Selection of the Most Suitable Culture Medium for Patient-Derived Lung Cancer Organoids.

Introduction: Patient-derived organoids have emerged as a promising in vitro model for precision medicine, particularly in cancer, but also in noncancer-related diseases. However, the optimal culture medium for culturing patient-derived lung organoids has not yet been agreed upon. This study aimed to shed light on the optimal selection of a culture media for developing studies using patient-derived lung organoids.

Discovering genes and microRNAs involved in human lung development unveils IGFBP3/miR-34a dynamics and their relevance for alveolar differentiation.

Background: During pseudoglandular stage of the human lung development the primitive bronchial buds are initially conformed by simple tubules lined by endoderm-derived epithelium surrounded by mesenchyme, which will progressively branch into airways and start to form distal epithelial saculles. For first time alveolar type II (AT2) pneumocytes appears. This study aims to characterize the genes and microRNAs involved in this differentiation process and decipher its role in the starting alveolar differentiation.

Outcomes of Combined Posterior Tibial Tendon Tendoscopy and Medializing Calcaneal Osteotomy for Stage IA Progressive Collapsing Foot Deformity.

Background: Posterior tibial tendon (PTT) tendoscopy and medializing calcaneal osteotomy (MCO) are among the available techniques for patients presenting with symptomatic flexible hindfoot valgus (stage IA) progressive collapsing foot deformity (PCFD). The aim of this study was to determine clinical and radiographic outcomes of combined PTT tendoscopy and MCO for patients presenting with symptomatic stage IA PCFD.

Methods: A retrospective cohort study was performed in order to determine clinical and radiographic outcomes of 30 combined PTT tendoscopies and MCO on 27 patients presenting with symptomatic stage IA PCFD, with a minimum follow-up of 24 months.

Anatomy of the Ankle and Subtalar Joint Ligaments: What We Do Not Know About It?

Understanding of the ankle and subtalar joint ligaments is essential to recognize and manage foot and ankle disorders. The stability of both joints relies on the integrity of its ligaments. The ankle joint is stabilized by the lateral and medial ligamentous complexes while the subtalar joint is stabilized by its extrinsic and intrinsic ligaments.

Characterization of the MicroRNA Cargo of Extracellular Vesicles Isolated from a Pulmonary Tumor-Draining Vein Identifies miR-203a-3p as a Relapse Biomarker for Resected Non-Small Cell Lung Cancer.

In resected non-small cell lung cancer (NSCLC), post-surgical recurrence occurs in around 40% of patients, highlighting the necessity to identify relapse biomarkers. An analysis of the extracellular vesicle (EV) cargo from a pulmonary tumor-draining vein (TDV) can grant biomarker identification. We studied the pulmonary TDV EV-miRNAome to identify relapse biomarkers in a two-phase study (screening and validation).

Human embryonic mesenchymal lung-conditioned medium promotes differentiation to myofibroblast and loss of stemness phenotype in lung adenocarcinoma cell lines.

Background: When genes responsible for normal embryonic development are abnormally expressed in adults, it can lead to tumor development. This can suggest that the same mechanism that controls embryonic differentiation can also control tumor differentiation. We hypothesize that the malignant phenotype of lung cancer cells could acquire benign characteristics when in contact with an embryonic lung microenvironment.

LncRNA Quantification from Extracellular Vesicles Isolated from Blood Plasma or Conditioned Media.

During the last years, the study of extracellular vesicles (EVs) and its cargo has gained interest in the scientific media. EVs have been found in all biofluids and it is postulated that all cells are capable to secrete a wide variety of these vesicles, which play a key role in different cell-to-cell communication processes as well as in the microenvironment modulation. In the EV cargo, DNA, protein, and RNA molecules can be found, including long noncoding RNAs (lncRNAs).

Monitoring HOTTIP levels on extracellular vesicles for predicting recurrence in surgical non-small cell lung cancer patients.

In resected non-small cell lung cancer (NSCLC), postsurgical recurrence is the major factor affecting long-term survival. The identification of biomarkers in extracellular vesicles (EV) obtained from serial blood samples after surgery could enhance early detection of relapse and improve NSCLC outcome. Since EV cargo contains long non-coding RNAs (lncRNAs), we aimed to analyze whether the oncogenic lncRNA HOTTIP, which higher expression in tumor tissue was related to worse outcome in NSCLC, could be detected in EV from NSCLC patients and serve as recurrence biomarker.

Lincp21-RNA as Predictive Response Marker for Preoperative Chemoradiotherapy in Rectal Cancer.

Preoperative chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer (RC) patients, but its use in non-responders can be associated with increased toxicities and resection delay. LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation. We aimed to study whether lincRNA-p21 expression levels can act as a predictive biomarker for neoadjuvant CRT response.

Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer.

Background: Circular RNAs (circRNAs) are non-coding RNAs with a circular structure that have recently emerged as important regulators of tumorogenesis. Recently, several circRNAS, including circ-10720 have been related to epithelial-mesenchymal transition (EMT) process. In the present study, we have analyzed the role of circ-10720 in non-small-cell lung cancer (NSCLC) and studied its prognostic relevance in resected stage I-IIIa NSCLC patients.

