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Aquest treball parteix de les consideracions de Bion sobre el verb intuir, que ell utilitza per descriure els estats mentals intangibles de l���analista i del pacient. Les autores reflexionen, en la teoria i en la cl��nica, principalment sobre els aspectes visuals de la intu��ci�� �����veure amb els ulls de la ment����� i conclouen que cal traduir en la praxi cl��nica alguns conceptes bionians que pertanyen al camp d���all�� inefable, especialment efica��os i f��rtils per afavorir i comprendre les transformacions en el treball amb els pacients. L'article inclou el relat d'un cas cl��nic que posa de manifest aquests aspectes., Revista Catalana de Psicoan��lisi, Vol. 38, N��m. 1 (2021): Revista Catalana de Psicoan��lisi

Cancer stem cells (CSCs) are a subpopulation of tumor cells with unlimited self-renewal capability, multilineage differentiation potential and long-term tumor repopulation capacity. CSCs reside in anatomically distinct regions within the tumor microenvironment, called niches, and this favors the maintenance of CSC properties and preserves their phenotypic plasticity. Indeed, CSCs are characterized by a flexible state based on their capacity to interconvert between a differentiated and a stem-like phenotype, and this depends on the activation of adaptive mechanisms in response to different environmental conditions. Heat Shock Proteins (HSPs) are molecular chaperones, upregulated upon cell exposure to several stress conditions and are responsible for normal maturation, localization and activity of intra and extracellular proteins. Noteworthy, HSPs play a central role in several cellular processes involved in tumor initiation and progression (i.e. cell viability, resistance to apoptosis, stress conditions and drug therapy, EMT, bioenergetics, invasiveness, metastasis formation) and, thus, are widely considered potential molecular targets. Furthermore, much evidence suggests a key regulatory function for HSPs in CSC maintenance and their upregulation has been proposed as a mechanism used by CSCs to adapt to unfavorable environmental conditions, such as nutrient deprivation, hypoxia, inflammation. This review discusses the relevance of HSPs in CSC biology, highlighting their role as novel potential molecular targets to develop anticancer strategies aimed at CSC targeting.

Introduction. Response of different types of cells on biomaterials is crucial for the applications of tissue engineering and regenerative medicine. It is recognized that cell behaviours depend largely by material surface characteristics. Objectives. The purpose of this study was to define the biologic response of MG63 cells to an innovative patented surface SYNTHEGRA®. Material and Methods. The MG63 morphology and distribution on the three different titanium disks surface were evaluated by microscopy analysis after staining with hematoxylin and eosin. Cell adhesion was determined by crystal violet assay at 48 hours while proliferation and cytotoxicity were performed by MTT assay at 24, 48, 72 and 240 hours. The expression and localization of N-cadherin and b-catenin were studied by immunofluorescence and confocal microscopy. Results. At 48 h the adhesion was similar in all titanium surfaces, no cytotoxic difference in cell viability were observed in all titanium disks when compared with controls, while the cell growth on p30 disks was significantly higher at 240 h than at 72 and 24 h. Morphological analysis show that cells are aligned along the grooves and inside the cavities. b-catenin appeared more diffuse and localized underneath the cell membrane, while N-cadherin signal was fainter in cells grown onto SYNTHEGRA® surface. Conclusion. This work put in evidence the performance of newly designed laser-micromachined surface for adhesion, growth and distribution of human osteoblast- like cells. SYNTHEGRA® surface inducing modification of N-cadherin and b-catenin expression and localization, which are suggestive of cells undergoing differentiation towards osteocytes, could be particularly suited for immediate load implant procedures., Italian Journal of Anatomy and Embryology, Vol 117, No 2 (Supplement) 2012

