Animal models: A useful tool to unveil metabolic changes in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one the most frequent and lethal human cancers. At present, no effective treatment for advanced HCC exist; therefore, the overall prognosis for HCC patients remains dismal. In recent years, a better knowledge of the signaling pathways involved in the regulation of HCC development and progression, has led to the identification of novel potential targets for therapeutic strategies. However, the obtained benefits from current therapeutic options are disappointing. Altered cancer metabolism has become a topic of renewed interest in the last decades, and it has been included among the core hallmarks of cancer. In the light of growing evidence for metabolic reprogramming in cancer, a wide number of experimental animal models have been exploited to study metabolic changes characterizing HCC development and progression and to further expand our knowledge of this tumor. In the present review, we discuss several rodent models of hepatocarcinogenesis, that contributed to elucidate the metabolic profile of HCC and the implications of these changes in modulating the aggressiveness of neoplastic cells. We also highlight the apparently contrasting results stemming from different animal models. Finally, we analyze whether these observations could be exploited to improve current therapeutic strategies for HCC

Reply to: "YAP in tumorigenesis: Friend or foe?"

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The Current Quality of Web-Based Information on the Treatment of Bipolar Disorder: A Systematic Search

Background: An important aspect of managing chronic disorders like bipolar disorder is to have access to relevant health information. This study investigates and compares the quality of information on the treatments of bipolar disorder that is available on English websites, as an international language, and on Italian websites, as a popular local language. Methods: A systematic review search was obtained from four search engines. We excluded unrelated materials, scientific papers, and duplicates. We analyzed popularity with PageRank; technological quality with Nibbler; readability with the Flesh Reading Ease test and Gulpease index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and on the extent of adherence to the HONCode. Results: 35 English and 31 Italian websites were included. The English websites were found to have a higher level of quality information and technological quality than the Italian ones. Overall, the websites were found to be difficult to read, requiring a high level of education. Conclusions: These results can be important to inform guidelines for the improvement of health information and help users to reach a higher level of evidence on the websites. Users should find the benefits of treatment, support for shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing treatment

Quality of information of websites dedicated to obesity: a systematic search to promote high level of information for Internet users and professionals

Background: The Internet is increasingly used as a source of information. This study investigates with a multidimensional methodology the quality of information of websites dedicated to obesity treatment and weight-loss interventions. We compared websites in English, a language that it is used for the international scientific divulgation, and in Italian, a popular local language. Methods: Level of Evidence: Level I, systematic review search on four largely used search engines. Duplicated and unrelated websites were excluded. We checked: popularity with PageRank; technological quality with Nibbler; readability with the Flesch Reading Ease test or the Gulpease readability index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and the adherence to the Health on the Net Code. Results: 63 Italian websites and 41 English websites were evaluated. English websites invested more in the technological quality especially for the marketing, experience of the user, and mobile accessibility. Both the Italian and English websites were of poor quality and readability. Conclusions: These results can inform guidelines for the improvement of health information and help Internet users to achieve a higher level of information. Users must find benefits of treatment, support to the shared decision-making, the sources used, the medical editor's supervision, and the risk of postponing the treatment

Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis

Although the expression of the stem/progenitor cell marker cytokeratin-19 (CK-19) has been associated with the worst clinical prognosis among all HCC subclasses, it is yet unknown whether its presence in HCC is the result of clonal expansion of hepatic progenitor cells (HPCs) or of de-differentiation of mature hepatocytes towards a progenitor-like cell phenotype. We addressed this question by using two rat models of hepatocarcinogenesis: the Resistant-Hepatocyte (R-H) and the Choline-methionine deficient (CMD) models. Our data indicate that the expression of CK-19 is not the result of a clonal expansion of HPCs (oval cells in rodents), but rather of a further step of preneoplastic hepatocytes towards a less differentiated phenotype and a more aggressive behavior. Indeed, although HCCs were positive for CK-19, very early preneoplastic foci (EPFs) were completely negative for this marker. While a few weeks later the vast majority of preneoplastic nodules remained CK-19 negative, a minority became positive, suggesting that CK-19 expression is the result of de-differentiation of a subset of EPFs, rather than a marker of stem/progenitor cells. Moreover, the gene expression profile of CK-19-negative EPFs clustered together with CK-19-positive nodules, but was clearly distinct from CK-19 negative nodules and oval cells. Conclusion: i) CK-19-positive cells are not involved in the early clonal expansion observed in rat hepatocarcinogenesis; ii) CK-19 expression arises in preneoplastic hepatocyte lesions undergoing malignant transformation; iii) CK-19 positivity in HCCs does not necessarily reflect the cell of origin of the tumor, but rather the plasticity of preneoplastic cells during the tumorigenic proces

Oncoplastic conservative surgery for breast cancer: long-term outcomes of our first ten years experience

The main goal of oncoplastic breast surgery (OBS) is to optimize cosmetic outcomes and reduce patient morbidity, while still providing an oncologically-safe surgical outcome and extending the target population of conservative surgery. Although the growing number of reported experiences with oncoplastic surgery, few studies account for the long-term outcomes

Random walks and search in time-varying networks

The random walk process underlies the description of a large number of real world phenomena. Here we provide the study of random walk processes in time varying networks in the regime of time-scale mixing; i.e. when the network connectivity pattern and the random walk process dynamics are unfolding on the same time scale. We consider a model for time varying networks created from the activity potential of the nodes, and derive solutions of the asymptotic behavior of random walks and the mean first passage time in undirected and directed networks. Our findings show striking differences with respect to the well known results obtained in quenched and annealed networks, emphasizing the effects of dynamical connectivity patterns in the definition of proper strategies for search, retrieval and diffusion processes in time-varying network

Total flow intensity, active flow intensity and volume related flow intensity as new quantitative metrics in optical coherence tomography angiography

Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal