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Medicina (Kaunas, Lithuania) Jun 2024Several cases reported in the literature have confirmed the link between pulmonary aspergillosis and various malignant diseases. Furthermore, it has been observed that...
Several cases reported in the literature have confirmed the link between pulmonary aspergillosis and various malignant diseases. Furthermore, it has been observed that the correlation between carcinoid tumor and lung adenocarcinoma is quite uncommon. The etiopathogenic mechanisms underlying these correlations remain poorly defined. We present the case of a patient with three of these diseases: a lung adenocarcinoma with a lepidic pattern, a typical carcinoid, and pulmonary aspergillosis. An additional noteworthy aspect of this case pertains to the timely detection of both lung malignancies. Thus, the necessity for further investigation to ascertain the pathogenic connection among the three diseases is underscored. The ultimate objective is to enhance the prognosis of individuals diagnosed with lung cancer, which is a prevailing malignant disease on a global scale.
Topics: Humans; Lung Neoplasms; Pulmonary Aspergillosis; Carcinoid Tumor; Adenocarcinoma; Male; Adenocarcinoma of Lung; Middle Aged; Aged
PubMed: 38929570
DOI: 10.3390/medicina60060953 -
Medicina (Kaunas, Lithuania) May 2024: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are...
: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. : Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. : A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma ( = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands ( = 0.000). : Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours.
Topics: Humans; Salivary Gland Neoplasms; Mucins; Male; Female; Adenoma, Pleomorphic; Middle Aged; Carcinoma, Mucoepidermoid; Adult; Aged; Carcinoma, Adenoid Cystic; Sialomucins
PubMed: 38929537
DOI: 10.3390/medicina60060920 -
Medicina (Kaunas, Lithuania) May 2024Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to...
Hepatocellular carcinoma (HCC) is a prevalent form of malignancy that is characterized by high mortality rates and prognosis that remain suboptimal, largely due to treatment resistance mechanisms. Recent studies have implicated cancer stem cells (CSCs), particularly those expressing epithelial cell adhesion molecule (EpCAM), in HCC progression and resistance. In the present study, we sought to assess EpCAM expression in HCC patients and its correlation with various clinicopathological parameters. Tissue samples from 42 HCC patients were subjected to immunohistochemical staining to evaluate EpCAM expression. Clinicopathological data were obtained including the size, grade and stage of tumors, vascular invasion status, alpha-fetoprotein levels, and cirrhosis status. The Chi square and Fisher's exact tests were employed to assess the association between categorical groups. Independent Student-t test or Mann-Whitney U test was used to investigate the association between continuous patient characteristics and survival. Immunohistochemical analysis revealed EpCAM expression in 52.5% of HCC cases. EpCAM-positive tumors exhibited characteristics indicative of aggressive disease, including larger tumor sizes ( = 0.006), greater tumor multiplicity ( = 0.004), higher grades ( = 0.002), more advanced stages ( = 0.003), vascular invasion ( = 0.023), elevated alpha-fetoprotein levels ( = 0.013), and cirrhosis ( = 0.052). Survival analysis demonstrated that EpCAM expression was significantly associated with lower overall rates of survival and higher rates of recurrence in HCC patients. Our findings suggest that EpCAM expression may serve as a prognostic biomarker for HCC with a potential role in patient management. Targeting EpCAM-positive CSCs may represent a promising approach to overcome treatment resistance and improve clinical outcomes in HCC. However, further investigation into the molecular mechanisms underlying EpCAM's role in HCC progression is warranted to facilitate the development of personalized therapeutic interventions.
Topics: Humans; Carcinoma, Hepatocellular; Epithelial Cell Adhesion Molecule; Liver Neoplasms; Male; Female; Middle Aged; Neoplastic Stem Cells; Biomarkers, Tumor; Aged; Adult; Immunohistochemistry; Prognosis; alpha-Fetoproteins
PubMed: 38929532
DOI: 10.3390/medicina60060915 -
Medicina (Kaunas, Lithuania) May 2024: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively.... (Review)
Review
: Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. : In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. : Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. : This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.
Topics: Humans; Male; Middle Aged; Prostatic Neoplasms; Carcinoma, Signet Ring Cell; Mucins; Adenocarcinoma; Fatal Outcome
PubMed: 38929494
DOI: 10.3390/medicina60060877 -
Medicina (Kaunas, Lithuania) May 2024Lung adenocarcinoma is a leading cause of cancer-related mortality despite recent therapeutic advances. Cancer stem cells have gained increasing attention due to their...
