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1.
Marco N. Iannone Stefano Stucchi Elia A. Turolla Chiara Beretta Samuele Ciceri Clizia Chinello Lisa Pagani Sergio Todde Patrizia Ferraboschi 《Journal of labelled compounds & radiopharmaceuticals》2022,65(3):48-62
In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies. 相似文献
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Klaus Schneider Marco Dilger Claudia Drossard Heidi Ott Eva Kaiser 《Journal of applied toxicology : JAT》2022,42(5):913-926
Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals. 相似文献
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Theresa M. Thole Joern Toedling Annika Sprüssel Sebastian Pfeil Larissa Savelyeva David Capper Clemens Messerschmidt Dieter Beule Stefanie Groeneveld-Krentz Cornelia Eckert Guido Gambara Anton G. Henssen Sabine Finkler Johannes H. Schulte Anja Sieber Nils Bluethgen Christian R. A. Regenbrecht Annette Künkele Marco Lodrini Angelika Eggert Hedwig E. Deubzer 《International journal of cancer. Journal international du cancer》2020,146(4):1031-1041
Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system. 相似文献
6.
Susanna Zanutto Chiara Maura Ciniselli Antonino Belfiore Mara Lecchi Enzo Masci Gabriele Delconte Massimo Primignani Giulia Tosetti Marco Dal Fante Linda Fazzini Aldo Airoldi Marcello Vangeli Francesca Turpini Giovanni Giuseppe Rubis Passoni Paolo Viaggi Monica Arena Roberta Ilaria Olimpia Motta Anna Maria Cantù Cristiano Crosta Giuseppe De Roberto Francesca Iannuzzi Andrea Cassinotti Valentina Dall'Olio Laura Tizzoni Gabriella Sozzi Emanuele Meroni Luigi Bisanti Marco Alessandro Pierotti Paolo Verderio Manuela Gariboldi 《International journal of cancer. Journal international du cancer》2020,146(4):1164-1173
Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most. 相似文献
7.
Marco Bandini Sebastiano Nazzani Michele Marchioni Felix Preisser Zhe Tian Marco Moschini Firas Abdollah Nazareno Suardi Markus Graefen Francesco Montorsi Shahrokh F. Shariat Fred Saad Alberto Briganti Pierre I. Karakiewicz 《Clinical genitourinary cancer》2019,17(1):72-78.e4
Background
The rate of noninterventional treatment (NIT) in prostate cancer (PCa) active surveillance (AS) candidates is on the rise. However, contemporary data are unavailable. We described community-based NIT rates within 16 Surveillance Epidemiology and End Results (SEER) registries between 2010 and 2014.Patients and Methods
We identified 23,360 PCa patients who fulfilled the University of California San Francisco AS criteria (prostate-specific antigen [PSA] < 10 ng/mL, clinical T stage ≤ T2a, Gleason score ≤ 6, and positive cores < 33%). Annual NIT rates as well as patient distribution according to PSA, age, number of positive cores, and clinical T stage were studied. Multivariable logistic regression analysis tested NIT predictors.Results
Between 2010 and 2014, the NIT rate increased from 30.2% to 57.5% (P = .004). Within 16 SEER registries, NIT rates ranged from 25.9% to 62%. NIT rate increased uniformly within all examined registries. Of patient and tumor characteristics (PSA > 4 ng/mL, cT2a and > 1 positive core) only the proportion of NIT patients aged < 65 years increased over time from 47.3% to 53.2% (P = .03). By multivariable logistic regression analysis predicting NIT rate, older age (odd ratio [OR] = 1.05), more contemporary year of diagnosis (OR = 1.41), and being unmarried (OR = 1.45) and uninsured (OR = 2.41) were independent predictors.Conclusion
The NIT rate has markedly increased across all examined SEER registries. Nonetheless, important differences distinguish those who received high-end NIT from low-end NIT. PCa characteristics of NIT patients remained unchanged over time. However, in addition to geographical differences in NIT rates, patient characteristics such as age, marital status, and insurance status represent potential NIT access barriers. 相似文献8.
Fabian Falkenstein Marco Gessi Daniela Kandels Ho-Keung Ng René Schmidt Monika Warmuth-Metz Brigitte Bison Juergen Krauss Rolf-Dieter Kortmann Beate Timmermann Ulrich-Wilhelm Thomale Michael H. Albert Arnulf Pekrun Eberhard Maaß Astrid K. Gnekow Torsten Pietsch 《International journal of cancer. Journal international du cancer》2020,147(8):2159-2175
Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment. 相似文献
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10.
Marco Maruzzo Umberto Basso Eugenio Borsatti Laura Evangelista Filippo Alongi Orazio Caffo Francesca Maines Sara Galuppo Rocco De Vivo Fable Zustovich Dario Palleschi Andrea Zivi Teodoro Sava Mariella Sorarù Roberto Iacovelli Maurizio Nicodemo Susanne Baier Lucia Fratino Vittorina Zagonel 《Clinical genitourinary cancer》2019,17(1):e187-e194