Search Results (2,318)

Background: Ovarian cancer remains the deadliest gynecologic malignancy, with its progression closely tied to age-associated remodeling of the tumor immune microenvironment. The laying hen serves as a valuable spontaneous model for human ovarian cancer. Its single-cell analyses may provide valuable insights into the immune-related axis linking ovarian aging to carcinogenesis. Methods: This study applied single-cell RNA sequencing to profile ovaries from three laying hen groups, including 35-week-old normal ovaries (A35w), 110-week-old normal ovaries (B110w), and 110-week-old ovarian cancer tissues (C110w). Key analyses had UCell-based scoring of senescence-related pathways and cancer hallmarks, differential expression analysis for overlapping dysregulated genes, LASSO regression-based prognostic model construction, and assessment of chemotherapy sensitivity and immune infiltration. Results: A comprehensive cellular landscape of chicken ovaries was established, identifying major immune populations including B cells, CD4+ T cells, CD8+ T cells, macrophages, and plasma cells. Senescence-related pathways and cancer hallmarks showed progressive activation in immune cells from A35w to B110w to C110w. A total of 216 genes commonly dysregulated in aging and carcinogenesis, reveal core links between immune dysfunction and malignant transformation. The 20-gene prognostic model derived from these genes stratified human ovarian cancer patients into high-risk and low-risk groups with significant overall survival differences, exhibited robust predictive performance across TCGA, GSE32063, and GSE140082. The model also predicted the differential chemotherapy sensitivity in high-risk and low-risk patients and correlated with specific immune infiltration patterns in the tumor microenvironment. Conclusions: Notably, this is the first single-cell RNA sequencing study of chicken ovarian cancer, and we constructed the 20-gene prognostic model for human ovarian cancer using 216 genes that change significantly in immune cells during both ovarian aging and carcinogenesis. This work provides support to establish the hen as a potential preclinical animal model and a translational tool to guide personalized therapy. Full article

Ovarian cancer (OC), the third most common gynecologic malignancy, is characterized by high mortality largely driven by chemotherapy resistance, leading to recurrence and metastasis. Using transcriptomic data from GSE73935, we constructed a weighted gene co-expression network and identified eight hub genes (IGF1R, CDH2, PDGFRA, CDKN1A, SHC1, SPP1, CAV1 and FGF18) associated with cisplatin resistance, among which CDH2 emerged as the most clinically relevant candidate. CDH2 demonstrated moderate diagnostic potential (AUC = 0.792) and was markedly upregulated in cisplatin-resistant A2780/CP70 cells. Independent validation using clinical single-cell RNA-seq data (GSE211956) confirmed its selective enrichment in resistant tumor cell subpopulations. Gene set enrichment analysis linked elevated CDH2 expression to p53 signaling, DNA replication, nucleotide excision repair, and Toll-like receptor pathways, with qPCR supporting upregulation of key downstream genes in resistant cells. Immune deconvolution further indicated that high CDH2 expression correlated with increased infiltration of NK cells, Tregs, macrophages, and neutrophils, and immunohistochemistry verified CDH2 overexpression in cisplatin-resistant tissues. In addition, virtual screening and drug sensitivity profiling identified several FDA-approved agents with potential relevance to CDH2-associated drug response. These findings indicate that CDH2 may serve as a candidate marker associated with cisplatin response in OC, and its association with immune cell infiltration provides further insight into mechanisms potentially underlying chemoresistance. Full article

Background and Clinical Significance: A paratubal leiomyoma is an exceptionally rare benign smooth muscle tumor arising from paratubal tissue, with only sporadic cases reported in the literature. Case Presentation: We present the case of a 72-year-old postmenopausal woman with intermittent spotting for three months. A pelvic examination revealed a retained intrauterine device, which was removed along with an old sanguineous discharge. A transvaginal ultrasound demonstrated a complex left adnexal mass with calcifications, and computed tomography (CT) confirmed a 7.8 × 5.5 × 4.7 cm lesion suggestive of an ovarian malignancy. Tumor markers showed mildly elevated CA-125 and carcinoembryonic antigen (CEA) levels. Endometrial sampling using a hysteroscopy and curettage revealed hyperplasia without atypia. The patient underwent a total laparoscopic hysterectomy with a bilateral salpingo-oophorectomy. A diagnostic laparoscopy revealed a well-circumscribed solid mass arising from the mesosalpinx, separate from the ovary and fallopian tube and consistent with a paratubal mass, which was successfully excised laparoscopically. Frozen sections suggested a fibroma, and the final pathology confirmed a paratubal leiomyoma with hyalinization, accompanied by adenomyosis and simple endometrial hyperplasia. The patient recovered uneventfully, and the 6-month follow-up showed no recurrence. This case highlights the diagnostic challenge of differentiating paratubal leiomyomas from ovarian tumors based on imaging alone. Histopathological examination is essential for confirmation. Conclusions: Awareness of paratubal leiomyomas as a differential diagnosis may prevent overtreatment and guide the appropriate surgical management of postmenopausal women presenting with adnexal masses. Full article