Lung adenocarcinoma is a leading cause of cancer-related mortality despite recent therapeutic advances. Cancer stem cells have gained increasing attention due to their ability to induce cancer cell proliferation through self-renewal and differentiation into multiple cell lineages. OCT4 and LIN28 (and their homologs A and B) have been identified as key regulators of pluripotency in mammalian embryonic (ES) and induced stem (IS) cells, and they are the crucial regulators of cancer progression. However, their exact role in lung adenocarcinoma has not yet been clarified. The aim of this study was to explore the role of the pluripotency factors OCT4 and LIN28 in a cohort of surgically resected human lung adenocarcinomas to reveal possible biomarkers for lung adenocarcinoma prognosis and potential therapeutic targets. The expressions of OCT4, LIN28A and LIN28B were analyzed in formalin-fixed, paraffin-embedded tissue samples from 96 patients with lung adenocarcinoma by immunohistochemistry. The results were analyzed with clinicopathologic parameters and were related to the prognosis of patients. Higher OCT4 expression was related to an improved 5-year overall survival (OS) rate ( < 0.001). Nuclear LIN28B expression was lower in stage I and II tumors ( < 0.05) compared to advanced stage tumors. LIN28B cytoplasmic expression was associated with 5-year OS rates not only in univariate ( < 0.005), but also in multivariate analysis (where age, gender, histopathological subtype and stage were used as cofactors, < 0.01 HR = 2.592). Patients with lower LIN28B expression showed improved 5-year OS rates compared to patients with increased LIN28B expression. Our findings indicate that OCT4 and LIN28B are implicated in lung adenocarcinoma progression and prognosis outcome; thus, they serve as promising prognostic biomarkers and putative therapeutic targets in lung adenocarcinomas.
Topics: Humans; Octamer Transcription Factor-3; Male; Female; RNA-Binding Proteins; Middle Aged; Lung Neoplasms; Adenocarcinoma of Lung; Aged; Adenocarcinoma; Prognosis; Biomarkers, Tumor; Adult; Survival Analysis; Immunohistochemistry; Aged, 80 and over
PubMed: 38929487
DOI: 10.3390/medicina60060870 -
Antioxidants (Basel, Switzerland) Jun 2024The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) represents the master regulator of the cellular antioxidant response and plays a critical... (Review)
Review
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) represents the master regulator of the cellular antioxidant response and plays a critical role in tumorigenesis. This includes a preventive effect of Nrf2 on cell death through ferroptosis, which represents an essential mechanism of therapy resistance in malignant tumors, such as pancreatic ductal adenocarcinoma (PDAC) as one of the most aggressive and still incurable tumors. Addressing this issue, we provide an overview on Nrf2 mediated antioxidant response with particular emphasis on its effect on mitochondria as the organelle responsible for the execution of ferroptosis. We further outline how deregulated Nrf2 adds to the progression and therapy resistance of PDAC, especially with respect to the role of ferroptosis in anti-cancer drug mediated cell killing and how this is impaired by Nrf2 as an essential mechanism of drug resistance. Our review further discusses recent approaches for Nrf2 inhibition by natural and synthetic compounds to overcome drug resistance based on enhanced ferroptosis. Finally, we provide an outlook on therapeutic strategies based on Nrf2 inhibition combined with ferroptosis inducing drugs.
PubMed: 38929135
DOI: 10.3390/antiox13060696 -
International Journal of Molecular... Jun 2024The tumor microenvironment (TME) is crucial in tumor development, metastasis, and response to immunotherapy. DNA methylation can regulate the TME without altering the...
Identification and Validation of Tumor Microenvironment-Associated Signature in Clear-Cell Renal Cell Carcinoma through Integration of DNA Methylation and Gene Expression.
The tumor microenvironment (TME) is crucial in tumor development, metastasis, and response to immunotherapy. DNA methylation can regulate the TME without altering the DNA sequence. However, research on the methylation-driven TME in clear-cell renal cell carcinoma (ccRCC) is still lacking. In this study, integrated DNA methylation and RNA-seq data were used to explore methylation-driven genes (MDGs). Immune scores were calculated using the ESTIMATE, which was employed to identify TME-related genes. A new signature connected with methylation-regulated TME using univariate, multivariate Cox regression and LASSO regression analyses was developed. This signature consists of four TME-MDGs, including , , , and , which exhibit high methylation and low expression in tumors. Validation was performed using qRT-PCR which confirmed their downregulation in ccRCC clinical samples. Additionally, the signature demonstrated stable predictive performance in different subtypes of ccRCC. Risk scores are positively correlated with TMN stages, immune cell infiltration, tumor mutation burden, and adverse outcomes of immunotherapy. Interestingly, the expression of four TME-MDGs are highly correlated with the sensitivity of first-line drugs in ccRCC treatment, especially pazopanib. Molecular docking indicates a high affinity binding between the proteins and pazopanib. In summary, our study elucidates the comprehensive role of methylation-driven TME in ccRCC, aiding in identifying patients sensitive to immunotherapy and targeted therapy, and providing new therapeutic targets for ccRCC treatment.
