ABSTRACT
AIMS: Interaction between programmed death-1 ligand (PD-L1) and its receptor programmed death 1 (PD-1) on T cells inactivates antitumour immune responses. PD-L1 expression has been associated with poor prognosis in renal cell carcinoma (RCC) and predicts adverse outcome. This study was designed to evaluate the impact of PD-L1 expression and the immune microenvironment on the clinical outcome in Xp11 translocation renal cell carcinoma (TRCC) and, therefore, their potential relevance as prognostic biomarkers. METHODS AND RESULTS: The present retrospective analysis investigated expression of PD-L1 and immune cells CD8, CD4, CD3, forkhead box protein 3 (FoxP3) and PD-1 in TRCC compared to other types of RCC. FFPE specimens were collected between 2011 and 2017 from 311 patients who underwent nephrectomy at our institution for RCC. Specimens were immunostained for PD-L1, CD8, CD4, CD3, FoxP3 and PD-1, and an outcome analysis was conducted. PD-L1 expression rate was highest in TRCC (68%, 16 of 25), followed by mucinous tubular and spindle cell RCC and collecting duct carcinoma (33%, one of three), papillary RCC (27%, seven of 26), clear cell RCC (16%, 29 of 233), chromophobe RCC (11%, two of 18) and multilocular cystic RCC (0%, none of three). In TRCC, PD-L1 expression was associated with poor recurrence-free survival (RFS) (P = 0.041). The CD4high and FoxP3high groups showed a significantly shorter RFS (P = 0.05 and P = 0.031, respectively) compared to CD4low and FOXPlow groups. CONCLUSION: PD-L1 expression was higher in TRCC than in other types of RCC. High PD-L1 tumour cell expression and tumour infiltration by CD4+ and FoxP3+ immune cells were associated with poor RFS in TRCC.
Subject(s)
B7-H1 Antigen/biosynthesis , CD4-Positive T-Lymphocytes/immunology , Carcinoma, Renal Cell/immunology , Kidney Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Chromosomes, Human, X/genetics , Female , Forkhead Transcription Factors/immunology , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Translocation, Genetic , Tumor Microenvironment/immunologyABSTRACT
BACKGROUND: Domperidone is an antidopaminergic drug that facilitates a function of the digestive smooth muscle. Depending on the Biopharmaceutical Classification System, domperidone is classified as class II with poor solubility and high permeability. METHOD/RESULTS: Solid dispersions were prepared by spray-drying with a polymer. The characterization of prepared solid dispersions was analyzed by scanning electron microscope, Fourier transform infrared spectroscopy, x-ray diffraction and differential scanning calorimeter. In vitro dissolution behavior was carried out in gastric juice (pH 1.2) and these results were compared with pure domperidone (active pharmaceutical ingredient). The dissolution rate was improved due to the influence of polymers. Stability assays were conducted by the same pre-experiment. Storage conditions of the solid dispersions were as follows: 25°C relative humidity 25% and 65°C relative humidity 80%. CONCLUSION: In this study, the goal is to improve the dissolution rate of domperidone by solid dispersions and to confirm stability of the prepared solid dispersions. It suggests that the content of polymers added in solid dispersions can affect the dissolution behavior and change dissolution rate of drug.
