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Background: The superiority of paclitaxel/ramucirumab over alternative therapeutic regimens in patients with gastric cancer has yet to be defined. Our aim was to evaluate whether second-line treatment with paclitaxel/ramucirumab is superior compared with other therapies. Patients and methods: Retrospective real-world data from patients with advanced adenocarcinoma of the stomach, gastroesophageal junction, or distal esophagus, treated at Departments of Medical Oncology, affiliated with the Hellenic Cooperative Oncology Group (HeCOG), were collected. All patients had received at least 2 months of second-line treatment. The primary endpoint was progression-free survival 1 (PFS1). Results: From March 2015 to March 2023, 179 patients received second-line treatment (median age 61.3 years). Of those, 77 (43%) received paclitaxel/ramucirumab, 21 (11.7%) irinotecan/5-fluorouracil (5-FU)/leucovorin, 16 (8.9%) docetaxel, and 65 (36.3%) other treatments. The efficacy of paclitaxel/ramucirumab was assessed by histological subtype: diffuse, intestinal, and mixed. For diffuse histology, the adjusted hazard ratio (aHR) for PFS1 was 1.03 [95% confidence interval (CI) 0.50-2.16] and for overall survival (OS) was 1.71 (95% CI 0.79-3.68). For intestinal histology, the aHR for PFS1 was 0.53 (95% CI 0.28-1.01) and for OS was 0.44 (95% CI 0.22-0.88), indicating a statistically significant OS benefit. Mixed histology showed no significant differences in PFS1 (aHR 1.00, 95% CI 0.23-4.37) or OS (aHR 1.10, 95% CI 0.32-3.82). Toxicity, dose reduction, and discontinuation rates were similar between paclitaxel/ramucirumab and other regimens. Conclusions: Second-line treatment with paclitaxel/ramucirumab was independently associated with OS compared with other regimens in patients with advanced intestinal-type gastric cancer. Identification of the most effective treatment for advanced gastric cancer remains a challenge.

The degeneration of axon terminals before the soma, referred to as “dying back”, is a feature of Parkinson’s disease (PD). Axonal assays are needed to model early PD pathogenesis as well as identify protective therapeutics. We hypothesized that defects in axon lysosomal trafficking as well as injury repair might be important contributing factors to “dying back” pathology in PD. Since primary human PD neurons are inaccessible, we developed assays to quantify axonal trafficking and injury repair using induced pluripotent stem cell (iPSC)-derived neurons with LRRK2 G2019S, which is one of the most common known PD mutations, and isogenic controls. We observed a subtle axonal trafficking phenotype that was partially rescued by a LRRK2 inhibitor. Mutant LRRK2 neurons showed increased phosphorylated Rab10-positive lysosomes, and lysosomal membrane damage increased LRRK2-dependent Rab10 phosphorylation. Neurons with mutant LRRK2 showed a transient increase in lysosomes at axotomy injury sites. This was a pilot study that used two patient-derived lines to develop its methodology; we observed subtle phenotypes that might correlate with heterogeneity in LRRK2-PD patients. Further analysis using additional iPSC lines is needed. Therefore, our axonal lysosomal assays can potentially be used to characterize early PD pathogenesis and test possible therapeutics.

Simple Summary: The standard of care for most women with advanced ovarian cancer is primary cytoreduction followed by platinum-based chemotherapy and paclitaxel. However, the use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is not inferior, according to prospective randomized trials. Ovarian cancer has a low mutational load but exhibits a high detection rate of molecular alterations in various genes. It remains unclear whether this is an intrinsic feature of ovarian cancer or if it is due to the administration of a platinum combination during NACT. Our study aimed to determine whether NACT affects the tumor's molecular profile. Any modifications in these areas would need to be identified in the initial therapeutic planning, especially in the era of poly (ADP-ribose) polymerase (PARP) inhibitors. Background: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is a therapeutic choice for women with advanced ovarian cancer. Whether NACT affects the tumor's molecular profile has not been determined. Methods: This was a retrospective study of patients with advanced-stage epithelial ovarian cancer treated with NACT at oncology departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Tumor molecular profiling was performed on formalin-fixed and paraffin-embedded (FFPE) tumor pre- and post-NACT tissues. Homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), tumor molecular alterations, and tumor mutational burden (TMB) via next-generation sequencing analysis were assessed. Results: Overall, tumors from 36 patients were assessed, and molecular profiling was evaluated in 20 paired tumor samples. HRD positivity exhibited no significant change between pre- and post-NACT tumors. The BRCA1/2 mutational status remained constant, irrespective of the treatment administration. Pre-NACT tumors tended to exhibit a lower percentage of intratumoral TILs compared to post-NACT tumors (p = 0.004). Differences in the mutation profile between pre- and post-treatment tissue were observed in 33.33% (6/18) of the cases. The mean tumor cell content (TCC) (p-value: 0.0840) and the mean genomic instability score (p-value: 0.0636) decreased slightly numerically after therapy. A moderate inverse relationship was observed between the pre-NACT TMB and the chemotherapy response score (p-value: 0.038), indicating this correlation is statistically significant. Conclusion: This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment. [ABSTRACT FROM AUTHOR]

This article presents experience in construction the National Unified Terminological System (NUTS) with an ontological structure based on international Unified Medical Language System (UMLS). UMLS has been adapted and enriched with formulations from national directories, relationships, extracted from the texts of scientific articles and electronic health records, and weight coefficients. [ABSTRACT FROM AUTHOR]