Three-dimensional lung reconstructions for the localization of lung nodules to be resected during surgery.

BACKGROUND: The localization of lung nodules is challenging during thoracoscopy. In this study, we evaluated the use of three-dimensional (3D) lung reconstruction for use in the operating room to guide the identification of lung nodules during thoracoscopy. METHODS: This was a single-center retrospective study. All consecutive patients undergoing thoracoscopic resection of lung nodules were included in the study. Patients were retrospectively divided into two groups based upon whether the thoracoscopic resection was performed with the assistance (3D group) or not (standard group) of 3D lung reconstruction. The operative time (minutes) to detect lung nodules was statistically compared between the two study groups in relation to the characteristics of lung nodules as size, localization, and distance from the visceral pleura. RESULTS: Our study population consisted of 170 patients: 85 in the 3D group and 85 in the standard group. No intergroup difference differences were found regarding the characteristics and histological diagnosis of lesions. The standard group compared to the 3D group was associated with a significantly longer operative time for the detection of lesions <10 mm (13.87 ± 2.59 vs. 5.52 ± 1.01, p < 0.001), lesions between 10 and 20 mm (5.05 ± 0.84 vs. 3.89 ± 0.92; p = 0.03), lesions localized in complex segments (7.49 ± 4.25 vs. 5.11 ± 0.97; p < 0.001), and deep lesions (9.58 ± 4.82 vs. 5.4 ± 1.01, p < 0.001). CONCLUSIONS: Our 3D lung reconstruction model for use in the operating room may be an additional tool for thoracic surgeons to guide the detection of small and deep nodules during thoracoscopy. It is a noninvasive and cost saving procedure and may be widely used.

Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial-Mesenchymal Transition.

Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression.

GSK343, an Inhibitor of Enhancer of Zeste Homolog 2, Reduces Glioblastoma Progression through Inflammatory Process Modulation: Focus on Canonical and Non-Canonical NF-κB/IκBα Pathways.

Glioblastoma (GB) is a tumor of the central nervous system characterized by high proliferation and invasiveness. The standard treatment for GB includes radiotherapy and chemotherapy; however, new therapies are needed. Particular attention was given to the role of histone methyltransferase enhancer of zeste-homolog-2 (EZH2) in GB. Recently, several EZH2-inhibitors have been developed, particularly GSK343 is well-known to regulate apoptosis and autophagy processes; however, its abilities to modulate canonical/non-canonical NF-κB/IκBα pathways or an immune response in GB have not yet been investigated. Therefore, this study investigated for the first time the effect of GSK343 on canonical/non-canonical NF-κB/IκBα pathways and the immune response, by an in vitro, in vivo and ex vivo model of GB. In vitro results demonstrated that GSK343 treatments 1, 10 and 25 µM significantly reduced GB cell viability, showing the modulation of canonical/non-canonical NF-κB/IκBα pathway activation. In vivo GSK343 reduced subcutaneous tumor mass, regulating canonical/non-canonical NF-κB/IκBα pathway activation and the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Ex vivo results confirmed the anti-proliferative effect of GSK343 and also demonstrated its ability to regulate immune response through CXCL9, CXCL10 and CXCL11 expression in GB. Thus, GSK343 could represent a therapeutic strategy to counteract GB progression, thanks to its ability to modulate canonical/non-canonical NF-κB/IκBα pathways and immune response.

Splenocolic fistula in a patient with diffuse large B-cell lymphoma: A case report and review of literature.

A fistula that connects the bowel to other organs, such as the urinary bladder or small intestine, is a relatively frequent complication, often associated with inflammatory diseases such as diverticulitis, Crohn's disease, colorectal cancer, or lymphoma. Splenocolic fistula is an extremely rare condition described in the literature. It can occur in cases of splenic tumors, including splenic diffuse large B cell lymphoma. We report the case of an 82-year-old man who presented with melaena, worsening asthenia, hypotension, and abdominal pain in the left flank and the ipsilateral lumbar region. Ultrasound and computed tomography documented splenomegaly, thickening of the splenic flexure of the colon, and the presence of a fistulous passage between the colon and the splenic hilum. The diagnosis of lymphoma was made following laparotomy and caudal splenopancreatectomy. Due to the aggressive clinical behavior of this type of lymphoma, splenectomy is the main treatment in patients with splenomegaly, abdominal pain, and tumor expansion.

