Preclinical immunotherapy with Cytokine-Induced Killer lymphocytes against epithelial ovarian cancer

Despite improvements in surgery and medical treatments, epithelial ovarian cancer (EOC) remains the most lethal gynaecological malignancy. Aim of this study is to investigate the preclinical immunotherapy activity of cytokine-induced killer lymphocytes (CIK) against epithelial ovarian cancers, focusing on platinum-resistant settings. We generated CIK ex vivo starting from human peripheral blood samples (PBMCs) collected from EOC patients. Their antitumor activity was tested in vitro and in vivo against platinum-resistant patient-derived ovarian cancer cells (pdOVCs) and a Patient Derived Xenograft (PDX), respectively. CIK were efficiently generated (48 fold median ex vivo expansion) from EOC patients; pdOVCs lines (n = 9) were successfully generated from metastatic ascites; the expression of CIK target molecules by pdOVC confirmed pre and post treatment in vitro with carboplatin. The results indicate that patient-derived CIK effectively killed autologous pdOVCs in vitro. Such intense activity was maintained against a subset of pdOVC that survived in vitro treatment with carboplatin. Moreover, CIK antitumor activity and tumor homing was confirmed in vivo within an EOC PDX model. Our preliminary data suggest that CIK are active in platinum resistant ovarian cancer models and should be therefore further investigated as a new therapeutic option in this extremely challenging setting

Visuospatial Deficits Are Associated with Pisa Syndrome and not Camptocormia in Parkinson's Disease

Background: Pisa syndrome (PS) and camptocormia (CC) are postural abnormalities frequently associated with Parkinson's disease (PD). Their pathophysiology remains unclear, but the role of cognitive deficits has been postulated. Objectives: To identify differences in the neuropsychological functioning of patients with PD with PS or CC compared with matched patients with PD without postural abnormalities. Methods: We performed a case-control study including 57 patients with PD with PS (PS+) or CC (CC+) and 57 PD controls without postural abnormalities matched for sex, age, PD duration, phenotype, and stage. Patients were divided into four groups: PS+ (n = 32), PS+ controls (PS−, n = 32), CC+ (n = 25), and CC+ controls (CC−, n = 25). We compared PS+ versus PS− and CC+ versus CC− using a neuropsychological battery assessing memory, attention, executive functions, visuospatial abilities, and language. Subjective visual vertical (SVV) perception was assessed by the Bucket test as a sign of vestibular function; the misperception of trunk position, defined as a mismatch between the objective versus subjective evaluation of the trunk bending angle >5°, was evaluated in PS+ and CC+. Results: PS+ showed significantly worse visuospatial performances (P = 0.025) and SVV perception (P = 0.038) than their controls, whereas CC+ did not show significant differences compared with their control group. Reduced awareness of postural abnormality was observed in >60% of patients with PS or CC. Conclusions: Low visuospatial performances and vestibular tone imbalance are significantly associated with PS but not with CC. These findings suggest different pathophysiology for the two main postural abnormalities associated with PD and can foster adequate therapeutic and prevention strategies