In recent years, immune checkpoint inhibitors have proved immense clinical progression in the treatment of certain cancers. The efficacy of immune checkpoint inhibitors is correlated with mismatch repair system deficiency and is exceptionally administered based exclusively on this biological mechanism independent of the cancer type. The promising effect of immune checkpoint inhibitors has left an increasing demand for analytical tools evaluating the mismatch repair status.
View Article and Find Full Text PDFFront Immunol
December 2023
Background And Aims: Inducible T-cell Co-Stimulator (ICOS) present on T-lymphocytes and its ligand ICOSL expressed by myeloid cells play multiple roles in regulating T-cell functions. However, recent evidence indicates that reverse signalling involving ICOSL is also important in directing the differentiation of monocyte-derived cells. In this study, we investigated the involvement of ICOS/ICOSL dyad in modulating macrophage functions during the evolution of metabolic dysfunction-associated steatohepatitis (MASH).
View Article and Find Full Text PDFAquaporins (AQPs) are small transmembrane proteins able to facilitate the passive transport of water and small molecules throughout cells. Several studies have demonstrated that modulation of AQPs' expression contributes to cancer development and progression. However, to date, very little is known about their involvement in malignant melanoma (MM) progression.
View Article and Find Full Text PDFBackground: Our aim was to evaluate the efficacy and anti-cancer action of a precision medicine approach involving a novel SIRT1-dependent pathway that, when disrupted, leads to the restoration of a functional p53 in human papillomavirus (HPV)-transformed cells.
Methods: The anticancer potential of inhibiting SIRT1 was evaluated by examining the effects of the specific SIRT1 inhibitor EX527 (also known as Selisistat) or genetic silencing, either individually or in conjunction with standard chemotherapeutic agents, on a range of HPV cancer cells and a preclinical mouse model of HPV16-induced cancer.
Results: We show that SIRT1 inhibition restores a transcriptionally active K382-acetylated p53 in HPV but not HPV cell lines, which in turn promotes G/G cell cycle arrest and inhibits clonogenicity specifically in HPV cells.
Bitter taste receptors are involved not only in taste perception but in various physiological functions as their anatomical location is not restricted to the gustatory system. We previously demonstrated expression and activity of the subtype hTAS2R46 in human airway smooth muscle and broncho-epithelial cells, and here we show its expression and functionality in human skeletal muscle cells. Three different cellular models were used: micro-dissected human skeletal tissues, human myoblasts/myotubes and human skeletal muscle cells differentiated from urine stem cells of healthy donors.
View Article and Find Full Text PDFPembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists.
View Article and Find Full Text PDFAccording to the driver-passenger model for colorectal cancer (CRC), the tumor-associated microbiota is a dynamic ecosystem of bacterial species where bacteria with carcinogenic features linked to CRC initiation are defined as "drivers", while opportunistic bacteria colonizing more advanced tumor stages are known as "passengers". We reasoned that also gut microbiota-associated metabolites may be differentially enriched according to tumor stage, and be potential determinants of CRC development. Thus, we characterized the mucosa- and lumen-associated microbiota (MAM and LAM, respectively) and mucosa-associated metabolites in low- vs.
View Article and Find Full Text PDFLung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking.
View Article and Find Full Text PDFHuman papillomaviruses (HPVs) from the beta genus are commensal viruses of the skin usually associated with asymptomatic infection in the general population. However, in individuals with specific genetic backgrounds, such as patients with epidermodysplasia verruciformis, or those with immune defects, such as organ transplant recipients, they are functionally involved in sunlight-induced skin cancer development, mainly keratinocyte carcinoma. Despite their well-established protumorigenic role, the cooperation between β-HPV infection, impaired host immunosurveillance, and UVB exposure has never been formally shown in animal models.
View Article and Find Full Text PDFDirofilariasis is a zoonosis caused by nematodes of the genus is cosmopolitan as regards its distribution in animals, being responsible for human pulmonary dirofilariasis in the New World. However, human infections by are exceptional in Europe, and the previously reported Italian cases of pulmonary dirofilariasis were due to . We performed a systematic literature review of the Italian cases of human dirofilariasis due to according to the PRISMA guidelines.
