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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]

Abstract: Objectives: To define the characteristics of necrotizing sarcoid granulomatosis (NGS) a very rare pulmonary disease hardly recognised by pulmonologists and pathologists. Data source: PubMed was searched for the term necrotising or necrotizing sarcoid granulomatosis. Study selection: All cases reported in the English literature were included. Results: NGS is presented at all ages (range 8‐68 years) with a median age of 42 years old. It shows female (62%) and Caucasian (80%) predominance. The most frequent symptoms are cough, fever, dyspnoea and chest pain. Extra‐pulmonary involvement is found in one third of the cases, with ocular being the most common (12.5%). At imaging, multiple nodules (64.75%) or a solitary mass (20.49%) are found accompanied by mediastinal lymphadenopathy at one third of the cases. It can be clinically mistaken for malignancy as it is tumour‐like, increases rapidly in size and it is hyperfixating in PET‐SCAN. Histologically, NGS is defined by large areas of necrosis, well‐formed granulomas and vascularitis. Conclusion: NGS is a disease often confounded clinically with malignancy or with sarcoidosis even histologically when all criteria are not strictly applied. This review provides NGS' characteristics and discusses its differential diagnosis form sarcoidosis, Wegener granulomatosis and tuberculosis. [ABSTRACT FROM AUTHOR]

Where treatments are administered to groups of patients or delivered by therapists, outcomes for patients in the same group or treated by the same therapist may be more similar, leading to clustering. Trials of such treatments should take account of this effect. Where such a treatment is compared with an un-clustered treatment, the trial has a partially nested design. This paper compares statistical methods for this design where the outcome is binary. Investigation of consistency reveals that a random coefficient model with a random effect for group or therapist is not consistent with other methods for a null treatment effect, and so this model is not recommended for this design. Small sample performance of a cluster-adjusted test of proportions, a summary measures test and logistic generalised estimating equations and random intercept models are investigated through simulation. The expected treatment effect is biased for the logistic models. Empirical test size of two-sided tests is raised only slightly, but there are substantial biases for one-sided tests. Three formulae are proposed for calculating sample size and power based on (i) the difference of proportions, (ii) the log-odds ratio or (iii) the arc-sine transformation of proportions. Calculated power from these formulae is compared with empirical power from a simulations study. Logistic models appeared to perform better than those based on proportions with the likelihood ratio test performing best in the range of scenarios considered. For these analyses, the log-odds ratio method of calculation of power gave an approximate lower limit for empirical power. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies have consistently shown that amongst staff working with MRI, transient symptoms directly attributable to the MRI system including dizziness, nausea, tinnitus, and concentration problems are reported. This study assessed symptom prevalence and incidence in radiographers and other staff working with MRI in healthcare in the UK. Methods: One hundred and four volunteer staff from eight sites completed a questionnaire and kept a diary to obtain information on subjective symptoms and work practices, and wore a magnetic field dosimeter during one to three randomly selected working days. Incidence of MRI-related symptoms was obtained for all shifts and prevalence of MRI-related and reference symptoms was associated to explanatory factors using ordinal regression. Results: Incident symptoms related to working with MRI were reported in 4 % of shifts. Prevalence of MRI-related, but not reference symptoms were associated with number of hours per week working with MRI, shift length, and stress, but not with magnetic field strength (1.5 and 3 T) or measured magnetic field exposure. Conclusions: Reporting of prevalent symptoms was associated with longer duration of working in MRI departments, but not with measured field strength of exposure. Other factors related to organisation and stress seem to contribute to increased reporting of MRI-related symptoms. Key Points: • Routine work with MRI is associated with increased reporting of transient symptoms • No link to the strength of the magnetic field was demonstrated. • Organisational factors and stress additionally contribute to reporting of MRI-related symptoms [ABSTRACT FROM AUTHOR]

