1.Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures.
Xu CHEN ; Hong-Ling LIU ; Jin-Sui WANG ; Feng-Hui ZHAO
Chinese Medical Sciences Journal 2023;38(2):130-137
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
2.Progress in diagnosis and treatment of ovarian metastases in rectal cancer.
Xue Lai HE ; Qin Xing CAO ; Ming Hui PANG
Chinese Journal of Gastrointestinal Surgery 2023;26(3):295-301
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
3.Chinese expert consensus on drug interaction management of poly ADP-ribose polymerase inhibitors.
Chinese Journal of Oncology 2023;45(7):584-593
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
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Female
;
Humans
;
Poly(ADP-ribose) Polymerase Inhibitors/pharmacology*
;
Consensus
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Ovarian Neoplasms/drug therapy*
;
Drug Interactions
;
Adenosine Diphosphate Ribose/therapeutic use*
5.Metformin improves polycystic ovary syndrome and activates female germline stem cells in mice.
Chun-Hong WANG ; Qiang-Qiang WANG ; Ya-Shan SU ; Ya-Qun SUN ; Miao SUN ; Xin-Rui LIU ; Hui-Ming MA ; Guang-Yong LI ; Xiao-Li DU ; Rui HE
Acta Physiologica Sinica 2022;74(3):370-380
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
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Cyclin D2
;
Female
;
Follicle Stimulating Hormone/therapeutic use*
;
Humans
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Luteinizing Hormone/therapeutic use*
;
Metformin/pharmacology*
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Mice
;
Mice, Inbred C57BL
;
Oogonial Stem Cells/metabolism*
;
Ovarian Cysts/drug therapy*
;
Ovarian Neoplasms
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Polycystic Ovary Syndrome/drug therapy*
;
Proliferating Cell Nuclear Antigen/therapeutic use*
;
TOR Serine-Threonine Kinases
6.Natural melanin-based nanoparticles with photothermal/photodynamic activities induce ovarian cancer cell death.
Jie Rong YANG ; Xiao Ping CHEN
Journal of Southern Medical University 2022;42(11):1681-1688
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
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Animals
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Mice
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Female
;
Melanins
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Ovarian Neoplasms/therapy*
;
Cell Death
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Nanoparticles
;
Antibodies
7.Curcumin Alleviates Hyperandrogenism and Promotes Follicular Proliferation in Polycystic Ovary Syndrome Rats: Insights on IRS1/PI3K/GLUT4 and PTEN Modulations.
Luo ZHENG ; Pei-Fang CHEN ; Wei-Chao DAI ; Zhi-Qun ZHENG ; Hui-Lan WANG
Chinese journal of integrative medicine 2022;28(12):1088-1095
OBJECTIVE:
To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS).
METHODS:
PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively.
RESULTS:
The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05).
CONCLUSION
The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.
Animals
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Female
;
Humans
;
Rats
;
Cell Proliferation
;
Curcumin/therapeutic use*
;
Follicle Stimulating Hormone
;
Glucose
;
Hyperandrogenism
;
Insulin Receptor Substrate Proteins/metabolism*
;
Insulin Resistance
;
Ovarian Cysts
;
Ovarian Neoplasms
;
Phosphatidylinositol 3-Kinase/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
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Polycystic Ovary Syndrome/drug therapy*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Rats, Sprague-Dawley
;
Testosterone
8.A challenge for colorectal surgeons: pathogenesis, progression and management of the secondary tumors of the ovary.
Jing Yi SHI ; Yong YANG ; An HUANG ; Jing Xuan XU ; Yu CHENG ; Yu Kun LI ; Jin GU
Chinese Journal of Gastrointestinal Surgery 2021;24(6):550-556
A common clinical problem encountered by colorectal surgeons is the secondary tumors of the ovary (STO), particularly in young female patients. Most STO are from the digestive tract, and the known possible metastatic mechanisms include lymphatic, hematogenous, and intraperitoneal spreading. The molecular and histopathological characteristics of STO from different sites are diverse. It is particularly important to correctly identify the origin and feature of STO, which should be clarified by combining medical history, histopathology, immunohistochemistry, molecular biology, imaging and other means. The prognosis of patients with STO is poor in general. Comprehensive therapies based on surgical resection can benefit some patients. There is no specific treatment for STO at present, but not giving up easily on these patients is the right choice that every surgeon should understand.
