. On Nov 26th 2021, WHO designated the new SARS-CoV-2 strain – named Omicron, from letter '' όμικρον" in the Greek alphabet - as a variant of concern (B.1.1529 variant). Potentially this new variant is associated with high transmissibility leading to elevated infectivity and probably increased re-infection rates. Its impact on morbidity/mortality remains under investigation. In the current paper, analyzing and comparing the alterations of SARS-CoV-2 S RNA sequences in the defined variants (Alpha to Omicron), we observed some interesting findings regarding the S1-RBD/S2 mutation/deletion equilibrium that maybe affect and modify its activity. [ABSTRACT FROM AUTHOR]

Occult cardiac injury following blunt trauma is more common than generally suspected. Myocardial lesions range from myocardial contusion to cardiac rupture. Myocardial contusion is not uncommon, it is usually a benign disorder which often remains undiagnosed. We report the case of a previously healthy 29-year-old man who was involved in a fight and suffered from blunt heart injury leading to contusion of the right atrium. The patient died soon after the injury and before admission to the Hospital. The diagnosis was made at autopsy.The present case is of special interest because of the unusual eliciting event and the rarity of the contusion site (right atrium). It is reported in order to raise the index of suspicion in physicians treating patients involved in a fight and aid in prompt diagnosis of myocardial contusion. [Copyright &y& Elsevier]

Solitary papillomas of the lung are rare. One of their subtypes is glandular papilloma with only a very few cases described in the literature. We describe a case of pulmonary glandular papilloma with emphasis in its differential diagnosis and its molecular analysis. A 64-years old former smoker was incidentally found to have an endobronchial tumor of the right main bronchus. Microscopic and immunohistochemical findings revealed a glandular papilloma. EGFR , KRAS and BRAF V600E mutation analysis, as well as HPV detection analysis revealed no mutation or HPV infection. Detailed differential diagnosis and literature review are presented. Glandular papillomas of the lung are usually central, affecting older patients than squamous or mixed squamous cell and glandular papillomas. In previously reported cases, one glandular papilloma with KRAS mutation and another one with BRAF mutation have been reported. The present case harbored no mutation or HPV infection. [ABSTRACT FROM AUTHOR]

Abstract: Autoimmune thyroid disease (AITD) has been associated with other autoimmune diseases such as chronic urticaria, insulin-dependent diabetes mellitus, Sjøgren''s syndrome, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, ankylosing spondylitis, and dermatomyositis (DM) . AITD is a common disorder affecting primarily women, and both genetic and environmental factors are included in its pathogenesis . DM is considered an autoimmune disease of the muscles and skin. Although AITD is the most common cause of hypothyroidism, to the best of our knowledge, only three cases of DM and AITD in the same patient have been reported in the last 40 years . We consider that both are developed from the same autoimmune background. Herein, we present a case of a 30-year-old man with a 4-year history of AITD who was diagnosed as suffering as well from DM. [Copyright &y& Elsevier]

Head and neck cancer poses a significant health problem worldwide. We set out to investigate the value of rapid intraoperative cell cycle analysis by flow cytometry for the intraoperative characterization of head and neck lesions and surgical margins. Seventy patients with head and neck lesions suspicious of malignancy were included in the study. There were 31 neoplastic and 39 benign lesions. Flow cytometry permitted the intraoperative detection of neoplastic lesions within 6 min with high sensitivity and specificity based on cell cycle fractions. In the cases in which surgical margins were assessed, intraoperative flow cytometry had complete concordance with pathology. Intreoperative flow cytometry is a novel promising technique for rapid intraoperative characterization of malignancy and tumour free resection margins in head and neck lesions. [ABSTRACT FROM AUTHOR]

Background Metastatic colorectal cancer (mCRC) affects 20% of patients diagnosed with colorectal malignancy and is a major cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR) blockade with monoclonal antibodies, in combination with chemotherapy, has been shown to benefit patients with RAS wild type tumours. Our project explores real-time assessment of mCRC mutational profile, by use of two methods of circulating tumour DNA (ctDNA) analysis, and its potential to better guide therapeutic decisions. Methods Baseline plasma samples were prospectively collected from 64 patients at diagnosis of mCRC and at disease progression. Analysis of KRAS and NRAS exons 2, 3 and 4 was performed with the highly sensitive BEAMing digital polymerase chain reaction (PCR) and next-generation sequencing (NGS). In a subgroup of patients, with baseline RAS mutations, mid-treatment liquid biopsies were performed, to assess the change in ctDNA RAS mutational load as response biomarker. Mutational status of matched tumour tissue, generated with a conventional PCR-based method or NGS, was prospectively recorded for all patients. Results Preliminary results of our study, presented at the EACR-ESMO Joint Conference on Liquid Biopsies, have shown detection of RAS mutations in the ctDNA from over 50% of patients, with a satisfactory plasma-tissue concordance. An update on these data, as well as on the predictive value of ctDNA RAS mutational load dynamics, will be presented. Disease progression data, in light of baseline RAS status, will also be revisited, as almost 20% of patients have progressed on first-line treatment. In addition, the concordance of BEAMing and NGS as liquid biopsy methods is to be studied in a subgroup of patients with available plasma samples. Conclusions The larger sample size and the maturity of this updated analysis further add on the value of our work, the results of which remain in line with the literature. Our study serves as a real-life example of the potential of liquid biopsies to detect RAS mutation status changes, allowing for precision-oncology therapeutic approaches in the continuum of care of metastatic colorectal cancer patients. Legal entity responsible for the study Department of Medical Oncology, University General Hospital of Ioannina. Funding Amgen, Hellenic Society of Medical Oncology (HeSMO) and Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN). Disclosure G. Pentheroudakis: Research grant / Funding (institution): Amgen. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Abstract: Intramuscular hemangiomas (IHs) are rare benign neoplasms usually seen in children, adolescents and young adults. Although lower extremities are the commonest localization, the localization at the foot is extremely rare since only a few cases have been reported. We report a case of mixed type IH of the flexor digitorum brevis muscle in a 12-year-old boy who was treated with surgical excision, with wide surgical margins. [Copyright &y& Elsevier]