Shmt2: a stat3 signaling new player in prostate cancer energy metabolism

Prostate cancer (PCa) is a multifactorial disease characterized by the aberrant activity of different regulatory pathways. STAT3 protein mediates some of these pathways and its activation is implicated in the modulation of several metabolic enzymes. A bioinformatic analysis indicated a STAT3 binding site in the upstream region of SHMT2 gene. We demonstrated that in LNCaP, PCa cells' SHMT2 expression is upregulated by the JAK2/STAT3 canonical pathway upon IL-6 stimulation. Activation of SHTM2 leads to a decrease in serine levels, pushing PKM2 towards the nuclear compartment where it can activate STAT3 in a non-canonical fashion that in turn promotes a transient shift toward anaerobic metabolism. These results were also confirmed on FFPE prostate tissue sections at different Gleason scores. STAT3/SHMT2/PKM2 loop in LNCaP cells can modulate a metabolic shift in response to inflammation at early stages of cancer progression, whereas a non-canonical STAT3 activation involving the STAT3/HIF-1α/PKM2 loop is responsible for the maintenance of Warburg effect distinctive of more aggressive PCa cells. Chronic inflammation might thus prime the transition of PCa cells towards more advanced stages, and SHMT2 could represent a missing factor to further understand the molecular mechanisms responsible for the transition of prostate cancer towards a more aggressive phenotyp

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Epithelioid sarcoma of the penis. Clinicopathologic study of a tumor with myogenic features and review of the literature concerning this unusual location

Soft tissue tumors of the penis are uncommon. We report here the clinicopathologic features of a penile epithelioid sarcoma (ES), review the literature concerning this unusual location and focalize our attention on its differentiation. The 34-year-old patient was admitted for abrupt urinary retention due to the growth of a firm and painful plaque on the left side of the shaft, three years previously clinically diagnosed as Peyronie's disease. Magnetic nuclear resonance revealed an infiltrating lesion of both corpora cavernosa. Histology of bioptic fragments showed a nodular malignant spindle and epithelioid cell tumor with focal necrosis and relatively high mitotic rate. Based on the immunohistochemical data (cytokeratin+, vimentin+, EMA+, CD34+, and S100-), the diagnosis of ES was strongly considered. Penectomy was undertaken and the diagnosis confirmed by both light and ultrastructural microscopy. The 22 month follow-up was free of recurrences and metastases. Although not dissimilar from the 10 previously described ES of the penis in terms of natural history and histology, the tumor reported here showed myogenic features as revealed by both immunohistochemistry (immunoreactivity for muscle specific actin) and ultrastructure (intercellular junctions, discontinuous basal lamina, pinocytotic vesicles and thin filaments with intercalated dense bodies). Although previously observed in ES of other sites, this feature has never been established in ES of the penis