Search Results (195)

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

The synthesis of 2-phenylbenzoxazole fluorosulfate derivatives was carried out using the SuFEx reaction. To study the anticancer properties of the obtained compounds, the cell lines PC-3 (obtained from prostate adenocarcinoma), BT-474, and MCF-7 (both obtained from breast carcinoma) were used. The cytotoxicity on murine 3T3L1 embryonic was also investigated. Among the tested compounds, the ortho-substituted fluorosulfate derivative (BOSo) exhibited significant cytotoxicity against MCF-7 cells. The biological findings are consistent with molecular docking results, which revealed a structural similarity between BOSo and known inhibitors of hER and HER2 receptors—tamoxifen and SYR127063. Therefore, BOSo shows promise as a potential therapeutic agent with antiproliferative properties. The photoluminescent characteristics of the fluorosulfate derivatives were examined in the solid state, in acetonitrile solution and in PBS, with the highest quantum yields reaching up to 64% for the para-fluorosulfate derivative in acetonitrile. Overall, these compounds demonstrate considerable potential for the development of new multifunctional molecular tools that combine biological activity with fluorescent properties. Full article

Background: Often, neoadjuvant therapy, which relies on the induction of double-strand breaks (DSBs), is used prior to surgery to shrink tumors by inducing cancer cell apoptosis. However, recent studies have suggested that this treatment may also induce a fluctuating state between senescence and stemness in PA-1 embryonal carcinoma cells, potentially affecting therapeutic outcomes. Thus, the respective epigenetic pathways are up or downregulated over a time period of days. These fluctuations go hand in hand with changes in spatial DNA organization. Methods: By means of Single-Molecule Localization Microscopy in combination with mathematical evaluation tools for pointillist data sets, we investigated the organization of euchromatin and heterochromatin at the nanoscale on the third and fifth day after etoposide treatment. Results: Using fluorescently labeled antibodies against H3K9me3 (heterochromatin tri-methylation sites) and H3K4me3 (euchromatin tri-methylation sites), we found that the induction of DSBs led to the de-condensation of heterochromatin and compaction of euchromatin, with a peak effect on day 3 after the treatment. On day 3, we also observed the co-localization of euchromatin and heterochromatin, which have marks that usually occur in exclusive low-overlapping network-like compartments. The evaluation of the SMLM data using topological tools (persistent homology and persistent imaging) and principal component analysis, as well as the confocal microscopy analysis of H3K9me3- and H3K4me3-stained PA-1 cells, supported the findings that distinct shifts in euchromatin and heterochromatin organization took place in a subpopulation of these cells during the days after the treatment. Furthermore, by means of flow cytometry, it was shown that the rearrangements in chromatin organization coincided with the simultaneous upregulation of the stemness promotors OCT4A and SOX2 and senescence promotors p21Cip1 and p27. Conclusions: Our findings suggest potential applications to improve cancer therapy by inhibiting chromatin remodeling and preventing therapy-induced senescence. Full article

Pluripotent stem cell (PSC)-based therapies are currently in clinical trials. However, one of the main safety concerns includes the potential for cancer formation of the PSC-derived products. Currently, the teratoma in vivo assay is accepted by regulatory agencies for identifying whether PSCs have the potential to become malignant. Yolk sac elements (YSE) are one of the elements that could arise from PSC. Whereas the other malignant element, embryonal carcinoma, is thoroughly studied, this is not the case for YSE. Therefore, more research is needed to assess the nature of YSE. We propose that it is imperative to include the formation of YSE in the safety assessment of PSC due to their close resemblance to the clinical entity of yolk sac tumor (YST), a human malignant germ cell tumor (hGCT). In this review, we extrapolate knowledge from YST to better understand YSE derived from PSC. We demonstrate that both share a similar morphology and that the same characteristic immunohistochemical markers can be used for their identification. We discuss the risk these tumors pose, thereby touching upon genetic abnormalities and gene expression that characterize them, as well as possible disease mechanisms. Integrating the molecular and immunohistochemical markers identified in this review into future research will help to better address the potential malignancy associated with PSC. Full article

