Molecular pathways and targeted therapies in head and neck cancers pathogenesis.

The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors, combined with the prevalent late-stage diagnosis, poses significant challenges for clinical management. Genomic sequencing endeavors have revealed extensive alterations in key signaling pathways that regulate cellular proliferation and survival. Initiatives to engineer therapies targeting these dysregulated pathways are underway, with several candidate molecules progressing to clinical evaluation phases, including FDA approval for agents like the EGFR-targeting monoclonal antibody cetuximab for K-RAS wild-type, EGFR-mutant HNSCC treatment. Non-coding RNAs (ncRNAs), owing to their enhanced stability in biological fluids and their important roles in intracellular and intercellular signaling within HNC contexts, are now recognized as potent biomarkers for disease management, catalyzing further refined diagnostic and therapeutic strategies, edging closer to the personalized medicine desideratum. Enhanced comprehension of the genomic and immunological landscapes characteristic of HNC is anticipated to facilitate a more rigorous assessment of targeted therapies benefits and limitations, optimize their clinical deployment, and foster innovative advancements in treatment approaches. This review presents an update on the molecular mechanisms and mutational spectrum of HNC driving the oncogenesis of head and neck malignancies and explores their implications for advancing diagnostic methodologies and precision therapeutics.

A Review and Comparative Analysis of Transoral Surgical Treatment versus Conservative Management in Early-Stage Oropharyngeal Cancer.

INTRODUCTION: Oropharyngeal cancer requires a comprehensive evaluation of treatment options, including surgery, radiation therapy, and chemotherapy. It is crucial to customize these treatments based on the stage of the tumor and the overall health of the patient, enabling personalized or combined approaches. Transoral surgical techniques have regained popularity due to the advancements and limitations of non-surgical strategies. The potential influence of surgical procedures on patients' quality of life highlights the need for careful intervention selection; among them, the transoral approach has proven to be especially beneficial for early-stage oropharyngeal neoplasms. METHODS: To explore potential treatments for early-stage oropharyngeal malignancies, this study carefully reviews the literature, using information from papers, current research, and global databases. The review protocol commenced on November 2023. A comprehensive search of the PUBMED database was undertaken, employing pertinent terms associated with oropharyngeal, transoral surgery or radiotherapy, robotic surgery, and chemotherapy. RESULTS: Treating early-stage oropharyngeal neoplasms is particularly intriguing due to the multitude of variables influencing treatment decisions, leading to ongoing debates in specialized literature. Regardless of the chosen approach, maintaining a high quality of life is crucial. To assess this, standardized questionnaires from the European Organization for Research and Treatment of Cancer were employed, revealing superior outcomes for patients solely undergoing surgical intervention. Additionally, in the realm of specialized literature, cases of HPV-positive oropharyngeal neoplasms are recognized for their heightened radiosensitivity and more favorable long-term prognosis. CONCLUSIONS: Surgical intervention and radiotherapy are the main treatment options for oropharyngeal cancer, and they can be used separately or together for maximum effectiveness. Amid ongoing discussions, determining the superior effectiveness between the two options continues to be a matter of debate. This study provides a comprehensive analysis, offering valuable perspectives for future discussions. Neoplasm in the oropharynx can be effectively treated using transoral microsurgery.

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy.

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.

Role of interferons in the antiviral battle: from virus-host crosstalk to prophylactic and therapeutic potential in SARS-CoV-2 infection.

Mammalians sense antigenic messages from infectious agents that penetrate the respiratory and digestive epithelium, as well as signals from damaged host cells through membrane and cytosolic receptors. The transduction of these signals triggers a personalized response, depending on the nature of the stimulus and the host's genetics, physiological condition, and comorbidities. Interferons (IFNs) are the primary effectors of the innate immune response, and their synthesis is activated in most cells within a few hours after pathogen invasion. IFNs are primarily synthesized in infected cells, but their anti-infective effect is extended to the neighboring cells by autocrine and paracrine action. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 2019 was a stark reminder of the potential threat posed by newly emerging viruses. This pandemic has also triggered an overwhelming influx of research studies aiming to unveil the mechanisms of protective versus pathogenic host immune responses induced by SARS-CoV-2. The purpose of this review is to describe the role of IFNs as vital players in the battle against SARS-CoV-2 infection. We will briefly characterize and classify IFNs, present the inductors of IFN synthesis, their sensors, and signaling pathways, and then discuss the role of IFNs in controlling the evolution of SARS-CoV-2 infection and its clinical outcome. Finally, we will present the perspectives and controversies regarding the prophylactic and therapeutic potential of IFNs in SARS-CoV-2 infection.

