Targeting FGFRs by pemigatinib induces G1 phase cell cycle arrest, cellular stress and upregulation of tumor suppressor microRNAs.

Background: Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy.

Circulating CD137 T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients.

Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlights the need to identify novel biomarkers to optimize treatment strategies. CD137 T cells have been identified as tumour-specific T cells correlated with immunotherapy responses in several solid tumours.

Proteomic characterization of extracellular vesicles released by third stage larvae of the zoonotic parasite (Nematoda: Anisakidae).

Introduction: is a sibling species within the (s.l.) complex requiring marine homeothermic (mainly cetaceans) and heterothermic (crustaceans, fish, and cephalopods) organisms to complete its life cycle.

Soluble PD-L1 as a Prognostic Factor for Immunotherapy Treatment in Solid Tumors: Systematic Review and Meta-Analysis.

Blocking the Programmed Cell Death Protein 1 (PD-1)/programmed death ligand-1 (PD-L1) axis has demonstrated great efficacy in cancer immunotherapy treatment and remains the central modality of immune targeting. To support the rational and tailored use of these drugs, it is important to identify reliable biomarkers related to survival. The role of the soluble form of the PD-L1 (sPD-L1) as a prognostic biomarker related to survival in solid cancer patients treated with immunotherapy has not yet been consistently evaluated.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis.

IgM-Rheumatoid factor confers primary resistance to anti-PD-1 immunotherapies in NSCLC patients by reducing CD137T-cells.

Background: ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated.

Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients.

Patients with non-small cell lung cancer (NSCLC) have been shown to benefit from the introduction of anti-PD1 treatment. However, not all patients experience tumor regression and durable response. The identification of a string of markers that are direct or indirect indicators of the immune system fitness is needed to choose optimal therapeutic schedules in the management of NSCLC patients.

Investigating Patterns of Immune Interaction in Ovarian Cancer: Probing the O-glycoproteome by the Macrophage Galactose-Like C-type Lectin (MGL).

Glycosylation, the posttranslational linking of sugar molecules to proteins, is notoriously altered during tumor transformation. More specifically in carcinomas, GalNAc-type -glycosylation, is characterized by biosynthetically immature truncated glycans present on the cancer cell surface, which profoundly impact anti-tumor immune recognition. The tumor-associated glycan pattern may thus be regarded as a biomarker of immune modulation.

Bevacizumab-Based Chemotherapy Triggers Immunological Effects in Responding Multi-Treated Recurrent Ovarian Cancer Patients by Favoring the Recruitment of Effector T Cell Subsets.

Increasing evidence strongly suggests that bevacizumab compound impacts the immunological signature of cancer patients and normalizes tumor vasculature. This study aims to investigate the correlation between the clinical response to bevacizumab-based chemotherapy and the improvement of immune fitness of multi-treated ovarian cancer patients. Peripheral blood mononuclear cells (PBMCs) of 20 consecutive recurrent ovarian cancer patients retrospectively selected to have received bevacizumab or non-bevacizumab-based chemotherapy (Bev group and Ctrl group, respectively) were analyzed.

TK Inhibitor Pazopanib Primes DCs by Downregulation of the β-Catenin Pathway.

Tyrosine kinase inhibitors (TKIs) target angiogenesis by affecting, for example, the VEGF receptors in tumors and have improved outcomes for patients with metastatic renal cell carcinoma (mRCC). Immune checkpoint inhibitors (ICIs) have also been proposed for treatment of mRCC with encouraging results. A better understanding of the activity of immune cells in mRCC, the immunomodulatory effects of TKIs, and the characteristics defining patients most likely to benefit from various therapies will help optimize immunotherapeutic approaches.

Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial.

Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months.

MGL Receptor and Immunity: When the Ligand Can Make the Difference.

