ABSTRACT
INTRODUCTION: Increasing number of older adults undergo cochlear implantation (CI). Accumulating evidence implicates that the outcome of implantation may not only depend on physical and psychological health status of patients but also on their age. In the present work, we analyzed the elderly (70-80) and very old (80+) patients who underwent CI regarding their hearing abilities, health-related quality of life (HRQoL), and psychological comorbidities. PATIENTS AND METHODS: Eighty-six patients were included in this prospective study. The patients were split into two groups: 70-80 years-old (nâ=â62) and ≥ 80 years-old (nâ=â24). Hearing performance was assessed with Freiburg monosyllabic test and Oldenburg inventory (OI); the health-related quality of life was measured with Nijmegen Cochlear Implantation Questionnaire (NCIQ); depressive symptoms with General Depression Scale (ADS-L); stress with Perceived Stress Questionnaire (PSQ) and anxiety with General Anxiety Disorder-7 (GAD-7). RESULTS: Prior to CI, the hearing performance (Ol) impacted positively the HRQoL of both groups whereas the perceived stress (PSQ) had a negative impact. Six months after implantation, the HRQoL of 70-80 group was still positively influenced by the hearing performance (Ol) whereas HRQoL of 80+ group was influenced by stress perception (negative impact) and anxiety (positive impact). Twelve months later, anxiety and depressive symptoms correlated negatively with HRQoL of both age groups. Hearing performance had the positive and anxiety the negative impact on HRQoL in both groups but in addition, the 80+ group seemed to benefit from an increased level of anxious symptoms. CONCLUSION: In elderly patients, the outcome of CI depends on their psychological status. Differences found between the age groups imply a need for an age-group targeted psychological counselling, which might further improve outcome of CI.
Subject(s)
Cochlear Implantation/psychology , Hearing Loss/psychology , Hearing Loss/surgery , Quality of Life , Treatment Outcome , Aged , Aged, 80 and over , Cochlear Implants , Comorbidity , Female , Hearing , Humans , Male , Prospective Studies , Speech Perception , Surveys and QuestionnairesABSTRACT
BACKGROUND: In this study, different variants of the anti-PSMA single-chain antibody fragment (scFv) D7 were cloned, varying in linker type, position of hexahistidine tags and VH-VL orientation. From these scFv, Pseudomonas exotoxin A-based immunotoxins were constructed and their biological activities against prostate cancer cells were compared. MATERIALS AND METHODS: Binding of the constructs to PSMA-expressing prostate cancer cells was determined by flow cytometry. ADP-ribosyltransferase activity was analysed and cytotoxicity was measured with WST-1 assays. RESULTS: Different linker types did not influence the characteristics of the scFv or immunotoxins. The addition of an N-terminal hexahistidine-tag, however, resulted in decreased expression, binding and cytotoxicity. scFv in VH-VL orientation showed the highest expression and binding, whereas immunotoxins in VL-VH orientation exhibited the best binding and cytotoxicity. CONCLUSION: The present study showed how structure influences the characteristics of scFv and immunotoxins. It is therefore suggested that for each individual construct the optimal structure has to be determined separately.
Subject(s)
Antigens, Surface/immunology , Glutamate Carboxypeptidase II/immunology , Immunotoxins/chemistry , Prostatic Neoplasms/immunology , Single-Chain Antibodies/chemistry , ADP Ribose Transferases/chemistry , ADP Ribose Transferases/genetics , ADP Ribose Transferases/immunology , Antigens, Surface/genetics , Antigens, Surface/metabolism , Bacterial Toxins/chemistry , Bacterial Toxins/genetics , Bacterial Toxins/immunology , Blotting, Western , Cell Line, Tumor , Cell Separation , Exotoxins/chemistry , Exotoxins/genetics , Exotoxins/immunology , Flow Cytometry , Glutamate Carboxypeptidase II/genetics , Glutamate Carboxypeptidase II/metabolism , Humans , Immunoglobulin Fragments/chemistry , Immunoglobulin Fragments/genetics , Immunoglobulin Fragments/immunology , Immunotoxins/genetics , Immunotoxins/immunology , Male , Molecular Sequence Data , Single-Chain Antibodies/genetics , Single-Chain Antibodies/immunology , Virulence Factors/chemistry , Virulence Factors/genetics , Virulence Factors/immunology , Pseudomonas aeruginosa Exotoxin AABSTRACT
The prostate-specific membrane antigen (PSMA) is abundantly expressed on prostate cancer epithelial cells and its expression correlates with tumor progression. Therefore, a specific immunotherapy against this antigen may be a novel therapeutic option for the management of prostate cancer. We generated an anti-PSMA single-chain antibody fragment (scFv), called D7, by phage display from the monoclonal antibody 3/F11. By C-terminal ligation of the toxic domain of Pseudomonas Exotoxin A (PE40) to the genes of D7, the immunotoxin D7-PE40 was generated. D7 and D7-PE40 specifically bound to PSMA transfectants and to the PSMA expressing prostate cancer cell line C4-2. In addition, D7-PE40 showed a high serum stability and induced a 50% reduction of viability (IC50) in C4-2 cells at a concentration of 140 pM. In vivo, D7-PE40 was well tolerated in SCID mice up to a single dose of 20 microg, whereas higher doses induced severe hepatotoxicity with deaths of the animals. Immunotoxin treatment of mice bearing C4-2 tumor xenografts caused a significant inhibition of tumor growth, whereas mice with PSMA-negative DU 145 tumors remained unaffected. Owing to its high and specific cytotoxicity and its capability to inhibit prostate tumor growth in vivo the immunotoxin D7-PE40 represents a promising candidate for the immunotherapy of prostate cancer.