Microparticles (MPs) are small plasma membrane vesicles released by several cell types (macrophages, platelets, endothelial cells, granulocytes, monocytes, lymphocytes) following chemical, physical and apoptotic stimuli. MPs bear a number of bioactive effectors that can be disseminate, exchanged, and transferred via MPs cell interactions. The hallmarks of lung disease in cystic fibrosis (CF) patients are a persistent infection with opportunistic bacterial pathogens such as the Gram-negative P. aeruginosa and an abnormal inflammatory response dominated by polymorphonuclear granulocytes (neutrophils). In CF airways, neutrophils undergo conventional activation and functional reprogramming. In our previous study, we isolated MPs in sputum and demonstrated that most of CF sputum MPs were of granulocyte origin. However, the neutrophil response is not capable to clear bacteria from the CF airways ensuing in exaggerated apoptosis. The aim of this study is to investigate if MPs isolated from the sputum of patients with pulmonary diseas, in particular CF and dyskinesia primary ciliar (DPC), contribute to induction of lung inflammation. Swiss CD11 mice (6–8 weeks old male) were induced by intratracheal administration of MPs isolated from the sputum of CF and DPC, LPS (20μg) or saline. Histologycal analysis was performed on H and E stained lung sections. In Bronchoalveolar lavage fluid (BALF) total cells were counted by trypan blue stain, whereas differential cell counts were performed on cytospin preparations stained with May-Grunwald Giemsa. LPS induced a significant increase of total cellular count as compared with controls. MPs obtained from CF patients in acute state were inflammatory as well, with a peak of total cell counts obtained with 100 x 106 MPs injected. Interestingly, MPs obtained from CF intermittent state were less pro-inflammatory in comparition to acute CF patients MPs, while DPC patients MPs determined an intermediate inflammatory levels, between those elicited by acute and intermittent CF MPs. The analysis of differential cell counts revealed that endotoxin, 50 and 100 x 106 MPs from Cfpatients, determined an increase in neutrophil numbers; no differences were found between acute and intemittent CF patients, whereas controls had only macrophages in their BALF. MPs from DPC patients have a different behaviour, since the most of inflammatory cells were macrophages. Our data suggest that MPs isolated from CF sputum could contribute to lung injury resultant in increase of total inflammatory cells and neutrophil recruitment., Italian Journal of Anatomy and Embryology, Vol 117, No 2 (Supplement) 2012

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Italian Journal of Anatomy and Embryology, Vol 115, No 1/2 (Supplement) 2010

Background: HPV-positive oral squamous cell carcinomas (OSCCs) are specific biological and clinical entities, characterized by a more favorable prognosis compared to HPV-negative OSCCs and occurring generally in non-smoking and non-drinking younger individuals. However, poor information is available on the molecular and the clinical behavior of HPV-positive oral cancers occurring in smoking/drinking subjects. Thus, this study was designed to compare, at molecular level, two OSCC cell lines, both derived from drinking and smoking individuals and differing for presence/absence of HPV infection.Methods: HPV-negative UPCI-SCC-131 and HPV16-positive UPCI-SCC-154 cell lines were compared by whole genome gene expression profiling and subsequently studied for activation of Wnt/beta Catenin signaling pathway by the expression of several Wnt-target genes, PCatenin intracellular localization, stem cell features and miRNA let-7e. Gene expression data were validated in head and neck squamous cell carcinoma (HNSCC) public datasets.Results: Gene expression analysis identified Wnt/beta Catenin pathway as the unique signaling pathway more active in HPV-negative compared to HPV-positive OSCC cells and this observation was confirmed upon evaluation of several Wnt-target genes (i.e., Cyclin D I, Cdh I, Cdkn2a, Cd44, Axing, c-Myc and TcfI). Interestingly, HPV-negative OSCC cells showed higher levels of total beta Catenin and its active form, increase of its nuclear accumulation and more prominent stem cell traits. Furthermore, miRNA let-7e was identified as potential upstream regulator responsible for the downregulation of Wnt/beta Catenin signaling cascade since its silencing in UPCI-SCC-154 cell resulted in upregulation of Wnt-target genes. Finally, the analysis of two independent gene expression public datasets of human HNSCC cell lines and tumors confirmed that Wnt/beta Catenin pathway is more active in HPV-negative compared to HPV-positive tumors derived from individuals with smoking habit.Conclusions: These data suggest that lack of HPV infection is associated with more prominent activation of Wnt/beta Catenin signaling pathway and gain of stem-like traits in tobacco-related OSCCs.

