New Diterpenes with Potential Antitumoral Activity Isolated from Plants in the Years 2017-2022

Diterpenes represent a wider class of isoprenoids, with more than 18,000 isolated compounds, and are present in plants, fungi, bacteria, and animals in both terrestrial and marine environments. Here, we report on the fully characterised structures of 251 new diterpenes, isolated from higher plants and published from 2017, which are shown to have antitumoral activity. An overview on the most active compounds, showing IC50 < 20 mu M, is provided for diterpenes of different classes. The most active compounds were extracted from 29 different plant families; particularly, Euphorbiaceae (69 compounds) and Lamiaceae (54 compounds) were the richest sources of active compounds. A better activity than the positive control was obtained with 33 compounds against the A549 cell line, 28 compounds against the MCF-7 cell line, 9 compounds against the HepG2 cell line, 8 compounds against the Hep3B cell line, 19 compounds against the SMMC-7721 cell line, 9 compounds against the HL-60 cell line, 24 compounds against the SW480 cell line, and 19 compounds against HeLa

Organic chemistry laboratories during the pandemic at the University of Trieste

Patrizia Nitti, Paolo Pengo, "Laboratori di chimica organica durante la pandemia all’Università di Trieste/Organic chemistry laboratories during the pandemic at the University of Trieste", in: QuaderniCIRD, 26 (2023), EUT Edizioni Università di Trieste, Trieste, 2023, pp.Sunday, 23rd February, 2020. I was at Manchester airport (UK) travelling back to Trieste after a short visit to my daughter, who lives in Sheffield (UK). I had just passed the security checks when I received a message from one of my colleagues, saying: «I don’t think that tomorrow you will have exams, the Rector has suspended all teaching activities because of the Coronavirus...». It was the beginning of an outbreak of global proportions. We explain here how the courses of “Laboratory of Organic Chemistry II” and “Laboratory of Organic Chemistry III” of the bachelor’s degree in Chemistry at the Department of Chemical and Pharmaceutical Sciences of the University of Trieste were designed and carried out between April and May 2020, during the pandemic and the lockdown, and how they were evaluated by the students.Domenica 23 febbraio 2020 ero all’aeroporto di Manchester (Regno Unito) in viaggio di ritorno a Trieste dopo una breve visita a mia figlia, che vive a Sheffield (Regno Unito). Avevo appena superato i controlli di sicurezza quando ho ricevuto un messaggio da un mio collega che diceva: «Non credo che domani avrete gli esami, il Rettore ha sospeso tutte le attività didattiche a causa del Coronavirus...». Fu l’inizio di un’epidemia di proporzioni globali. In questo contributo si illustra come sono stati progettati e svolti tra aprile e maggio 2020 i corsi di “Laboratorio di Chimica Organica II” e “Laboratorio di Chimica Organica III” della Laurea triennale in Chimica presso il Dipartimento di Scienze Chimiche e Farmaceutiche dell’Università degli Studi di Trieste durante la pandemia e il lockdown e come sono stati successivamente valutati dagli studenti che li hanno frequentati

Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma

Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are stil unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (score less than or equal to1) was associated to lower MIB-1 labelling index, compared to cases with SCCA score greater than or equal to2 (mean +/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, P<0.05). Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18 liver tumours but in none of the corresponding nontumour samples. From sequence alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours

Clinical utility of plasma KRAS, NRAS and BRAF mutational analysis with real time PCR in metastatic colorectal cancer patients -The importance of tissue/plasma discordant cases

Background: Tumor tissue (T) mutational analysis represents the standard for metastatic colorectal cancer (mCRC); however, circulating tumor DNA (ctDNA) detected by liquid biopsy in plasma (PL) can better represent tumor heterogeneity. Methods: mCRC patients undergoing standard first-line chemotherapy with known T-KRAS/NRAS/BRAF status were enrolled in the present prospective study. PL mutations were assessed within 2 weeks before chemotherapy start with real time PCR and correlated with T status and Progression free survival (PFS). Clinical and biochemical variables including also total number of tumor lesions (TNL) and the sum of maximum diameter (SMD) of all lesions were assessed as potential predictors of T/PL discordance. RESULTS: Among 45 enrolled patients, all BRAF mutations were concordant between T and PL and there were 20% of patients RAS discordant: 9% wild type in T and mutated in PL and 11% mutated in T and wild type in PL. T mutations were significantly associated to median PFS (mPFS of 4.5, 8.3 and 22.9 months for T-BRAF mutated, T-RAS mutated, and T-wild type patients, respectively, p for trend 0.00014). PL mutations further refined prognosis: RAS wild type in T and mutated in PL had significantly shorter PFS than concordant RAS wild type in T and PL: mPFS 9.6 vs. 23.3 months, respectively, p = 0.02. Patients RAS mutated in T and wild type in PL had longer PFS than concordant RAS mutated in T and PL: 24.4 vs. 7.8 months, respectively, p = 0.008. At a multivariate cox regression analysis for PFS, PL mutations were independent prognostic factor superior to T analysis (HR 0.13, p = 0.0008). At multivariate logistic regression analysis TNL and SMD were significant predictors of discordant cases. Conclusions: PL mutational analysis allows a better prognostication than T analysis alone and could help in mCRC treatment management