C-type lectin receptors (CLRs) on antigen-presenting cells (APCs) facilitate uptake of carbohydrate antigens for antigen presentation, modulating the immune response in infection, homeostasis, autoimmunity, allergy, and cancer. In this review, we focus on the role of the macrophage galactose type C-type lectin (MGL) in the immune response against self-antigens, pathogens, and tumor associated antigens (TAA). MGL is a CLR exclusively expressed by dendritic cells (DCs) and activated macrophages (MØs), able to recognize terminal GalNAc residues, including the sialylated and nonsialylated Tn antigens.

The Macrophage Galactose-Type C-Type Lectin (MGL) Modulates Regulatory T Cell Functions.

Regulatory T cells (Tregs) are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL.

A modified triple pelvic osteotomy for the treatment of hip hypoplasia.

Background: The prevalence of hip dysplasia is 1 in 1000. Several pelvic osteotomy methods have been developed to prevent early osteoarthritis, such as triple osteotomy. In this study we are going to introduce our new technique that was done on 4 patients with favorable short-term results.

Microvesicle cargo of tumor-associated MUC1 to dendritic cells allows cross-presentation and specific carbohydrate processing.

Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumor-associated glycoproteins. In cancer, MUC1 loses polarity and becomes overexpressed and hypoglycosylated.

Surgical management of acetabular fractures: a case series.

Introduction: For decades, acetabular fractures were treated conservatively. Judet et al. in 1960s established the operative treatment of these fractures by continuous improvement of pre-operative evaluation and classification of fractures.

Outcomes of pin and plaster versus locking plate in distal radius intraarticular fractures.

Background: Distal radius fractures are among the most prevalent fractures predictive of probable occurrence of other osteoporotic fractures. They are treated via a variety of methods, but the best treatment has not been defined yet.

Objectives: This study was performed to compare the results of open reduction and internal fixation with locking plates versus the pin and plaster method.

Environmental variables associated with immature stage habitats of culicidae collected in aboriginal villages in Pahang, Malaysia.

Many of the most widely spread vector-borne diseases are water related, in that the mosquito vectors concerned breed or pass part of their lifecycle in or close to water. A major reason for the study of mosquito larval ecology is to gather information on environmental variables that may determine the species of mosquitoes and the distribution of larvae in the breeding habitats. Larval surveillance studies were conducted six times between May 2008 and October 2009 in Pos Lenjang, Kuala Lipis, Pahang.

Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation.

Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner. Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC-based anticancer immunotherapy.

HER2-based recombinant immunogen to target DCs through FcγRs for cancer immunotherapy.

Dendritic cell (DC)-based immunotherapy is an attractive approach to induce long lasting antitumor effector cells aiming to control cancer progression. DC targeting is a critical step in the design of DC vaccines in order to optimize delivery and processing of the antigen, and several receptors have been characterized for this purpose. In this study, we employed the FcγRs to target DCs both in vitro and in vivo.

Immune effects of trastuzumab.

Trastuzumab's targeted therapy has become a stronghold for human epidermal growth factor receptor 2 positive breast cancer patients. This humanized monoclonal antibody binds to the extracellular juxta-membrane domain of HER2 and inhibits the proliferation and survival of HER2 dependent cancer cells. The ways by which this molecule exerts its action have been partially elucidated but several new mechanisms are being constantly identified.

RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients.

Radiofrequency tumor ablation (RFA) is a therapeutic modality for liver cancer patients inducing localized tumor necrosis with maximal preservation of normal liver parenchyma. We investigated the immunomodulatory effects exerted by RFA treatment in liver cancer patients with metastatic liver lesions (13 patients) or hepatocellular carcinoma (HCC) (4 patients). Analysis of lymphocyte subsets by flow cytometry revealed that after RFA, CD3+ T cells, in particular CD4+, were decreased in metastatic cancer patients, while no change was observed in HCC patients.

A comparative analysis of serum and serum-free media for generation of clinical grade DCs.

Dendritic cells (DCs) are the most potent antigen presenting cells and are therefore widely used in cancer immunotherapy. An optimal method for the generation of DCs for clinical use remains to be established. The aim of the study was to find a serum-free media (SFM) able to generate reproducible and functional cultures of DCs for clinical studies.