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1.
Int J Mol Med ; 54(2)2024 Aug.
Article in English | MEDLINE | ID: mdl-38940355

ABSTRACT

The ubiquitin (Ub)­proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including skeletal cell differentiation and bone homeostasis. The Ub ligase E3 promotes the transfer of Ub to the target protein, especially transcription factors, to regulate the proliferation, differentiation and survival of bone cells, as well as bone formation. In turn, the deubiquitinating enzyme removes Ub from modified substrate proteins to orchestrate bone remodeling. As a result of abnormal regulation of ubiquitination, bone cell differentiation exhibits disorder and then bone homeostasis is affected, consequently leading to osteoporosis. The present review discussed the role and mechanism of UPS in bone remodeling. However, the specific mechanism of UPS in the process of bone remodeling is still not fully understood and further research is required. The study of the mechanism of action of UPS can provide new ideas and methods for the prevention and treatment of osteoporosis. In addition, the most commonly used osteoporosis drugs that target ubiquitination processes in the clinic are discussed in the current review.


Subject(s)
Osteoporosis , Ubiquitin , Ubiquitination , Humans , Osteoporosis/metabolism , Osteoporosis/pathology , Animals , Ubiquitin/metabolism , Proteasome Endopeptidase Complex/metabolism , Bone Remodeling , Ubiquitin-Protein Ligases/metabolism
2.
Placenta ; 152: 1-8, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38729066

ABSTRACT

INTRODUCTION: The majority of unexplained recurrent pregnancy loss (URPL) cases have been attributed to immune abnormalities. Inappropriate changes in microbiota could lead to immune disorders. However, the specific role of uterine cavity microbiota in URPL remains unclear, and only a limited number of related studies are available for reference. METHODS: We utilized double-lumen embryo transfer tubes to collect uterine cavity fluid samples from pregnant women in their first trimester. Subsequently, we conducted 16S rRNA sequencing to analyze the composition and abundance of the microbiota in these samples. RESULTS: For this study, we enlisted 10 cases of URPL and 28 cases of induced miscarriages during early pregnancy. Microbial communities were detected in all samples of the URPL group (100 %, n = 10), whereas none were found in the control group (0 %, n = 28). Among the identified microbes, Lactobacillus and Curvibacter were the two most dominant species. The abundance of Curvibacter is correlated with the number of NK cells in peripheral blood (r = -0.759, P = 0.018). DISCUSSION: This study revealed that during early pregnancy, Lactobacillus and Curvibacter were the predominant colonizers in the uterine cavity of URPL patients and were associated with URPL. Consequently, alterations in the dominant microbiota may lead to adverse pregnancy outcomes.


Subject(s)
Abortion, Habitual , Microbiota , Uterus , Humans , Female , Pregnancy , Abortion, Habitual/microbiology , Adult , Uterus/microbiology , Pregnancy Trimester, First , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/analysis , Lactobacillus/isolation & purification , Case-Control Studies
3.
Biophys J ; 123(12): 1722-1734, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38773770

ABSTRACT

Cervical cancer ranks fourth in female mortality. Since the mechanisms for pathogenesis of cervical cancer are still poorly understood, the effective treatment options are lacking. Beclin-1 exhibits an inhibitory role in cervical cancer via suppressing the proliferation, invasion, and migration of cervical cancer cells. It is reported that USP19 removes the K11-linked ubiquitination of Beclin-1 to protect Beclin-1 from proteasomal degradation. Interestingly, we found that hypoxia induced a significant decrease of both Beclin-1 and USP19, suggesting that hypoxia could dually inhibit the protein level of Beclin-1 through a type 2 coherent feed-forward loop (C2-FFL, hypoxia ⊸ Beclin-1 integrating with hypoxia ⊸ USP19 → Beclin-1) to promote the occurrence and development of cervical cancer. Furthermore, mathematical modeling revealed that under the hypoxic environment of solid tumor, the hypoxia/USP19/Beclin-1 coherent feed-forward loop could significantly reduce the protein level of Beclin-1, greatly enhance the sensitivity of Beclin-1 to hypoxia, strikingly restrict the heterogeneity of Beclin-1, and contribute to the low positive rate of Beclin-1 in cervical cancer. It is expected to have significance for elucidating the underlying mechanisms of the occurrence and development of cervical cancer and to provide novel targets and strategies for prevention and treatment of cervical cancer.


Subject(s)
Beclin-1 , Uterine Cervical Neoplasms , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Female , Beclin-1/metabolism , Humans , Models, Biological , Feedback, Physiological , Cell Hypoxia , Cell Line, Tumor
4.
BMC Geriatr ; 24(1): 144, 2024 Feb 10.
Article in English | MEDLINE | ID: mdl-38341561

ABSTRACT

BACKGROUND: This study aimed to compare the balance ability and functional brain oxygenation in the prefrontal cortex (PFC) among older adults with mild cognitive impairment (MCI) under single and dual tasks, and also investigate their relationship. Neural regulatory mechanisms of the brain in the MCI were shed light on in balance control conditions. METHODS: 21 older adults with MCI (female = 12, age: 71.19 ± 3.36 years) were recruited as the experimental group and 19 healthy older adults (female = 9, age: 70.16 ± 4.54 years) as the control group. Participants completed balance control of single task and dual task respectively. Functional near-infrared spectroscopy (fNIRS) and force measuring platform are used to collect hemodynamic signals of the PFC and center of pressure (COP) data during the balance task, respectively. RESULTS: The significant Group*Task interaction effect was found in maximal displacement of the COP in the medial-lateral (ML) direction (D-ml), 95% confidence ellipse area (95%AREA), root mean square (RMS), the RMS in the ML direction (RMS-ml), the RMS in the anterior-posterior (AP) direction (RMS-ap), sway path (SP), the sway path in the ML direction (SP-ml), and the sway path in the AP direction (SP-ap). The significant group effect was detected for five regions of interest (ROI), namely the left Brodmann area (BA) 45 (L45), the right BA45 (R45), the right BA10 (R10), the left BA46 (L46), and the right BA11 (R11). Under single task, maximal displacement of the COP in the AP direction (D-ap), RMS, and RMS-ap were significantly negatively correlated with R45, L45, and R11 respectively. Under dual task, both RMS and 95%AREA were correlated positively with L45, and both L10 and R10 were positively correlated with RMS-ap. CONCLUSION: The MCI demonstrated worse balance control ability as compared to healthy older adults. The greater activation of PFC under dual tasks in MCI may be considered a compensatory strategy for maintaining the standing balance. The brain activation was negatively correlated with balance ability under single task, and positively under dual task. TRIAL REGISTRATION: ChiCTR2100044221 , 12/03/2021.


Subject(s)
Brain , Cognitive Dysfunction , Humans , Female , Aged , Brain/physiology , Postural Balance/physiology
5.
Cancer Med ; 12(5): 5409-5419, 2023 03.
Article in English | MEDLINE | ID: mdl-36341543

ABSTRACT

OBJECTIVE: This study aims to demonstrate the advantages of NGS molecular classification in EC diagnosis and to assess whether molecular classification could be performed on curettage specimens and its concordance with subsequent hysterectomy specimens. METHODS: 80 patients with hysterectomy specimens and 35/80 patients with paired curettage specimens were stratified as POLE mut, MSI-H, TP53 wt, or TP53 abn group by NGS panel. Histotype, tumor grade, IHC results, and other pathological details were taken from original pathological reports. RESULTS: The correlation analysis of 80 patients with hysterectomy specimens between NGS molecular classification and clinicopathological characters displayed that the POLE mut group was associated with EEC (87.5%) and TP53 abn subtype was correlated to a later stage (Stage II-IV, 47.6%), G3 (76.2%), serous histology (61.9%) and myometrial invasion ≥50% (47.6%). A favorable concordance (31/32, 96.9%) was shown in MSI analysis and MMR IHC results, and the agreement rate of p53 IHC and TP53 mutation was 81.5% (53/65). Compared with the p53 IHC abnormal group, the TP53 mutation group had a higher correlation with high-risk factors. A high level of concordance (31/35, 88.0%) of NGS molecular classification was achieved between curettage specimens and hysterectomy specimens while grade and histotype (including unclassified group) from curettage specimens and hysterectomy specimens showed only moderate levels of agreement, 54.3% (19/35) and 68.6% (24/35), respectively. CONCLUSION: NGS molecular classification achieved on curettage samples showed high concordance with the final hysterectomy specimens, demonstrating superior to the conventional pathological assessment of grade and histotype and potential utilization in clinical practice.


