Archivio istituzionale della ricerca - Università dell'Insubria
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Effetto di PRODH e ROS nella tumorigenesi e progressione del cancro del polmone
No full textIl cancro al polmone è la principale causa di morte per tumore in tutto il mondo. Per migliorare i risultati terapeutici è necessario comprendere più a fondo i meccanismi molecolari alla base della sua patogenesi. Questa tesi esplora il ruolo della prolina deidrogenasi (PRODH) nello sviluppo e nella progressione dell'adenocarcinoma polmonare (ADC).
La PRODH ossida la prolina, generando elettroni che favoriscono la produzione di ATP o di specie reattive dell'ossigeno (ROS), con potenziali effetti pro- o antitumorali.
Modulando l'espressione di PRODH in linee cellulari di ADC polmonare, abbiamo valutato le caratteristiche correlate alla tumorigenesi, tra cui la proliferazione in 2D e 3D, la produzione di ROS, l'apoptosi, la senescenza, la transizione epiteliale-mesenchimale (EMT), l'angiogenesi e il reclutamento dei monociti.
I nostri dati indicano che PRODH, tramite produzione di ROS, induce la senescenza cellulare, riducendo la proliferazione. Tuttavia, il fenotipo secretorio associato alla senescenza promuove il reclutamento dei monociti e l'angiogenesi. Sebbene PRODH non induca l'EMT, compromette l'adesione cellula-cellula e l'organizzazione del citoscheletro, facilitando potenzialmente la disseminazione cellulare e le metastasi. Pertanto, PRODH può svolgere diversi ruoli nella progressione del cancro ai polmoni: mentre inizialmente agisce come soppressore tumorale attraverso la senescenza indotta dai ROS, in seguito può contribuire allo sviluppo del tumore diminuendo l'adesione cellula-cellula e rimodellando il microambiente tumorale.
Questi risultati supportano il potenziale ruolo di PRODH come bersaglio terapeutico o marcatore diagnostico nel cancro ai polmoni.Lung cancer is the leading cause of cancer-related deaths worldwide. Improving patient outcomes requires a deeper understanding of the molecular mechanisms driving its pathogenesis. This thesis explores the role of proline dehydrogenase (PRODH) in lung adenocarcinoma (ADC) development and progression.
PRODH oxidises proline, generating electrons that support ATP or reactive oxygen species (ROS) production, with potential pro- or anti-tumourigenic effects.
By modulating PRODH expression in lung ADC cell lines, we assessed features related to tumourigenesis, including 2D and 3D proliferation, ROS production, apoptosis, senescence, epithelial-to-mesenchymal transition (EMT), angiogenesis, and monocyte recruitment.
Our data indicate that PRODH induces ROS-dependent senescence, reducing proliferation. However, the resulting Senescence-Associated Secretory Phenotype promotes monocyte recruitment and angiogenesis. Although PRODH does not induce EMT, it impairs cell-cell adhesion and cytoskeletal organisation, potentially facilitating cell dissemination and metastasis. Thus, PRODH may exert different roles in lung cancer progression: while initially acting as a tumour suppressor through ROS-induced senescence, it may later contribute to tumour development by decreasing cell-cell adhesion and remodelling the tumour microenvironment.
These findings support the potential of PRODH as a therapeutic target or diagnostic marker in lung cancer
Associazione tra particolato totale sospeso indoor e microbiota delle vie aeresse superiori in lavoratori d’ufficio
No full textEncouraged by the 2025 US Guidelines to Lower Systolic Blood Pressure Below 120 mm Hg. From Guidelines to Clinical Practice
No full textModifica della struttura dell’organo amministrativo nelle s.r.l. e revoca implicita dell’amministratore
No full textLa nota analizza criticamente il lodo arbitrale pubblicato, in cui si afferma che, nel passaggio da un
organo amministrativo monocratico a uno collegiale, si verifica la revoca implicita dell’amministratore unico
priva di giusta causa, con conseguente obbligo di risarcirlo. Tuttavia, il collegio arbitrale aggiunge che, se
l’amministratore ingiustamente revocato era stato nominato a tempo indeterminato, non ha diritto al
risarcimento del danno se la revoca è accompagnata da un congruo preavviso.
