Viral Entry Inhibitors Protect against SARS-CoV-2-Induced Neurite Shortening in Differentiated SH-SY5Y Cells.

The utility of human neuroblastoma cell lines as in vitro model to study neuro-invasiveness and neuro-virulence of SARS-CoV-2 has been demonstrated by our laboratory and others. The aim of this report is to further characterize the associated cellular responses caused by a pre-alpha SARS-CoV-2 strain on differentiated SH-SY5Y and to prevent its cytopathic effect by using a set of entry inhibitors. The susceptibility of SH-SY5Y to SARS-CoV-2 was confirmed at high multiplicity-of-infection, without viral replication or release.

Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer.

Netrin-1 is upregulated in cancers as a protumoural mechanism. Here we describe netrin-1 upregulation in a majority of human endometrial carcinomas (ECs) and demonstrate that netrin-1 blockade, using an anti-netrin-1 antibody (NP137), is effective in reduction of tumour progression in an EC mouse model. We next examined the efficacy of NP137, as a first-in-class single agent, in a Phase I trial comprising 14 patients with advanced EC.

Pharmacological targeting of netrin-1 inhibits EMT in cancer.

Epithelial-to-mesenchymal transition (EMT) regulates tumour initiation, progression, metastasis and resistance to anti-cancer therapy. Although great progress has been made in understanding the role of EMT and its regulatory mechanisms in cancer, no therapeutic strategy to pharmacologically target EMT has been identified. Here we found that netrin-1 is upregulated in a primary mouse model of skin squamous cell carcinoma (SCC) exhibiting spontaneous EMT.

NR2F2 controls malignant squamous cell carcinoma state by promoting stemness and invasion and repressing differentiation.

The nongenetic mechanisms required to sustain malignant tumor state are poorly understood. During the transition from benign tumors to malignant carcinoma, tumor cells need to repress differentiation and acquire invasive features. Using transcriptional profiling of cancer stem cells from benign tumors and malignant skin squamous cell carcinoma (SCC), we identified the nuclear receptor NR2F2 as uniquely expressed in malignant SCC.

Deciphering functional tumor states at single-cell resolution.

Within a tumor, cancer cells exist in different states that are associated with distinct tumor functions, including proliferation, differentiation, invasion, metastasis, and resistance to anti-cancer therapy. The identification of the gene regulatory networks underpinning each state is essential for better understanding functional tumor heterogeneity and revealing tumor vulnerabilities. Here, we review the different studies identifying tumor states by single-cell sequencing approaches and the mechanisms that promote and sustain these functional states and regulate their transitions.

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

Background: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation.

Methods: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs.

Fat1 deletion promotes hybrid EMT state, tumour stemness and metastasis.

FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype.

Direct examination, histopathology and fungal culture for the diagnosis of onychomycosis: A retrospective, comparative study on 2245 specimens.

Background: Onychomycosis affects 5.5% of the general population and represents up to 50% of all nail diseases. Diagnosis and pathogen identification are essential in order to plan an adequate treatment.

A Novel Approach for Quantifying Cancer Cells Showing Hybrid Epithelial/Mesenchymal States in Large Series of Tissue Samples: Towards a New Prognostic Marker.

In cancer biology, epithelial-to-mesenchymal transition (EMT) is associated with tumorigenesis, stemness, invasion, metastasis, and resistance to therapy. Evidence of co-expression of epithelial and mesenchymal markers suggests that EMT should be a stepwise process with distinct intermediate states rather than a binary switch. In the present study, we propose a morphological approach that enables the detection and quantification of cancer cells with hybrid E/M states, i.

Perineural Invasion as a Clue to Malignant Behavior in a Dermatofibroma.

Dermatofibroma (DF) represents one of the most common mesenchymal proliferations of the skin. Their recurrence rate, even when incompletely excised, is very low, whereas the atypical, aneurysmal, and cellular variants have recurrence rates of up to 20% each. Extraordinary rare malignant lesions with metastases to lymph nodes and/or lung have been described.