Subject(s)
Endometrial Neoplasms , Tumor Suppressor Protein p53 , Female , Humans , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/analysis , Hysterectomy , Immunohistochemistry , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Microsatellite Instability
6.
J Obstet Gynaecol Res ; 48(7): 1867-1875, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35537684

ABSTRACT

AIM: The purpose of this study was to investigate the surgical techniques and clinical feasibility of nonuterine manipulator and enclosed colpotomy to avoid cancer cell spillages in laparoscopic radical trachelectomy (LRT) for patients with early-stage cervical cancer. METHODS: We performed the newly optimized surgical techniques of round ligament suspension and vaginal purse-string suture in LRT in 12 patients with early-stage cervical cancer from May 2019 to October 2020. Surgical information and postoperative results were recorded. RESULTS: All 12 patients successfully underwent LRT with round ligament suspension and vaginal purse-string suture, and no conversion to laparotomy was required. The median operation time was 268.5 min (range 200-320 min), including 5 min of round ligament suspension, and the median blood loss was 20 mL (range 5-50 mL). The median number of pelvic lymph nodes removed was 27 (range 19-35), and median amounts of paracervical tissue was 24 mm (range 21-26 mm) and vaginal tissue was 18 mm (range 16-26 mm). No intraoperative complication or serious postoperative complications were reported. CONCLUSION: Round ligament suspension and vaginal purse-string suture techniques are feasible and effective in LRT. They can replace uterine manipulator and unprotected colpotomy with satisfactory perioperative outcomes.


Subject(s)
Laparoscopy , Round Ligaments , Trachelectomy , Uterine Cervical Neoplasms , Female , Humans , Laparoscopy/methods , Round Ligaments/pathology , Suture Techniques , Sutures , Trachelectomy/methods , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery
7.
Genomics ; 114(3): 110359, 2022 05.
Article in English | MEDLINE | ID: mdl-35364265

ABSTRACT

Tibetan Mastiff has adapted to the extreme environment of the Qinghai-Tibetan Plateau. Yet, the underlying mechanisms of its high-altitude-adaptation and origin remains elusive. Here, we generated the draft genomes of Mongolia Mastiff, Tibetan Mastiff, and Canis Lupus. The phylogenetic tree uncovered that Tibetan Mastiff and Mongolia Mastiff were derived from Canis Lupus species. The comparative genomic analyses identified that the expansion of gene families related to DNA repair and damage response, and contraction related to ATPase activity revealed the genetic adaptations of Tibetan Mastiff and Canis Lupus to high altitude. In addition, the Tibetan Mastiff and Canis Lupus had signals of positive selection for genes involved in fatty-acid α/ß- oxidation for highland adaptation. Notably, the positively selected TERT of Tibetan Mastiff should be an adaptive trait for correcting DNA damage. These findings suggested that the Tibetan Mastiff and Canis Lupus evolves basic strategies for adaptation to high altitude.


Subject(s)
Wolves , Dogs , Animals , Wolves/genetics , Phylogeny , Tibet , Altitude , Mongolia , Adaptation, Physiological/genetics , Genomics
8.
J Minim Invasive Gynecol ; 29(5): 673-682, 2022 05.
Article in English | MEDLINE | ID: mdl-35051658