This article considers the estimation of power and sample size in experimental and quasi-experimental intervention studies, where there is clustering of subjects within one or both intervention arms, for both continuous and binary outcomes. A new command, clsampsi, which has a wide range of options, calculates the power and sample size needed (that is, the number of clusters and cluster size) by using the noncentral F distribution as described by Moser, Stevens, and Watts (1989, Communications in Statistics-Theory and Methods 18: 3963-3975). For comparative purposes, this command can also produce power and sample-size estimates on the basis of existing methods that use a normal approximation. [ABSTRACT FROM AUTHOR]

It is known that measurement error leads to bias in assessing exposure effects, which can however, be corrected if independent replicates are available. For expensive replicates, two-stage (2S) studies that produce data 'missing by design', may be preferred over a single-stage (1S) study, because in the second stage, measurement of replicates is restricted to a sample of first-stage subjects. Motivated by an occupational study on the acute effect of carbon black exposure on respiratory morbidity, we compare the performance of several bias-correction methods for both designs in a simulation study: an instrumental variable method (EVROS IV) based on grouping strategies, which had been recommended especially when measurement error is large, the regression calibration and the simulation extrapolation methods. For the 2S design, either the problem of 'missing' data was ignored or the 'missing' data were imputed using multiple imputations. Both in 1S and 2S designs, in the case of small or moderate measurement error, regression calibration was shown to be the preferred approach in terms of root mean square error. For 2S designs, regression calibration as implemented by Stata software is not recommended in contrast to our implementation of this method; the 'problematic' implementation of regression calibration although substantially improved with use of multiple imputations. The EVROS IV method, under a good/fairly good grouping, outperforms the regression calibration approach in both design scenarios when exposure mismeasurement is severe. Both in 1S and 2S designs with moderate or large measurement error, simulation extrapolation severely failed to correct for bias. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by some molecules collectively known as adhesion molecules (CAMs). CAMs are ubiquitously expressed proteins playing a central role in controlling cell migration, proliferation, survival, and apoptosis. Besides their key function in physiological maintenance of tissue integrity, CAMs play an eminent role in various pathological processes such as cardiovascular disorders, atherogenesis, atherosclerotic plaque progression and regulation of the inflammatory response. CAMs such as selectins, integrins, and immunoglobulin superfamily take part in interactions between leukocyte and vascular endothelium (leukocyte rolling, arrest, firm adhesion, migration). Experimental data and pathologic observations support the assumption that pathogenic microorganisms attach to vascular endothelial cells or sites of vascular injury initiating intravascular infections. In this review a paradigm focusing on cell adhesion molecules pathophysiology and infective endocarditis development is given. [ABSTRACT FROM AUTHOR]

Nuclear grooves are longitudinal invaginations of the nuclear envelope bilayer, which constitute a characteristic feature of papillary thyroid carcinoma. Their pathogenesis is not yet clear, but there is evidence for the involvement of a signaling pathway downstream of the protooncogene RET. The presence of nuclear grooves is not specific for papillary thyroid carcinoma because it has been documented in other types of thyroid neoplasms, in nonneoplastic thyroid lesions, in ovarian neoplasms (Brenner, adult granulosa cell, and transitional cell tumors), in breast carcinomas, in cervicovaginal and endometrial smears, in papillary neoplasms of several organs (such as papillary transitional cell carcinoma of the bladder, papillary renal cell carcinoma, papillary endometrioid carcinoma of the prostate), in thymic carcinomas, and in nonepithelial tumors. [ABSTRACT FROM AUTHOR]

We review the available information regarding the role of adhesive molecules as potential participants in the complex events of fertilization, embryogenesis, implantation and placentation. Studies that specifically relate to the expression and modulation of adhesive molecules in fertilization, embryogenesis, and implantation have been identified in the literature and by Medline searches. Cell-cell and cell-extracellular matrix interactions play a critical role in various developmental processes and in the cascade of events that lead to implantation and to the normal development of the fetus during pregnancy. Adhesion molecules influence, directly or indirectly, numerous aspects of cell behaviour, cell migration, cell growth, cell survival, cell proliferation, angiogenesis, invasion and metastasis. [ABSTRACT FROM AUTHOR]