We conducted a study to explore the potential of an enriched coumarin extract from Cachrys libanotis for the prevention and treatment of various diseases. The extract was prepared using pressurized cyclic solid–liquid extraction, and its safety profile was thoroughly evaluated using both cellular and embryonic models. Our main goal was to uncover a mixture of bioactive compounds that could offer therapeutic benefits. The following parameters were assessed: (i) extract composition; (ii) antioxidant activity; (iii) effects on cell viability and morphology; (iv) irritant potential (in ovo); and (v) antimicrobial activity against nine microbial strains. Chromatographic and spectrometric analyses confirmed that the main specialized metabolites in C. libanotis extract were furanocoumarins, with xanthotoxin, bergapten, and isopimpinellin identified as the three predominant constituents. Treatment with the C. libanotis extract did not induce significant alterations in the adherent human keratinocytes, with confluence and epithelial morphology comparable to control cells. Conversely, viable cells declined in the breast carcinoma cell line (MDA-MB-231). Moreover, the C. libanotis extract exhibited a promising antimicrobial activity against two Gram-negative pathogens, Shigella flexneri and Salmonella typhimurium. Full article

Background: Ovarian cancer remains the most lethal gynecological cancer, primarily due to its asymptomatic nature in early stages and consequent late diagnosis. Early detection improves survival, but current biomarkers lack sensitivity and specificity. Cell-free DNA (cfDNA) released from tumor cells captures tumor-associated epigenetic alterations and represents a promising source for minimally invasive biomarkers. Among these, aberrant DNA methylation occurs early in tumorigenesis and may reflect underlying disease biology. This study aimed to investigate genome-wide cfDNA methylation profiles in patients with ovarian cancer, benign ovarian conditions, and healthy controls to identify cancer-associated methylation patterns that may inform future biomarker development. Results: We performed genome-wide cfDNA methylation profiling using cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) on plasma samples from 40 patients with high-grade serous ovarian carcinoma, 38 patients with benign ovarian conditions, and 38 healthy postmenopausal women. A total of 536 differentially methylated regions (DMRs) were identified between ovarian cancer and controls (n = 76), with 97% showing hypermethylation in ovarian cancer. DMRs were enriched in CpG islands and gene bodies and depleted in repetitive elements, consistent with known cancer-associated methylation patterns. Fifteen genes showed robust hypermethylation across analyses. These genes exhibited methylation across intronic, exonic, and upstream regulatory regions. Separate comparisons of ovarian cancer to each control group (benign and healthy) supported the reproducibility of these findings. Gene Ontology enrichment analysis revealed enrichment in gland development, embryonic morphogenesis, and endocrine regulation, suggesting biological relevance to ovarian tumorigenesis. Conclusions: This study identifies consistent cfDNA hypermethylation patterns in ovarian cancer, affecting genes involved in developmental regulation and hormone-related processes. Our findings underscore the potential of cfMeDIP-seq for detecting tumor-specific methylation signatures in plasma and highlight these 15 hypermethylated genes as biologically relevant targets for future studies on cfDNA methylation in ovarian cancer. Full article

Background: Testicular germ cell tumors (GCTs) are highly curable malignancies, particularly when diagnosed early. However, cardiac metastases are exceedingly rare—occurring in less than 1% of cases—and pose significant diagnostic and therapeutic challenges. Intracardiac involvement is exceptionally uncommon and typically necessitates a multidisciplinary approach for optimal management. Objective: To present a rare case of metastatic testicular GCT with intracardiac extension in a young male, underscoring the diagnostic complexity and therapeutic considerations of this unusual clinical scenario. Case Report: A 23-year-old male presented with diffuse abdominal pain, dyspnea, and a palpable right testicular mass. Imaging revealed a testicular tumor with metastases to the lungs, liver, retroperitoneal lymph nodes, and a large intracardiac mass extending from the inferior vena cava into the right atrium. Histopathology confirmed a mixed-germ cell tumor consisting of 75% seminoma, 20% embryonal carcinoma, and 5% teratoma. The patient underwent radical right orchiectomy followed by chemotherapy with the BEP regimen (bleomycin, etoposide, cisplatin). Cardiac magnetic resonance imaging confirmed the intracardiac mass, which significantly decreased in size after treatment. Serum tumor markers (AFP and β-hCG) also showed substantial post-treatment declines, corresponding with clinical improvement. Conclusions: This case highlights a rare presentation of metastatic testicular GCT with intracardiac involvement, emphasizing the importance of recognizing atypical metastases. Despite its complexity, the patient responded well to chemotherapy, reinforcing the effectiveness of current treatments. Long-term follow-up and a multidisciplinary approach are essential for monitoring recurrence and complications, contributing to the understanding of rare metastatic patterns and the need for further research. Full article

