Explore the vast range of titles available.

The ten chapters of this volume exploit the potentials of stem cells biology in translational medicine in a very clear way also thanks to nice color illustrations together with tricks and suggestions useful to get reproducible results...

Clathrin is one of the interesting “moonlighting proteins” which perform multiple functions relevant to biochemical or biophysical aspects. It can be considered the master regulator of vesicular trafficking being the main player of the Clathrin-Mediated Endocytosis (CME)...

The statement \"Plastics define the way we live today\" summarizes the findings of the Plastic Europe 2020 final document (https://plasticseurope.org/knowledge-hub/plastics-the-facts-2020/). Sadly, this also means that the plastic waste generated over the next decade is likely to become unmanageable. By 2050, plastic usage is expected to triple, resulting in a similar increase in plastic waste, with approximately half of it ending up in landfills. Emerging research indicates that micro and nanoplastics have been found in various human organs, including the gonads, placenta, blood, arteries, lungs, liver, kidney, and even the brain. This raises significant questions about their pervasive presence within our bodies and their potential threat to health. In addition to their harmful effects, these \"forever particles\" (micro/nanoplastics) can serve as Trojan horses, transporting additional pollutants such as bacteria and heavy metals into our bodies. In this review, we explore key aspects of the plastics crisis and urge the scientific community -especially those in the fields of cytochemistry and histochemistry, which adeptly connect morphology with function- to investigate the harmful effects of micro and nanoplastics that we encounter daily through ingestion or inhalation. This research should focus on various physiological levels, including DNA, cells, and tissues.

PurposeFDG-positive neuroendocrine tumors (NETs) have a poorer prognosis and exhibit shorter response duration to peptide receptor radionuclide therapy (PRRT). The aim of this prospective phase II study was to evaluate the efficacy and toxicity of PRRT with 177Lu-DOTATATE associated with metronomic capecitabine as a radiosensitizer agent in patients with advanced progressive FDG-positive gastro-entero-pancreatic (GEP) NETs.Patients and methodsPatients with advanced somatostatin receptor- and FDG-positive G1-G3 GEP-NETs (Ki67 < 55%) were treated with a cumulative activity of 27.5 GBq of 177Lu-DOTATATE divided in five cycles of 5.5 GBq each every 8 weeks. Capecitabine (1000–1500 mg daily) was administered orally in the inter-cycle period between 177Lu-DOTATATE treatments. Prior to commencing capecitabine, all patients were triaged with the dihydropyrimidine dehydrogenase (DPD) test. Only DPD-proficient individuals were enrolled. The primary objectives were disease control rate (DCR) and safety. Secondary aims included progression-free (PFS) and overall survival (OS). Treatment response was assessed per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). Toxicity was assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.ResultsFrom August 2015 to December 2016, 37 subjects were consecutively enrolled. A total of 25 (68%) were affected by pancreatic neuroendocrine tumors (P-NETs), and 12 (32%) had gastrointestinal neuroendocrine tumors (GI-NETs). By grading (WHO 2010 classification), 12 patients (32%) had G1 (Ki67 ≤ 2%), 22 (59%) had G2 (3% < Ki67 ≤ 20%), and 3 patients (9%) had G3 (Ki67 > 20%) NETs. Grade 3 (G3) or 4 (G4) hematological toxicity occurred in 16.2% of patients. Other G3-G4 adverse events were diarrhea in 5.4% of cases and asthenia in 5.4%. No renal toxicity was observed for the duration of follow-up. In 37 patients, 33 were evaluable for response. Objective responses included partial response (PR) in 10 patients (30%) and stable disease (SD) in 18 patients (55%), with a DCR of 85%. The median follow-up was 38 months (range 4.6–51.1 months). The median PFS was 31.4 months (17.6–45.4), and mOS was not reached.ConclusionsThis study demonstrated that the combination of PRRT with 177Lu-DOTATATE and metronomic capecitabine is active and well tolerated in patients with aggressive FDG-positive G1-G3 GEP-NETs. These data constitute the basis for a randomized study of PPRT alone vs. PRRT plus metronomic capecitabine.

PurposeRadioligand therapy (RLT) with 177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate cancer (mCRPC). The present study was designed to define the safety and initial response to a minimal effective injected activity/cycle of 177Lu-PSMA-617 in mCRPC patients. New protective agents for salivary glands and kidney were co-administered and dosimetry was carried out.Patients and methodsA prospective single-arm, open label phase II study on mCRPC was activated at our institute in April 2017. Patients with histologically confirmed advanced mCRPC previously treated with standard life-prolonging agents were enrolled. Folic polyglutamate tablets were orally administered as parotid gland protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake before the injection of 3.7–5.5 GBq of 177Lu-PSMA-617 repeated four times at interval of 8 weeks. The adsorbed dose calculation was performed with MIRD formalism (OLINDA/EXM software). The Bryant and Day design was used to estimate the sample size taking account of both activity and toxicity.ResultsForty-three eligible patients were evaluated for toxicity and initial response. Dosimetry was carried out in 13 patients. Two (4.8%) patients had G3 and 8 (19.5%) had G2 hematological toxicity. Only 3 (6.9%) patients had mild G1 salivary gland toxicity and 8 (19.5%) had G1 renal toxicity. A decrease of ≥ 30% in prostate-specific antigen (PSA) was achieved after the first cycle in 17 (40.5%) patients, of whom 13 had a PSA decline of >50% after the second cycle. The median adsorbed doses were 0.65 mGy/MBq (range 0.33–2.63) for parotid glands, 0.42 mGy/MBq (0.14–0.81) for kidneys, 0.036 mGy/MBq (0.023–0.067) for red marrow, and 0.038 mGy/MBq (0.018–0.135) for the whole body.ConclusionIn advanced, heavily pre-treated mCRPC patients, 3.7 GBq/cycle of 177Lu-PSMA-617 was safe and produced early biochemical and imaging responses at PSMA whole-body scan post injection. Dosimetry of salivary glands suggests that the co-administration of polyglutamate tablets may reduce salivary gland uptake.Clinical trial registrationEU Clinical Trials Register No.: 2016-002732-32; NCT03454750. Collection and assembly of data: April 2017 and February 2019.

