Magnetic resonance tomography

Multi-organ-on-chip approach in cancer research

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Preclinical mouse models of hepatocellular carcinoma: An overview and update.

Rutin (RUT) is considered one the most attractive flavonoids from a therapeutic perspective due to its multispectral pharmacological activities including antiradical, anti-inflammatory, antiproliferative, and antimetastatic among others. Still, this compound presents a low bioavailability what narrows its clinical applications. To overcome this inconvenience, the current paper was focused on the synthesis, characterization, and toxicological assessment of two RUT bioconjugates obtained by enzymatic esterification with oleic acid (OA) and linoleic acid (LA)—rutin oleate (RUT-O) and rutin linoleate (RUT-L), as flavonoid precursors with improved physicochemical and biological properties. Following the enzymatic synthesis in the presence of Novozyme® 435, the two bioconjugates were obtained, their formation being confirmed by RAMAN and FT-IR spectroscopy. The in vitro and in ovo toxicological assessment of RUT bioconjugates (1–100 µM) was performed using 2D consecrated cell lines (cardiomyoblasts - H9c2(2-1), hepatocytes—HepaRG, and keratinocytes—HaCaT), 3D reconstructed human epidermis tissue (EpiDerm™), and chick chorioallantoic membranes, respectively. The results obtained were test compound, concentration—and cell-type dependent, as follows: RUT-O reduced the viability of H9c2(2-1), HepaRG, and HaCaT cells at 100 µM (to 77.53%, 83.17%, and 78.32%, respectively), and induced cell rounding and floating, as well as apoptotic-like features in the nuclei of all cell lines, whereas RUT-L exerted no signs of cytotoxicity in all cell lines in terms of cell viability, morphology, and nuclear integrity. Both RUT esters impaired the migration of HepaRG cells (at 25 µM) and lack irritative potential (at 100 µM) in vitro (tissue viability >50%) and in ovo (irritation scores of 0.70 for RUT-O, and 0.49 for RUT-L, respectively). Computational predictions revealed an increased lipophilicity, and reduced solubility, drug-likeness and drug score of RUT-O and RUT-L compared to their parent compounds—RUT, OA, and LA. In conclusion, we report a favorable toxicological profile for RUT-L, while RUT-O is dosage-limited since at high concentrations were noticed cytotoxic effects.

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Rutin bioconjugates as potential nutraceutical prodrugs: An in vitro and in ovo toxicological screening

Organoids as research models for hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective.

\nThe number of surgical procedures for abdominal wall defects is increasing, often requiring the insertion of plastic material meshes. Surveillance of patients with inserted plastic meshes requires an accurate determination of the position of the mesh. However, this is a difficult task, depending on the kind of mesh, magnetic resonance imaging (MRI) protocol or consistence of the surrounding tissue (fat, muscle, aponeurosis). The aim of our research was to develop an experimental model to test the ability of MRI to identify the exact position of surgical plastic meshes: polypropylene or polyester. To simulate the placement of a mesh in human body we developed a model built up from two pieces of tissue with dimensions of 40 cm x 20 cm, harvested from a pig with a weight of 120 kg. The meshes were situated for MRI evaluation between the two pieces: abdominal pig muscle respectively suprajacent abdominal pig wall subcutaneous fat, approximately 2 cm high. Five surgical meshes were scanned through six MRI sequences, in view of establishing an optimal MRI scanning protocol and best visible meshes. The MRI scans were evaluated by 5 radiologists with different degrees of training. Our results showed that the experimental model developed by us can be successfully used to test the ability of MRI to visualize different kind of plastic meshes. Also, our experiment has revealed that T1fl2D sequence is the best in highlighting meshes from surrounding tissue, and the best visualized Mesh was number 4, made of polyester. In conclusion, based on our experimental model, we should select a plastic mesh or MRI protocol which will allow an optimal post implantation monitoring. Modern technology of material�s fabrication can help to better identify the mesh itself using MRI scanning.\n

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MRI Surveillance of Plastic Material Surgical Meshes: Experimental Model - Interim Results

Background and Objectives: Endometrial hyperplasia (EH) is a precursor lesion to endometrial cancer (EC), and when cellular atypia is present, in 40% of cases, they are diagnosed with EC on hysterectomy. Usually, EH is clinically manifested by uterine bleeding. In patients with oral anticoagulant therapy (OAT), the uterus is the second most common source of bleeding. The aim of the study was to show that uterine bleeding in postmenopausal patients undergoing OAT may reveal precancerous endometrial lesions with atypia, or neoplastic lesions in patients with an initial diagnosis of endometrial hyperplasia without atypia (non-atypical endometrial hyperplasia, NAEH) on dilation and curettage (D&C). We will be able to estimate the risk of a postmenopausal female patient with uterine bleeding during an OAT to have a precancerous endometrial lesion. Materials and Methods: The subjects of the study were 173 female patients with uterine bleeding, who have had total hysterectomy with bilateral salpingoovarectomy, of whom 99 underwent an OAT. There were 101 female patients initially diagnosed with NAEH, of which 60 did not have anticoagulant treatment (mean age 57.36 ± 6.51) and 41 had anticoagulant treatment (mean age 60.39 ± 7.35) (p = 0.006). From the pathology diagnosis moment, the surgery was performed at 42.09 ± 14.54 days in patients without OAT and after 35.39 ± 11.29 days in those who received such treatment (p = 0.724). Results: Initial diagnosis of NAEH established at D&C was changed at the final diagnosis after hysterectomy in EH with cellular atypia (atypical endometrial hyperplasia AEH) or EC in 18.18% of patients without OAT, and in 40.54% of patients who received this treatment. Conclusions: Based on a logistic regression model, it is estimated that female patients with an initial histopathological diagnosis of NAEH and who underwent OAT have, on average, 4.85 times greater odds (OR = 4.85, 95% CI 1.79–14.06) than the others of being identified postoperatively with more advanced lesions.

Risk of More Advanced Lesions at Hysterectomy after Initial Diagnosis of Non-Atypical Endometrial Hyperplasia in Patients with Postmenopausal Bleeding and Oral Anticoagulant Treatment.

Alexandru Blidisel

Papers

Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective.

MRI Surveillance of Plastic Material Surgical Meshes: Experimental Model - Interim Results

Risk of More Advanced Lesions at Hysterectomy after Initial Diagnosis of Non-Atypical Endometrial Hyperplasia in Patients with Postmenopausal Bleeding and Oral Anticoagulant Treatment.