Reduction/loss of E-cadherin is associated with the development and progression of many epithelial tumours. Dysadherin, recently characterised by members of our research team, has an anti-cell–cell adhesion function and downregulates E-cadherin in a post-transcriptional manner. The aim of the present study was to study the role of dysadherin in breast cancer progression, in association with the E-cadherin expression and the histological type. We have selected ductal carcinoma, which is by far the most common type and lobular carcinoma, which has a distinctive microscopic appearance. Dysadherin and E-cadherin expression was examined immunohistochemically in 70 invasive ductal carcinomas, no special type (NST), and 30 invasive lobular carcinomas, with their adjacent in situ components. In ductal as well as in lobular carcinoma dysadherin was expressed only in the invasive and not in the in situ component, and this expression was independent of the E-cadherin expression. Specifically, all 10 (100%) Grade 1, 37out of 45(82.2%) Grade 2 and six out of 15 (40%) Grade 3 invasive ductal carcinomas showed preserved E-cadherin expression, while ‘positive dysadherin expression’ was found in six out of 10 (60%) Grade 1, 34 out of 45(75.5%) Grade 2 and all 15 (100%) Grade 3 neoplasms. None of the 30 infiltrating lobular carcinomas showed preserved E-cadherin expression, while all the 30 infiltrating lobular carcinomas exhibited ‘positive dysadherin expression’. Dysadherin may play an important role in breast cancer progression by promoting invasion and, particularly in lobular carcinomas, it might also be used as a marker of invasion.British Journal of Cancer (2007) 96, 1404–1408. doi:10.1038/sj.bjc.6603743 www.bjcancer.com Published online 17 April 2007 [ABSTRACT FROM AUTHOR]

Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell-cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part. [ABSTRACT FROM AUTHOR]

Integrins are a family of adhesion molecules performing a major role in multiple cellular functions. Their contribution in carcinogenesis and metastatic process are the object of intense research activity worldwide during the last decades. This review focuses on the existing knowledge about integrin expression in head and neck squamous cell carcinoma (HNSCC) as it has been acquired mainly by immunohistochemical methods and by in vitro assays. The elucidation of the exact role of integrins and the study of expressive alterations of these molecules in cancer cells, may result in novel therapeutical approaches for useful applications in the clinical routine of HNSCC in the future. [ABSTRACT FROM AUTHOR]

Purpose. Estrogen receptor β (ERβ) is the second identified receptor mediating the effects of estrogen on target tissues. The role of ERβ in cancer pathobiology is largely unknown, because specific antibodies have not been available until recently. Initial studies have shown that ERβ expression declines in breast, ovarian, prostatic, and colon carcinomas. Tamoxifen, a synthetic anti-estrogen compound that is a mixed agonist/antagonist of estrogen receptor α (ERα) and a pure antagonist of ERβ, has moderate beneficial effects in human astrocytic neoplasms. However, most published studies agree that glial tumors do not express ERα. The purpose of this study was to explore the expression of ERβ in astrocytic neoplasms. Methods. ERβ expression was monitored immunohistochemically in 56 cases of astrocytomas of all grades (grade I–IV) and in adjacent non-neoplastic brain tissue. Results. Moderate or strong nuclear immunopositivity was obtained in non-neoplastic astrocytes and in low-grade astrocytomas, whereas the majority of high-grade tumors were immunonegative or displayed weak immunoreactivity. The progressive decline in ERβ expression paralleled the increase in tumor grade. Conclusions. In as much as ERβ is possibly the only ER expressed in astrocytes, its decreased expression may play an important role in astrocytic tumor initiation and in the potential response of glial neoplasms to tamoxifen. [ABSTRACT FROM AUTHOR]

Investigates the immunohistochemical expression of vascular endothelial growth factor (VEGF) and C-KIT in melanocytic lesions Immunostaining for VEGF observed only in melanomas; C-kit expression found in melanomas and in nevi; Indication that assessment of VEGF expression may aid in the differential diagnosis between dysplastic nevi and melanomas.