View Article and Find Full Text PDFGermline mutations in the tumor suppressor gene BRCA1-associated protein-1 () lead to tumor predisposition syndrome (-TPDS), characterized by high susceptibility to several tumor types, chiefly melanoma, mesothelioma, renal cell carcinoma, and basal cell carcinoma. Here, we present the results of our ten-year experience in the molecular diagnosis of -TPDS, along with a clinical update and cascade genetic testing of previously reported -TPDS patients and their relatives. Specifically, we sequenced germline DNA samples from 101 individuals with suspected -TPDS and validated pathogenic variants (PVs) by assessing somatic loss in matching tumor specimens.
View Article and Find Full Text PDFRichter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy-chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbours a different IGHV rearrangement compared to the CLL phase. We investigated the CLL phase of clonally unrelated RS to test whether the RS clone was already identifiable prior to clinicopathologic transformation, albeit undetectable by conventional approaches.
View Article and Find Full Text PDFBackground: ICOS and its ligand ICOSL are immune receptors whose interaction triggers bidirectional signals that modulate the immune response and tissue repair.
Aim: The aim of this study was to assess the in vivo effects of ICOSL triggering by ICOS-Fc, a recombinant soluble form of ICOS, on skin wound healing.
Methods: The effect of human ICOS-Fc on wound healing was assessed, in vitro, and, in vivo, by skin wound healing assay using ICOS and ICOSL knockout (KO) mice and NOD-SCID-IL2R null (NSG) mice.
A 66-year-old man presented with a 2.8 cm lesion of the left vocal cord. On contrast-enhanced computed tomography scans, the tumor extended to the supraglottis, subglottis, paraglottic space and anterior commissure, causing partial obstruction of the laryngeal lumen.
View Article and Find Full Text PDFRecently, we demonstrated that inducible T-cell costimulator (ICOS) shares its unique ligand (ICOSL) with osteopontin (OPN), and OPN/ICOSL binding promotes tumor metastasis and angiogenesis in the 4T1 breast cancer model. Literature showed that OPN promotes melanoma metastasis by suppressing T-cell activation and recruiting myeloid suppressor cells (MDSC). On the opposite, ICOS/ICOSL interaction usually sustains an antitumor response.
View Article and Find Full Text PDFIntroduction: Malignant pleural mesothelioma (MPM) is a tumour associated with asbestos exposure. Approximately, 10% of patients with MPM carry a germline pathogenic variant (PV), mostly in DNA repair genes, suggesting the occurrence of inherited predispositions.
Aim: This article aimed to 1) search for new predisposing genes and assess the prevalence of PVs in DNA repair genes, by next-generation sequencing (NGS) analysis of germline DNA from 113 unselected patients with MPM and 2) evaluate whether these patients could be sensitive to tailored treatments.
Breast reconstruction has gained from lipofilling the possibility to recover the aesthetic outcome of anatomical profile in a more natural appearance. However, until today, the long-term graft survival remains unpredictable, and sometimes it does not guarantee a well-adequate aesthetic result. In the present work, the morphological changes, occurring in fat mass used for refilling, harvested by the Coleman's procedure or through the washing/fragmenting procedure were analysed.
View Article and Find Full Text PDFGlioblastoma (GBM) is a fatal tumor whose aggressiveness, heterogeneity, poor blood-brain barrier penetration, and resistance to therapy highlight the need for new targets and clinical treatments. A step toward clinical translation includes the eradication of GBM tumor-initiating cells (TICs), responsible for GBM heterogeneity and relapse. By using patient-derived TICs and xenograft orthotopic models, we demonstrated that the selective lysine-specific histone demethylase 1 inhibitor DDP_38003 (LSD1i) is able to penetrate the brain parenchyma in vivo in preclinical models, is well tolerated, and exerts antitumor activity in molecularly different GBMs.
View Article and Find Full Text PDFMastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL).
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