Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck with an extremely poor five-year survival rate of approximately 50 to 55%, despite significant advances in ...diagnostic and therapeutic procedures over the past three decades ...
The aim of this study was to determine, by immunohistochemical methods, the expression of nEGFR and markers of cell proliferation (Ki-67), cell cycle (mEGFR, p53, cyclin D1), and tumor stem cells ...(ABCG2) in 59 pathohistological samples of healthy oral mucosa, 50 oral premalignant changes (leukoplakia and erythroplakia), and 52 oral squamous cell carcinomas (OSCC). An increase in the expression of mEGFR and nEGFR was found with the development of the disease (
< 0.0001). In the group of patients with leukoplakia and erythroplakia, we found a positive correlation between nEGFR and Ki67, p53, cyclin D1, and mEGFR, whereas in the group of patients with OSCC, we found a positive correlation between nEGFR and Ki67, mEGFR (
< 0.05). Tumors without perineural (PNI) invasion had a higher expression of p53 protein than tumors with PNI (
= 0.02). Patients with OSCC and overexpression of nEGFR had shorter overall survival (
= 0.004). The results of this study suggest a potentially important independent role of nEGFR in oral carcinogenesis.
Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the ...antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.
Gliomas are notably challenging to treat due to their invasive nature and resistance to conventional therapies. The ABCG2 protein has attracted attention for its role in multidrug resistance, ...complicating treatment effectiveness. This study scrutinized the relationship between ABCG2 expression and glioma grade and the role of ABCG2 in the process of glioma progression, aiming to evaluate ABCG2 expression as a predictive factor of tumor progression and patient survival. Conducted at Dubrava University Hospital, Zagreb, Croatia, the study analyzed 152 glioma specimens from 2013 to 2022, assessing ABCG2 expression alongside standard clinical markers. A significant association was found between patients' survival and the ABCG2 profile (
= 0.003,
= 0.24), separately for patients who underwent chemotherapy (
= 0.0004,
= 0.32) and radiotherapy (
= 0.003,
= 0.29). Furthermore, the ABCG2 profile was significantly associated with disease progression (
= 0.007,
= 0.23), tumor grade (
= 0.0002,
= 0.31), and Ki67 expression (
= 0.0004,
= 0.31). ABCG2-positive tumor cells only showed association with Ki67 expression (
= 0.002,
= 0.28). The ABCG2 profile was found to affect the overall patient survival (
= 0.02) and represent a moderate indicator of tumor progression (
= 0.01), unlike the percentage of ABCG2-positive tumor cells. ABCG2 may serve as a marker of angiogenesis and vascular abnormalities within tumors, predicting glioma progression and treatment response. Targeting ABCG2 could enhance chemoradiotherapy efficacy and improve patient outcomes, which highlights its value in assessing tumor aggressiveness and designing treatment strategies.
Tumor necrosis is a recurrent characteristic of head and neck squamous cell carcinomas (HNSCCs). There is a need for more investigations on the influence of biomolecules released by these necrotic ...foci in the HNSCC tumor microenvironment. It is suspected that a fraction of the biomolecules released by necrotic cells are damage-associated molecular patterns (DAMPs), which are known to be natural endogenous ligands of Toll-like receptors (TLRs), including, among others, proteins and nucleic acids. However, there has been no direct demonstration that biomolecules released by HNSCC necrotic cells can activate TLRs. Our aim was to investigate whether some of these molecules could behave as agonists of the TLR3, either in vitro or in vivo. We chose a functional approach based on reporter cell exhibiting artificial TLR3 expression and downstream release of secreted alkaline phosphatase. The production of biomolecules activating TLR3 was first investigated in vitro using three HNSCC cell lines subjected to various pronecrotic stimuli (external irradiation, serum starvation, hypoxia and oxidative stress). TLR3 agonists were also investigated in necrotic tumor fluids from five oral cancer patients and three mouse tumor grafts. The release of biomolecules activating TLR3 was demonstrated for all three HNSCC cell lines. External irradiation was the most consistently efficient stimulus, and corresponding TLR3 agonists were conveyed in extracellular vesicles. TLR3-stimulating activity was detected in the fluids from all five patients and three mouse tumor grafts. In most cases, this activity was greatly reduced by RNAse pretreatment or TLR3 blocking antibodies. Our data indicate that TLR3 agonists are consistently present in necrotic fluids from HNSCC cells and mainly made of dsRNA fragments. These endogenous agonists may induce TLR3, which might lead to a protumorigenic effect. Regarding methodological aspects, our study demonstrates that direct investigations—including functional testing—can be performed on necrotic fluids from patient tumors.