ABSTRACT

STUDY OBJECTIVES: The purpose of this study was to evaluate the feasibility of "cuff-sleeve" sutures for reconstructing a functional neocervix in laparoscopic radical trachelectomy (RT). DESIGN: A retrospective analysis of a case series. SETTING: A teaching hospital. PATIENTS: Twenty-five patients who were diagnosed as early-stage cervical cancer from June 2017 to October 2020 in Sun Yat-sen Memorial Hospital. INTERVENTIONS: Laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients successfully underwent the laparoscopic RT with the "cuff-sleeve" suture method for cervicovaginal reconstruction, and no intraoperative complications occurred or conversion to laparotomy was needed. For all patients, approximately 80% of the cervical length was removed. Surgical radicality and negative surgical margins were also confirmed. During a median follow-up time of 29 months (range 8-48 months), no severe postoperative complications were observed. No cervical stenosis or secondary abnormal menstruation was reported. After the removal of the uterine stent 6 months after surgery, the neocervix length was approximately 14 mm (range 10-19 mm) and almost all the neocervixes were restored closely to the original anatomy. Four of 8 patients attempting actively to conceive were successful, and the cervical length of these pregnant patients was greater than or equal to 15 mm in all but one measurement at different gestational age. Three patients were ongoing pregnant, and the other had delivered successfully with a 16- mm cervix at term without cerclage. CONCLUSION: The "cuff-sleeve" suture method in cervicovaginal reconstruction is feasible in laparoscopic RT. This simplified suture technique can provide a functional neocervix to reduce cervical stenosis and incompetence.


Subject(s)
Laparoscopy , Trachelectomy , Uterine Cervical Neoplasms , Constriction, Pathologic/surgery , Feasibility Studies , Female , Humans , Laparoscopy/methods , Pregnancy , Retrospective Studies , Suture Techniques , Sutures , Trachelectomy/methods , Uterine Cervical Neoplasms/surgery
9.
Cell Mol Life Sci ; 78(23): 7427-7434, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34714359

ABSTRACT

Viral infections pose a severe threat to humans by causing many infectious, even fatal, diseases, such as the current pandemic disease (COVID-19) since 2019, and understanding how the host innate immune system recognizes viruses has become more important. Endosomal and cytosolic sensors can detect viral nucleic acids to induce type I interferon and proinflammatory cytokines, subsequently inducing interferon-stimulated genes for restricting viral infection. Although viral RNA and DNA sensing generally rely on diverse receptors and adaptors, the crosstalk between DNA and RNA sensing is gradually appreciated. This minireview highlights the overlap between the RNA- and DNA-sensing mechanisms in antiviral innate immunity, which significantly amplifies the antiviral innate responses to restrict viral infection and might be a potential novel target for preventing and treating viral diseases.


Subject(s)
COVID-19/immunology , DNA, Viral/immunology , Immunity, Innate/immunology , RNA, Viral/immunology , SARS-CoV-2/immunology , COVID-19/prevention & control , Cytokines/metabolism , Endosomes/immunology , Humans , Interferon Type I/metabolism , Membrane Proteins/immunology , Nuclear Proteins/immunology , Phosphoproteins/immunology
10.
Cancer Cell Int ; 21(1): 252, 2021 May 07.
Article in English | MEDLINE | ID: mdl-33962626

ABSTRACT

PURPOSE: The role of HHLA2, a new immune checkpoint ligand, is gradually being elucidated in various solid tumours. However, its role in ovarian cancer remains unclear; thus, its expression profile and clinical significance in ovarian cancer must be examined. METHODS: We performed immunohistochemistry to examine HHLA2 expression in 64 ovarian cancer tissues and 16 normal ovarian tissues. The relationships between HHLA2 expression and clinicopathological features, prognosis, and CD8+ tumour-infiltrating lymphocytes (TILs) in patients were analysed. Additionally, the Cancer Cell Line Encyclopedia database was used to analyse the correlation between HHLA2 expression and PD-L1 or B7x expression. Furthermore, the biological function of HHLA2 in ovarian cancer cells was initially explored. RESULTS: Only 17.2% of ovarian cancer patients showed HHLA2 expression, which was significantly associated with the differentiation of ovarian cancer cells (p = 0.027), and well-differentiated tumours expressed higher levels of HHLA2. The density of CD8+ TIL was associated with increased HHLA2 expression (p = 0.017), and the CD8+ TIL count was higher in the HHLA2-positive group than that in the HHLA2-negative group (p = 0.023). Moreover, multivariate analysis identified HHLA2 expression as an independent prognostic factor that predicted improved survival (p = 0.049; HR = 0.156; 95% CI = 0.025-0.992). Additionally, we also found that overexpressing HHLA2 inhibited the proliferation of ovarian cancer cells. CONCLUSION: HHLA2 is associated with tumour differentiation and high CD8+ TIL levels; and predicts improved survival in ovarian cancer. Along with previously reported findings that HHLA2 behaves as a co-stimulatory ligand, our study suggests that the loss of HHLA2 may contribute to the immunosuppressive microenvironment and progression of ovarian cancer.