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]

Oxidative stress has been implicated in several chronic pathological conditions, leading to cell death and injury. Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) have several overlapping mechanisms as they are both characterized by increased oxidative stress, inflammation, insulin resistance, and autophagy dysfunction. The objective of this study was to elucidate the possible neuroprotective effect of empagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i), against hydrogen peroxide-induced neurotoxicity in primary hippocampal neurons derived from wild-type (WT) and transgenic AD rats (TgF344-AD). An in vitro oxidative stress model was established using hydrogen peroxide to induce damage to neurons. Empagliflozin pretreatment was tested on this model initially through a cell viability assay. Flow cytometry and cell sorting were employed to discriminate the apoptotic and necrotic neuronal cell populations. Finally, the morphological and morphometric features of the neurons, including dendritic length and spine density, were evaluated using the SNT ImageJ plug-in following immunostaining with GFP. Sholl analysis was used to evaluate the impact of empagliflozin and hydrogen peroxide on dendritic arborization. Empagliflozin tended to ameliorate hydrogen peroxide-induced toxicity in primary neurons derived from WT rats and led to the preservation of dendritic spine density in both WT and TgF344-AD neurons (one-way ANOVA, p < 0.05). A modest improvement in dendrites’ length was also observed. Empagliflozin pretreatment can partially mitigate dendritic and spine alterations induced by hydrogen peroxide in primary neurons. These results underscore the impact of empagliflozin on neuronal morphology and highlight its potential as a candidate for the treatment and/or prevention of AD. [ABSTRACT FROM AUTHOR]

Examines the mechanisms of neuronal cell death after neurotrophic factor deprivation. Apoptotic internucleosomal cleavage and necrotic random degradation of PC12 cell deoxyribonucleic acid (DNA); Agents preventing PC12 cell DNA fragmentation; Effects of phorbol ester TPA on DNA fragmentation; Role of ribonucleic acid (RNA), protein synthesis and calcium in internucleosomal DNA cleavage.

Background and Aim: Medical humanities is a multidisciplinary field, consisting of humanities (theory of literature and arts, philosophy, ethics, history and theology), social sciences (anthropology, psychology and sociology) and arts (literature, theater, cinema, music and visual arts), integrated in the undergraduate curriculum of Medical schools. The aim of the present study is to discuss medical humanities and support the necessity of introduction of a medical humanities course in the curriculum of Greek medical schools. Materials, Methods and Results: Through the relevant Pub-Med search as well as taking into account various curricula of medical schools, it is evident that medical education today is characterized by acquisition of knowledge and skills and development of medical values and attitudes. Clinical observation with the recognition of key data and patterns in the collected information, is crucial in the final medical decision, i.e. in the complex process, through which doctors accumulate data, reach conclusions and decide on therapy. All sciences included in medical humanities are important for the high quality education of future doctors. The practice of Medicine is in large an image-related science. The history of anatomy and art are closely related, already from the Renaissance time. Studies have shown that attendance of courses on art critics improves the observational skills of medical students. Literature is the source of information about the nature and source of human emotions and behavior and of narratives of illness, and increases imagination. Philosophy aids in the development of analytical and synthetical thinking. Teaching of history of medicine develops humility and aids in avoiding the repetition of mistakes of the past, and quite often raises research and therapeutic skepticism. The comprehension of medical ethics and professional deontology guides the patient-doctor relationship, as well as the relations between physicians and their colleagues. The Medical Humanities course, which is already integrated in the undergraduate curriculum of many medical schools of Europe, USA and Australia, includes lectures by experts and students' presentations on the above-mentioned areas and could be offered, for a semester, during the first years. Conclusion: The aim of Medical Humanities course is the development of imagination and interpretation of data through analytical complex procedures, the development of skills of close observation and careful interpretation of the patient "language" and the enhancement of empathy for the patients, as well as the development of the physician-patient relationship and finally the conceptualization/construction of personal and professional values. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about the developments in the molecular basis of colorectal cancer by Sanford D. Markowitz and Monica M. Bertagnolli in the December 17, 2009 issue.

