Objective: Inhibitors of the angiotensin converting enzyme (ACE) are the primarily chosen drugs to treat heart failure and hypertension. Moreover, an imbalance in tissue ACE/ACE2 activity is implicated in COVID-19. In the present study, we tested the relationships between circulating and tissue (lung and heart) ACE levels in men. Methods: Serum, lung (n = 91) and heart (n = 72) tissue samples were collected from Caucasian patients undergoing lung surgery or heart transplantation. ACE I/D genotype, ACE concentration and ACE activity were determined from serum and tissue samples. Clinical parameters were also recorded. Results: A protocol for ACE extraction was developed for tissue ACE measurements. Extraction of tissue-localized ACE was optimal in a 0.3% Triton-X-100 containing buffer, resulting in 260 ± 12% higher ACE activity over detergent-free conditions. SDS or higher Triton-X-100 concentrations inhibited the ACE activity. Serum ACE concentration correlated with ACE I/D genotype (II: 166 ± 143 ng/mL, n = 19, ID: 198 ± 113 ng/mL, n = 44 and DD: 258 ± 109 ng/mL, n = 28, p < 0.05) as expected. In contrast, ACE expression levels in the lung tissue were approximately the same irrespective of the ACE I/D genotype (II: 1423 ± 1276 ng/mg, ID: 1040 ± 712 ng/mg and DD: 930 ± 1273 ng/mg, p > 0.05) in the same patients (values are in median ± IQR). Moreover, no correlations were found between circulating and lung tissue ACE concentrations and activities (Spearman’s p > 0.05). In contrast, a significant correlation was identified between ACE activities in serum and heart tissues (Spearman’s Rho = 0.32, p < 0.01). Finally, ACE activities in lung and the serum were endogenously inhibited to similar degrees (i.e., to 69 ± 1% and 53 ± 2%, respectively). Conclusion: Our data suggest that circulating ACE activity correlates with left ventricular ACE, but not with lung ACE in human. More specifically, ACE activity is tightly coordinated by genotype-dependent expression, endogenous inhibition and secretion mechanisms.

Secondary bladder neoplasms are uncommon and they represent only 2% of all malignant bladder tumors.

Background: Thymic carcinoma is a rare and highly malignant tumor with a dismal prognosis, which occasionally coexists with myasthenia gravis (MG). This study aims to investigate the MG incidence on a surgical cohort of patients with thymic carcinoma and to explore its influence on long-term survival. Methods: the prospectively collected data from the ESTS database on thymic epithelial tumors were reviewed. Clinical, pathological, and survival information on thymic carcinoma were analyzed. Results: the analysis was conducted on 203 patients, with an equal gender distribution (96 males and 107 females). MG was detected in 22 (10.8%) patients, more frequently elderly (>60 years, p = 0.048) and male (p = 0.003). Induction therapy was performed in 22 (10.8%) cases. After surgery, 120 (59.1%) patients had a Masaoka stage II–III while complete resection (R0) was achieved in 158 (77.8%). Adjuvant therapy was performed in 68 cases. Mean follow-up was 60 (SD = 14) months. The 3-year, 5-year and 10-year survival rates were 79%, 75% and 63%, respectively. MG did not seem to influence long-term survival (5-year survival in non-MG–TCs 78% vs. 50% in MG–TCs, p = ns) as age < 60 years, female gender, early Masaoka stage, and postoperative radiotherapy did, conversely. Conclusions: myasthenia occurred in about 10% of thymic carcinomas and it did not seem to affect significantly the long-term prognosis in surgically treated thymic carcinoma-patients.

Pulmonary carcinoma remains a highly aggressive malignancy driven by complex signaling and epigenetic dysregulation. This study investigates a novel oncogenic pathway involving the Mg^2+/Mn²⁺-dependent protein phosphatase 1B PPM1B/myosin phosphatase (MP)/protein arginine methyltransferase 5 (PRMT5) axis, which promotes carcinogenesis by symmetrically dimethylating histone H2A and suppressing tumor suppressor genes. We hypothesized that loss of PPM1B would activate this pathway and drive tumorigenesis. Western blotting, PCR, and immunohistochemistry revealed a significant reduction in PPM1B expression in both squamous cell carcinoma (SCC) and human lung adenocarcinoma (ADC) compared to normal lung tissues, which correlated with worse patient survival. Despite an increase in total MYPT1, the regulatory subunit of MP, its inhibitory phosphorylation at Thr853 was significantly elevated in both tumor types. The inactivation of MP corresponded with a significant increase in the activating phosphorylation of PRMT5 at Thr80, especially in SCC, which was linked to a particularly poor prognosis. Downstream, this resulted in a dramatic elevation in the symmetric dimethylation of histone H2A, leading to decreased expression of retinoblastoma protein. Our findings demonstrate that decreased PPM1B expression drives the oncogenic activation of the MP/PRMT5 axis. This mechanism contributes to the aggressive nature of SCC, establishing PPM1B as a promising prognostic marker in lung cancer.