Dopo aver inquadrato le norme applicabili, la nota approfondisce se la modifica della struttura
dell’organo amministrativo possa costituire giusta causa di revoca, in particolare quando esso risulti
inadeguato ai sensi dell’art. 2086, comma 2°, c.c. In secondo luogo, si evidenziano i problemi legati
all’adozione di criteri soggettivi nella valutazione della congruità del preavviso.The paper critically analyzes the published arbitration award, which states that, in the transition from a
one-man governing body to a collegial one, there is an implied removal of the sole director without just cause,
resulting in an obligation to compensate him. However, the arbitrators add that if the unjustly removed director
had been appointed for an indefinite term, he is not entitled to damages if the removal is accompanied by
adequate notice.
After framing the applicable rules, the paper investigates whether the restructuring of the governing body
can constitute just cause for removal, particularly when it is inadequate within the meaning of Article 2086(2)
of the Italian Civil Code. Then, the problems associated with the adoption of subjective criteria in assessing the
adequacy of notice are highlighted
ARCADIA fully depleted CMOS MAPS development with LFoundry 110 nm CIS
No full textFully depleted CMOS sensors represent a significant step forward in radiation detection, combining the advantages of monolithic active pixel sensors with the enhanced signal collection efficiency of depleted bulk materials. The ARCADIA Collaboration established a technology platform for the development and production of deep sub-micron fully depleted CMOS monolithic sensors with excellent collection efficiency, advancing this semiconductor detector technology with IP cores, ASICs, and back-end dedicated acquisition systems. The sensor technology was demonstrated on system-ready full chip monolithic active pixel sensors with high rate capability and very low power for the detection of charged particles and photons. Innovative CMOS monolithic LGADs featuring a shallow gain layer and implementing a low-gain avalanche diode were developed for time-of-flight detectors, while other prototype ASICs have implemented multi-threshold photon-counting architectures for X-ray imaging. The implementation of fully depleted monolithic strip sensors with embedded electronics and low power density makes the proposed approach a good candidate for future detectors in space applications. The ARCADIA technology will find applications in medical instruments, nuclear imaging and dosimetry, frontier detectors for experimental high energy, and astroparticle physics. This review details the main development achievements by describing the technology demonstrators fabricated and tested and provides a detailed overview of the characteristics and architecture of the ARCADIA-MD3 full-chip monolithic active pixel sensor
Evidence for multi-rifting in the Variscan-Alpine cycle transition: insights from the European western Southern Alps
No full textWe investigate the transition between the Paleozoic Variscan cycle and the Mesozoic-Cenozoic Alpine supercontinent cycle, both of which have played a pivotal role in shaping the central European-Mediterranean plate architecture. Two main scenarios have been proposed so far for this transition: (i) a single, long-lasting, Permo-Triassic rifting event, culminating in the opening of the Alpine Tethys, or (ii) multiple, distinct rifting events, predating the onset of the Alpine cycle. Our study focuses on the European western Southern Alps (Varese area, N. Italy), where we document the tectonic events from the early Permian to the Middle Triassic. Through a combined tectono-stratigraphic and thermochronological analysis, we identify an initial early Permian rifting stage linked to magmatic activity, followed by early-middle Permian transcurrent tectonics. This phase is truncated by a middle Permian regional-scale erosional event that marks the cessation of this tectonic phase. Subsequently, during the Middle Triassic, a second phase initiated, which we interpret as the onset of the Alpine Tethys opening. This phase likely corresponds to an early stretching stage that predates the well-documented Late Triassic crustal-thinning phase. Based on our findings, we propose that the Middle Triassic stretching phase represents the first stage of the Alpine Tethys rifting, thereby challenging the hypothesis of a continuous Permo-Triassic long-lasting extension
