ABSTRACT
INTRODUCTION: Multiple myeloma (MM) is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow. Despite intense research to develop new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) has been shown to be effective in vivo in a MM model. In order to define where alpha-RIT stands in MM treatment, the aim of this study was to compare Melphalan, MM standard treatment, with alpha-RIT using a [213Bi]-anti-mCD138 antibody in a syngeneic MM mouse model. METHODS: C57BL/KaLwRij mice were grafted with 1 × 10(6) 5T33 murine MM cells. Luciferase transfected 5T33 cells were used for in vivo localization. The first step of the study was to assess the dose-response of Melphalan 21 days after engraftment. The second step consisted in therapeutic combination: Melphalan followed by RIT at day 22 or day 25 after engraftment. Toxicity (animal weight, blood cell counts) and treatment efficacy were studied in animals receiving no treatment, injected with Melphalan alone, RIT alone at day 22 or day 25 (3.7 MBq of [213Bi]-anti-CD138) and Melphalan combined with alpha-RIT. RESULTS: Fifty percent of untreated mice died by day 63 after MM engraftment. In mice treated with Melphalan alone, only the 200 µg dose improved median survival. No animal was cured after Melphalan treatment whereas 60% of the mice survived with RIT alone at day 22 after tumor engraftment with only slight and reversible hematological radiotoxicity. No therapeutic effect was observed with alpha-RIT 25 days after engraftment. Melphalan and alpha-RIT combination does not improve overall survival compared to RIT alone, and results in increased leukocyte and red blood cell toxicity. CONCLUSIONS: Alpha-RIT seems to be a good alternative to Melphalan. Association of these two treatments provides no benefit. The perspectives of this work would be to evaluate RIT impact on the regimens incorporating the novel agents bortezomide, thalidomide and lenalidomide.
Subject(s)
Bismuth/therapeutic use , Chemoradiotherapy/methods , Melphalan/pharmacology , Multiple Myeloma/therapy , Radioimmunotherapy/methods , Radioisotopes/therapeutic use , Syndecan-1/immunology , Animals , Cell Line, Tumor , Chemoradiotherapy/adverse effects , Female , Melphalan/therapeutic use , Mice , Mice, Inbred C57BL , Multiple Myeloma/pathology , Optical Imaging , Radioimmunotherapy/adverse effectsABSTRACT
Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in autopsy studies. In clinical pratice however, the prevalence of DLB is much lower with important intercenter variations. Among the reasons for this low sensitivity of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of Lewy bodies with Alzheimer's disease pathology, which dominates the clinical phenotype. With the avenue of targeted therapies against the protein agregates, new clinical scales able to apprehend the coexistence of Lewy pathology in Alzheimer's disease are expected.
Subject(s)
Lewy Bodies/pathology , Lewy Body Disease/pathology , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/pathology , Diagnostic Techniques, Neurological , Disease Progression , Humans , Lewy Body Disease/diagnosis , Parkinson Disease/diagnosis , Parkinson Disease/pathologyABSTRACT
OBJECTIVES: The lymph node metastasis is an important prognostic factor in prostatic cancer. The aim of this prospective study was to evaluate the relevance of the sentinel lymph node biopsy by laparoscopy in staging locoregional patients with clinically localized PC. PATIENTS AND METHODS: A transrectal ultrasound-guided injection by 0.3 mL/100 MBq (99m)Tc-sulfur rhenium colloid in each prostatic lobe was performed the day before surgery. The detection was realized intraoperatively with a laparoscopic probe (Clerad(®) Gamma Sup) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by hematoxyline-phloxine-safran staining and followed by immunochemistry if SLN is free. RESULTS: Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases were included. The intraoperative detection rate was 68/70 (97%). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14%). The internal iliac region was the first metastatic site (40.9%). A metastatic sentinel node in common iliac region beyond the ureteral junction was present in 18.2%. A non-negligible sentinel metastatic region was the common iliac area (18.2%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59% of lymph node metastases. CONCLUSION: The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limited the risk of surgical extended dissection while maintaining the accuracy of the information.
