Exosomes are cell-secreted nanoparticles containing various molecules including small vesicles, microRNAs (miRNAs), messenger RNAs or bioactive proteins which are thought to be of paramount importance for intercellular communication. The unique effects of exosomes in terms of cell penetration capacity, decreased immunogenicity and inherent stability, along with their key role in mediating information exchange among tumor cells and their surrounding tumor microenvironment (TME), render them a promising platform for drug targeted delivery. Compared to synthetic drugs, exosomes boast a plethora of advantages, including higher biocompatibility, lower toxicity and increased ability of tissue infiltration. Nevertheless, the use of artificial exosomes can be limited in practice, partly due to their poor targeting ability and partly due to their limited efficacy. Therefore, efforts have been made to engineer stem cell-derived exosomes in order to increase selectiveness and effectivity, which can then become loaded with various active substances depending on the therapeutic approach followed. Erythropoietin-producing human hepatocellular receptors (EPHs), along with their ligands, the EPH family receptor interacting proteins (ephrins), have been extensively investigated for their key roles in both physiology and cancer pathogenesis. EPHs/ephrins exhibit both tumorigenic and tumor suppressing properties, with their targeting representing a promising, novel therapeutic approach in cancer patients’ management. In our review, the use of ephrin-loaded exosomes as a potential therapeutic targeted delivery system in cancer will be discussed.

The significant heterogeneity in clinical outcomes among patients with bladder cancer has highlighted the existence of different biological subtypes of muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Meanwhile, immune checkpoint proteins and their interference with tumor-related immune-evasive strategies has led to the development of several immunotherapeutic drugs targeting programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1). However, the lack of any known biomarker that could predict responses to immunotherapy has led to a more agnostic therapeutic approach. Here, we present a study conducted in 77 bladder cancer (BC) patients (n = 77), ranging from stages pTa to pT2. Tumor specimens were resected via transurethral resection of bladder tumor (TURBT) and consistuted of 24 low-grade (LG) and 53 high-grade (HG) tumors. Patients’ tumors were then categorized into molecular subtypes, via immunohistochemistry (CK5/6 and GATA3). Furthermore, all tumor specimens were stained with anti-PD-L1 and demonstrated significant correlations with basal immunophenotype, stage pT2 and HG tumors. As such, we attempted to stratify patients into groups of likely-responders and likely-not-responders to immunotherapy with anti-PD-L1, based on their molecular phenotype. Finally, in acknowledging the fact that there is a universal lack of biomarkers associated with predicting BC response to immunotherapeutic drugs, we tested all tumors for deficiency of mismatch repair proteins (MMR).

Pancreatic cancer is set to become the most lethal and common type of cancer worldwide. This is partly attributed to the mutational burden that affects core signaling pathways and the crosstalk of tumor cells with their surrounding microenvironment, but it is also due to modern eating habits. Hyperadiposity along with the constant rise in metabolic syndrome’s incidence contribute to a state of metaflammation that impacts immune cells and causes them to shift towards an immunosuppressive phenotype that, ultimately, allows tumor cells to evade immune control. Unfortunately, among the conventional therapeutic modalities and the novel therapeutic agents introduced, pancreatic cancer still holds one of the lowest response rates to therapy. Human antigen R (HuR), an RNA binding protein (RBP), has been repeatedly found to be implicated in pancreatic carcinogenesis and chemotherapy resistance through the posttranscriptional binding and regulation of mRNA target genes. Additionally, its overexpression has been linked to adverse clinical outcomes, in terms of tumor grade, stage, lymph node status and metastasis. These properties suggest the prospective role that HuR’s therapeutic targeting can play in facilitating pancreatic neoplasia and could provide the means to overcome chemoresistance.

We report the case of a 64-year-old male who died suddenly short after his admission to hospital because of strong chest pain and before any clinical diagnosis was established. His medical history included coronary disease with coronary by-pass surgery at the age of 40 years old, uncontrolled hypertension, diabetes mellitus, and elevated levels of cholesterol. The autopsy revealed quite a rare case of Stanford A aortic dissection with extension to the common and internal carotid arteries; the subclavian, axillary, brachial, and radial arteries; three coronary arteries; the superior mesenteric artery; and the iliac arteries. There was no histological evidence of aortitis or connective tissue disease. The death did not result from the rupture of the aortic dissection, but from myocardial ischemia due to coronary occlusion in combination with hemodynamic disturbance from stress caused by the extended aortic dissection.

Urinary bladder diverticula are formed by the herniation of the mucosa into the muscle layer of the bladder wall, often ending with a narrow neck that communicates with the bladder lumen. They may be congenital or acquired, and they most often affect males. Urinary bladder diverticula discovery during autopsy incidence described in the literature is approximately 5–10%. Various causative factors have been described, including urinary tract obstruction (e.g., benign prostate hyperplasia) and neurogenic and iatrogenic causes. The most described site of occurrence is adjacent to the ureteral orifice. Their clinical presentation does not often facilitate diagnosis, as most are small and asymptomatic. Complications of urinary bladder diverticulosis include infections, lithiasis, neoplasia, pressure on adjacent tissues, obstruction, and rupture. Indeed, urinary bladder diverticula may lead to spontaneous bladder rupture in extremely rare cases. This paper presents the case of an 87-year-old female suffering from atrial fibrillation and under anticoagulant therapy who was pronounced dead in a hospital and was subsequently referred to our department for medico-legal examination. Upon macroscopic examination of the body, intra-abdominal hemorrhage was observed in the vicinity of the urinary bladder, extraperitoneally. A meticulous examination excluded the possibility of injury as the cause of this finding, and tissue samples were collected for histopathological examination. A ruptured urinary diverticulum was discovered and confirmed histopathologically. Death was attributed to intra-abdominal hemorrhage after rupture of urinary bladder diverticulum. A forensic pathologist should be aware of this diagnosis, as although extremely rare, such pathology may lead to death, especially when the patient is under anticoagulant therapy.