ABCC1 Is a ΔNp63 Target Gene Overexpressed in Squamous Cell Carcinoma.

The transcription factor ΔNp63 plays a pivotal role in maintaining the integrity of stratified epithelial tissues by regulating the expression of distinct target genes involved in lineage specification, cell stemness, cell proliferation and differentiation. Here, we identified the ABC transporter subfamily member as a novel ΔNp63 target gene. We found that in immortalized human keratinocytes and in squamous cell carcinoma (SCC) cells, ∆Np63 induces the expression of ABCC1 by physically occupying a p63-binding site (p63 BS) located in the first intron of the gene locus.

Manipulating the tumor immune microenvironment to improve cancer immunotherapy: IGF1R, a promising target.

Cancer immunotherapy has made impressive advances in improving the outcome of patients affected by malignant diseases. Nonetheless, some limitations still need to be tackled to more efficiently and safely treat patients, in particular for those affected by solid tumors. One of the limitations is related to the immunosuppressive tumor microenvironment (TME), which impairs anti-tumor immunity.

Two bullets in the gun: combining immunotherapy with chemotherapy to defeat neuroblastoma by targeting adrenergic-mesenchymal plasticity.

Neuroblastoma (NB) is a childhood tumor that originates in the peripheral sympathetic nervous system and is responsible for 15% of cancer-related deaths in the pediatric population. Despite intensive multimodal treatment, many patients with high-risk NB relapse and develop a therapy-resistant tumor. One of the phenomena related to therapeutic resistance is intratumor heterogeneity resulting from the adaptation of tumor cells in response to different selective environmental pressures.

Arthrodesis versus dynamic neutralization: A short/mid- and long-term retrospective evaluation in degenerative disk disease treatment.

Study Design: This was a retrospective comparative study.

Objectives: The aim of this study was to perform a clinical and radiological retrospective evaluation of the most used techniques for the lumbar degenerative disk disease (DDD) treatment: arthrodesis versus dynamic neutralization (DN)-Dynesys dynamic stabilization system.

Methods: The study included 58 consecutive patients affected by lumbar DDD, 28 treated with rigid stabilization and 30 with DN at our department between 2003 and 2013.

Posterior spinal fusion in patients with spinal muscular atrophy: a surgical technique to allow intrathecally inject nusinersen.

Background: Nusinersen, the recently approved medical therapy in the treatment of spinal muscular atrophy (SMA), has revolutionized the natural history of this disease. Until now, surgical treatment of scoliosis in SMA patients was an exclusion criterion for drug therapy. In fact, the bone graft positioned posteriorly during surgery, in order to obtain a solid fusion, prevented the lumbar puncture necessary for the intrathecal administration of the drug.

Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma.

Background: Poor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we identified a combinatorial in situ immunomodulation strategy based on the administration of selected immunogenic drugs and immunotherapy to sensitize poorly T-cell-infiltrated neuroblastoma (NB) to the host antitumor immune response.

Methods: 975A2 and 9464D NB cell lines derived from spontaneous tumors of TH-MYCN transgenic mice were employed to study drug combinations able of enhancing the antitumor immune response using in vivo and ex vivo approaches.

Targeting the antigen processing and presentation pathway to overcome resistance to immune checkpoint therapy.

Despite the significant clinical advances with the use of immune checkpoint inhibitors (ICIs) in a wide range of cancer patients, response rates to the therapy are variable and do not always result in long-term tumor regression. The development of ICI-resistant disease is one of the pressing issue in clinical oncology, and the identification of new targets and combination therapies is a crucial point to improve response rates and duration. Antigen processing and presentation (APP) pathway is a key element for an efficient response to ICI therapy.

Benign Acute Childhood Myositis: Our Experience on Clinical Evaluation.

Background: Benign acute childhood myositis (BACM) is a transient condition mainly affecting children of school age characterized by muscle pain, typically localized to the calf muscle with symmetrical lower extremity pain and difficulty in walking. Usually, the symptomatology is preceded by a viral infection including influenza, parainfluenza, rotavirus, and mycoplasma.

Methods: The case series was conducted in four pediatric hospitals in Catania, Italy, over a 12-year observational period.

ERAP1 Controls the Interaction of the Inhibitory Receptor KIR3DL1 With HLA-B51:01 by Affecting Natural Killer Cell Function.

The endoplasmic reticulum aminopeptidase ERAP1 regulates innate and adaptive immune responses by trimming peptides for presentation by major histocompatibility complex (MHC) class I molecules. Previously, we have shown that genetic or pharmacological inhibition of ERAP1 on murine and human tumor cell lines perturbs the engagement of NK cell inhibitory receptors Ly49C/I and Killer-cell Immunoglobulin-like receptors (KIRs), respectively, by their specific ligands (MHC class I molecules), thus leading to NK cell killing. However, the effect of ERAP1 inhibition in tumor cells was highly variable, suggesting that its efficacy may depend on several factors, including MHC class I typing.

Non-occlusive mesenteric ischemia (NOMI) and prognostic signs at CT: reperfusion or not reperfusion that is the question!

Purpose: Non-occlusive mesenteric ischemia (NOMI) is a misdiagnosed and dangerous condition. To our knowledge, a comprehensive evaluation of CT parameters that can predict the outcome of patients suffering from NOMI is still missing.

Materials And Methods: Contrast-enhanced CT examination of 84 patients with a confirmed diagnosis of NOMI (37 with clinical and laboratory confirmation and 47 biopsy or surgery proven) was retrospectively reviewed by assessing vessels, mesentery, bowel, and peritoneal cavity CT quantitative and dichotomous parameters, and data were analyzed with Fisher's test.

ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that enters cells via the ACE2 receptor.

Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment.

Tumor-infiltrating CD8 T cells have been shown to play a crucial role in controlling tumor progression. However, the recruitment and activation of these immune cells at the tumor site are strictly dependent on several factors, including the presence of dendritic cells (DCs), the main orchestrators of the antitumor immune responses. Among the various DC subsets, the role of cDC1s has been demonstrated in several preclinical experimental mouse models.

Secondary Scoliosis as a Complication of Acute Transverse Myelitis in a Child.

Acute transverse myelitis (ATM) is a rare neurological condition that affects the spinal cord. Several events, including infections, autoimmune conditions, inflammatory, and drug-induced factors, may cause this disorder. Correct and rapid etiological diagnosis is necessary in order to start appropriate treatment that mainly consists of immunomodulating therapy, high dose intravenous corticosteroids, and in plasma exchange in noninfectious cases.

Surgical treatment of scoliosis in neurofibromatosis type I: A retrospective study on posterior-only correction with third-generation instrumentation.

Background: Scoliosis is the most common orthopedic complication of neurofibromatosis type I. Scoliosis can be occurred with two patterns: dystrophic or idiopathic-like. In adolescence, in consideration of bone dystrophy, osteopenia, and often associated hyperkyphosis, most of the authors recommend an anterior-posterior approach.

Impact of Natural Occurring Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection.

Human cytomegalovirus (HCMV) is a β-herpesvirus that causes serious problems in people with a compromised immune system, whereas it coexists asymptomatically within the host with a healthy immune system. Like other viruses, HCMV has adopted multiples strategies to manipulate the host's immune responses. Among them, expression of viral microRNAs (miRNAs) is one of the most intriguing.

DHA Affects Microtubule Dynamics Through Reduction of Phospho-TCTP Levels and Enhances the Antiproliferative Effect of T-DM1 in Trastuzumab-Resistant HER2-Positive Breast Cancer Cell Lines.

Trastuzumab emtansine (T-DM1) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugated to the microtubule-targeting agent emtansine (DM1). T-DM1 is an effective agent in the treatment of patients with HER2-positive breast cancer whose disease has progressed on the first-line trastuzumab containing chemotherapy. However, both primary and acquired tumour resistance limit its efficacy.

The fragile X mental retardation protein regulates tumor invasiveness-related pathways in melanoma cells.

The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. FMRP affects metastasis formation in a mouse model for breast cancer. Here we show that FMRP is overexpressed in human melanoma with high Breslow thickness and high Clark level.

CPEB1 restrains proliferation of Glioblastoma cells through the regulation of p27(Kip1) mRNA translation.

The cytoplasmic element binding protein 1 (CPEB1) regulates many important biological processes ranging from cell cycle control to learning and memory formation, by controlling mRNA translation efficiency via 3' untranslated regions (3'UTR). In the present study, we show that CPEB1 is significantly downregulated in human Glioblastoma Multiforme (GBM) tissues and that the restoration of its expression impairs glioma cell lines growth. We demonstrate that CPEB1 promotes the expression of the cell cycle inhibitor p27(Kip1) by specifically targeting its 3'UTR, and competes with miR-221/222 binding at an overlapping site in the 3'UTR, thus impairing miR-221/222 inhibitory activity.

Prolonged Pseudohypoxia Targets Ambra1 mRNA to P-Bodies for Translational Repression.

Hypoxia has been associated with several pathological conditions ranging from stroke to cancer. This condition results in the activation of autophagy, a cyto-protective response involving the formation of double-membraned structures, the autophagosomes, in the cytoplasm. In this study, we investigated the cellular mechanisms regulating the autophagy gene Ambra1, after exposure to a hypoxia mimetic, cobalt chloride (CoCl2).

TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: relevance in human colorectal tumors.

TNF receptor-associated protein 1 (TRAP1) is an HSP90 chaperone involved in stress protection and apoptosis in mitochondrial and extramitochondrial compartments. Remarkably, aberrant deregulation of TRAP1 function has been observed in several cancer types with potential new opportunities for therapeutic intervention in humans. Although previous studies by our group identified novel roles of TRAP1 in quality control of mitochondria-destined proteins through the attenuation of protein synthesis, molecular mechanisms are still largely unknown.

Treatment of peritoneal carcinomatosis from colonic cancer by cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC). Experience of ten years.

Introduction: Peritoneal carcinomatosis (PC) is one of the routes of dissemination of abdominal neoplasms and is generally considered a lethal disease, with a poor prognosis by conventional chemotherapeutic treatments. While systemic chemotherapy has little impact on the treatment of peritoneal disease, some centers have reported encouraging results with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). This approach is based on surgical cytoreduction of the primary tumour, peritonectomy (stripping of implants on the peritoneal surface) and HIPEC.

Management of pseudomyxoma peritonei by cytoreduction+HIPEC (hyperthermic intraperitoneal chemotherapy): results analysis of a twelve-year experience.

Background: Pseudomyxoma peritonei (PMP) is a rare peritoneal carcinomatosis, characterized by a slowly progressive disease process with a large amount of mucus containing occasional epithelial cells. PMP is histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA) and an intermediate or discordant feature group (ID). Recent studies have shown that most cases of PMP originate from ruptured appendiceal tumors with progressive dissemination in the peritoneal cavity of mucin-producing epithelial cells.

Primary duodenal adenocarcinoma.

Aims And Background: Primary duodenal adenocarcinoma is a rare tumor with a poorly defined natural history and prognostic factors. It presents with nonspecific symptoms, and for this reason the diagnosis is often delayed. It is a serious problem for the surgeon because of the difficulty in obtaining an early diagnosis and standardizing basic tenets for an appropriate surgical approach.