Background/Aim: This case report navigates through the challenges of a complex clinical scenario involving germ cell tumors (GCTs), one of the most frequently encountered malignancies in adolescents and young adults. Case report: We present the case of an 18-year-old patient exhibiting atypical clinical manifestations, prompting emergent extensive surgical intervention. Upon admission to the Oncology Department, the adolescent presented with jaundice and dyspnea, being diagnosed with pure non-seminomatous embryonal carcinoma, a poor-risk prognosis group. Based on his prognostic group, the patient should have undergone chemotherapy with a well standardized regimen, but the imminent “liver visceral crisis” did not allow for the standard dose chemotherapy administration, so an adapted regimen of chemotherapy was considered and the full number of cycles was applied after this induction cycle. The treatment journey was protracted, emphasizing the need for early recognition and intervention in such cases. A comprehensive ongoing evaluation, including imagistic examinations and laboratory tests, revealed the presence of extensive refractory disease, which led to urgent treatment. Conclusions: This case provides valuable insights into the management of advanced testicular germ cell tumor in young patients facing imminent organ failure and underlines the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided. Full article

Krüppel-like factor 4 (KLF4) is a highly conserved zinc-finger transcription factor involved in cellular processes such as development, differentiation, and cell cycle regulation. Previous studies show that mouse embryonic fibroblasts (MEFs) null for Klf4 exhibit increased genomic instability. While KLF4 is regarded as a tumor suppressor in many human cancers, its role in DNA repair mechanisms remains unknown. In this study, cultured MEFs wild type (+/+) and null (−/−) for Klf4 and human carcinoma colorectal (RKO) cells were studied as a model for human colorectal cancer. Etoposide, a chemotherapeutic topoisomerase II poison, was employed to investigate KLF4’s role in DNA damage repair. Following etoposide treatment, immunostaining and Western blotting revealed cells expressing Klf4 exhibited lower levels of γ-H2AX, a biomarker for DNA damage, compared to cells without Klf4. Moreover, after DNA damage, cells expressing Klf4 exhibited increased levels of BRCA1 and Rad51, known tumor suppressor genes. Finally, genes involved in DNA damage response (DDR), ATR, and Chk1 were upregulated in cells containing functional KLF4, offering a possible mechanism for KLF4’s role in mediating DDR. Our results indicate that KLF4 plays a crucial role in maintaining genetic stability by enhancing cell DDR, supporting previous findings that KLF4 functions as a tumor suppressor. Full article

Background and Objectives: Oral cancer remains a critical global health concern, with oral squamous cell carcinoma (OSCC) being the most prevalent form. Oral potentially malignant disorders (OPMDs), such as oral leukoplakia (OLK), oral lichen planus (OLP), and actinic cheilitis (AC), often precede OSCC. Identifying reliable biomarkers is vital for assessing malignant transformation risk. The present study aimed to evaluate the immunohistochemical expression of differentiated embryonic chondrocyte 1 (DEC1), a marker of dysplasia severity, and cluster of differentiation 44 (CD44), which is associated with cancer progression, in OPMD and OSCC tissues. Materials and Methods: A retrospective analysis was conducted on 145 biopsy specimens from January 2015 to January 2023, comprising normal mucosa (NM), OLK, OLP, AC, and OSCC. DEC1 and CD44 expression levels were assessed using immunohistochemical staining. Positivity scores were determined based on staining intensity and extent, with statistical analyses performed using SPSS software (SPSS Inc., Chicago, IL, USA, version 29.0 for Windows). Results: It was found that CD44 expression significantly increased across OPMD and OSCC compared to NM (p < 0.001). Conversely, DEC1 expression was consistent across lesion types and dysplasia levels. CD44 expression was the highest in AC and OSCC, underscoring its potential role as a progression marker. Conclusions: The results indicate that CD44 is a more sensitive marker for assessing dysplastic severity and malignant transformation, while DEC1 may serve as a complementary marker for early-stage evaluation. Further research involving larger cohorts is needed to confirm these findings. Full article