The association between lncRNA H19 and EZH2 expression in patients with EBV-positive laryngeal carcinoma.

OBJECTIVE: Laryngeal cancer is the second most common malignancy in the head and neck, with Epstein-Barr virus infection as a risk factor. Our aim is to evaluate correlations between the expression of lncRNA H19 and EBV infection in laryngeal cancer and H19 involvement in neoplastic progression through EZH2 association. MATERIALS AND METHODS: 30 paired laryngeal tissue specimens (neoplastic and non-neoplastic) were included in the study. Nucleic acid isolation and cDNA synthesis was performed according to the manufacturer's protocol. EBV DNA and expression of lytic (BZLF1) and latent (LMP1) forms of infection were assessed in PCR assays; expression levels of H19 and EZH2 were quantified in qRT-PCR. Data was analysed using GraphPad Prism 5.0. RESULTS: Higher H19 relative expression in neoplastic vs paired non-neoplastic samples was found (p < 0.0001) with a significant increase in EBV DNA positive neoplasms (p = 0.0434). An inverse correlation between H19 and EZH2 expression levels was noticed in EBV positive cases. Additionally, increased levels of H19 in LMP1 positive samples compared with those positive for BZLF1 was found (p = 0.0593). CONCLUSIONS: lncRNA H19 and EZH2 significantly contribute to the development of laryngeal carcinoma, being correlated with EBV infection markers.

The Role of Biomaterials in Upper Digestive Tract Transoral Reconstruction.

This study aims to establish whether the use of biomaterials, particularly polydimethylsiloxane (PDMS), for surgical reconstruction of the esophagus with templates, Montgomery salivary tube, after radical oncology surgery for malignant neoplasia is an optimal choice for patients' safety and for optimal function preservation and organ rehabilitation. Structural analysis by Raman spectrometry and biomechanical properties with dynamic mechanical analysis are performed for fatigue strength and toughness, essential factors in durability of a prosthesis in the reconstruction practice of the esophagus. Nanocomposites with silicone elastomers and nanoparticles used in implantable devices and in reconstruction surgery present risks of infection and fatigue strength when required to perform a mechanical effort for long periods of time. This report takes into account the effect of silver (Ag) nanoparticles on the fatigue strength using polydimethylsiloxane (PDMS) matrix, representative for silicon elastomers used in implantable devices. PDMS with 5% (wt) Ag nanoparticles of 100-150 nm during mechanical fatigue testing at shear strength loses elasticity properties after 400 loading-unloading cycles and up to 15% shear strain. The fatigue strength, toughness, maximum shear strength, as well as clinical properties are key issues in designing Montgomery salivary tube and derivates with appropriate biomechanical behavior for each patient. Prosthesis design needs to indulge both clinical outcomes as well as design methods and research in the field of biomaterials.

Influence of Staphylococcus aureus attachment to the herpes simplex virus infected cells.

The purpose of this study was to investigate the response of HeLa cells to the interaction with inactivated Staphylococcus aureus cells and live challenge with herpes simplex virus (HSV).The results of this study are indicating that the interaction between the HeLa cells and S. aureus inactivated whole cells could modulate the host cell apoptosis and cytokine production, and therefore, influence the progression of HSV infection. The pre-treatment of HeLa cells with heat inactivated bacterial whole cells protects them from the occurrence of HSV mediated cytopathic effect, while the post viral infection treatment with bacterial cells prevents the high activation of bax/bcl-2 apoptotic pathway, a process that could change the fate of the infectious process triggered by the virus, and eventually reduce its multiplication rate. The pre-treatment of HeLa monolayer with inactivated bacterial cells 24 hours before the viral infection is increasing the expression level of TNF-a, IL-6 and IL-8 pro-inflammatory cytokines genes, also suggesting that bacterial antigens could contribute to the decrease of viral multiplication rate.