QuaderniCIRD n. 26 (2023)

Vedere: https://www.openstarts.units.it/handle/10077/3544

Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control

The coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented burden on healthcare systems around the world and a severe global socioeconomic crisis, with more than 750 million confirmed cases and at least 7 million deaths reported by 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov NCT04335201), a phase II, single-arm, multicenter, open-label trial was designed in mid-2020 to assess the safety and efficacy of defibrotide in treating patients with COVID-19 pneumonia. Defibrotide was administered at a dose of 25 mg/kg/d intravenously, divided into four daily doses over a planned 14-day period for patients with COVID-19 pneumonia receiving non-invasive ventilation. The primary endpoint was Respiratory Failure Free Survival (RFFS); Overall Survival (OS), the number of post-recovery days, and adverse events were the secondary endpoints. For comparison, a contemporaneous control cohort receiving standard of care only was retrospectively selected by applying the eligibility criteria of the DEFI-VID19 trial. To adjust for the imbalance between the two cohorts in terms of baseline variable distributions, an outcome regression analysis was conducted. In adjusted analysis, patients receiving defibrotide reported a trend towards higher RFFS (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .0037]). Despite concomitant thromboprophylaxis with low molecular weight heparin, the safety profile of defibrotide proved to be favorable. Taken together, our findings suggest that defibrotide may represent a valuable addition to the COVID-19 therapeutic options

Anti-HIV-1 Response Elicited in Rabbits by Anti-Idiotype Monoclonal Antibodies Mimicking the CD4-Binding Site

Antibodies against conserved epitopes on HIV-1 envelope glycoproteins (Env), such as the gp120 CD4-binding site (CD4bs), could contribute to protection against HIV-1. Env-based immunogens inducing such a response could be a major component of future anti-HIV-1 strategies. In this proof-of-concept study we describe the generation of two anti-idiotype (AI) murine antibodies mimicking the CD4bs epitope. Sera were collected from long-term non-progressor patients to obtain CD4bs-directed IgG, through sequential purification steps. The purified IgG were then used as Fab fragments to immunize mice for hybridoma generation. Two hybridomas (P1 and P2), reacting only against the CD4bs-directed IgG, were identified and characterized. The P1 and P2 antibodies were shown to recognize the idiotype of the broadly neutralizing anti-CD4bs human mAb b12. Both P1 and P2 Fabs were able to induce a strong anti-gp120 response in rabbits. Moreover, the rabbits' sera were shown to neutralize two sensitive tier 1 strains of HIV-1 in an Env-pseudotype neutralization assay. In particular, 3/5 rabbits in the P1 group and 1/5 in the P2 group showed greater than 80% neutralizing activity against the HXB2 pseudovirus. Two rabbits also neutralized the pseudovirus HIV-MN. Overall, these data describe the first anti-idiotypic vaccine approach performed to generate antibodies to the CD4bs of the HIV-1 gp120. Although future studies will be necessary to improve strength and breadth of the elicited neutralizing response, this proof-of-concept study documents that immunogens designed on the idiotype of broadly neutralizing Abs are feasible and could help in the design of future anti-HIV strategies

L’ambito chimico. Il PAS A012 - Chimica agraria; il PAS A013 - Chimica e Tecnologie chimiche; il PAS C240 - Laboratorio di Chimica e Chimica industriale e il PAS C350 - Laboratorio di Tecnica microbiologica

Dopo una breve cronologia degli eventi che portarono all’attivazione dei PAS di ambito chimico (A012, A013, C240 e C350) viene illustrata l’offerta formativa dei quattro percorsi, la tipologia dei corsisti iscritti e le difficoltà organizzative causate dalla contemporanea attivazione dei TFA A012 e A013. Infine vengono riportati i risultati ottenuti dai corsisti all’esame di abilitazione.After a brief overview of events leading to the implementation of PAS in chemistry (A012, A013, C240, C350), this paper summarizes the training available for these curricula, the profile of the students enrolled, and the organizational problems resulting from the simultaneous running of the TFA A012 and A013.Finally, the students‘ habilitation results will be illustrated