Search

Advanced cell therapy medicinal products (ATMP) are at the forefront of a new range of biopharmaceuticals. The use of ATMP has evolved and increased in the last decades, representing a new approach to treating diseases that are not effectively managed with conventional treatments. The standard worldwide recognized for drug production is the Good Manufacturing Practices (GMP), widely used in the pharma production of synthesized drugs but applying also to ATMP. GMP guidelines are worldwide recognized standards to manufacture medicinal products to guarantee high quality, safety, and efficacy. In this report, we describe the pre-clinical and the GMP upgrade of peripheral blood mononuclear cell (PBMC) preparation, starting from peripheral blood and ending up with a GMP-grade clinical product ready to be used in patients with critical limb ischemia (CLI). We also evaluated production in hypoxic conditions to increase PBMC functional activity and angiogenic potential. Furthermore, we extensively analyzed the storage and transport conditions of the final product as required by the regulatory body for ATMPs. Altogether, results suggest that the whole manufacturing process can be performed for clinical application. Peripheral blood collected by a physician should be transported at room temperature, and PBMCs should be isolated in a clean room within 8 h of venipuncture. Frozen cells can be stored in nitrogen vapors and thawed for up to 12 months. PBMCs resuspended in 5% human albumin solution should be stored and transported at 4 °C before injection in patients within 24 h to thawing. Hypoxic conditioning of PBMCs should be implemented for clinical application, as it showed a significant enhancement of PBMC functional activity, in particular with increased adhesion, migration, and oxidative stress resistance. We demonstrated the feasibility and the quality of a GMP-enriched suspension of monocytes as an ATMP, tested in a clean room facility for all aspects related to production in respect of all the GMP criteria that allow its use as an ATMP. We think that these results could ease the way to the clinical application of ATMPs.

Trattamento precoce domiciliare covid-19. Make an offer inNFT (Non-Fungible Token): https://opensea.io/assets/matic/0x2953399124f0cbb46d2cbacd8a89cf0599974963/35464008959780386460867213261413604412693850614154561847474562047209755377665

Proposal for an integrated pharmacological and biological therapyto accelerate the recovery and to prevent the hospitalisation of patients infected with Sars-Cov-2 Make an offer inNFT (Non-Fungible Token): https://opensea.io/assets/matic/0x2953399124f0cbb46d2cbacd8a89cf0599974963/35464008959780386460867213261413604412693850614154561847474562047209755377665

Background Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specific antigen (PSA) serum test, even if it showed clear limits. Among the new tests currently under study, one of the most promising is the prostate cancer gene 3 (PCA3), a non-coding mRNA whose level increases up to 100 times in PCa tissues when compared to normal tissues. With the present study we contribute to the validation of the clinical utility of the PCA3 test and to the evaluation of its prognostic potential. Methods 407 Italian men, with two or more PCa risk factors and at least a previous negative biopsy, entering the Urology Unit of Regina Elena National Cancer Institute, were tested for PCA3, total PSA (tPSA) and free PSA (fPSA and f/tPSA) tests. Out of the 407 men enrolled, 195 were positive for PCa and 114 of them received an accurate staging with evaluation of the Gleason score (Gs). Then, the PCA3 score was correlated to biopsy outcome, and the diagnostic and prognostic utility were evaluated. Results Out of the 407 biopsies performed after the PCA3 test, 195 (48%) resulted positive for PCa; the PCA3 score was significantly higher in this population (p

A randomized adjuvant trial compared tamoxifen 20 mg daily for 5 years with high-dose oral medroxyprogesterone acetate (MPA) 1 g orally for 9 months. One hundred ninety-four patients with histologically proven primary node-negative breast carcinoma were enrolled between December 1990 and October 1996, with 98 patients randomized into the tamoxifen arm and 96 into the MPA arm. At a median follow-up of 86 months, 25 relapses and 13 deaths were recorded. The relapse-free survival rate at 7 years in the tamoxifen arm was 93%, versus 81% in the MPA arm (P = 0.02). The difference was observed in patients with stage T2 disease (100% in the tamoxifen group vs. 64% in the MPA group; P = 0.01), in younger and/or premenopausal patients (in patients50 years of age, 100% in the tamoxifen arm vs. 81% in the MPA arm [P = 0.02], and in patientsor = 50 years of age, 90% in the tamoxifen arm vs. 82% in the MPA arm [P = 0.16]). Also, the overall survival rate at 7 years was lower in women50 years of age (P = 0.04).

The functional results and complications of 2 different ureteroileal anastomoses were evaluated in patients with bladder cancer undergoing radical cystectomy and orthotopic ileal bladder substitution.Between 1989 and 1995, 102 patients underwent creation of a low pressure neobladder. In the first 50 cases the ureteroileal anastomosis was created with a split-cuff nipple technique as an additional antireflux mechanism. In the next 52 cases the ureteroileal anastomoses were constructed via the direct end-to-side technique counting on the antireflux protection of the afferent tubular limb.Stenosis occurred in 7 of the 100 ureters (6 patients) treated with the split-cuff nipple technique and 7 of 104 treated with a direct end-to-side anastomosis. This complication occurred more commonly in the left ureter (11 of 14 patients). Reflux was noted at cystography in 10 cases with the split-cuff nipple method and 12 with end-to-side anastomoses, and was symptomatic in only 3 patients. Four ureteral strictures were treated successfully with primary open repair. Percutaneous dilation and stenting were performed for 8 ureteral strictures: 2 cases were successful, 3 failed and 3 are unresolved.We observed no differences between the antireflux split-cuff and end-to-side anastomoses with regard to stricture formation or ureteral reflux. Therefore, we do not believe that there is a need to create antireflux ureteral anastomoses due to the tubular afferent ileal segment and given that the reflux is asymptomatic in most patients. Strictures may be treated with percutaneous balloon dilation and stenting but open repair appeared to be more effective.