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.

Introduction: X-linked hypophosphatemia (XLH) is a rare genetic disorder caused by PHEX mutations, characterized by chronic hypophosphatemia and renal phosphate wasting, resulting in skeletal, dental, and extra-skeletal complications. To date, no data from Malaysia are currently available on clinical characteristics or health-related quality of life (HRQoL) in paediatric patients. Methodology: This cross-sectional study evaluated HRQoL among children and adolescents with XLH, using validated PROMIS (PatientReported Outcomes Measurement Information System) instruments, sociodemographic and clinical factors associated with HRQoL. This includes children and adolescents with confirmed XLH followed up at Universiti Malaya Medical Centre (UMMC) between November 2024 and March 2025. Results: Seventeen patients were analyzed (76.5% female and 23.5% male). The mean age at symptom onset was 2.82 ± 2.42 years, with a mean age at diagnosis of 5.21 ± 3.29 years. All patients continued to have musculoskeletal complications, including short stature (76.5%), bowing of legs (76.5%), bone/joint pain (47.1%), muscle pain (47.1%), and dental complications (52.9%). Serum alkaline phosphatase improved significantly (p = 0.011); persistent hypophosphatemia and ongoing musculoskeletal manifestations indicated suboptimal disease control. Elevated parathyroid hormone levels and an increase in urine calciumto-creatinine ratio (p = 0.020) lead to secondary hyperparathyroidism and nephrocalcinosis. Adherence to conventional therapy was poor. Non-adherence was associated with worse pain outcomes (higher pain interference [p = 0.037] and greater pain intensity [p = 0.025]). PROMIS scores revealed severely impaired mobility (mean T-score 31.31 ± 12.17), increased fatigue (mean T-score 54.22 ± 7.60), and high pain interference (mean T-score 63.11 ± 9.50). Larger household size was also strongly associated with higher pain intensity (p = 0.004). Conclusion Malaysian children and adolescents with XLH continue to have significantly poor HRQoL, particularly in mobility, fatigue, and pain. These findings highlight the need for access to targeted therapies, such as burosumab, to improve long-term outcomes and QOL in XLH patients.
Adolescent ; Child ; Familial Hypophosphatemic Rickets ; Malaysia ; Quality of Life

Conventional cancer therapies, such as radiotherapy and chemotherapy, often damage normal cells and may induce new tumors. Oncolytic viruses (OVs) selectively target tumor cells while sparing normal cells. Most OVs used in clinical trials have been genetically engineered to enhance their ability to target tumor cells and activate immune responses. To develop a specific OV-based approach for treating cervical cancer, this study constructed an oncolytic adenovirus that delivered a base editor targeting oncogenes to achieve efficient killing of tumor cells through inhibiting tumor growth and directly lysing tumor cells. We utilized the human telomerase reverse transcriptase (TERT) promoter to drive the expression of adenovirus early region 1A (E1A) and successfully constructed the P-hTERT-E1A-GFP vector, which was validated for its activity in cervical cancer cells. Given the critical role of the MYC oncogene in the research of oncology, identifying efficient editing sites for the MYC oncogene is a key step in this study.Three MYC-targeting gRNAs were engineered and co-delivered with ABE8e base editor plasmids into HEK293T cells. Following puromycin selection, Sanger sequencing demonstrated differential editing efficiencies: MYC-1 (43%), MYC-2 (25%), and MYC-3 (35%), identifying MYC-1 as the most efficient editing locus. By constructing the P-ABEs-hTERT-E1A-GFP and P-MYC gRNA-hTERT-E1A-GFP vectors, we successfully packaged the virus and confirmed its specificity and efficacy. The experimental results demonstrate that this novel oncolytic adenovirus effectively inhibits the growth of HeLa cells in vitro, providing new experimental evidence and potential strategies for treating cervical cancer based on the HeLa cell model.
Humans ; Uterine Cervical Neoplasms/pathology* ; Oncolytic Viruses/genetics* ; Female ; HEK293 Cells ; Oncolytic Virotherapy/methods* ; Adenoviridae/genetics* ; Gene Editing/methods* ; Telomerase/genetics* ; Adenovirus E1A Proteins/genetics* ; Genetic Vectors/genetics* ; HeLa Cells

Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

Primary female genital system lymphoma(PFGSL)is a rare subtype of extranodal lymphoma and patients commonly present in the department of gynecology.At present,there is a lack of uniform standards for the treatment of PFGSL.Although the classification of lymphoid neoplasmas was updated by the World Health Organization classification of haematolymphoid tumors in 2016,PFGSL was still not elaborated in sufficient detail.Most cases of PFGSL are non-Hodgkin lymphoma,involving the ovary and cervix.In some cases,involvement of uterine corpus,vagina,and vulva is reported.In this article,we report two cases of non-Hodgkin lymphoma in the female genital system,one from the uterus and the other from the ovary.By presenting the diagnosis and treatment of the two cases and reviewing the literature,we aim to provide a reference for clinicians in recognizing and treating rare cases.
Female ; Humans ; Genital Neoplasms, Female/diagnosis* ; Lymphoma, Non-Hodgkin/diagnosis* ; Ovarian Neoplasms

Objective To investigate the effect of the small molecule inhibitor C42 of kallikrein-related peptidase 7(KLK7)on ovarian cancer with elevated expression of KLK7 and evaluate the feasibility of C42 as a new therapeutic strategy for ovarian cancer.Methods The CCK-8 assay,flow cytometry,cell scratch assay,Transwell assay,and Western blotting were employed to assess the effects of C42 on the proliferation,migration,and invasion of the ovarian cancer cell line SKOV3,which was characterized by high KLK7 expression.Additionally,a subcutaneous xenograft model of ovarian cancer was established with SKOV3 cells in nude mice to evaluate the effects of C42 on the tumor growth and metastasis.The expression levels of proteins associated with tumor metastasis and invasion in the tumor tissue were examined by immunohistochemical techniques.Results The cellular experiment showed that C42 suppressed the proliferation,migration,and invasion(all P<0.001)of SKOV3 cells,compared with the control group.The animal experiment showed that compared with the control group,the 10.2 mg/kg C42 group exhibited a decreased tumor weight(P=0.009) and attenuated liver metastases.Immunohistochemical staining revealed that the 10.2 mg/kg C42 group demonstrated down-regulated expression of the tumor proliferation marker Ki-67(P=0.002)and the tumor metastasis and invasion-associated proteins such as matrix metalloproteinase-9(P=0.027)and Vimentin(P=0.039).Conclusion The small molecule inhibitor C42 of KLK7 effectively suppresses the proliferation,migration,and invasion of ovarian cancer SKOV3 cells.
Female ; Humans ; Ovarian Neoplasms/drug therapy* ; Kallikreins/antagonists & inhibitors* ; Animals ; Mice, Nude ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C

BACKGROUND: Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells. METHODS: Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa). RESULTS: The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa. CONCLUSIONS MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