This systematic review investigates the impact of chronic stress on treatment outcomes among cancer patients with divergent survival rates, focusing on breast, prostate, pancreatic, and ovarian cancers. The analysis explores how chronic stress influences molecular pathways and tumor progression while comparing cancers with five-year survival rates above and below 50%. A comprehensive literature search was conducted in PubMed and Scopus for studies published between 2014 and 2025 using combinations of keywords related to “chronic stress,” “psychological stress,” “psychotherapy,” and selected cancer types. All studies met the inclusion criteria according to the PRISMA 2020 guidelines. Evidence suggests that chronic stress is associated with the activation of neuroendocrine and immune mechanisms, including β-adrenergic and glucocorticoid signaling. These multifactorial processes are associated with disease progression and survival, particularly in pancreatic and ovarian cancers; however, these links remain primarily associative rather than causative. Conversely, psychotherapeutic interventions alleviate stress-related biological responses, improve quality of life, and may indirectly enhance therapeutic efficacy. By structuring the evidence around cancers with higher versus lower five-year survival, our review provides a survival informed synthesis of cancer type specific stress biology and stress-mitigating interventions, highlighting potentially targetable pathways and clear evidence gaps for future trials. The findings underscore the need to integrate psychological care into oncological practice to improve overall outcomes. Full article

Cisplatin, a platinum-based compound, is a cornerstone of modern chemotherapy and remains widely used against a variety of solid tumors, including testicular, ovarian, lung, bladder, and head and neck cancers. Its anticancer activity is primarily attributed to the formation of DNA crosslinks, which obstruct replication and repair, ultimately leading to apoptosis. However, the clinical value of cisplatin is constrained by two major challenges: its toxic profile and the development of resistance. Cisplatin toxicity arises from its interaction not only with tumor DNA but also with proteins and nucleic acids in healthy tissues, resulting in a range of adverse effects, including, but not limited to, nephrotoxicity, ototoxicity, neurotoxicity, and gastrointestinal injury. In pediatric patients, permanent hearing loss represents a particularly debilitating complication. On the other hand, tumor cells can evade cisplatin cytotoxicity through diverse mechanisms, including reduced intracellular drug accumulation, enhanced DNA repair, detoxification by thiol-containing molecules, and alterations in apoptotic signaling. These resistance pathways severely compromise treatment outcomes and often necessitate alternative or combination strategies. This review examines the chemical structure of cisplatin, the molecular mechanisms of cisplatin cytotoxicity and cisplatin-induced resistance, as well as the main applications in cancer management and the complications associated with its clinical use. Full article

Chemotherapy causes primordial follicle apoptosis, resulting in premature ovarian insufficiency (POI) and infertility. In this study, we found that intraperitoneal injection of retinoic acid (RA) and calcitriol partially reversed the cyclophosphamide and doxorubicin treatment-induced decrease in primordial follicles in neonatal mouse ovaries. Furthermore, RA and calcitriol co-treatment reversed cyclophosphamide treatment-induced PI3K/Akt activity and FOXO3a nuclear export in the oocytes within primordial follicles, suggesting that the oocyte transcriptional activity was decreased, which in turn reduced the binding of chemotherapeutic drugs to DNA. Consistent with these findings, RA and calcitriol co-treatment reversed cyclophosphamide treatment-induced changes in reactive oxygen species (ROS), DNA damage response proteins (γH2AX, p-CHK2, p-p53, PUMA, BAX, Cleaved Caspase-3, and cPARP), and antioxidant proteins (NRF2, HO-1, and GPX4). Moreover, RA and calcitriol co-treatment preserved fertility in cyclophosphamide-treated mice without impairing cyclophosphamide’s antitumor efficacy in MCF-7 tumor-bearing mice. Thus, RA and calcitriol protect mouse primordial follicles from cyclophosphamide treatment-induced apoptosis by inhibiting cyclophosphamide treatment-induced oocyte transcriptional activity and enhancing antioxidant capacity. Our results suggest a potential strategy for preserving ovarian reserve during chemotherapy in female cancer patients. Full article

