BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

BACKGROUND AND OBJECTIVES

Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.

METHODS

A laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS

Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION

Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.

Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry

Abstract Embryonal rhabdomyosarcoma (ERMS) is a primitive and aggressive soft tissue tumor that arises from premature mesenchymal cells and accounts for less than 1% of prostate malignancies. We present the case of a 26-year-old Filipino male who initially sought consultation and work-up for acute urinary retention. Although his prostate-specific antigen (PSA) level was normal, a kidney-ureter-bladder (KUB) ultrasound revealed an incidental finding of an enlarged prostate gland. Subsequent imaging tests (MRI and CT) identified a large, partially exophytic mass on the prostate with intravesical extension. The patient underwent a biopsy via transurethral resection at another institution, which yielded findings of a poorly differentiated carcinoma, primarily suggesting prostatic adenocarcinoma with a Gleason score of 10 (5+5). A request for slide review was submitted to our institution, and subsequent immunohistochemistry (IHC) studies—highlighting the tumor's immunoreactivity to myogenin and desmin—confirmed the diagnosis of ERMS. In this report, we discuss the clinical features, pathogenesis, treatment, diagnosis, and prognosis of this rare prostate tumor.
Embryonal rhabdomyosarcoma ; Immunohistochemistry ; Prostate ; Young adult

Angiomyolipoma with epithelial cysts (AMLEC) is a rare subtype of angiomyolipoma that may closely mimic both malignant and benign neoplasms. We report a case of AMLEC in an 18-year-old female presenting with acute flank pain and radiologic suspicion for malignancy. This case highlights the diagnostic challenges posed by AMLEC, emphasizes its characteristic histopathologic and immunohistochemical features, and reviews current concepts regarding its pathogenesis. This case represents the first documented case of AMLEC in the Philippines.

Human ; Angiomyolipoma ; Kidney Neoplasms ; Immunohistochemistry

OBJECTIVES: To identify potential molecular targets of quercetin in the treatment of clear cell renal carcinoma (ccRCC). METHODS: The therapeutic targets of quercetin were screened from multiple databases by network pharmacology analysis, and the targets significantly correlated with ccRCC were screened from 4907 plasma proteins using a Mendelian randomization method. The drug-disease network model was constructed to screen the potential key targets. The functions of these targets were evaluated via bioinformatics analysis, and the screened targets were verified in cultured ccRCC cells. RESULTS: Network pharmacology analysis combined with Mendelian randomization identified TP53 (OR=3.325, 95% CI: 1.805-6.124, P=0.0001), ARF4 (OR=0.173, 95% CI: 0.065-0.456, P=0.0003), and DPP4 (OR=0.463, 95% CI: 0.302-0.711, P=0.0004) as the core targets in quercetin treatment of ccRCC. Bioinformatics analysis showed that TP53 was highly expressed in ccRCC, and patients with high TP53 expressions had worse survival outcomes. Molecular docking studies showed that the binding energy between quercetin and TP53 was -5.83 kcal/mol. In cultured 786-O cells, CCK-8 assay and wound healing assay showed that treatment with quercetin significantly inhibited cell proliferation and migration. Quercetin treatment also strongly suppressed the expression of TP53 at both the mRNA and protein levels in 786-O cells as shown by RT-qPCR and Western blotting. CONCLUSIONS TP53 may be the key target of quercetin in the treatment of ccRCC, which sheds light on potential molecular mechanism that mediate the therapeutic effect of quercetin.
Humans ; Quercetin/pharmacology* ; Carcinoma, Renal Cell/genetics* ; Cell Proliferation/drug effects* ; Kidney Neoplasms/genetics* ; Cell Movement/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Cell Line, Tumor ; Computational Biology

OBJECTIVES: To establish a three-dimensional (3D) visualization-based classification of the left hepatic portal vein (LHPV) and left hepatic vein (LHV) systems using 3D reconstruction technology to facilitate precise segmental/subsegmental resection of left liver lesions. METHODS: Thin-slice contrast-enhanced CT datasets from 244 patients were reconstructed using MI-3DV Works software. The spatial anatomy (origins, branching patterns, and spatial relationships) of the LHPV and LHV branches was analyzed to determine their 3D classifications and segmental liver divisions for guiding surgical planning for anatomical left liver resections. RESULTS: The 3D models of the third- and fourth-order branches of the LHPV and LHV were successfully reconstructed for all the 244 patients. Two types of the LHPV system were identified, where the LHPV either had independent origins [242 cases (99.1%)] or had right anterior portal branches arising from the LHPV trunk [2 cases (0.9%)]. 3D classifications identified two types of the Segment II of the LHPV (based on branch number), 3 types of the Segment III (by spatial distribution of the branches), compact vs dispersed types of the left lateral lobe (determined by Segment II/III branches proximity), 3 types of the Segment IV (by branch number and origin), and 3 types the fourth hilar vessels (transverse branches of the left portal vein) for their supplied segments. The LHV system had two drainage types into the inferior vena cava, and the umbilical fissure veins were classified into 3 types by drainage patterns and distance to the venous roots. These classifications combined with liver segmentations allowed individualized surgical planning for segment-specific resections. CONCLUSIONS The 3D classification of the LHPV and LHV provides valuable clinical guidance for precise anatomical resections of left liver lesions using liver segments or subsegments as anatomical units to enhance surgical accuracy and improve the outcomes of hepatobiliary surgery.
Humans ; Hepatectomy/methods* ; Imaging, Three-Dimensional ; Hepatic Veins/anatomy & histology* ; Portal Vein/anatomy & histology* ; Liver/surgery* ; Liver Neoplasms/blood supply* ; Tomography, X-Ray Computed ; Female

This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.
Humans ; Cerebral Cortex/anatomy & histology* ; Male ; Female ; Magnetic Resonance Imaging ; Adult ; Connectome/methods* ; Young Adult ; Nerve Net/anatomy & histology* ; Neural Pathways ; Depressive Disorder, Major/diagnostic imaging*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*