Weighted gene co-expression network analysis reveals key stromal prognostic markers in pancreatic cancer.

In recent years, it has been shown that stroma compartment can favor tumor proliferation and aggressiveness. Although extensive research with network analyses such as Weighted Gene Co-expression Network Analysis (WGCNA) has been conducted on pancreatic cancer and its stromal components, WGCNA has not previously been applied to isolate and identify genes associated with the abundance of stroma and survival outcome from bulk RNA data. We investigated the gene expression profile and clinical information of 140 pancreatic ductal adenocarcinoma patients from TCGA.

ALOA, a pipeline for preliminary analysis of spatial profiling imaging data.

In the last decade, it has been recognized that tumors do not exist in isolation but interact with surrounding cells, blood vessels, immune cells, and extracellular matrix components. This understanding has shifted the focus from tumor cells alone to the broader context in which they exist, known as tumor microenvironment (TME). The TME is highly heterogeneous, consisting of various cell types, mainly cancer cells, immune cells, and stromal cells.

Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges in terms of prognosis and treatment. Recent research has identified splicing deregulation as a new cancer hallmark. Herein, we investigated the largely uncharacterized alternative splicing profile and the key splicing factor SF3B1 in PDAC pancreatic cells and tissues as a potential discovery source of plausible drug targets and new predictive biomarkers of clinical outcome.

ABCB1 overexpression through locus amplification represents an actionable target to combat paclitaxel resistance in pancreatic cancer cells.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer and the chemotherapies such as gemcitabine/nab-paclitaxel are confronted with intrinsic or acquired resistance. The aim of this study was to investigate mechanisms underlying paclitaxel resistance in PDAC and explore strategies to overcome it.

Methods: Three paclitaxel (PR) and gemcitabine resistant (GR) PDAC models were established.

Differential Sensitivity to Ionizing Radiation in Gemcitabine-Resistant and Paclitaxel-Resistant Pancreatic Cancer Cells.

Purpose: Chemoresistance remains a major challenge in treating pancreatic ductal adenocarcinoma (PDAC). Although chemoradiation has proven effective in other tumor types, such as head and neck squamous cell carcinoma, its role in PDAC and effect on acquired chemoresistance have yet to be fully explored. In this study, we investigated the sensitivity of gemcitabine-resistant (GR) and paclitaxel-resistant (PR) PDAC cells to ionizing radiation (IR) and their underlying mechanisms.

Phosphoproteomics guides effective low-dose drug combinations against pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a limited set of known driver mutations but considerable cancer cell heterogeneity. Phosphoproteomics provides a readout of aberrant signaling and has the potential to identify new targets and guide treatment decisions. Using two-step sequential phosphopeptide enrichment, we generate a comprehensive phosphoproteome and proteome of nine PDAC cell lines, encompassing more than 20,000 phosphosites on 5,763 phospho-proteins, including 316 protein kinases.

Prognostic Significance of Integrin Subunit Alpha 2 (ITGA2) and Role of Mechanical Cues in Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma (PDAC).

Introduction: PDAC is an extremely aggressive tumor with a poor prognosis and remarkable therapeutic resistance. The dense extracellular matrix (ECM) which characterizes PDAC progression is considered a fundamental determinant of chemoresistance, with major contributions from mechanical factors. This study combined biomechanical and pharmacological approaches to evaluate the role of the cell-adhesion molecule ITGA2, a key regulator of ECM, in PDAC resistance to gemcitabine.

Endoscopic Endonasal Repair of Congenital Choanal Atresia: Predictive Factors of Surgical Stability and Healing Outcomes.

Background: To assess the long-term outcomes and independent predictors of surgical success of a one-stage minimally invasive surgical procedure for congenital choanal atresia (C.C.A.

VITOM-3D assisted paramedian forehead flap for nasal reconstruction.

Background: The study was designed with the purpose of showing the potential advantages of the VITOM-3D assisted paramedian forehead flap for nasal reconstruction.

Methods: A 72 years-old female patient presented to our department with a wide left nasal defect. On her clinical history she referred a basal cell carcinoma of the left nasal skin treated with multiple excision in another center without reconstruction.

Interrelationship between miRNA and splicing factors in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of diagnosis at late stage and inherent/acquired chemoresistance. Recent advances in genomic profiling and biology of this disease have not yet been translated to a relevant improvement in terms of disease management and patient's survival. However, new possibilities for treatment may emerge from studies on key epigenetic factors.