Adenosine Targeting as a New Strategy to Decrease Glioblastoma Aggressiveness.

Glioblastoma is the most commonly malignant and aggressive brain tumor, with a high mortality rate. The role of the purine nucleotide adenosine and its interaction with its four subtypes receptors coupled to the different G proteins, A1, A2A, A2B, and A3, and its different physiological functions in different systems and organs, depending on the active receptor subtype, has been studied for years. Recently, several works have defined extracellular adenosine as a tumoral protector because of its accumulation in the tumor microenvironment. Its presence is due to both the interaction with the A2A receptor subtype and the increase in CD39 and CD73 gene expression induced by the hypoxic state. This fact has fueled preclinical and clinical research into the development of efficacious molecules acting on the adenosine pathway and blocking its accumulation. Given the success of anti-cancer immunotherapy, the new strategy is to develop selective A2A receptor antagonists that could competitively inhibit binding to its endogenous ligand, making them reliable candidates for the therapeutic management of brain tumors. Here, we focused on the efficacy of adenosine receptor antagonists and their enhancement in anti-cancer immunotherapy.

Case Report: Splenic Ischemia Induced by Volvulus of Ileum.

A 31-year-old female patient was admitted to the emergency department with signs and symptoms of acute abdomen. Urgent CT scan was performed and small bowel volvulus, with whirlpool sign, was noted and torsion of the spleen was also involved too.

Potential Therapeutic Effects of PPAR Ligands in Glioblastoma.

Glioblastoma (GB), also known as grade IV astrocytoma, represents the most aggressive form of brain tumor, characterized by extraordinary heterogeneity and high invasiveness and mortality. Thus, a great deal of interest is currently being directed to investigate a new therapeutic strategy and in recent years, the research has focused its attention on the evaluation of the anticancer effects of some drugs already in use for other diseases. This is the case of peroxisome proliferator-activated receptors (PPARs) ligands, which over the years have been revealed to possess anticancer properties. PPARs belong to the nuclear receptor superfamily and are divided into three main subtypes: PPAR-α, PPAR-ß/δ, and PPAR-γ. These receptors, once activated by specific natural or synthetic ligands, translocate to the nucleus and dimerize with the retinoid X receptors (RXR), starting the signal transduction of numerous genes involved in many physiological processes. PPARs receptors are activated by specific ligands and participate principally in the preservation of homeostasis and in lipid and glucose metabolism. In fact, synthetic PPAR-α agonists, such as fibrates, are drugs currently in use for the clinical treatment of hypertriglyceridemia, while PPAR-γ agonists, including thiazolidinediones (TZDs), are known as insulin-sensitizing drugs. In this review, we will analyze the role of PPARs receptors in the progression of tumorigenesis and the action of PPARs agonists in promoting, or not, the induction of cell death in GB cells, highlighting the conflicting opinions present in the literature.

Carbon Dots: An Innovative Tool for Drug Delivery in Brain Tumors.

Brain tumors are particularly aggressive and represent a significant cause of morbidity and mortality in adults and children, affecting the global population and being responsible for 2.6% of all cancer deaths (as well as 30% of those in children and 20% in young adults). The blood-brain barrier (BBB) excludes almost 100% of the drugs targeting brain neoplasms, representing one of the most significant challenges to current brain cancer therapy. In the last decades, carbon dots have increasingly played the role of drug delivery systems with theranostic applications against cancer, thanks to their bright photoluminescence, solubility in bodily fluids, chemical stability, and biocompatibility. After a summary outlining brain tumors and the current drug delivery strategies devised in their therapeutic management, this review explores the most recent literature about the advances and open challenges in the employment of carbon dots as both diagnostic and therapeutic agents in the treatment of brain cancers, together with the strategies devised to allow them to cross the BBB effectively.