Unveiling metabolo-genomic insights of potent antitumoral and antibiotic activity in sp. VB1 from Valparaíso Bay.

sp. VB1, an actinomycete isolated from marine sediments in Valparaíso Bay, Chile, synthesizes antimicrobial and antiproliferative compounds. This study presents comprehensive metabolomics and comparative genomics analyses of strain VB1.

Low-Level Expression of p-S6 Is Associated with Nodal Metastasis in Patients with Head and Neck Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. The incidence of metastasis for cSCC is estimated to be around 1.2-5%.

Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma.

Background: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC.

Methods: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing.

Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors.

Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma.

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3.

Sox2 and βIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas.

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and βIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors.

Loss of p16 expression is a risk factor for recurrence in sinonasal inverted papilloma.

Background: The purpose of this study was to evaluate p16, p53, EGFR, pEGFR protein expression and HPV infection as possible markers of tumor progression in a series of sinonasal inverted papilloma (SNIP) and sinonasal squamous cell carcinoma (SNSCC).

Methods: A series of 49 SNIP, 11 SNSCC associated with SNIP (SNIP-SNSCC) and 52 SNSCC not associated with SNIP were analyzed for p16, p53, EGFR, and phosphorylated EGFR (pEGFR) expression by immunohistochemistry. Human papillomavirus (HPV) infection status was evaluated by DNA-PCR.

Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors.

The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low.

A Novel External Auditory Canal Squamous Cell Carcinoma Cell Line Sensitive to CDK4/6 Inhibition.

Objective: To characterize cell line CAE606 derived from a squamous cell carcinoma (SCC) of the external auditory canal (EAC) and to show its usefulness as a model for testing candidate therapeutic agents.

Study Design: Preclinical translational research.

Setting: Biomedical research institute.

Aberrant Signaling Pathways in Sinonasal Intestinal-Type Adenocarcinoma.

Sinonasal intestinal-type adenocarcinoma (ITAC) is strongly related to occupational exposure to wood and leather dust, however, little is known on the genetic alterations involved in tumor development and progression. The aim of this study was to identify tumorigenic signaling pathways affected by gene mutations and their relation to clinical features. We applied whole exome sequencing of 120 cancer-related genes in 50 ITACs and analyzed the signaling activity of four specific pathways frequently affected by mutations.

Prognostic and Therapeutic Implications of Immune Classification by CD8 Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30-50%. As immunotherapy may be a new therapeutic option, we analyzed CD8 tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8 TILs and PD-L1) in a series of 57 SNSCCs.

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma.

Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes.

Clinical evaluation of the synbiotic Prodefen Plus® in the prevention of the antibiotic-associated diarrhoea in subjects requiring antibiotic treatment.

Prodefen® is a dietary food supplement formulated as a synbiotic that has shown additional benefit to the standard supportive therapy in the management of acute viral diarrhoea in children. There is scarce evidence of this synbiotic in adults. The objective of this randomised double blind placebo-controlled clinical trial was to evaluate the efficacy and safety of Prodefen Plus® in the prevention of antibiotic-associated diarrhoea (AAD) in an adult population requiring either antibiotic treatment for an oral infection or antibiotic prophylaxis for a dental surgical procedure in a dental consultation.

CD8 Tumour-Infiltrating Lymphocytes and Tumour Microenvironment Immune Types as Biomarkers for Immunotherapy in Sinonasal Intestinal-Type Adenocarcinoma.

Background: Intestinal-type adenocarcinoma (ITAC) is a rare tumour occurring in the ethmoid sinus. Recent years have brought advances in endoscopic surgery and precision radiotherapy; however, five-year overall survival has not improved and remains at 35-80%, depending on tumour stage and histology. Therefore, there is a need for new therapeutic options.

Development of a clinical-dermoscopic model for the diagnosis of urticarial vasculitis.

The clinical criteria for the diagnosis of urticarial vasculitis lack accuracy, according to previous studies. The aim of the study was to assess the accuracy of a clinical and a clinical-dermoscopic model for the differential diagnosis of chronic spontaneous urticaria (CSU) and urticarial vasculitis (UV). Dermoscopic images of lesions with histopathologically confirmed diagnosis of CSU and UV were evaluated for the presence of selected criteria (purpuric patches/globules (PG) and red linear vessels).

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

Background: To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment.

Methods: We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data.

IDH2 Mutation Analysis in Undifferentiated and Poorly Differentiated Sinonasal Carcinomas for Diagnosis and Clinical Management.

A large number of tumor types arise from the mucosa of the sinonasal cavities. Although presenting clinically distinct behavior, due to poorly differentiated histologic features, they can be difficult to classify correctly. Our aim was to investigate whether IDH2 and IDH1 mutations may be specific to a subset of undifferentiated and poorly differentiated sinonasal carcinomas.

Lectin-like transcript 1 (LLT1) expression is associated with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

The interaction of lectin-like transcript 1 (LLT1) with CD161 inhibits Natural Killer cell activation. Overexpression of LLT1 contributes to the immunosuppressive properties of tumor cells. However, there are little data about LLT1 expression in human solid tumors.

Correlation of focal adhesion kinase expression with nodal metastasis in patients with head and neck cutaneous squamous cell carcinoma.

Background: Focal adhesion kinase (FAK) and cortactin overexpression is frequently detected in a variety of cancers, and has been associated with poor clinical outcome. However, there are no data in cutaneous squamous cell carcinoma (cSCC).

Objective: To investigate the relationship of FAK and cortactin expression with the clinicopathologic features and the impact on the prognosis of cSCC patients.

Genetic profiling of poorly differentiated sinonasal tumours.

The sinonasal cavities harbour a variety of rare tumour types. Many carry a poor prognosis while therapeutic options are limited. Histopathological classification can be difficult, especially for poorly differentiated tumours such as olfactory neuroblastoma (ONB), sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC).

Programmed death ligand-1 expression as immunotherapeutic target in sinonasal cancer.

Background: Sinonasal cancer carries a poor prognosis, especially in recurrent stages, and it is a disease with very limited treatment options.

Methods: The expression of programmed death ligand-1 (PD-L1) as a marker for immunotherapy was evaluated in 53 sinonasal squamous cell carcinoma (SCC) and 126 intestinal-type adenocarcinoma (ITAC) samples. Results were correlated to clinicopathological characteristics and follow-up data.

The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes.

B-1 lymphocytes are known to increase the metastatic potential of B16F10 melanoma cells via the extracellular signal-regulated kinase (ERK) pathway. Since IL-10 is associated with B-1 cells performance, we hypothesized that IL-10 could be implicated in the progression of melanoma. In the present work, we found that the C57BL/6 mice, inoculated with B16F10 cells that were co-cultivated with B-1 lymphocytes from IL-10 knockout mice, developed fewer metastatic nodules than the ones which were injected with the melanoma cells that were cultivated in the presence of wild-type B-1 cells.

Genomic profiling of intestinal-type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes.

Background: Patients with intestinal-type sinonasal adenocarcinoma (ITAC) have an unfavorable prognosis and new therapeutic approaches are needed to improve clinical management.

Methods: Genetic analysis of 96 ITACs was performed by microarray comparative genomic hybridization and immunohistochemistry and correlated to previously obtained mutation, methylation, and protein expression data, and with pathological characteristics and clinical outcome.

Results: Seven copy number alterations (CNAs) were significantly associated with unfavorable clinical outcome: gains at 1q22-23, 3q28-29, 6p22, and 13q31-33, and losses at 4p15-16, 4q32-35, and 10q24.