LincRNA-p21 Levels Relates to Survival and Post-Operative Radiotherapy Benefit in Rectal Cancer Patients.

LincRNA-p21 is a long non-coding RNA involved in the p53 pathway and angiogenesis regulation that acts as prognostic marker in several tumors. In the present study, we aimed to analyze the clinical value of lincRNA-p21 in 177 resected stage I-III colorectal cancer (CRC) patients. Tumor and normal paired tissue and plasma samples from tumor-draining mesenteric veins and paired peripheral veins were analyzed.

Nectin-2 Expression on Malignant Plasma Cells Is Associated with Better Response to TIGIT Blockade in Multiple Myeloma.

Purpose: T-cell immunoreceptor with Ig and ITIM domain (TIGIT) blockade could represent an alternative therapeutic option to release the immune response in patients with multiple myeloma. Here we analyzed the expression of TIGIT and its ligands poliovirus receptor (PVR) and nectin-2 in the bone marrow (BM) of patients with monoclonal gammopathies and the efficacy of TIGIT blockade activating antimyeloma immunity.

Experimental Design: Expression levels of TIGIT and its ligands were characterized by flow cytometry and ELISA.

The tibiocalcaneal bundle of the deltoid ligament - Prevalence and variations.

Introduction: A precise understanding of the anatomy of the multiple bundles of the deltoid ankle ligament might have clinical impact. The most relevant deltoid anatomical series report a variable frequency of the tibiocalcaneal ligament, possibly the most important bundle to be reconstructed in medial ankle insufficiency. Our purpose was to access the deltoid's tibiocalcaneal ligament morphology in a large anatomical study as well as to perform a historical literature review on the reasons for its variable prevalence.

Loss of the Immune Checkpoint CD85j/LILRB1 on Malignant Plasma Cells Contributes to Immune Escape in Multiple Myeloma.

Mechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We hypothesized that CD85j (), an inhibitory immune checkpoint for B cell function, may play a role in MM pathogenesis. In this study, we report that patients with active MM had significantly lower levels of CD85j and its ligand S100A9.

Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression.

Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012.

Prognostic impact of immunoparesis at diagnosis and after treatment onset in patients with light-chain amyloidosis.

Objectives: Immunoparesis (IP) is a risk factor associated with an unfavourable outcome in several plasma cell disorders. It has been suggested that its presence in light-chain (AL) amyloidosis could be associated with worse prognosis. However, the relevance of IP after treatment has not been evaluated to date.

The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in and models of multiple myeloma by blockade of Ikaros and MYC signaling.

Most patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequent reduction in IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinational effect of an MYC-interfering therapy with lenalidomide/dexamethasone.

Impact of Autologous Stem Cell Transplantation on the Incidence and Outcome of Oligoclonal Bands in Patients with Light-Chain Amyloidosis.

The emergence of oligoclonal bands (OB) in patients with multiple myeloma achieving a complete remission (CR) after autologous stem cell transplantation (ASCT) and the use of novel agents is a well-recognized event. The presence of OB is associated with favorable outcome. However, the emergence of OB in light-chain (AL) amyloidosis has never been investigated.

A serum microRNA signature associated with complete remission and progression after autologous stem-cell transplantation in patients with multiple myeloma.

We have examined serum microRNA expression in multiple myeloma (MM) patients at diagnosis and at complete response (CR) after autologous stem-cell transplantation (ASCT), in patients with stable monoclonal gammopathy of undetermined significance, and in healthy controls. MicroRNAs were first profiled using TaqMan Human MicroRNA Arrays. Differentially expressed microRNAs were then validated by individual TaqMan MicroRNA assays and correlated with CR and progression-free survival (PFS) after ASCT.

Epigenetic regulation of microRNA expression in Hodgkin lymphoma.

Epigenetic mechanisms are crucial for the inactivation of key genes related to the survival of Hodgkin lymphoma (HL) cells, and methylation is a frequent epigenetic mechanism of microRNA silencing. We have examined the methylation-induced silencing of tumor suppressor microRNAs in HL cell lines and confirmed our results in patient lymph nodes. In addition, we evaluated the in vitro effectiveness of 5-aza-2-deoxycytidine (5-Aza-dC) in HL cell lines.

Role of miR-200 family members in survival of colorectal cancer patients treated with fluoropyrimidines.

Background And Objectives: Surgery is the standard treatment for colorectal cancer (CRC), and adjuvant chemotherapy has been shown to be effective in stage III but less so in stage II. We have analyzed the expression of the miR-200 family in tissue samples from resected CRC patients and correlated our findings with survival to adjuvant treatment with fluoropyrimidines.

Methods: Tumor tissue samples were obtained from 127 surgically resected patients with stage I-III CRC.

MiR-SNPs as markers of toxicity and clinical outcome in Hodgkin lymphoma patients.

Background: In recent years, microRNA (miRNA) pathways have emerged as a crucial system for the regulation of tumorogenesis. miR-SNPs are a novel class of single nucleotide polymorphisms that can affect miRNA pathways.

Design And Methods: We analyzed eight miR-SNPs by allelic discrimination in 141 patients with Hodgkin lymphoma and correlated the results with treatment-related toxicity, response, disease-free survival (DFS) and overall survival (OS).