High-grade serous ovarian carcinoma (HGSC) is predominantly diagnosed at advanced stages with extensive peritoneal metastasis. A pivotal early event in HGSC development is the peritoneal seeding of tumor cells originating from the fallopian tube epithelial (FTE) precursor lesions. Ovulation releases follicular fluid (FF), which is known to contain oncogenic factors that promote FTE cell transformation. However, the specific mechanisms and factors within FF that drive the early metastatic seeding of precancerous FTE cells remain poorly defined. We investigated the role of FF in the peritoneal dissemination of FTE-derived cells, and the abundance of fibronectin (FN) as a potential key mediator. Functional assays were performed using FN-depleted FF to assess its impact on migration, invasion, anchorage-independent growth, and peritoneal attachment. The role of the fibronectin receptor, integrin β1 (ITGB1), and the signaling pathways were evaluated via knockdown studies. In vivo xenograft models were used to quantify peritoneal seeding, and mechanistic studies elucidated the involved signaling pathways. We identified FN as a critical component of FF, present at high concentrations (~210 µg/mL), that potently drives FTE cell migration, invasion, and peritoneal seeding. Depletion of FN from FF abrogated the majority of these pro-metastatic activities in vitro and led to a dramatic 82% reduction in peritoneal tumor seeding in vivo. Knockdown of ITGB1 similarly impaired seeding. Mechanistically, FF-derived FN activates the ITGB1/FAK-SRC signaling pathway to promote tumor cell motility and colonization. Our study establishes FF-fibronectin as an important regulator of the early peritoneal seeding of HGSC precursor cells. These findings reveal a direct link between ovulation and HGSC development, suggesting that targeting the FN-ITGB1 signaling axis may offer a novel preventive strategy for high-risk individuals. Full article

Background: Intracellular miRNA transfer is an intriguing and lesser-described mode of intracellular communication. Epithelial ovarian carcinoma, of which the high-grade serous histotype represents the most common and deadliest form, is characterized by a microenvironment consisting of tumor and stromal cells, ascitic fluid, and extracellular matrix, presenting a rich milieu of factors that can affect neighboring cells. Methods: We examined the mode of miR transfer in serous ovarian carcinoma cell lines cultured on different extracellular matrix supports both in two-dimensional and three-dimensional formats coupled with traditional, live-cell time-lapse, multiphoton fluorescence imaging modalities, and fluorescence-activated cell sorting approaches. Results: Our data demonstrate that miR can transfer between cells both in culture and in vivo. Moreover, transferred miRNA results in target-specific gene expression changes in recipient cells. Our data indicate that miR transfer occurs via extracellular vesicles, which shuttle from and within the donor and recipient cells via endocytic pathways recruiting sorting, early, late, and recycling endosomes. Conclusions: Our study highlights the phenomenon of miR transfer as a mode of communication between serous ovarian cancer cells, which can affect both treatment and diagnostics of this disease. Full article

Background/Objectives: Epithelial ovarian cancer (EOC) constitutes the predominant form of ovarian malignancies. The primary goal of this study was to determine predictors of patient survival and construct a nomogram for survival prediction in individuals diagnosed with epithelial ovarian cancer. Methods: A retrospective cohort analysis was performed, including 418 patients who received treatment for epithelial ovarian cancer at Tu Du Hospital from January 2015 to December 2019. The median follow-up time was 77.1 months (range: 5.7–121.6 months). Survival analyses were conducted using the log-rank test and Cox proportional hazard regression analysis. A nomogram was developed, incorporating KELIM and other statistically significant variables. Results: The median follow-up time was 77.1 months. The observed cumulative mortality rates were 1.4% (95% confidence interval [CI]: 0.7–3.2), 10.4% (95% CI: 7.8–13.8), and 16.5% (95% CI: 13.2–20.6) at 1, 3, and 5 years, respectively. Factors demonstrating a significant correlation with survival included KELIM < 1 (HR = 1.78 [95% CI: 1.16–2.72]), pre-treatment CA-125 levels ≥ 35 U/mL (HR = 2.47 [95% CI: 1.10–5.55]), FIGO stages III-IV (HR = 2.40 [95% CI: 1.36–4.21]), and the presence of residual tumor tissue following surgical intervention (HR = 3.14 [95% CI: 1.75–5.65]). Conclusions: Prognosis is significantly influenced by KELIM, pre-treatment CA-125, tumor stage, and residual tumor post-surgery. The nomogram developed here offers a tool to assist in personalized prognostic assessments of Vietnamese EOC patients. Full article