As a result of SARS-CoV-2 infection, inflammation develops, which promotes oxidative stress, leading to modification of phospholipid metabolism. Therefore, the aim of this study is to compare the ...effects of COVID-19 on the levels of phospholipid and free polyunsaturated fatty acids (PUFAs) and their metabolites produced in response to reactions with reactive oxygen species (ROS) and enzymes (cyclooxygenases-(COXs) and lipoxygenase-(LOX)) in the plasma of patients who either recovered or passed away within a week of hospitalization. In the plasma of COVID-19 patients, especially of the survivors, the actions of ROS and phospholipase A2 (PLA2) cause a decrease in phospholipid fatty acids level and an increase in free fatty acids (especially arachidonic acid) despite increased COXs and LOX activity. This is accompanied by an increased level in lipid peroxidation products (malondialdehyde and 8-isoprostaglandin F2α) and lipid mediators generated by enzymes. There is also an increase in eicosanoids, both pro-inflammatory as follows: thromboxane B2 and prostaglandin E2, and anti-inflammatory as follows: 15-deoxy-Δ-12,14-prostaglandin J2 and 12-hydroxyeicosatetraenoic acid, as well as endocannabinoids (anandamide-(AEA) and 2-arachidonylglycerol-(2-AG)) observed in the plasma of patients who recovered. Moreover, the expression of tumor necrosis factor α and interleukins (IL-6 and IL-10) is increased in patients who recovered. However, in the group of patients who died, elevated levels of N-oleoylethanolamine and N-palmitoylethanolamine are found. Since lipid mediators may have different functions depending on the onset of pathophysiological processes, a stronger pro-inflammatory response in patients who have recovered may be the result of the defensive response to SARS-CoV-2 in survivors associated with specific changes in the phospholipid metabolism, which could also be considered a prognostic factor.
The aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients ...did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes, which was 6% higher on average in those patients who died. Granulocytes were isolated from the blood of 15 healthy people and survivors and 15 patients who died within a week, and who were selected post hoc for analysis according to their matching gender and age. They differed only in the lethal outcome, which could not be predicted upon arrival at the hospital. The proteins level (respective ELISA), antioxidant activity (spectrophotometry), and lipid mediators (UPUPLC–MS) were measured in the peripheral blood granulocytes obtained via gradient centrifugation. The levels of Nrf2, HO-1, NFκB, and IL-6 were higher in the granulocytes of COVID-19 patients who died within a week, while the activity of cytoplasmic Cu,Zn-SOD and mitochondrial Mn-SOD and IL-2/IL-10 were lower in comparison to the levels observed in survivors. Furthermore, in the granulocytes of those patients who died, an increase in pro-inflammatory eicosanoids (PGE2 and TXB2), together with elevated cannabinoid receptors 1 and 2 (associated with a decrease in the anti-inflammatory 15d-PGJ2), were found. Hence, this study suggests that by triggering transcription factors, granulocytes activate inflammatory and redox signaling, leading to the production of pro-inflammatory eicosanoids while reducing cellular antioxidant capacity through SOD, thus expressing an altered response to COVID-19, which may result in the onset of systemic oxidative stress, ARDS, and the death of the patient.
Significant advances in reconstructive head and neck surgery with free microvascular flaps have had a positive impact on esthetic outcomes and quality of life. However, complications still occur in ...some patients. This study investigated the influence of the Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP score), an immunonutritive marker, on complications and flap success. The retrospective analysis included 194 patients who underwent reconstruction of head and neck defects with free microvascular flaps. The HALP score correlated strongly with overall complications, including flap necrosis, infection, fistula, and hematoma. Hemoglobin, albumin, lymphocytes, and platelets individually showed associations with specific complications. HALP score was an extremely strong predictor of complications (AUC = 0.85). HALP score may be valuable for assessing patient status and predicting complications in microvascular free-flap reconstruction to allow timely interventions and improve outcomes. Further research is needed to investigate additional predictors and improve postoperative care.
The aim of this study was to analyze the demographic variables and causes and characteristics of mandibular angle fractures managed at several European departments of maxillofacial surgery.
This ...study was based on a multicenter systematic database that allowed the recording of data from all patients with mandibular angle fractures between January 1, 2013, and December 31, 2017. The following data were recorded: gender, age, etiology, side of angle fracture, associated mandibular fractures, presence of third molar, intermaxillary fixation, and osteosynthesis.
The study included 1,162 patients (1,045 male and 117 female patients). A significant association was found between the presence of a third molar and the diagnosis of an isolated angle fracture (P < .0000005). Furthermore, assaults were associated with the presence of voluptuary habits (P < .00005), a younger mean age (P < .00000005), male gender (P < .00000005), and left-sided angle fractures (P < .00000005).
Assaults and falls actually represent the most frequent causes of angle fractures. The presence of a third molar may let the force completely disperse during the determination of the angle fracture, finding a point of weakness.
Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have ...recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored. However, protein adducts of the lipid peroxidation product 4-hydroxynonenal (HNE) were higher in the plasma of the deceased patients, while total antioxidant capacity was below the detection limit for the majority of sera samples in both groups. Moreover, levels of the HNE-protein adducts were constant in the plasma of the deceased patients, while in survivors, they have shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting to COVID-19 aggression, which were not efficient in patients who died. Immunohistochemistry revealed the abundant presence of HNE-protein adducts in the lungs of deceased patients indicating that HNE is associated with the lethal outcome. It seems that HNE was spreading from the blood vessels more than being a consequence of pneumonia. Due to the limitations of the relatively small number of patients involved in this study, further research on HNE and antioxidants is needed. This might allow a better understanding of COVID-19 and options for utilizing antioxidants by personalized, integrative biomedicine approach to prevent the onset of HNE-mediated vitious circle of lipid peroxidation in patients with aggressive inflammatory diseases.
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