11.
Med Sci Monit ; 26: e928826, 2020 Dec 25.
Article in English | MEDLINE | ID: mdl-33361739

ABSTRACT

BACKGROUND The utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis. MATERIAL AND METHODS A retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002-2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated. RESULTS A total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml. CONCLUSIONS The incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.


Subject(s)
CA-125 Antigen/metabolism , Endometrial Neoplasms/pathology , Ovarian Neoplasms/secondary , Receptors, Estrogen/metabolism , Female , Humans , Middle Aged , Multivariate Analysis , Prognosis , ROC Curve , Receptors, Progesterone/metabolism , Retrospective Studies , Risk Factors
12.
Int J Clin Exp Pathol ; 13(5): 1197-1205, 2020.
Article in English | MEDLINE | ID: mdl-32509095

ABSTRACT

OBJECTIVE: To explore the expression and clinical significance of Gal-3 and NFκB pathway related factors in epithelial ovarian carcinoma cells. METHODS: 99 histologic specimens of epithelial ovarian cancer and 20 normal ovarian histologic specimens were collected, and the expressions of Gal-3, IκB and p65 were detected by immunohistochemistry. Their relationship with clinical characteristics was analyzed. RESULTS: The expression of Gal-3 and p65 was negatively correlated with the overall survival rate (P<0.05), while the expression of IκB was positively correlated with the overall survival rate (P<0.05). Expression of Gal-3, p65 and IκB were found associated with EOC platinum resistance (P<0.05), and expression of Gal-3 and p65 correlated with pathologic grading (P<0.05). IκB and Gal-3 were associated with the recurrence of EOC (P<0.05). IκB may be related to clinical stage (P<0.05). Multivariate analysis results showed that abnormal expression of Gal-3 may be an independent prognostic risk factors for the drug resistance to platinum-based chemotherapy (95% CI=5.336~34.112, P<0.05). The expression of Gal-3, p65, and IκB can be clinical immunohistochemical indicators that determine the prognosis of EOC, but the amount of Gal-3 expression was related to the epithelial ovarian cancer's pathologic type and overall survival, which suggested that Gal-3 can be used as a prognostic factor in epithelial ovarian cancer. CONCLUSION: Targeted therapy of Gal-3 may become an effective potential new method against epithelial ovarian cancer.

13.
Med Sci Monit ; 24: 7952-7957, 2018 Nov 06.
Article in English | MEDLINE | ID: mdl-30398217

ABSTRACT

BACKGROUND The aim of this study was to compare magnetic resonance imaging (MRI) and hysteroscopy (HS) for assessing cervical involvement in early-stage endometrial adenocarcinoma in order to establish a more reliable screening method to aid in clinical decision-making. MATERIAL AND METHODS A retrospective analysis was performed on the clinicopathological data from 88 patients with stage I or II endometrial adenocarcinoma who underwent MRI and HS prior to surgery in the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Chi-square and Fisher's exact tests were performed to compare the accuracy, sensitivity, specificity, and positive and negative predictive values in the diagnosis of cervical involvement by MRI and HS. The relationship between clinicopathological factors and the deviation of diagnosis by MRI and HS from that by pathology was also analyzed. RESULTS The accuracy of assessing cervical conditions was 93.2% by MRI and 55.7% by HS. Among these variables, the accuracy, specificity, and positive predictive values of MRI were significantly different from those of HS, while the sensitivity and negative predictive values of MRI and HS were not significantly different from each other. Age, tumor size, tumor differentiation, and depth of myometrial invasion were not associated with the differences in cervical assessment between MRI and HS. However, the tumor location may affect assessment by HS. CONCLUSIONS MRI is better than HS for cervical assessment. The negative predictive values of both MRI and HS are high and unsatisfactory.