The article presents a letter to the editor discussing the article "Molecular basis of metastasis," by AC Chiang and J. Massagué, published in the December 25, 2008 issue of the journal.

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 cancerous cell presents the sequence of events that follows the neoplastic transformation of a single mammary epithelial cell from its point of view. After multiple cell cycles, a mass is generated and becomes mammographically detectable and palpable. Metastases through the lymphatics are generated. Despite mastectomy and subsequent chemotherapy, the patient dies from widely metastatic disease, and the neoplastic cells die too. The final triumph becomes their Waterloo! The patient with her death defeats cancer! [ABSTRACT FROM AUTHOR]

The article presents a case study of a 70-year-old smoker with peripheral pulmonary lesion. It discusses pulmonary dirofilariasis, Dirofilariae, and D immitis. Patient's histopathological examination is done since there are neither specific imaging findings with no further treatment proposed. Images of computed tomography scan showing a peripheral lesion of the left lower lobe is shown along with the pulmonary artery branch.

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]

Background: During the last decade direct oral anticoagulants (DOAC) have been established in various fields of medicine.Their use in microsurgery has not been evaluated yet though. This study aims to evaluate their efficacy in microsurgery and additionally compare them with a well established antithrombotic agent.Materials and Methods: The right femoral artery of 101 rats divided into 4 groups, was crushed and anastomosed. Group A (20 rats) received placebo therapy (1 ml NaCl 0.9%, orally), while Group B (27 rats), Group C (27 rats) and Group D (27 rats) received rivaroxaban (3 mg/kg, orally), dabigatran (30 mg/kg, orally) and enoxaparin (30 mg/kg, subcutaneously) respectively. All drugs were administered 3 h preoperatively and once daily for the following postoperative days until the sacrifice of the animals. Patency was evaluated at 1st, 7th and 20th postoperative day. Following patency evaluation the rats were sacrificed and the vessels were harvested for histological examination.Results: None of the rats died postoperatively. Patency rates of rivaroxaban group (78%), dabigatran group (70%) and enoxaparin group (63%) were statistically similar, but significantly higher than the placebo-treated control group (p < 0.05). Cells with morphologic features of endothelial cells were evident 7 days after the injury.Conclusion: The results of this study demonstrate the following: (1) rivaroxaban and dabigatran through inhibition of thrombus formation significantly enhanced the patency rate compared to placebo treatment (2) the antithrombotic efficacy of rivaroxaban and dabigatran in compromised microvessels was similar to that of enoxaparin, the most widely used antithrombotic agent. [ABSTRACT FROM AUTHOR]

The article presents a pathological image of an atypical mitosis present in a giant cell malignant fibrous histiocytoma or undifferentiated pleomorphic sarcoma with giant cells in the retroperitoneal region of a male patient. In addition, the mitosis resembles a circus dog, and is said to represent abnormalities in chromatid dissociation during cell division and reflecting specific centrosomal alterations involved in carcinogenesis.

The balanopreputial sulcus is believed to be the most frequent site of the so-called Tyson's glands. The intriguing feature of these anatomical structures is their mere existence, which has been doubted. Herein, the authors present a case of a 24-year-old man who underwent surgical treatment of his phimosis. On microscopic examination of the specimen, glands with morphological features similar to those described by Tyson were noted. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to Maltese (White) Cross configuration/resemblance particles in some pathologies.