Context Dependency of Epithelial-to-Mesenchymal Transition for Metastasis.

Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis. Here, we assessed in different models of primary skin squamous cell carcinomas (SCCs) whether EMT is associated with metastasis.

EMT Transition States during Tumor Progression and Metastasis.

Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features. In cancer, EMT is associated with tumor initiation, invasion, metastasis, and resistance to therapy. Recently, it has been demonstrated that EMT is not a binary process, but occurs through distinct cellular states.

Phenotypic Plasticity: Driver of Cancer Initiation, Progression, and Therapy Resistance.

Our traditional understanding of phenotypic plasticity in adult somatic cells comprises dedifferentiation and transdifferentiation in the context of tissue regeneration or wound healing. Although dedifferentiation is central to tissue repair and stemness, this process inherently carries the risk of cancer initiation. Consequently, recent research suggests phenotypic plasticity as a new paradigm for understanding cancer initiation, progression, and resistance to therapy.

Identification of the tumour transition states occurring during EMT.

In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea.

Heteronanoparticles by self-Assembly of Doxorubicin and Cyclopamine Conjugates.

The preparation of heteronanoparticles (NPs) with doxorubicin (DOXO) and cyclopamine (CYP) conjugates is presented. Biological evaluation on A431 cell lines confirms the maintenance of the activity of the parental drugs. The study shows that self-assembled NPs reduce tumor growth and toxicity of chemotherapy.

[Apocrine hidrocystoma associated with gouty tophi of the pinna].

Background: Apocrine hidrocystomas, also known as apocrine cystadenomas, are bening cystic tumours derived from the secretory portion of apocrine sweat glands.

Clinical Case: A 78-year old female was referred to our division for assesment an asymptomatic translucent, well-defined cystic lesion located on the upper helix. The histological features were consistent with apocrine hidrocystoma coexisting with gouty tophi.

Increased Angiogenesis and Lymphangiogenesis in Metastatic Sentinel Lymph Nodes Is Associated With Nonsentinel Lymph Node Involvement and Distant Metastasis in Patients With Melanoma.

Lymph node angio- and lymphangio-genesis have been shown to play an important role in the premetastatic niche of sentinel lymph nodes. In the current study we have investigated the association of angio- and lympangio-genesis related parameters in metastatic sentinel lymph nodes of patients with melanoma with the presence of nonsentinel and distant organ metastasis. Peritumoral and intratumoral relative blood and lymphatic vessel areas (evaluated by Chalkley method), blood and lymphatic microvessel densities, and the rates of blood and lymphatic vessel proliferation were assessed in primary tumors and sentinel lymph node metastasis of 44 patients with melanoma using CD34/Ki-67 and D240/Ki-67 immunohistochemical double staining.

Peritumoral D2-40 Chalkley score independently predicts metastases and survival in patients with cutaneous malignant melanoma.

Background: Many observational studies investigated the prognostic significance of angiogenesis and lymphangiogenesis in patients with melanoma. However, the obtained results are rather contradictory, probably due to the lack of the consensus methodology.

Methods: To investigate the prognostic significance of angiogenesis and lymphangiogenesis-related parameters in patients with melanoma, we performed a retrospective investigation following the consensus recommendations for angiogenesis and lymphangiogenesis quantification in solid tumors and reporting recommendations for tumor marker (REMARK) criteria for reporting the results.

Melanomas arising on skin with chronic sun-induced damage exhibit low degree of angiogenesis and lymphangiogenesis.

Differences in gene expression between melanomas arising on skin intermittently and chronically sun-exposed areas were described. Additionally, several studies have shown differences in clinical characteristics and prognosis, suggesting distinct biological pathways in the development of these tumors. We performed a retrospective investigation aimed on evaluation of the differences in angiogenesis and lymphangiogenesis between melanomas arising on skin with and without signs of chronic sun-induced damage.

Squamous cell carcinomas of the skin explore angiogenesis-independent mechanisms of tumour vascularization.

Aims. To evaluate the vascularization in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin. Methods.