Background/Objectives: This report examines the future of academic studies involving investigational therapeutic radiopharmaceuticals within the framework of Regulation (EU) No. 536/2014. It discusses the impact of Good Manufacturing Practice (GMP) requirements (EudraLex-Volume 4-Good Manufacturing Practice guidelines) on the development of radiopharmaceuticals, based on local experience and analysis. Methods: The report was drafted by analysing multiple factors, including the European regulatory context regarding EMA guidance for investigational medicinal products (IMPs) and GMP requirements for radiopharmaceuticals, as well as position papers from various scientific associations. An analysis of all the relevant changes was conducted by a multidisciplinary team comprising radiopharmacists, nuclear medicine physicians, research experts and technology transfer specialists. They conducted a literature review to examine the clinical implications of the regulatory change and assess the impact of Regulation 536/2014 on academic clinical trials. Results: IRST has around 20 years’ experience in radiopharmaceutical clinical research. From 2008 to 2025, it conducted 16 clinical trials with radiopharmaceuticals under the Directive, and it is currently promoting five studies under the Regulation. During this time, more than 1000 patients were enrolled. The transition was based on staff training in quality documentation, the constitution of a contract research organisation (CRO) to ensure data quality and transfer, careful budget planning, the evaluation of innovative business models and the role of a Contract Development and Manufacturing Organization (CDMO). These integrated approaches enabled IRST to transform regulatory constraints into an opportunity to enhance its organisational model, improve data reliability, and strengthen its position as a centre of excellence for radiopharmaceutical research and production. Conclusions: The implementation of EU Regulation 536/2014 has significantly impacted academic research centres, especially those specialising in radiopharmaceuticals. Adhering to Good Manufacturing Practice (GMP) for therapeutic radiopharmaceuticals requires a considerable investment in infrastructure and personnel. However, the regulation also presents opportunities for research centres to enhance their capabilities. Meeting GMP standards can help institutions improve the quality and reliability of their clinical trials, potentially making them more competitive in the international research arena.

Background/Objectives: Fibroblast activation protein (FAP) is highly expressed in tumor stroma and selected inflammatory conditions, offering a promising target for molecular imaging. [68Ga]Ga-FAPI-46 is a DOTA-based FAP inhibitor with excellent tumor-to-background ratio and potential advantages over [18F]FDG in low-glycolytic tumors. This article aims to highlight the quality elements that are relevant to clinical practice and to describe the development of an investigational medicinal product dossier for a bicentric clinical trial involving [68Ga]Ga-FAPI-46. Methods: The radiolabeling was performed by the two facilities using different automated synthesizers, but with the same specifications and acceptance criteria Results: Three validation batches per site were analyzed for radiochemical/radionuclidic purity, pH, endotoxin, sterility, and bioburden according to European Pharmacopoeia standards. Stability was as sessed up to 2 h post-synthesis. All batches met predefined acceptance criteria. Conclusions: Despite differences in radiosynthesizer modules, product quality and process reproducibility were maintained across both centers. [68Ga]Ga-FAPI-46 can be reliably produced in academic settings under GMP-like conditions, enabling multicenter clinical research and facilitating IMPD submissions for broader adoption of FAP-targeted PET imaging.

Prof. Turksen is a very well known scientist in the stem cell biology field and he is also internationally known for his fundamental studies on claudin-6. In addition to his research activity he is editor for the Stem Cell Biology and Regenerative Medicine series (Humana Press) and editor-in-chief of Stem Cell Reviews and Reports...

This is the time of the precision medicine, as President Barak Obama addressed the Nation on January 20, 2015 in a State of the Union Address: Tonight, I'm launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes — and to give all of us access to the personalized information we need to keep ourselves and our families healthier (Francis S. Collins and Harold Varmus, A New Initiative on Precision Medicine; N Engl J Med 2015;372:793-795). This new field already show several actors, not only the NIH but also private company like APPLE, MICROSOFT and others, investing a lot of many: all together already several billions, dollars or euro doesn’t matter, a fact that testify how hot is becoming this new biomedical perspective...

One of the most exciting advances in life science research is the development of 3D cell culture systems to obtain complex structures called organoids and spheroids. These 3D cultures closely mimic in vivo conditions, where cells can grow and interact with their surroundings. This allows us to better study the spatio-temporal dynamics of organogenesis and organ function. Furthermore, physiologically relevant organoids cultures can be used for basic research, medical research, and drug discovery. Although most of the research thus far focuses on the development of heart, liver, kidney, and brain organoids, to name a few, most recently, these structures were obtained using dental stem cells to study in vitro tooth regeneration. This review aims to present the most up-to-date research showing how dental stem cells can be grown on specific biomaterials to induce their differentiation in 3D. The possibility of combining engineering and biology principles to replicate and/or increase tissue function has been an emerging and exciting field in medicine. The use of this methodology in dentistry has already yielded many interesting results paving the way for the improvement of dental care and successful therapies.