Robust bi-objective mean-CVaR portfolio selection: Applications to energy sector
Get PDFA new approach to optimizing or hedging a portfolio of financial positions is presented and tested with applications to energy market. Motivated by uncertainty in the estimation of problem data we consider robust bi-objective optimization problems with mean and conditional value-at-risk objective functions where the underlying probability distribution of portfolio return is only known to belong to a certain set. To tackle the problem of uncertainty we consider two different approaches: in the first one, uncertainty is represented by an elliptic set centered at the sample estimators of mean and covariance matrix; in the second one, uncertainty takes into account experts beliefs. For both approaches, we derive analytical semi-closed-form solutions for the worst case mean-CVaR portfolio; in addition, we provide a characterization of the location of the robust Pareto frontier with respect to the corresponding original Pareto frontier
Innate Priming and Tumor-Associated Macrophage Reprogramming: A Commentary on Emerging Immunotherapeutic Strategies
Get PDFThe dynamic and multifaceted role of tumorassociated macrophages (TAMs) within the tumor microenvironment (TME) has garnered substantial attention in recent years, owing to their profound influence on tumor progression, immune modulation, and therapeutic response. In their review, “The Role of Innate Priming in Modifying Tumor-associated Macrophage Phenotype”,
Topham et al. delve into the complexities of TAM plasticity and the mechanisms driving their phenotypic polarization. TAMs, which originate from recruited monocytes or resident macrophages, are inherently shaped by the immunological, metabolic, and epigenetic landscapes of the TME. Depending on local cues, TAMs can adopt either pro-tumorigenic or anti-tumorigenic phenotypes, thus playing a pivotal role in determining the trajectory of cancer development and treatment outcomes
Minimally invasive surgical techniques (MISTs) for benign prostatic hyperplasia: results from a Delphi consensus project to shed light on controversial topics
No full textPurpose: To conduct a Delphi consensus in order to address key uncertainties and provide expert insights to bridge the gap between guidelines and real-world practice concerning minimally invasive surgical techniques (MISTs) for benign prostatic hyperplasia (BPH). Methods: The Advisory Board developed 343 statements on 35 debated topics in the surgical management of BPH, each including multiple items rated on a 9-point Likert scale. The questionnaire was emailed to a Panel of 28 Italian urologists with 5-year experience in MISTs for the first round of voting. Statements that did not reach consensus were identified as “hot topics” and underwent a second round of voting during a Consensus conference, attended by all first-round participants, where the results were reviewed, debated, and re-voted upon anonymously. Results: The Panel agreed in defining TPLA, Rezum, iTIND, PAE and Urolift as MISTs, but no consensus was reached regarding Aquablation. Essential characteristics for being defined as MISTs were considered the feasibility in outpatient and one-night stay settings, minimal bleeding risk, early postoperative recovery of daily activities and a reduced impact on urinary continence and ejaculatory function. The Panel agreed that, compared to TURP, PAE, TPLA, Rezum, iTIND and Urolift were associated with lower postoperative bleeding rates, lower operative and hospitalization time, lower risk of postoperative incontinence; non consensus on these topics was achieved for Aquablation. The Panel agreed that flow rates after PAE, TPLA, iTIND and Urolift were worse than TURP, however, no consensus was achieved for Rezum and Aquablation. A high risk of retreatment was recognized for TPLA, iTIND and Urolift, but this was not the case for Rezum and Aquablation. iTIND and Urolift were deemed as the best options for prostate volume 30 ml, TPLA, Rezum and Aquablation for prostate volume 30–80 ml while no consensus was obtained for the best approach in larger volumes. No consensus was achieved for various aspects of postoperative management of MISTs. Conclusions: Results from this Delphi project confirmed the lack of agreement on certain topics related to MISTs for BPH including the ideal treatment for large prostate volumes, functional outcomes and postoperative management