Topics: Carcinoma, Renal Cell; Humans; Tumor Microenvironment; DNA Methylation; Kidney Neoplasms; Gene Expression Regulation, Neoplastic; Pyrimidines; Indazoles; Sulfonamides; Biomarkers, Tumor; Female; Molecular Docking Simulation; Gene Expression Profiling; Male
PubMed: 38928496
DOI: 10.3390/ijms25126792 -
International Journal of Molecular... Jun 2024Pancreatic ductal adenocarcinoma (PDAC)'s resistance to therapies is mainly attributed to pancreatic cancer stem cells (PCSCs). Mitochondria-impairing agents can be used...
Pancreatic ductal adenocarcinoma (PDAC)'s resistance to therapies is mainly attributed to pancreatic cancer stem cells (PCSCs). Mitochondria-impairing agents can be used to hamper PCSC propagation and reduce PDAC progression. Therefore, to develop an efficient vector for delivering drugs to the mitochondria, we synthesized tris(3,5-dimethylphenyl)phosphonium-conjugated palmitic acid. Triphenylphosphonium (TPP) is a lipophilic cationic moiety that promotes the accumulation of conjugated agents in the mitochondrion. Palmitic acid (PA), the most common saturated fatty acid, has pro-apoptotic activity in different types of cancer cells. TPP-PA was prepared by the reaction of 16-bromopalmitic acid with TPP, and its structure was characterized by H and C NMR and HRMS. We compared the proteomes of TPP-PA-treated and untreated PDAC cells and PCSCs, identifying dysregulated proteins and pathways. Furthermore, assessments of mitochondrial membrane potential, intracellular ROS, cardiolipin content and lipid peroxidation, ER stress, and autophagy markers provided information on the mechanism of action of TPP-PA. The findings showed that TPP-PA reduces PDAC cell proliferation through mitochondrial disruption that leads to increased ROS, activation of ER stress, and autophagy. Hence, TPP-PA might offer a new approach for eliminating both the primary population of cancer cells and PCSCs, which highlights the promise of TPP-derived compounds as anticancer agents for PDAC.
Topics: Humans; Mitochondria; Pancreatic Neoplasms; Palmitic Acid; Organophosphorus Compounds; Proteomics; Cell Line, Tumor; Carcinoma, Pancreatic Ductal; Cell Proliferation; Membrane Potential, Mitochondrial; Reactive Oxygen Species; Apoptosis; Proteome; Antineoplastic Agents; Neoplastic Stem Cells; Autophagy
PubMed: 38928494
DOI: 10.3390/ijms25126790 -
International Journal of Molecular... Jun 2024Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach...
Higher EpCAM-Positive Extracellular Vesicle Concentration in Ascites Is Associated with Shorter Progression-Free Survival of Patients with Advanced High-Grade Serous Carcinoma.
Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.
Topics: Humans; Epithelial Cell Adhesion Molecule; Extracellular Vesicles; Female; Ascites; Middle Aged; Aged; Biomarkers, Tumor; Progression-Free Survival; Cystadenocarcinoma, Serous; Ovarian Neoplasms; Prognosis; Adult; Neoplasm Grading
PubMed: 38928484
DOI: 10.3390/ijms25126780 -
International Journal of Molecular... Jun 2024Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian...
Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian tumors and their associations with tumor subtype, stage, and clinical outcome. A retrospective analysis was conducted on 64 patients under 18 years old, examining demographic data, tumor characteristics, immunohistochemical staining, and clinical outcomes. Our results show that SALL4 was significantly expressed in adenocarcinoma, dysgerminoma (DSG), mixed germ cell tumors (GCTs), and immature teratoma, while OCT3/4 was highly expressed in DSG and mixed GCTs. Both markers are associated with a higher tumor grade and stage, indicating a more aggressive disease. The SALL4 positivity expression was correlated with high alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) levels, while OCT3/4 positivity significantly predicted the risk of subsequent metastasis. The mean progression-free survival (PFS) was notably shorter in patients with positive markers. These findings underscore the diagnostic and prognostic value of SALL4 and OCT3/4 in pediatric ovarian tumors, aligning with previous research and supporting their use in clinical practice for better disease management and patient outcomes.
Topics: Humans; Female; Ovarian Neoplasms; Biomarkers, Tumor; Child; Adolescent; Child, Preschool; Retrospective Studies; Prognosis; Octamer Transcription Factor-3; Romania; Infant; Transcription Factors; Teratoma
PubMed: 38928458
DOI: 10.3390/ijms25126752