The term melanosis in the gastrointestinal tract refers to the accumulation of pigment deposits in the mucosa. Melanosis of the colon is not uncommon and has been associated with certain conditions, however melanosis of the small intestine is extremely rare. Herein, we describe a case in which we observed melanosis not only in the colon, but in the terminal ileum as well, associated with the use of anthraceneline laxatives. The clinical significance of this condition is not clear, however Gastroenterologists and Pathologists should be aware of its existence. [ABSTRACT FROM AUTHOR]

Presents verbal alimentary metaphors in pathology. Likeness of an apoplectic leiomyoma to an egg; Similarity of an anaplastic large cell lymphoma to a doughnut; Likeness of an oligodendroglioma cell to fried eggs; Neoplasms that look like coffee beans.

Simple Summary: This study aims to explore the connection between tumor-associated macrophages (TAMs) and the programmed cell death protein 1(PD-1)/programmed death ligand 1 (PD-L1) pathway in gastric cancer (GC). Immune checkpoint inhibitors (ICIs) have shown promise in cancer treatment. Here, we investigate their potential in GC. TAMs, abundant in the tumor microenvironment (TME), can express PD-1, which interacts with PD-L1 on cancer cells. This systematic review indicates that high PD-L1 expression correlates with increased TAM infiltration and may lead to worse patient outcomes. This suggests that TAMs could be crucial in regulating the PD-1/PD-L1 network in GC. Enhanced comprehension of this intricate relationship may offer opportunities for optimizing the efficacy of ICIs in this malignancy. Background: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). Aim of the study: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. Methods: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. Results: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. Conclusions: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC. [ABSTRACT FROM AUTHOR]

The accurate assessment of malignancy and the precise characterization of cancer type are pivotal in guiding clinical decisions and ensuring optimal patient outcomes. The challenging task of identifying the primary site of carcinoma, especially during a surgical procedure, is not always possible and necessitates the exploration of novel, innovative diagnostic techniques. In this report, we detail a unique case of carcinoma of unknown primary origin encountered during an orthopedic surgical procedure. We introduce a novel intraoperative flow cytometry (iFC) methodology, distinctly different from traditional flow cytometry, which is tailored for real-time assessment during surgeries. This iFC technique, applied in a bone metastasis case of unknown primary origin, enabled DNA content analysis and the quantification of cytokeratin for rapid malignancy characterization, presenting an avenue for immediate surgical guidance and decision making. The case was distinctively characterized using iFC, shedding light on the potential of this emerging technique. iFC has been gaining traction because of its ability to facilitate cancer cell assessment and margin evaluation. It has been successfully applied across a wide spectrum of neoplastic conditions. Our innovative, two-step approach using iFC encompasses (1) DNA content analysis, which serves as a reliable indicator for the detection of cancer cells, and (2) the quantification of cytokeratin, a pivotal marker, which aids in the characterization and classification of a malignancy. In this case, the malignancy was classified as a carcinoma. The findings obtained from iFC were subsequently validated through pathology assessment, confirming the accuracy and reliability of our approach. This noteworthy case strengthens the potential of iFC as a novel tool in malignancy assessment, which is not just limited to cell cycle analysis but instead extends beyond this application. The promising results obtained from this case study serve as a testament to the need for more extensive research in clinical studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is one of the most common and deadly malignancies worldwide. Microscopic examination of histological and cytological lung specimens can be a challenging and time-consuming process. Most of the time, accurate diagnosis and classification require histochemical and specific immunohistochemical staining. Currently, Artificial Intelligence-based methods show remarkable advances and potential in Pathology and can guide lung cancer diagnosis, subtyping, prognosis prediction, mutational status characterization, and PD-L1 expression estimation, performing with high accuracy rates. This systematic review aims to provide an overview of the current advances in Deep Learning-based methods on lung cancer by using histological and cytological images. Lung cancer is one of the deadliest cancers worldwide, with a high incidence rate, especially in tobacco smokers. Lung cancer accurate diagnosis is based on distinct histological patterns combined with molecular data for personalized treatment. Precise lung cancer classification from a single H&E slide can be challenging for a pathologist, requiring most of the time additional histochemical and special immunohistochemical stains for the final pathology report. According to WHO, small biopsy and cytology specimens are the available materials for about 70% of lung cancer patients with advanced-stage unresectable disease. Thus, the limited available diagnostic material necessitates its optimal management and processing for the completion of diagnosis and predictive testing according to the published guidelines. During the new era of Digital Pathology, Deep Learning offers the potential for lung cancer interpretation to assist pathologists' routine practice. Herein, we systematically review the current Artificial Intelligence-based approaches using histological and cytological images of lung cancer. Most of the published literature centered on the distinction between lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung carcinoma, reflecting the realistic pathologist's routine. Furthermore, several studies developed algorithms for lung adenocarcinoma predominant architectural pattern determination, prognosis prediction, mutational status characterization, and PD-L1 expression status estimation. [ABSTRACT FROM AUTHOR]