CT characters versus morphopathological characters in pharyngeal squamous cell carcinoma.

Pharyngeal squamous cell carcinoma is a rare neoplasm, whose incidence increases with age. Computed tomography (CT) imaging is an easy way to explore the pharyngeal region, having the advantage of being able to highlight and characterize the existence of a tumor in this region, and to determine its local extension and lymphatic metastasis. In this group were included a total of 27 patients, who, following the histopathological findings were diagnosed with pharyngeal squamous cell carcinoma and who have previously received a CT scan. CT examination protocol included a native scan and post-intravenous administration of contrast medium, in both the arterial phase and in parenchymal and venous phase. The scan was made with 2 mm thin sections, subsequently were performed coronal and sagittal reconstructions. The examination plan included the thoracic region down to the aperture. The paper tries to establish correlations between the morphological appearance and semiological computed tomography characters of the lesions.

Insights on Metal Based Dental Implants and their Interaction with the Surrounding Tissues.

At present, the use of dental implants is a very common practice as tooth loss is a frequent problem and can occur as a result of disease or trauma. An implant is usually made of biocompatible materials that do not cause rejection reactions and allow the implant union with the respective bone. To achieve this goal, the implant surface may have different structures and coatings, generally used to increase the adherence of the implant to the bone and to decrease the risk of the periimplantar inflammatory reactions. This review gives some insights of the metal based materials used for dental implants, their limits, improvement strategies as well as the pathophysiology, diagnosis, treatment and prevention of periimplantary diseases.

Metallic-based micro and nanostructures with antimicrobial activity.

The spectacular progress of research in the nanotechnology field led to the achievement of important knowledge of materials at the atomic and molecular scale and the extent of the use of nanoparticles in the design of medical products, ecological processes, cosmetics and other biotechnological applications. One of the current focuses of the medical applications of nanotechnology is the development of new strategies to inhibit the activity of different microorganisms. The purpose of this review was to present the antimicrobial activity of metal cations in micro- and nanoparticulate forms and the dependence of this biological activity on shape, size and physico-chemical conditions.

Significance of serum antibodies against HSP 60 and HSP 70 for the diagnostic of infectious diseases.

Heat shock proteins (HSP) represent important antigenic targets for the immune response, playing an important role in the pathology and infectious diseases control. The purpose of this work was to investigate the levels of HSP60 and HSP70 specific antibodies in the bloodstream of patients with different bacterial infections and cancer, in order to evaluate their potential role as diagnosis markers of different infectious diseases. Detection of specific anti-HSP 60 and HSP 70 serum levels was performed by ELISA. Statistical analysis of data by multivariate logistic regression was performed using GraphPadPrism software and statistical tests based on chi-square and Student t-test. High levels of anti-HSP60 were found in patients with localized infections, while the levels of anti- HSP70 were higher in the group with generalized infections. The serum levels of both anti-HSP 60 and anti-HSP70 were significantly increased in patients with Gram-negative bacterial infections, as compared with patients harbouring infections produced by Gram-positive and fungal strains, demonstrating their potential use as additional diagnosis and prognosis markers in infections with this etiology.

A histopathological and immunohistochemical approach of surgical emergencies of GIST. An interdisciplinary study.

The tailored approach to gastrointestinal stromal tumors (GISTs) has led to better prognosis for these types of tumors. Also, finding out GIST's pathology has led to a better understanding of oncogenesis and cancer therapy in general. The rapid expansion of molecular and pathological knowledge of GISTs has given this disease a promising future. We analyze 30 cases of GISTs operated on in our clinic with confirmed diagnosis by immunohistochemistry. Most of the cases were acute cases that required urgent surgical therapy. An extended analysis of these cases is performed in order to underline their special features. We recorded 17 GISTs of the stomach, 12 GISTs of the small bowel and one esophageal GIST. Of the 30 cases, 15 cases required urgent surgery presenting with GI bleeding or shock following intraperitoneal rupture and bleeding or intestinal obstruction. Of the 15 cases that required urgent surgery 12 cases presented with serosal involvement. Twenty-four cases presented spindle cell histology, four cases were epithelioid and two cases presented mixed cellularity. Although acute presentation of GISTs is not the rule, 15 of 30 of our cases required immediate surgery and a high proportion of them (12/15) presented with serosal involvement. Serosal involvement may warrant the need for a macroscopic classification of GISTs and correlation to therapy. While overall mortality was not high in our series, morbidity is affected by acute presentation, though not specifically pertaining to the diagnosis of GIST. Acute presentations were more frequent, in our series, for small bowel GISTs, compared to gastric GISTs. Serosal involvement was more frequent in the group with acute presentation compared with non-acute GISTs and was present at the most cases of small bowel GISTs with acute onset. The Ki-67 index showed no difference between acute and non-acute onset of GISTs.

