1,721,065 research outputs found
Nucleotide Excision Repair and head and neck cancers
No full textGenome integrity maintenance is crucial for cell survival and for counteracting cancer onset and progression. Mammary cells invest great amount of energy in DNA repair, in order to avoid errors accumulation in DNA sequence. Nucleotide Excision Repair (NER) removes a broad spectrum of DNA damages, mainly bulky DNA lesions. Tissues of Head and Neck region are heavily exposed to bulky lesions inducing carcinogens, this making NER process of great interest in the field. Here we review the recent literature about NER in HNC and we also discuss the role played by NER in HNSCC in the chromatin context; to this aim we particularly focus on the role played by histones chaperon CAF-1, essential in restoring the chromatin structure following DNA replication and DNA damage repair, including NER. A better understanding of basic mechanisms underlying the DNA damage response, particularly involving NER, especially in the chromatin context, will provide us with new promising way to bypass the repair block, possibly becoming an unexpected mode of "transversal" control also of the proliferative deregulation, classically observed in HNSCC
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Post-translational modification by sumoylation and ubiquitinylation of H4 (D10S170), the product of first and most frequently observed RET-fused gene
No full textA deep learning model to predict Ki-67 positivity in oral squamous cell carcinoma
No full textAnatomical pathology is undergoing its third revolution, transitioning from analogical to digital pathology and incorporating new artificial intelligence technologies into clinical practice. Aside from classification, detection, and segmentation models, predictive models are gaining traction since they can impact diagnostic processes and laboratory activity, lowering consumable usage and turnaround time. Our research aimed to create a deep-learning model to generate synthetic Ki-67 immunohistochemistry from Haematoxylin and Eosin (H&E) stained images. We used 175 oral squamous cell carcinoma (OSCC) from the University Federico II's Pathology Unit's archives to train our model to generate 4 Tissue Micro Arrays (TMAs). We sectioned one slide from each TMA, first stained with H&E and then re-stained with anti-Ki-67 immunohistochemistry (IHC). In digitised slides, cores were disarrayed, and the matching cores of the 2 stained were aligned to construct a dataset to train a Pix2Pix algorithm to convert H&E images to IHC. Pathologists could recognise the synthetic images in only half of the cases in a specially designed likelihood test. Hence, our model produced realistic synthetic images. We next used QuPath to quantify IHC positivity, achieving remarkable levels of agreement between genuine and synthetic IHC. Furthermore, a categorical analysis employing 3 Ki-67 positivity cut-offs (5%, 10%, and 15%) revealed high positive-predictive values. Our model is a promising tool for collecting Ki-67 positivity information directly on H&E slides, reducing laboratory demand and improving patient management. It is also a valuable option for smaller laboratories to easily and quickly screen bioptic samples and prioritise them in a digital pathology workflow
A Digital Workflow for Automated Assessment of Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma Using QuPath and a StarDist-Based Model
Full text linkThe search for reliable prognostic markers in oral squamous cell carcinoma (OSCC) remains a critical need. Tumor-infiltrating lymphocytes (TILs), particularly T lymphocytes, play a pivotal role in the immune response against tumors and are strongly correlated with favorable prognoses. Computational pathology has proven highly effective for histopathological image analysis, automating tasks such as cell detection, classification, and segmentation. In the present study, we developed a StarDist-based model to automatically detect T lymphocytes in hematoxylin and eosin (H&E)-stained whole-slide images (WSIs) of OSCC, bypassing the need for traditional immunohistochemistry (IHC). Using QuPath, we generated training datasets from annotated slides, employing IHC as the ground truth. Our model was validated on Cancer Genome Atlas-derived OSCC images, and survival analyses demonstrated that higher TIL densities correlated with improved patient outcomes. This work introduces an efficient, AI-powered workflow for automated immune profiling in OSCC, offering a reproducible and scalable approach for diagnostic and prognostic applications
Metformin radiosensitizes OSCC in 2D and 3D models: possible involvement of CAF-1
No full textObjective. This study investigated metformin as a sensitizer for radiotherapy in oral squamous cell carcinoma (OSCC) to reduce the radiation intensity. It evaluated the drug’s effect on Chromatin Assembly Factor-1 (CAF-1) expression, whose high levels correlate with worse prognosis of this cancer. Methods. The effects of metformin, alone and with radiotherapy, were evaluated on CAL27 (HPV-) and SCC154 (HPV+) OSCC cells. The analyses were performed on cell monolayers by colony-forming assay, motility, and confocal microscopy. In spheroid 3D models, the sensitizing effect of metformin was assessed by measuring areas. CAF-1 expression affected by metformin was evaluated via Western blot, and its role was investigated by siRNAs. Results. Metformin reduced the cells’ ability to form colonies, migrate and invade, and promoted the acquisition of a less aggressive phenotype by increased E-cadherin and decreased N-cadherin expressions. Moreover, metformin lowered the IC50 of radiotherapy and showed strong effects on spheroid growth. Metformin downmodulated the expression of the major subunits of CAF-1, and the knockdown of this protein by siRNAs elicited a metformin-like effect on cell aggressiveness. Conclusions. Metformin emerged as a promising adjuvant drug in OSCC because of its effects on cell aggressiveness and radiosensitizing action. These activities could be CAF-1-mediated
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
