BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Humans ; Ovarian Neoplasms/drug therapy* ; Folate Receptor 1/metabolism* ; Female ; Immunohistochemistry/standards* ; Consensus ; Biomarkers, Tumor/metabolism* ; Fallopian Tube Neoplasms/pathology*

This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel (abpaclitaxel) and anlotinib for ovarian cancer. In this study, 44 patients diagnosed with platinum-resistant ovarian cancer were enrolled. Patients received ab-paclitaxel along with anlotinib until disease progression or intolerable toxicity. Efficacy was assessed according to RECIST 1.1 criteria or Rustin's criteria. The primary endpoint was the investigator-evaluated objective response rate (ORR). 44 patients were enrolled between January 2021 and March 2023 with a median age of 49 years. Twenty-nine had measurable lesions and 15 had non-measurable lesions. Overall, the investigator-evaluated ORR was 56.8% (25/44; 95% CI 0.411-0.713) in intention-to-treat population and 58.1% (25/43; 95% CI 0.422-0.726) in per-protocol population. The median progression-free survival was 9.8 months, and the median duration of response was 7.4 months. For safety, grade 3/4 adverse events (AEs) included leukopenia, gum pain, hypertension, and hand-foot syndrome. The response rates were 55.0% (11/20) in patients with previous use of antiangiogenic reagents and who had previous use of PARP inhibitors. The combination of ab-paclitaxel and anlotinib showed promising anti-tumor activity and a manageable safety profile in platinum-resistant ovarian cancer. Patients with previous use of antiangiogenic drugs or PARP inhibitors still benefited from this protocol.
Humans ; Female ; Middle Aged ; Indoles/therapeutic use* ; Quinolines/therapeutic use* ; Carcinoma, Ovarian Epithelial/drug therapy* ; Adult ; Ovarian Neoplasms/drug therapy* ; Prospective Studies ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Aged ; Drug Resistance, Neoplasm ; Albumin-Bound Paclitaxel/therapeutic use* ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival ; Paclitaxel/administration & dosage* ; Treatment Outcome

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

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.
Humans ; Female ; Colorectal Neoplasms/pathology* ; Hyperthermia, Induced ; Peritoneal Neoplasms/secondary* ; Rectal Neoplasms/therapy* ; Ovarian Neoplasms/therapy* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures

Poly ADP-ribose polymerase inhibitors (PARPi), which approved in recent years, are recommended for ovarian cancer, breast cancer, pancreatic cancer, prostate cancer and other cancers by The National Comprehensive Cancer Network (NCCN) and Chinese Society of Clinical Oncology (CSCO) guidelines. Because most of PARPi are metabolized by cytochrome P450 enzyme system, there are extensive interactions with other drugs commonly used in cancer patients. By setting up a consensus working group including pharmaceutical experts, clinical experts and methodology experts, this paper forms a consensus according to the following steps: determine clinical problems, data retrieval and evaluation, Delphi method to form recommendations, finally formation expert opinion on PARPi interaction management. This paper will provide practical reference for clinical medical staff.
Male ; Female ; Humans ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Consensus ; Ovarian Neoplasms/drug therapy* ; Drug Interactions ; Adenosine Diphosphate Ribose/therapeutic use*

Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.
Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Carcinoma, Small Cell/pathology* ; Carcinoma, Ovarian Epithelial ; Ovarian Neoplasms/therapy* ; Prognosis