Colorectal Neoplasms/therapy*
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Female
;
Humans
;
Krukenberg Tumor
;
Ovarian Neoplasms/surgery*
;
Prognosis
;
Surgeons
9.Characteristics and survival of ovarian cancer patients treated with neoadjuvant chemotherapy but not undergoing interval debulking surgery
Ying L LIU ; Olga T FILIPPOVA ; Qin ZHOU ; Alexia IASONOS ; Dennis S CHI ; Oliver ZIVANOVIC ; Yukio SONODA ; Ginger J GARDNER ; Vance A BROACH ; Roisin E O'CEARBHAILL ; Jason A KONNER ; Carol AGHAJANIAN ; Kara LONG ROCHE ; William P TEW
Journal of Gynecologic Oncology 2020;31(1):17-
ovarian cancer treated with NACT from 7/1/15–12/1/17. Fisher exact and Wilcoxon rank-sum tests were used to compare clinical characteristics by surgical status. The Kaplan-Meier method was used to estimate survival outcomes. Log-rank test and Cox proportional hazards model were applied to assess the relationship of covariates to outcome, and time-dependent covariates were applied to variables collected after diagnosis.RESULTS: Of 224 women who received NACT, 162 (72%) underwent IDS and 62 (28%) did not undergo surgery. The non-surgical group was older (p<0.001), had higher Charlson comorbidity index (CCI; p<0.001), lower albumin levels (p=0.007), lower Karnofsky performance scores (p<0.001), and were more likely to have dose reductions in NACT (p<0.001). Reasons for no surgery included poor response to NACT (39%), death (15%), comorbidities (24%), patient preference (16%), and loss to follow-up (6%). The no surgery group had significantly worse overall survival (OS) than the surgery group (hazard ratio=3.34; 95% confidence interval=1.66–6.72; p<0.001), after adjustment for age, CCI, and dose reductions.CONCLUSIONS: A significant proportion of women treated with NACT do not undergo IDS, and these women are older, frailer, and have worse OS. More studies are needed to find optimal therapies to maximize outcomes in this high-risk, elderly population.]]>
Aged
;
Comorbidity
;
Cytoreduction Surgical Procedures
;
Diagnosis
;
Drug Therapy
;
Female
;
Follow-Up Studies
;
Humans
;
Methods
;
Neoadjuvant Therapy
;
Ovarian Neoplasms
;
Patient Preference
;
Proportional Hazards Models
;
Prospective Studies
10.ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience
Giulia AMADIO ; Claudia MARCHETTI ; Emanuele Rocco VILLANI ; Domenico FUSCO ; Francesca STOLLAGLI ; Carolina BOTTONI ; Mariagrazia DISTEFANO ; Giuseppe COLLOCA ; Giovanni SCAMBIA ; Anna FAGOTTI
Journal of Gynecologic Oncology 2020;31(1):6-
ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition.METHODS: This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (<65 years, group 1) and elderly (≥65 years, group 2). A binary logistic model was applied to correlate clinical variables and severe (grade ≥3) toxicity risk.RESULTS: Overall, 283 patients with EOC were included, with 72 (25.4%) older patients compared with 211 (74.6%) younger women. Bevacizumab had been administered to 234 patients (82.7%) as first-line treatment and in 49 (17.3%) with recurrent disease. At diagnosis, elderly patients presented with at least one comorbidity and were taking at least 1 medication in 84.7% and 80.6% of the cases respectively, compared with correspondingly 47.4% and 37.4% in group 1 (p<0.001). Nonetheless, the occurrence of serious (grade ≥3) adverse events did not increase among the older group. Creatinine serum levels >1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity.CONCLUSIONS: Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk.]]>
Aged
;
Bevacizumab
;
Case-Control Studies
;
Comorbidity
;
Creatinine
;
Diagnosis
;
Drug Therapy
;
Female
;
Glomerular Filtration Rate
;
Humans
;
Logistic Models
;
Ovarian Neoplasms

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