Harnessing Nitric Oxide-Donating Benzofuroxans for Targeted Inhibition of Carbonic Anhydrase IX in Cancer.

We describe here the design and antitumor evaluation of benzofuroxan-based nitric oxide (NO)-donor hybrid derivatives targeting human carbonic anhydrases (hCAs) IX and XII. The most effective compounds, and , demonstrated potent dual action, exhibiting low nanomolar inhibition constants against hCA IX and significant NO release. Notably, compound showed significant antiproliferative effects against various cancer cell lines, particularly renal carcinoma A-498 cells.

Ocular pharmacological and biochemical profiles of 6-thioguanine: a drug repurposing study.

Introduction: The purine analog 6-thioguanine (6TG), an old drug approved in the 60s to treat acute myeloid leukemia (AML), was tested in the diabetic retinopathy (DR) experimental setting along with a molecular modeling approach.

Methods: A computational analysis was performed to investigate the interaction of 6TG with MC1R and MC5R. This was confirmed in human umbilical vein endothelial cells (HUVECs) exposed to high glucose (25 mM) for 24 h.

Clinical Potential of YY1-Hypoxia Axis for Vascular Normalization and to Improve Immunotherapy.

Abnormal vasculature in solid tumors causes poor blood perfusion, hypoxia, low pH, and immune evasion. It also shapes the tumor microenvironment and affects response to immunotherapy. The combination of antiangiogenic therapy and immunotherapy has emerged as a promising approach to normalize vasculature and unlock the full potential of immunotherapy.

Combination of Genomic Landsscape and 3D Culture Functional Assays Bridges Sarcoma Phenotype to Target and Immunotherapy.

Genomic-based precision medicine has not only improved tumour therapy but has also shown its weaknesses. Genomic profiling and mutation analysis have identified alterations that play a major role in sarcoma pathogenesis and evolution. However, they have not been sufficient in predicting tumour vulnerability and advancing treatment.

Basic Pathogenic Mechanisms and Epigenetic Players Promoted by Extracellular Vesicles in Vascular Damage.

Both progression from the early pathogenic events to clinically manifest cardiovascular diseases (CVD) and cancer impact the integrity of the vascular system. Pathological vascular modifications are affected by interplay between endothelial cells and their microenvironment. Soluble factors, extracellular matrix molecules and extracellular vesicles (EVs) are emerging determinants of this network that trigger specific signals in target cells.

Spontaneous cancer remission after COVID-19: insights from the pandemic and their relevance for cancer treatment.

Early in the COVID-19 pandemic, it emerged that the risk of severe outcomes was greater in patients with co-morbidities, including cancer. The huge effort undertaken to fight the pandemic, affects the management of cancer care, influencing their outcome. Despite the high fatality rate of COVID-19 disease in cancer patients, rare cases of temporary or prolonged clinical remission from cancers after SARS-CoV-2 infection have been reported.

Microbiota Effect on Trimethylamine N-Oxide Production: From Cancer to Fitness-A Practical Preventing Recommendation and Therapies.

Trimethylamine N-oxide (TMAO) is a microbial metabolite derived from nutrients, such as choline, L-carnitine, ergothioneine and betaine. Recently, it has come under the spotlight for its close interactions with gut microbiota and implications for gastrointestinal cancers, cardiovascular disease, and systemic inflammation. The culprits in the origin of these pathologies may be food sources, in particular, high fat meat, offal, egg yolk, whole dairy products, and fatty fish, but intercalated between these food sources and the production of pro-inflammatory TMAO, the composition of gut microbiota plays an important role in modulating this process.

Long-Term Results of Complex Abdominal Aortic Aneurysm Open Repair.

This study investigated the long-term outcomes of patients treated with open surgical repair for complex abdominal aortic aneurysms (c-AAAs). A total of 119 patients with c-AAAs undergoing repair between January 2010 and June 2016 in a high-volume aortic center were included. The long-term imaging follow-up consisted of yearly abdominal ultrasound examinations and 5-year computed tomography angiography.

Type 1A Endoleak after TEVAR in the Aortic Arch: A Review of the Literature.

Aortic arch repair is a challenging intervention. Open surgical repair is still considered the gold standard, but in high-risk patients, it is not always a reasonable option, making endovascular approaches an enticing, when not the only available, alternative for treatment. The strategies more commonly adopted are surgical supra-aortic trunk (SAT) rerouting followed by deployment of a standard thoracic endoprosthesis, chimney techniques, custom-made scalloped, fenestrated, and branched devices, and in situ or physician-modified fenestrations.