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]

An abstract of the study "Medicine and Humanities in the Era of Electronic Information Exchange," by Anna Batistatou is presented.

A personal narrative of the author's experience with a 55-year-old patient, named Oscar X.

The article discusses that the stolen painting of Edward Munch, the Scream, one of the world's most recognizable paintings, was recovered by the policeman during an operation on August 31, 2006 in Oslo, Norway. It is stated that the painting was stolen last two years from the Oslo museum. Furthermore, Munch had painted several versions of Scream.

The article presents a pathological image of the bone trabecula on a transiliac biopsy from a 62-year-old white woman. The said bone resembles a mask, and the osteocytes and lacunae are well appreciated with the standard hematoxylin and eosin stain. Traditionally, bone tumors were said to be difficult to diagnose, but with comparative genomic hybridation, the hidden secrets of bone is unmasked.

The article discusses the use of immunohistochemical markers in assessing the peritumoral vascular invasion on sections stained with the standard hematoxylin and eosin. Peritumoral vascular invasion has been recently added to the St. Gallen criteria for adjuvant treatment of patients with operable breast cancer but due to the difficulty of assessing such an invasion, immunohistochemical stains are used. Moreover, immunohistochemical markers can also distinguish blood from lymph vessels.

The article reports on the case of twins discovered in a leiomyosarcoma of a 57-year-old woman, who presented with vaginal bleeding. The first face detected through a microscope projected consists of endothelial cells lining a small vessel within the tumor. The sibling was covered and revealed itself only upon immunohistochemical staining for vimentin.

Presents the case of a 32-year-old woman who presented with a pigmented lesion, measuring 0.8 cm in greatest diameter, in her back. Diagnosis of a compound nevus; Observation of a dilated lymphatic channel deep in the reticular dermis; First demonstration of nevus cells growing within a lymphatic valve.

Presents a medical microscopic imaging of a vegetable cells.

Presents the case of oxyuris (Enterobius) vermicularis in human cecum. Appearance of cuticular wing-like expansions; Presence of pinworm in cecum; Causes of oxyuris vermicularis.

