Influence of adjuvant therapies on organ-specific recurrence of cutaneous melanoma: A multicenter study on 1383 patients of the prospective DeCOG registry ADOReg.

This study investigated whether adjuvant treatments in stage III cutaneous melanoma (CM) influenced patterns of recurrence. Patients with primary (n = 1033) or relapsed CM (n = 350) who received adjuvant therapies with Nivolumab (N), Pembrolizumab (P), or Dabrafenib and Trametinib (D + T) were extracted from the prospective multicenter real-world skin cancer registry ADOReg. Endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), organ-specific DMFS, and overall survival (OS).

Endothelial cells drive organ fibrosis in mice by inducing expression of the transcription factor SOX9.

Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it is unclear to what extent endothelial cells also might contribute. We detected increased expression of the transcription factor in endothelial cells in several different mouse fibrosis models.

Deficiency of Stabilin-1 in the Context of Hepatic Melanoma Metastasis.

Background: This study analyzed the role of Stabilin-1 on hepatic melanoma metastasis in preclinical mouse models.

Methods: In mice (Stab1 KO), liver colonization of B16F10 and Wt31 melanoma was investigated. The numbers, morphology, and vascularization of hepatic metastases and the hepatic microenvironment were analyzed by immunofluorescence.

Automated Machine Learning Analysis of Patients With Chronic Skin Disease Using a Medical Smartphone App: Retrospective Study.

Background: Rapid digitalization in health care has led to the adoption of digital technologies; however, limited trust in internet-based health decisions and the need for technical personnel hinder the use of smartphones and machine learning applications. To address this, automated machine learning (AutoML) is a promising tool that can empower health care professionals to enhance the effectiveness of mobile health apps.

Objective: We used AutoML to analyze data from clinical studies involving patients with chronic hand and/or foot eczema or psoriasis vulgaris who used a smartphone monitoring app.

Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury.

Liver sinusoidal endothelial cells (LSECs) rapidly clear lipopolysaccharide (LPS) from the bloodstream and establish intimate contact with immune cells. However, their role in regulating liver inflammation remains poorly understood. We show that LSECs modify their chemokine expression profile driven by LPS or interferon-γ (IFN-γ), resulting in the production of the myeloid- or lymphoid-attracting chemokines CCL2 and CXCL10, respectively, which accumulate in the serum of LPS-challenged animals.

Hepatic passaging of NRAS-mutant melanoma influences adhesive properties and metastatic pattern.

Background: Liver metastasis is a poor prognostic factor for treatment of advanced cutaneous melanoma with either immunotherapy or targeted therapies. In this study we focused on NRAS mutated melanoma, a cohort with high unmet clinical need.

Methods: WT31 melanoma was repeatedly passaged over the liver after intravenous injections five times generating the subline WT31_P5IV.

Cutaneous leukocytoclastic vasculitis after second dose of mRNA COVID-19 vaccine.

Numerous cutaneous reactions following COVID-19 vaccination have already been described. Vasculitis, however, is a rare adverse event, occurring mainly after the first COVID-19 vaccination. Herein, we report a patient with IgA-positive cutaneous leukocytoclastic vasculitis, unresponsive to a moderate dose of systemic corticosteroid that erupted after the second dose of the Pfizer/BioNTech vaccine.

Lyve-1 deficiency enhances the hepatic immune microenvironment entailing altered susceptibility to melanoma liver metastasis.

Background: Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding to hyaluronan, LYVE-1 can mediate adhesion of leukocytes and cancer cells to endothelial cells. Here, we assessed the impact of LYVE-1 on physiological liver functions and metastasis.

Angiogenic and molecular diversity determine hepatic melanoma metastasis and response to anti-angiogenic treatment.

Background: Cutaneous melanoma exhibits heterogeneous metastatic patterns and prognosis. In this regard, liver metastasis, which is detected in ~ 10-20% of stage 4 patients, came to the fore of melanoma research, as it recently evolved as decisive indicator of treatment resistance to immune checkpoint inhibition.

Methods: Hepatic metastases were induced by intrasplenic injection of five different murine melanoma cell lines.

Radiotherapy and newly approved cancer drugs - A quantitative analysis of registered protocols for drugs approved for the treatment of solid tumors.

Background/purpose: To evaluate the usage of RT in trial protocols for anti-cancer drugs approved by the US Food and Drug Administration (FDA).

Methods: Drugs which had been granted an FDA approval between 2010 and 2017 for the treatment of solid tumors in adults were identified. Use of RT in relation to each drug's approval date was reviewed on ClinicalTrials.

Bone marrow sinusoidal endothelium controls terminal erythroid differentiation and reticulocyte maturation.