The unfolded protein response (UPR) is a stress response activated by the accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum (ER) and its uncontrolled activation is mechanistically responsible for several human pathologies, including metabolic, neurodegenerative, and inflammatory diseases, and cancer. Indeed, ER stress and the downstream UPR activation lead to changes in the levels and activities of key regulators of cell survival and autophagy and this is physiologically finalized to restore metabolic homeostasis with the integration of pro-death or/and pro-survival signals. By contrast, the chronic activation of UPR in cancer cells is widely considered a mechanism of tumor progression. In this review, we focus on the relationship between ER stress, apoptosis, and autophagy in human breast cancer and the interplay between the activation of UPR and resistance to anticancer therapies with the aim to disclose novel therapeutic scenarios. The hypothesis that autophagy and UPR may provide novel molecular targets in human malignancies is discussed.

TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.

Background: Simple epithelial keratins appear early during embryonic development and are expressed in non-stratified, ductal and pseudo-stratified epithelial tissues. CK19, the lowest molecular weight keratin, is also expressed in basal layer of squamous epithelia of mucosal surfaces. Previous studies have shown that High Risk-Human Papilloma Virus (HR-HPV) epithelial infection induces cell immortalization via E6 and E7 viral proteins and this, in turn, impairs cytokeratin expression in cancerous cells lines derived from uterine cervix. Here, we demonstrate the possible relationship between HR-HPV+ oral/oropharyngeal cancer and the high levels of CK19 expression. Methods: We analyzed 38 cases of Oral Squamous Cell Carcinomas/ Oro-Pharyngeal Squamous Cell Carcinomas (OSCCs/OPSCCs) by Immunohistochemistry (IHC) using specific antibody (Ab) detecting CK19, by In Situ Hybridization (ISH) and Polymerase Chain Reaction (PCR) based methods in order to define the HPV infectious status. We also evaluated the variation of CK19 expression in UPCI-SCC-131 (HPV-) and UPCI-SCC-154 (HPV+) cell lines by immunocytochemistry (ICC) and flow cytometry. Results: CK19 OSCC/OPSCC score has been identified multiplying percentage of cancer expressing cells to staining intensity. CK19 expression score in OSCCs/OPSCCs was very different between HPV+ (mean: 288.0 ± 24.3) and HPV- cancers (mean: 66.2 ± 96.9). This difference was statistically significant (p < 0.001) with a strong evidence of correlation (p < 0.001; Spearman's R: +0.72). ROC curve analysis was performed on CK19 expression index related to HPV positivity. Heterogeneous areas of immunoreactivity varying in percentage value, intensity and/or localization were observed in normal epithelium, both perilesional and distant from the tumor with important differences between HR-HPV+ and HR-HPV- carcinomas. By ICC and flow cytometry, the two analyzed cell lines were both CK19 positive but showed a different level of expression, in particular it should be noted that the UPCI-SCC-154 (HPV+) cell line had a higher expression than UPCI-SCC-131 (HPV-). Conclusions: In this study we demonstrated, for the first time, strong association between CK19 up-regulation and HR-HPV+ OSCCs/OPSCCs. This test has a good accuracy. We identified ROC curve with a cut-off > 195 for HR-HPV positive results (Sensitivity: 92.3 %; Specificity: 89.3 %). Furthermore, in OSCC/OPSCC, the CK19 test may be useful in identifying HR-HPV infection, the latter being related to HPV E7 potential to disrupt normal cytokeratin expression pattern.

TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = 0.002). There is no statistical correlation between TLR4 intensity and PCR HPV results (p > 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = 0.0001) and between TLR4 expression index and HR-HPV infection (p = 0.001). These data show that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA. TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = 0.002). There is no statistical correlation between TLR4 intensity and PCR HPV results (p > 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = 0.0001) and between TLR4 expression index and HR-HPV infection (p = 0.001). These data show that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.