OBJECTIVES: Ovarian cancer is a common gynecologic malignancy, with poor prognosis in advanced stages. This study aimed to identify differentially expressed long noncoding RNA (lncRNA) associated with ovarian cancer prognosis and to explore the effects of lncRNA RP11-499E18.1 on the malignant biological behavior of ovarian cancer cells. METHODS: Ovarian cancer-related lncRNA datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed and prognostically relevant tumor-suppressive lncRNAs were screened using lncRNA sequencing combined with clinical data. Reverse transcription PCR (RT-PCR) was used to detect the expression of lncRNA RP11-499E18.1 in ovarian cancer tissues, adjacent normal tissues, the IOSE80 normal ovarian epithelial cell line, and various ovarian cancer cell lines. Fluorescence in situ hybridization (FISH) was performed to determine its subcellular localization. Ovarian cancer cell lines CaOV3 and SKOV3 were divided into 3 groups: a negative control (NC) group, a knockdown (si-RP11-499E18.1) group, and a overexpression (pcDNA-RP11-499E18.1) group. Methyl thiazolyl tetrazolium (MTT) and Transwell assays were used to assess the effects of lncRNA RP11-499E18.1 on cell proliferation and migration. Western blotting was used to evaluate its effect on epithelial-mesenchymal transition (EMT)-related molecules. BALB/c nude mice were injected with CaOV3 cells transfected with pcDNA-RP11-499E18.1 (experimental group) or empty vector (control group), and tumor growth was monitored. Immunohistochemistry was used to assess the expression of Caspase 3 and Ki67 in tumor tissues. RESULTS: LncRNA sequencing identified RP11-499E18.1 as a differentially expressed and associated with prognosis. GEO data analysis showed that low RP11-499E18.1 expression was correlated with shorter overall and progression-free survival (both P<0.05). Its expression was significantly lower in ovarian cancer tissues and cell lines compared to normal controls (P<0.05 or P<0.001), and it was localized in both the nucleus and cytoplasm. In CaOV3 and SKOV3 cells, proliferation rates increased significantly in the si-RP11-499E18.1 group and decreased in the pcDNA-RP11-499E18.1 group (P<0.05 or P<0.001). Cell migration was enhanced in the si-RP11-499E18.1 group and suppressed in the pcDNA-RP11-499E18.1 group. Overexpression increased E-cadherin and decreased vimentin expression, while knockdown had the opposite effect. Tumor volume in the mouse model was significantly smaller in the experimental group (P<0.001), with increased Caspase 3 and decreased Ki67 expression in tumor tissues (both P<0.05). CONCLUSIONS LncRNA RP11-499E18.1 inhibits proliferation, migration, and EMT of ovarian cancer cells, and its low expression is associated with poor prognosis.
Female ; Humans ; RNA, Long Noncoding/physiology* ; Ovarian Neoplasms/pathology* ; Cell Line, Tumor ; Animals ; Mice ; Mice, Nude ; Cell Proliferation ; Prognosis ; Mice, Inbred BALB C ; Gene Expression Regulation, Neoplastic ; Cell Movement ; Epithelial-Mesenchymal Transition

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

OBJECTIVES: Renal cell carcinoma (RCC) is a malignant renal tumor that poses a significant threat to patient health. Accurate preoperative pathological grading plays a crucial role in determining the appropriate treatment for this disease. Currently, deep learning technology has become an important method for pathological grading of RCC. However, existing methods primarily rely on single-phase computed tomography (CT) imaging for analysis and prediction, which has limitations such as missing small lesions, one-sided evaluation, and local focusing issues. Therefore, this study proposes a multi-modal deep learning algorithm that integrates multi-phase enhanced CT images with clinical variable data, aiming to provide a basis for predicting the pathological grading of RCC. METHODS: First, the algorithm took four-phase enhanced CT images from the plain scan, arterial phase, venous phase, and delayed phase, along with clinical variables, as inputs. Then, an embedding encoding module was used to extract heterogeneous information from the clinical variables, and a 3-dimensional (3D) ResNet50 model was employed to capture spatial information from the multi-phase enhanced CT image data. Finally, a Fusion module deeply integrated the feature information from clinical variables and each phase's CT image features, further utilizing a cross-self-attention mechanism to achieve multi-phase feature fusion. This approach comprehensively captures the deep semantic information from the patient data, fully leveraging the complementary advantages of multi-modal and multi-phase data. To validate the effectiveness of the proposed method, a total of 1 229 RCC patients were approved by ethics review were included to train the model. RESULTS: Experimental results demonstrated superior performance compared to traditional radiomics and state-of-the-art deep learning methods, achieving an accuracy of 83.87%, a recall rate of 95.04%, and an F1-score of 82.23%. CONCLUSIONS The proposed algorithm exhibits strong stability and sensitivity, significantly enhancing the predictive performance of RCC pathological grading. It offers a novel approach for accurate RCC diagnosis and personalized treatment planning.
Humans ; Carcinoma, Renal Cell/pathology* ; Deep Learning ; Kidney Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Algorithms ; Neoplasm Grading ; Male ; Female ; Middle Aged