Within the bone marrow microenvironment, endothelial cells (EC) exert important functions. Arterial EC support hematopoiesis while H-type capillaries induce bone formation. Here, we show that BM sinusoidal EC (BM-SEC) actively control erythropoiesis.

Retrospective analysis and time series forecasting with automated machine learning of ascariasis, enterobiasis and cystic echinococcosis in Romania.

The epidemiology of neglected tropical diseases (NTD) is persistently underprioritized, despite NTD being widespread among the poorest populations and in the least developed countries on earth. This situation necessitates thorough and efficient public health intervention. Romania is at the brink of becoming a developed country.

Imbalanced Activation of Wnt-/β-Catenin-Signaling in Liver Endothelium Alters Normal Sinusoidal Differentiation.

Endothelial wingless-related integration site (Wnt)-/β-catenin signaling is a key regulator of the tightly sealed blood-brain barrier. In the hepatic vascular niche angiokine-mediated Wnt signaling was recently identified as an important regulator of hepatocyte function, including the determination of final adult liver size, liver regeneration, and metabolic liver zonation. Within the hepatic vasculature, the liver sinusoidal endothelial cells (LSECs) are morphologically unique and functionally specialized microvascular endothelial cells (ECs).

Benefits of Metformin Combined with Pemetrexed-Based Platinum Doublets as a First-Line Therapy for Advanced Lung Adenocarcinoma Patients with Diabetes.

Lung cancer remains a challenge in daily practice. Chemotherapy is first considered for advanced lung adenocarcinoma bearing no active driver mutations. Maintaining drug efficacy and overcoming drug resistance are essential.

Complete division of the pedicle of the forehead flap is possible after 1 week of engraftment in selected patients.

Background: Recent studies have demonstrated that early division of the forehead flap (FHF) is possible if angiography is performed or a remnant of the pedicle is left behind. Whether or not careful selection of patients allows for complete division of the pedicle has not been studied.

Objective: To assess if careful selection of patients allows for early complete division of the FHF.

Additive Antiproliferative and Antiangiogenic Effects of Metformin and Pemetrexed in a Non-Small-Cell Lung Cancer Xenograft Model.

Lung cancer is heterogeneous and challenging to cope with once it has progressed. Chemotherapy is the first step once no active driver mutation has been discovered. Non-antitumor drugs have been found to be beneficial when used as adjuvants to chemotherapy.

Association of and Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients.

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory - and -specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis.

Podoplanin is required for tumor cell invasion in cutaneous squamous cell carcinoma.

The invasiveness of late-stage cutaneous squamous cell carcinoma (cSCC) is associated with poor patients' prognosis and linked to strong upregulation of the glycoprotein Podoplanin (PDPN) in cancer cells. However, the function of PDPN in these processes in cSCC carcinogenesis has not been characterized in detail yet. Employing a CRISPR/Cas9-based loss-of-function approach on murine cSCC cells, we show that the loss of Pdpn results in decreased migration and invasion in vitro.

Angiodiversity and organotypic functions of sinusoidal endothelial cells.

'Angiodiversity' refers to the structural and functional heterogeneity of endothelial cells (EC) along the segments of the vascular tree and especially within the microvascular beds of different organs. Organotypically differentiated EC ranging from continuous, barrier-forming endothelium to discontinuous, fenestrated endothelium perform organ-specific functions such as the maintenance of the tightly sealed blood-brain barrier or the clearance of macromolecular waste products from the peripheral blood by liver EC-expressed scavenger receptors. The microvascular bed of the liver, composed of discontinuous, fenestrated liver sinusoidal endothelial cells (LSEC), is a prime example of organ-specific angiodiversity.

Metformin Increases Survival in Hypopharyngeal Cancer Patients with Diabetes Mellitus: Retrospective Cohort Study and Cell-Based Analysis.

Hypopharyngeal squamous cell carcinoma (HSCC) is usually diagnosed at an advanced stage, leading to a poor prognosis. Even after improvement of surgical techniques, chemotherapy, and radiation technology, the survival rate of HSCC remains poor. Metformin, which is commonly used for type 2 diabetes mellitus (DM), has been suggested to reduce the risk of various cancer types.

Exploring the transcriptomic network of multi-ligand scavenger receptor Stabilin-1- and Stabilin-2-deficient liver sinusoidal endothelial cells.

The Class H scavenger receptors Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are two of the most highly expressed genes in liver sinusoidal endothelial cells (LSECs). While Stab1-deficient (Stab1KO) and Stab2-deficient (Stab2KO) mice are phenotypically unremarkable, Stab1/2-double-deficient (StabDKO) mice exhibit perisinusoidal liver fibrosis, glomerulofibrotic nephropathy and a reduced life expectancy. These conditions are caused by insufficiently scavenged circulating noxious blood factors.