Background/Objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors. This study aimed to assess the potential of differentially expressed miRNAs in differential diagnosis and prognostication among TGCT patients with various histologic subtypes. Methods: Transcriptomic analysis of 134 patients from The Cancer Genome Atlas (TCGA)-TGCT database was conducted. miRNA differential expression analysis among seminomatous, embryonal carcinoma, mixed GCT, and teratoma was performed, followed by ROC curve analysis of the most significantly up- and downregulated miRNAs, respectively. Statistical associations of miRNA expression with AJCC stage were also investigated along with miRNA target network analysis and evaluation of miRNA detection in patients’ fluids. Results: Upregulation of seven miRNAs (hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-200a, hsa-mir-200b, hsa-mir-203b, hsa-mir-375, hsa-mir-582) and downregulation of seven additional miRNAs (hsa-mir-105-1, hsa-mir-105-2, hsa-mir-4433a, hsa-mir-548x, hsa-mir-5708, hsa-mir-6715a, hsa-mir-767) were identified. miRNAs displayed a high sensitivity/specificity of 0.94/1.0 (AUC = 0.98) for the upregulated and 0.97/0.94 (AUC = 0.96) for the downregulated signature. Deregulated expression of these miRNAs was significantly associated with AJCC stage and distant organ metastasis (p < 0.001), overall supporting their prognostic strength. Both signatures were detectable in body fluids, particularly urine. miRNA target network analysis supported the functional role of these miRNAs in the regulation of cancer-related processes such as cell proliferation via deregulation of pivotal oncogenes. Conclusions: These findings support the clinical value of two novel miRNA signatures in differential diagnosis and prognostic stratification of various histologic subtypes of TGCT, with potential treatment implications. Full article

Background and Aim: Ex vivo fluorescence confocal microscopy (FCM) systems are innovative optical imaging tools that create virtual high-resolution histological images without any standard tissue processing, either freezing or fixing in formalin and embedding in paraffin. These systems have opened an era that would revolutionize pathological examination by providing rapid, real-time assessments across various pathology subspecialties, potentially replacing conventional methods that are tissue- and time-consuming. This study aimed to present the first utilization of FCM in pediatric surgical oncology, focusing on assessing the benefits, particularly in facilitating rapid and accurate diagnosis. Methods: This preliminary study comprised five consecutive patients undergoing surgical biopsy for disease characterization and surgical strategy selection. After biopsy, tissue samples were prepared and analyzed using FCM without sectioning. A pathologist who evaluated macroscopic and microscopic images, once obtained remotely, could promptly indicate any interventions that require timeliness. Samples were then evaluated with conventional methods. Results: All five lesions were deemed suitable for evaluation. Preliminary diagnoses utilizing FCM included atypical Spitz nevus (1), Wilm’s tumor (1), lymph node reactive hyperplasia (1), malignant germ cell tumor of the testis (1), and Hodgkin’s lymphoma (1). Final histopathological analyses revealed atypical Spitz nevus (1), Wilm’s tumor (1), hyperplastic lymphadenopathy with a prevalent marginal pattern (1), mixed nonseminomatous malignant germinal neoplasm consisting of embryonal carcinoma (90%) and yolk sac tumor (10%), and Hodgkin’s lymphoma nodular sclerosis variant (1). In the case of diagnosis of atypical Spitz nevus, the widening of the resection margins was performed in the same surgery. In the case of testicular neoplasm, radical orchiectomy was performed. A high level of agreement between FCM evaluation and definitive histological examination was observed for all parameters evaluated. Conclusions: FCM represents a significant advancement in pathological imaging technology, offering potential benefits in enhancing traditional tissue processing methods. This preliminary report marks the first application of FCM in pediatric surgical oncology. Our findings underscore the promising role of FCM as an adjunctive tool in pediatric oncology, facilitating prompt diagnosis and treatment initiation. Full article