China ; Female ; Humans ; Ovarian Neoplasms/therapy* ; Quality Control

Polycystic ovary syndrome (PCOS) is a common disease caused by complex endocrine and metabolic abnormalities in women of childbearing age. Metformin is the most widely used oral hypoglycemic drug in clinic. In recent years, metformin has been used in the treatment of PCOS, but its mechanism is not clear. In this study, we aimed to investigate the effect of metformin on PCOS and its mechanism through PCOS mouse model. Female C57BL/6J mice aged 4-5 weeks were intragastrically given letrozole (1 mg/kg daily) combined with a high-fat diet (HFD) for 21 days to establish the PCOS model. After modeling, metformin (200 mg/kg daily) was intragastrically administered. One month later, the body weight and oral glucose tolerance test (OGTT) were measured. Hematoxylin eosin (H&E) staining was used to detect the pathological changes of ovary. The serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), E₂ and testosterone (T) were measured by ELISA. The expression of DDX4/MVH was detected by immunohistochemistry. DDX4/MVH and PCNA were co-labeled by immunofluorescence. The protein levels of DDX4/MVH, PCNA, cyclin D2, AMPK and mTOR were detected by Western blot. The results showed that after metformin treatment, the body weights of PCOS mice were gradually returned to normal, glucose tolerance was significantly improved, serum E₂ levels were increased, while AMH, LH, T levels and LH/FSH ratio were decreased. Ovarian polycystic lesions were reduced with reduced atresia follicles. Furthermore, the number of proliferative female germline stem cells (FGSCs) and levels of proliferation related proteins (PCNA, cyclin D2) were significantly increased, and the p-mTOR and p-AMPK levels were markedly up-regulated. These results suggest that metformin treatment not only improves hyperandrogenemia, glucose intolerance and polycystic ovarian lesions in PCOS, but also activates the function of FGSCs. The underlying mechanism may be related to the phosphorylation of AMPK and mTOR. These findings provide new evidence to use metformin in the treatment of PCOS and follicular development disorder.
AMP-Activated Protein Kinases ; Animals ; Cyclin D2 ; Female ; Follicle Stimulating Hormone/therapeutic use* ; Humans ; Luteinizing Hormone/therapeutic use* ; Metformin/pharmacology* ; Mice ; Mice, Inbred C57BL ; Oogonial Stem Cells/metabolism* ; Ovarian Cysts/drug therapy* ; Ovarian Neoplasms ; Polycystic Ovary Syndrome/drug therapy* ; Proliferating Cell Nuclear Antigen/therapeutic use* ; TOR Serine-Threonine Kinases

OBJECTIVE: To investigate the physicochemical characteristics of natural melanin-like nanoparticles (PDA NPs) and their synergistic anti-tumor efficacy with photothermal and photodynamic (PTT/PDT) therapy. METHODS: The chemically synthesized PDA NPs were characterized using transmission electron microscope (TEM), dynamic light scattering (DLS) and Zeta potential analysis, and their photothermal and photodynamic properties were assessed with near-infrared excitation light (NIR). The antitumor efficacy of free PDA or PDA combined with NIR irradiation (0.7 and 1.0 W/cm²) was evaluated in ovarian cancer cells using flow cytometry, Cell Counting Kit-8 (CCK-8), and Transwell assay and in a mouse model bearing subcutaneous ovarian cancer xenograft. RESULTS: The synthesized PDA NPs showed a spherical morphology with diameters around 100 nm and a zeta potential of -20 mV. Upon NIR irradiation at 0.7 and 1.0 W/cm², the particles underwent temperature changes (ΔT) of about 15 and 30 ℃, respectively, and produced a large amount of singlet oxygen, demonstrating their excellent PTT/PDT properties. In ovarian cancer cells, treatment with PDA NPs alone did not induce obvious changes in reactive oxygen species (ROS) production or mitochondrial membrane potential (MTP), but when combined with NIR irradiation, these particles caused a significant increase of ROS and a reduction of MTP (P < 0.001), and such changes were more prominent with high power NIR (P < 0.01). PDA NPs alone showed no obvious cytotoxicity, but the combination of PDA with NIR irradiation produced potent killing effect on ovarian cancer cells (P < 0.001), and the effect was much stronger with a high power irradiation (P < 0.001). While PDA alone showed no inhibitory effect on tumor cell metastasis, the combined treatment with PDA and NIR irradiation, especially at a high power, significantly suppressed invasion and migration of ovarian cancer cells (P < 0.001). In the tumor-bearing mouse model, the combined treatment, but not PDA alone, produced a significant inhibitory effect on tumor growth (P < 0.001). CONCLUSION PDA NPs combined with NIR has a strong anti-tumor effect, suggesting a potential new therapeutic strategy for ovarian cancer.
Humans ; Animals ; Mice ; Female ; Melanins ; Ovarian Neoplasms/therapy* ; Cell Death ; Nanoparticles ; Antibodies