Sarcoma Common MHC-I Haplotype Restricts Tumor-Specific CD8+ T Cell Response.

The major histocompatibility complex (MHC) class I expression in cancer cells has a crucial impact on the outcome of T cell-mediated cancer immunotherapy. We now determined the HLA class I allelic variants and their expression in PD-L1-deficient and positive rare sarcoma tissues. Tumor tissues were HLA-I classified based on HLA-A and -B alleles, and for class II, the HLA-DR-B by Taqman genomic PCRs.

Through-and-through femorofemoral wire retrograde technique for the E-nside precannulated inner branch thoracoabdominal stent graft.

The E-nside multibranched stent graft (Jotec GmbH, Hechingen, Germany) is the first and only off-the-shelf thoracoabdominal prosthesis with precannulated inner branches. Usually, after the device deployment, target vessel stenting will be facilitated by antegrade inner branch cannulation to retrieve the precannulated guide. In the literature, the use of antegrade access has been associated with the potential risk of cerebral and systemic embolization.

Lysosome purinergic receptor P2X4 regulates neoangiogenesis induced by microvesicles from sarcoma patients.

The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo.

Splenic artery transposition for hepatic arterial reconstruction in a locally advanced pancreatic cancer: a case report and literature review.

Objective: During pancreatic surgery for malignancies, hepatic revascularization is needed in case of en bloc resection with hepatic artery involvement. In these cases, the use of the splenic artery is described in the literature, including transposition and interposition techniques.

Patients And Methods: We report the case of pancreatic cancer resection with involvement of the right hepatic artery, anomalous arising from the superior mesenteric artery, and hepatic revascularization with splenic artery reconstruction.

TEVAR for traumatic thoracic injury with the first-generation stent graft.

Thoracic endovascular aortic repair (TEVAR) is a life-saving treatment for blunt thoracic aortic injury. We report long-term outcomes of two young patients who underwent TEVAR for blunt thoracic aortic injury with first-generation thoracic stent grafts. The off-label use of the endograft affected the outcomes: one case of open surgery conversion due to an aortoesophageal fistula and one case of endovascular relining for a voluminous pseudoaneurysm associated with a type III endoleak.

Emergent expansion of clinical epigenetics in patients with cardiovascular diseases.

Purpose Of Review: Cardiovascular diseases (CVDs) are typically caused by multifactorial events including mutations in a large number of genes. Epigenetic-derived modifications in the cells are normal but can be amended by aging, lifestyle, and exposure to toxic substances. Major epigenetic modifications are DNA methylation, histone modification, chromatin remodeling as well as the noncoding RNAs.

Clinical Epigenetics of Neuroendocrine Tumors: The Road Ahead.

Neuroendocrine tumors, or NETs, are cancer originating in neuroendocrine cells. They are mostly found in the gastrointestinal tract or lungs. Functional NETs are characterized by signs and symptoms caused by the oversecretion of hormones and other substances, but most NETs are non-functioning and diagnosis in advanced stages is common.

Long-term follow-up of adventitial cyst surgical excision in external iliac vein.

Adventitial cystic disease of the venous system is an extremely rare condition. Forty-five cases have been described in the literature during the last 70 years, but they may not be representative of the real incidence of this pathologic process. We report a case of an adventitial cyst compressing the right external iliac vein and presenting with edema of the ipsilateral leg.

Epigenetic therapies of osteoporosis.

The study of epigenetics reaches its 50th anniversary, however, its clinical application is gradually coming into the clinical setting. Osteoporosis is one of the major and widely diffused bone diseases. Pathogenic mechanisms at the epigenetic level may interfere with bone remodeling occurring during osteoporosis.

Epigenetic Dysregulation in Advanced Kidney Cancer: Opportunities for Therapeutic Interventions.

Understanding the complex epigenome of advanced renal cell carcinoma may lead to novel epigenomic-based pharmaceutical strategies and identify new targets for therapeutic interventions. Epigenetic changes, such as DNA methylation and histone acetylation, modulate the activity of significant oncogenic signaling pathways by regulating gene expression. Such pathways include the WNT-β-catenin pathway, the von Hippel-Lindau-hypoxia-inducible factor pathway, and epithelial-mesenchymal transition pathway.