Background and Clinical Significance: Anti-Müllerian hormone (AMH) is a dimeric glycoprotein secreted from the granulosa cells of the preantral and small antral follicles, which has entered routine clinical practice as a valuable tool for the diagnosis of different ovarian disorders. Increased AMH levels have been recommended as a criterion for polycystic ovary syndrome (PCOS). However, its widespread use remains limited due to analytical diversity and contradictory age-specific thresholds, among other factors that modulate AMH levels. Case Presentation: Herein, we present a rare case series of women with increased AMH levels. The difficulties in the differential diagnosis of patients with elevated AMH levels, because of PCOS combined with pituitary dysfunction, increased ovarian volume, or granulosa cell tumors (GCTs), are discussed. Conclusions: The presented rare cases of increased AMH emphasize the important role of AMH as a diagnostic marker in women with hypogonadotropic hypogonadism and granulosa cell tumors. On the other hand, it is still unknown if increased AMH produced by unusually enlarged or supernumerary ovaries should be considered as actual PCOS cases or as a specific subgroup. Additionally, the unusual case of GCTs with pronounced AMH and LH increase but normal steroids supports the pathophysiological role of AMH for the development of neuroendocrine dysfunction. Moreover, it suggests that GCTs should be considered in the differential diagnosis of chronic anovulation even in women with normal ovarian steroid production in case of unusually high AMH levels for the age. Further studies are needed to explain PCOS heterogeneity and to ensure proper differential diagnosis for every affected woman. Full article

Endometrial hyperplasia (EH) comprises a spectrum of abnormal proliferative changes in the endometrium, ranging from benign glandular overgrowth to lesions with substantial malignant potential. The importance of risk stratification and early identification is highlighted by the growing recognition of EH as a precursor to endometrial cancer. The main causes of EH, according to epidemiological research, include obesity, polycystic ovarian syndrome (PCOS), metabolic dysfunction, and extended exposure to unopposed estrogen. Emerging molecular markers, histological analysis, and imaging are all necessary for a proper diagnosis of EH because it might appear with vague clinical symptoms such as irregular uterine bleeding. Surgical intervention or progestin therapy are two possible management techniques for EH, depending on the lesion’s intricacy and the patient’s medical history, including fertility issues. Personalized therapy techniques and recent developments in molecular profiling have the potential to enhance patient outcomes by matching treatment to tumor biology and individual risk profiles. This review highlights the translational potential of molecular insights while synthesizing the most recent data on the epidemiology, risk factors, diagnostic techniques, and therapy of EH. A deeper comprehension of these elements is necessary to maximize treatment results and stop the development of endometrial cancer. Full article

Background: The five-year survival rate of patients with ovarian cancer remains less than 50%, secondary to chemotherapy resistance. Purpose: This study aims to evaluate the effects of itraconazole as a supplementary treatment with paclitaxel and carboplatin on malignancy response and in preventing the initial development of chemoresistance in chemotherapy-naïve patients with advanced ovarian epithelial cancer. Method: This randomized placebo-controlled double-blind study involved 60 chemotherapy-naïve patients with advanced epithelial ovarian malignancy who were randomized into two arms; the placebo and itraconazole groups. The placebo group received six chemotherapy cycles and four inactive capsules, while the itraconazole group received six chemotherapy cycles and 400 mg oral itraconazole for five days per cycle. Results: Following completion of six chemotherapy cycles and when contrasted with the control arm, the itraconazole arm demonstrated statistically significant improvements in tumor response. The objective response rate was 80% in the itraconazole group compared with 47% in the placebo group (p = 0.015), while the disease control rate was 100% versus 80%, respectively (p = 0.023). The median progression-free survival (PFS), defined as the time point at which 50% of patients experienced disease progression or death, was 13.5 months for the overall study population. PFS was evaluated as a fixed-time endpoint at 18 months following completion of chemotherapy for the overall study population. Progression-free survival was significantly improved in the itraconazole group, with 70% of patients remaining progression-free compared with 26.7% in the placebo group (p = 0.001). Also, the itraconazole group produced significant declines in the serum levels of CA-125 (p = 0.005) and p-glycoprotein (p = 0.042) with significant elevation in VEGFR-2 (p = 0.006) as compared to the control group. Itraconazole was safe and its use was associated with a significant improvement in the quality of life (QOL). Conclusions: Itraconazole could represent a promising add-on therapy to enhance tumor response to chemotherapy in patients with ovarian cancer. Full article