Green algae of the genus Coelastrella have attracted the attention of scientists due to their rich biochemical composition and potential for application in phytomedicine. The present study investigated the influence of light on the bioactive capacity of extracts from the Bulgarian strain of the green microalgae Coelastrella sp. BGV. Three LED lights were examined—red/blue (C1), blue (C2), and control white light (C3). The respective ethanol extracts were analyzed for the total content of phenolic antioxidants. The antimicrobial activity was tested using the disk-diffusion method against 10 microorganisms. The antiproliferative and cytotoxic effects on cervical carcinoma HeLa and hepatocellular carcinoma HepG2 cell lines, as well as non-tumorigenic embryonal fibroblasts BALB/3T3 control, were evaluated using a cell viability assay. The overall results highlighted blue light as a factor enhancing the antioxidant, antibacterial, and cytotoxic activities of the C2 microalgal extract. Additionally, the investigated mechanism of the antitumor activity revealed a proapoptotic effect. In contrast, the C1 extract exhibited weaker activity and selectivity, while the C3 extract was the least active but demonstrated high cytotoxic selectivity. This study could contribute to expanding knowledge about the high biological potential of green microalgae and the development of biotechnological approaches for its regulation. Full article

Hepatocellular carcinoma is characterized by high recurrence rates and poor prognosis. Cancer stem cells contribute to tumor heterogeneity, treatment resistance, and recurrence. This study aims to identify key genes associated with stemness and immune cell infiltration in HCC. We analyzed RNA sequencing data from The Cancer Genome Atlas to calculate mRNA expression-based stemness index in HCC. A weighted gene co-expression network analysis was performed to identify stemness-related gene modules. A single-sample gene set enrichment analysis was used to evaluate immune cell infiltration. Key genes were validated using RT-qPCR. The mRNAsi was significantly higher in HCC tissues compared to adjacent normal tissues and correlated with poor overall survival. WGCNA and subsequent analyses identified 10 key genes, including minichromosome maintenance complex component 2, cell division cycle 6, forkhead box M1, NIMA-related kinase 2, Holliday junction recognition protein, DNA topoisomerase II alpha, denticleless E3 ubiquitin protein ligase homolog, maternal embryonic leucine zipper kinase, protein regulator of cytokinesis 1, and kinesin family member C1, associated with stemness and low immune cell infiltration. These genes were significantly upregulated in HCC tissues. A functional enrichment analysis revealed their involvement in cell cycle regulation. This study identified 10 key genes related to stemness and immune cell infiltration in HCC. These genes, primarily involved in cell cycle regulation, may serve as potential targets for developing more effective treatments to reduce HCC recurrence and improve patient outcomes. Full article

Thyroid gland diseases remain clinical challenges due to the lack of reliable in vitro models to examine molecular pathways of thyrocytes development, maturation, and functional maintenance. This study aimed to develop in vitro thyrocytes model using a stem cell culture, P19 embryonal carcinoma which requires no feeder layer, differentiation into mature and functional thyrocytes that allow molecular and genetic manipulation for studying thyroid diseases. The procedure utilizes Activin A and thyroid stimulating hormone (TSH) to first induce embryoid body endoderm formation enriched in thyrocyte progenitors. Following dissociating embryoid bodies, thyrocyte progenitors are plated in Matrigel as monolayer cultures that allows thyrocyte progenitors mature to functional thyrocytes. These thyrocytes further maturate to form follicle-like structures expressing and accumulating thyroglobulin that can be secreted into the medium upon TSH stimulation. Thyrocyte differentiation-maturation process is monitored by the expression of essential transcriptional factors and thyrocyte-specific functional genes. Further, the applicability of this system is validated by introducing a siRNA control. Following molecular manipulation, the system can still be guided to differentiate into mature and functional thyrocytes. This system spans a time frame of 14 days, suitable for detailed molecular studies to dissect pathways and molecular players in thyrocytes development and functional maintenance. Full article