Focal adhesion kinase inhibition synergizes with nab-paclitaxel to target pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC.

Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study.

Background And Purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique.

Materials And Methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.

Omics Analysis of Educated Platelets in Cancer and Benign Disease of the Pancreas.

Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC "dangerous liaisons" are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts.

Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study.

Background: Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies.

Methods: ABitude is an Italian, observational, prospective, multicenter study of mCRPC patients receiving abiraterone plus prednisone in clinical practice. Chemotherapy-naïve mCRPC patients were consecutively enrolled at abiraterone start (February 2016 to June 2017) and are being followed for 3 years, with evaluation approximately every 6 months.

"Open Sesame?": Biomarker Status of the Human Equilibrative Nucleoside Transporter-1 and Molecular Mechanisms Influencing its Expression and Activity in the Uptake and Cytotoxicity of Gemcitabine in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive tumor characterized by early invasiveness, rapid progression and resistance to treatment. For more than twenty years, gemcitabine has been the main therapy for PDAC both in the palliative and adjuvant setting. After the introduction of FOLFIRINOX as an upfront treatment for metastatic disease, gemcitabine is still commonly used in combination with nab-paclitaxel as an alternative first-line regimen, as well as a monotherapy in elderly patients unfit for combination chemotherapy.

Simultaneous Integrated Radiotherapy Boost to the Dominant Intraprostatic Lesion: Final Results of a Phase I/II Trial.

Background/aim: Late toxicity and long-term outcomes of a phase I-II trial on patients with prostate cancer treated with an integrated boost to the dominant intraprostatic lesion (DIL) are reported.

Patients And Methods: Patients were treated using intensity-modulated radiotherapy, with a simultaneous integrated boost to the DIL, defined on staging magnetic resonance imaging, delivering 72 Gy in 1.8 Gy/fraction to prostate/seminal vesicles and 80 Gy in 2 Gy/fraction to the DIL.

Design, synthesis and biological evaluation of second-generation benzoylpiperidine derivatives as reversible monoacylglycerol lipase (MAGL) inhibitors.

An interesting enzyme of the endocannabinoid system is monoacylglycerol lipase (MAGL). This enzyme, which metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG), has attracted great interest due to its involvement in several physiological and pathological processes, such as cancer progression. Experimental evidences highlighted some drawbacks associated with the use of irreversible MAGL inhibitors in vivo, therefore the research field concerning reversible inhibitors is rapidly growing.

Computational Analysis of Phosphoproteomics Data in Multi-Omics Cancer Studies.

Multiple types of molecular data for the same set of clinical samples are increasingly available and may be analyzed jointly in an integrative analysis to maximize comprehensive biological insight. This analysis is important as separate analyses of individual omics data types usually do not fully explain disease phenotypes. An increasing number of studies have now been focusing on multi-omics data integration, yet not many studies have included phosphoproteomics data, an important layer for understanding signaling pathways.

Co-expression analysis of pancreatic cancer proteome reveals biology and prognostic biomarkers.

Purpose: Despite extensive biological and clinical studies, including comprehensive genomic and transcriptomic profiling efforts, pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease, with a poor survival and limited therapeutic options. The goal of this study was to assess co-expressed PDAC proteins and their associations with biological pathways and clinical parameters.

Methods: Correlation network analysis is emerging as a powerful approach to infer tumor biology from omics data and to prioritize candidate genes as biomarkers or drug targets.

Oncotype DX Predictive Nomogram for Recurrence Score Output: The Novel System ADAPTED01 Based on Quantitative Immunochemistry Analysis.

Purpose: Oncotype DX (ODX) predicts breast cancer recurrence risk, guiding the choice of adjuvant treatment. In many countries, access to the test is not always available. We used correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) assessed by ODX to develop a decision supporting system for clinical use.

BIT-ART: Multicentric Comparison of HDR-brachytherapy, Intensity-modulated Radiotherapy and Tomotherapy for Advanced Radiotherapy in Prostate Cancer.

Background/aim: The aim of the study was to evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity in patients with high- or intermediate-risk prostate cancer.

Patients And Methods: We evaluated data of patients from three Radiation Oncology Departments (Rome, Lübeck and Perugia). Patients treated in Rome underwent exclusive intensity-modulated-radiotherapy (IMRT) or IMRT plus high-dose-rate interventional radiotherapy (HDR-IRT).

Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells.

A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC) ranging from 0.23 to 11.