Background/Objectives: Peritoneal carcinomatosis is the leading cause of death in advanced ovarian cancer (AOC). Mesothelial cells lining the peritoneum modulate tumor implantation, yet the role of their apoptosis in metastasis development remains unclear. This study investigated the relationship between mesothelial cell apoptosis and metastatic spread in ovarian cancer (OC). Methods: The study included 26 patients with AOC, 11 with early-stage OC (EOC), and 13 healthy controls. Apoptotic activity in parietal peritoneal wall and omental mesothelial cells was assessed using the TUNEL technique. Metastases were classified as pushing or infiltrating. Associations with the peritoneal cancer index (PCI), BRCA mutation, and homologous recombination deficiency (HRD) status were analyzed. Results: Mesothelial cells adjacent to AOC metastases exhibited significantly higher apoptotic activity compared to controls (p < 0.05). Apoptosis was greater near infiltrating metastases than near pushing ones in both parietal (p < 0.01) and omental (p = 0.04) sites. The infiltration pattern was consistent between omental and parietal metastases (R = 0.588, p < 0.01). No significant differences in apoptosis were found between EOC and healthy controls, or in tumor and stromal cells between invasion types. Mesothelial apoptosis was independent of PCI, BRCA mutation, and HRD status. Conclusions: Our study suggests that mesothelial cell apoptosis may be associated with peritoneal spread in OC. Mesothelial cell apoptosis is more pronounced near infiltrative-type lesions, independent of BRCA/HRD status. These findings highlight mesothelial apoptosis as a relevant process in peritoneal dissemination. Further studies are needed to clarify its role in ovarian cancer progression. Full article

Background and Objectives: BRCA1-interacting protein C-terminal helicase 1 (BRIP1) encodes a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer type 1 (BRCA1). It also participates in DNA damage repair and tumor suppression; thus, its mutations may be associated with an increased risk of several cancers, including fallopian tube and ovarian cancer. Recent research has explored whether BRIP1 dysregulation also contributes to the development and progression of other malignancies. This study investigated the clinical and prognostic value of BRIP1 in colorectal cancer (CRC). Materials and Methods: We first analyzed The Cancer Genome Atlas (TCGA) dataset to evaluate the prognostic significance of BRIP1 mRNA expression in CRC. BRIP1 expression was subsequently examined in tumor tissues from 60 CRC patients, and its associations with clinicopathological characteristics and clinical outcomes were assessed. Results: In rectal cancer, a higher BRIP1 expression was associated with younger age. In colon cancer, BRIP1 expression was correlated with gender, lymphatic invasion, carcinoembryonic antigen (CEA) level, pathological stage, M stage, N stage, microsatellite instability (MSI) status, and anatomical tumor location. Survival analysis showed that low BRIP1 expression was associated with poorer overall survival in both rectal and colon cancers significantly. In CRC patient tissues, lower BRIP1 expression was further related to elevated CEA levels and unfavorable clinical outcomes. Lower BRIP1 mRNA expression is significantly associated with aggressive clinicopathological features and poor prognosis in CRC. Conclusions: BRIP1 may serve as a promising biomarker for risk stratification and a potential therapeutic target in the management of CRC. Full article

Background: Primary ovarian signet-ring cell carcinoma (POSRCC) is exceedingly rare. Most previously reported cases have involved primary ovarian mucinous neoplasms containing signet-ring cells. Methods: We report a unique case of advanced primary ovarian adenocarcinoma with a signet-ring cell component, accompanied by features inconsistent with typical mucinous morphology, which distinguished it from most previously documented cases. A review of the literature is also provided. Results: A 57-year-old woman presented with abdominal pain. Imaging revealed a 10 cm pelvic mass. Surgical exploration and pathological examination revealed poorly differentiated adenocarcinoma with focal signet-ring cell features in both ovaries. Extensive preoperative and postoperative evaluation revealed no evidence of an alternative primary tumor. The tumor did not meet diagnostic criteria for mucinous carcinoma. Therefore, the final diagnosis was primary ovarian poorly differentiated adenocarcinoma with a focal signet-ring cell component, FIGO stage IIIC. The patient received six cycles of adjuvant paclitaxel and carboplatin, followed by four cycles of single-agent bevacizumab for maintenance therapy. Despite treatment, disease recurred eight months after surgery, and the patient died of disease progression 18 months postoperatively. Conclusions: This case highlights the aggressive behavior of non-mucinous POSRCC and underscores the diagnostic challenge in distinguishing primary from metastatic ovarian signet-ring cell carcinoma. Awareness of this rare entity is crucial for accurate diagnosis and appropriate management. Full article