Fluorescence analysis of apoptosis induced by Pseudomonas aeruginosa in endothelial cells.

Intracellular invasion of professional phagocytic cells like monocytes and macrophages by a pathogen usually triggers the apoptosis of the host cells. The aim of this study was to evaluate if Pseudomonas aeruginosa, although not considered a classic intracellular pathogen, could adhere to endothelial cell surface, invade the intracellular compartment and subsequently induce apoptosis of the cells. The adherence and invasion capacity of P. aeruginosa to endothelial cells was monitored using Cravioto's adapted method. The apoptotic cells were evidenced by staining with Acridine orange/Ethidium bromide. The qualitative assay of bacterial adherence to the cellular substrate revealed that all tested strains adhered to endothelial cells surface, exhibiting a diffuse, aggregative or mixed (diffuse-aggregative or localized-aggregative) pattern and 20-70% adherence rates. The adherence of P. aeruginosa induced the reorganization of cytoskeleton filaments and formation of endocytic membrane expansions. Cell free P. aeruginosa culture supernatants did not induce any cell death response, as noticed in case of whole bacterial culture, showing the capacity to induce apoptosis of endothelial cells. The fluorescence microscopy examination revealed chromatin condensation, fragmented nuclei, and membrane blebbing and apoptotic bodies in pathogen invaded cells.

Biomedical applications of synthetic, biodegradable polymers for the development of anti-infective strategies.

The emergence of antibiotic resistance in microbial strains is representing one of the major threats to public health worldwide, due to the decreased or total cancelling of the available antibiotics effectiveness, correlated with the slow development of novel antibiotics. Due to their excellent biodegradability and biocompatibility, the synthetic polymers could find a lot of biomedical applications, such as the development of biomaterials with optimized properties and of drug delivery systems. This review is focusing on the applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization.

Polymicrobial wound infections: pathophysiology and current therapeutic approaches.

Acute and chronic wounds represent a very common health problem in the entire world. The dermal wounds are colonized by aerobic and anaerobic bacterial and fungal strains, most of them belonging to the resident microbiota of the surrounding skin, oral cavity and gut, or from the external environment, forming polymicrobial communities called biofilms, which are prevalent especially in chronic wounds. A better understanding of the precise mechanisms by which microbial biofilms delay repair processes together with optimizing methods for biofilm detection and prevention may enhance opportunities for chronic wounds healing. The purpose of this minireview is to assess the role of polymicrobial biofilms in the occurrence and evolution of wound infections, as well as the current and future preventive and therapeutic strategies used for the management of polymicrobial wound infections.

Methods of investigating metastatic lymph nodes in head and neck cancer.

ABSTRACT: When dealing with patients who have head and neck cancer - squamous cell carcinoma and have clinically N0 neck disease it is very difficult to assess the real extension of the malignant proccess. This is why several techniques are curently in use to determine the actual TNM clasiffication for each patient in order to apply best suited therapy management. Up until today the staging of the neck has been done by using a combination of the physical exam and conventional imaging studies. Recent studies and research have tried to determine weather the use of sentinel lymph node biopsy is a more reliable tool in predicting occult metastasis in cancer patients with clinically N0 neck disease. There are no guidelines in this matter and as such the use of the sentinel lymph node detection technique is yet to be used on a routine basis. The authors are trying to assess the benefits of different paraclinical investigation regarding the improvement of overall survival rates in patients with T1/T2 squamous cell carcinoma of the head and neck and N0 neck disease.