We analyzed the expression of Jun family in relation to CD30 expression, cell proliferation and B-cell differentiation immunophenotypes [Germinal Center and non-Germinal Center] in diffuse large B-cell lymphomas (DLBCL). Expression and high expression of phosphorylated-c-Jun (p-c-Jun), JunB, JunD and CD30 (cut-off scores 20% and 50%, respectively) was found in 18/103, 49/103, 72/101 and 26/102 cases, respectively, and in 6/103, 27/103, 60/101 and 21/102 cases, respectively. The following significant positive correlations were observed: (a) JunB with cyclin A (p = 0.046), cyclin B1 (p = 0.033), cyclin E (p = 0.003), MUM-1 (p = 0.002) and CD30 (p < 0.001), (b) JunD with Ki67 (p = 0.002) and cyclin E (p = 0.014), (c) p-c-Jun with CD30 (p = 0.015), and (d) high p-c-Jun with cyclin A (p = 0.034). The positive correlation between expression of JunB, JunD and p-c-Jun and tumor cell proliferation in DLBCL, suggests that increased JunB, JunD and p-c-Jun expression may be involved in the pathogenesis of DLBCL by increasing tumor cell proliferation. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune disease that targets myelinated axons in the central nervous system (CNS). Cancer of unknown primary site (CUP) is a well-recognised clinical disorder, accounting for 3–5% of all malignant epithelial tumors. CUP is clinically characterised as an aggressive disease with early dissemination. Studies of cancer risk in MS patients have shown inconsistent findings. An increased risk of malignancy in patients with MS has been suggested, but recently serious questions have been raised regarding this association. Use of disease-modifying therapies might contribute to an increased cancer risk in selected MS patients. The concurrence of MS and CUP is exceptionally rare. Here we describe the case of a neuroendocrine carcinoma of unknown primary diagnosed in a male patient with a nine-year history of MS. The discussion includes data from all available population-based register studies with estimates of certain malignancies in patients with MS. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor-infiltrating lymphocytes (TILs) have been reported to contribute to breast cancer (BC) prognosis. The aim of our study was to investigate the prognostic impact of CD8+ TILs and their subtypes in patients with early breast cancer treated with sequential, dose-dense adjuvant chemotherapy. Tumors of 627 patients were examined for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2). Our results showed that high expression of sCD8, iCD8, and tCD8 correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. We confirmed that patients with high iCD8+ and tCD8+ TILs had longer DFS and OS, as compared to those with low counts/mm2. Survival benefit was retained when adjusting for classical clinical and pathological characteristics, but was not correlated to specific BC subtype. More data are needed to empower the prognostic role of TILs and establish their use in clinical practice. Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients' tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC. [ABSTRACT FROM AUTHOR]

Purpose Angiogenesis is a crucial phenomenon in the development and progression of breast cancer (BC), but the clinical significance of angiogenesis-related proteins in metastatic BC remains unknown. This study investigates the prognostic value of vascular endothelial growth factor receptors 1, 2, 3 (VEGFR1, VEGFR2, VEGFR3) as well as vascular endothelial growth factors A and C (VEGFA and VEGFC) in metastatic BC patients treated with trastuzumab-based regimens. Materials and Methods Two hundred female patients were included. Protein and mRNA expression of the studied angiogenesis-related factors were evaluated by immunohistochemistry and quantitative polymerase chain reaction, respectively. Results High expression of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in the tumor cells was observed in 43.5%, 24.2%, 36%, 29.5%, and 43%, respectively. Stromal elements expressed high levels of VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 in 78.9%, 93.3%, 90.7%, 90.2%, and 74.8% of tumors with available data. High tumor cell expression of VEGFR1 was a favorable prognosticator for survival among patients with human epidermal growth factor receptor 2 (HER2)-positive tumors (hazard ratio [HR], 0.55; p=0.013). A trend towards longer progression-free survival was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2 (HR, 0.60; p=0.059). Conclusion VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens. [ABSTRACT FROM AUTHOR]

Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal tissue tumor. Its differential diagnosis from similar tumors, such as low differentiated squamous cell carcinoma, fibrosarcoma, desmoplastic melanoma, atypical fibroxanthoma (AFX), may be difficult, as they have similar clinical and histological presentation. We present a case of an 83-year-old man exhibiting an exophytic scalp lesion. Excision of the lesion was performed, ensuring clear surgical margins and pathologic examination revealed an invasive pleomorphic dermal sarcoma. This case highlights a rare case of a large pleomorphic dermal sarcoma, and it discusses the histological, molecular features, its differential diagnosis and management of PDS. [ABSTRACT FROM AUTHOR]