Subject(s)
Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/diagnosis , Adenocarcinoma/pathology , Adult , Aged , China , Endometrial Neoplasms/pathology , Female , Humans , Hysteroscopy/methods , Magnetic Resonance Imaging/methods , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity
14.
Cancer Manag Res ; 10: 3963-3971, 2018.
Article in English | MEDLINE | ID: mdl-30310317

ABSTRACT

PURPOSE: This study was designed to explore the expression levels of Galectin-3 (Gal-3) and ß-catenin in serous epithelial ovarian cancer (SEOC), the linkage between their expressions, and the clinicopathological features of SEOC patients. PATIENTS AND METHODS: Seventy-four SEOC patients' specimens were detected for Gal-3 and ß-Catenin expressions using immunohistochemistry, and the association between ß-catenin or Gal-3 protein expressions and clinicopathological features, treatment effects, and prognosis were analyzed using SPSS 19.0. Western blot was used to analyze protein expressions of Wnt/ß-catenin pathway in ovarian cancer cell lines. RESULTS: There was a statistically significant positive correlation between Gal-3 and ß-catenin expressions in SEOC (r=0.304 and P=0.001). Gal-3 expression was related to the grade (P=0.037), clinical stage (P=0.034), platinum resistance (P=0.030), and recurrence (P=0.001) in SEOC. There was a significant correlation between ß-catenin with recurrence in SEOC (P=0.035). Platinum resistance (P=0.003) and Gal-3 expression (P<0.001) were independent risk factors for poorer overall survival (OS). OS of the strongly positive Gal-3 group was significantly lower than that of the negative and weakly positive groups (log-rank test, P=0.001). OS of the positive ß-catenin group was lower than that of the negative ß-catenin group (log-rank test, P=0.034). Downregulating Gal-3 expression attenuated the protein expressions of Wnt/ß-catenin pathway in ovarian cancer cell lines. CONCLUSION: Gal-3 might activate Wnt/ß-catenin signaling pathway in SEOC. Hence, Gal-3 may serve as a prognostic factor for SEOC. Targeting Gal-3 may be a promising new treatment approach for SEOC.

15.
J Pediatr Adolesc Gynecol ; 31(3): 304-310, 2018 Jun.
Article in English | MEDLINE | ID: mdl-28993225

ABSTRACT

STUDY OBJECTIVE: Nonepithelial malignant ovarian tumors are rare in the pediatric and adolescent population. The aim of this study was to observe the spectrum of pathology, presentation, outcome, and risk factors for survival of pediatric nonepithelial malignant ovarian tumors in a Chinese pediatric population. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This was a retrospective study of 171 girls (median age at presentation of 14 years) diagnosed with primary malignant ovarian tumors between 1990 and 2014 at the Yat-Sen Memorial Hospital and Cancer Center of Sun Yat-sen University. Symptoms, pathological data, treatments, and outcomes were obtained retrospectively from the medical records. RESULTS: Most (85.96%, 147/171) tumors occurred in patients aged 10-18 years and most cases were International Federation of Gynecology and Obstetrics stage I (68.42%, 117/171). The predominant pathological type was germ cell tumors (87.13%, 149/171). All patients underwent surgery, and 87 (50.88%, 87/171) underwent conservative incomplete staging surgery (unilateral salpingo-oophorectomy or tumor excision). The 5-year progression-free survival (PFS) was 59.2%. The 5-year overall survival (OS) was 88.7%. Surgical hospital (hazard ratio, 0.388; 95% confidence interval, 0.213-0.706; P = .002) was independently associated with PFS. Recurrence state (hazard ratio, 163.26; 95% confidence interval, 1.321-20,181.875; P = .038) was independently associated with OS. CONCLUSION: Ovarian cancers in children and adolescents have features of good prognosis. Girls who received their first surgery in a tertiary hospital had better PFS. Patients who did not suffer recurrence had better OS.


Subject(s)
Ovarian Neoplasms/pathology , Adolescent , Antineoplastic Agents/therapeutic use , Child , Child, Preschool , Conservative Treatment/methods , Female , Follow-Up Studies , Humans , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Pregnancy , Prognosis , Retrospective Studies , Survival Rate
16.
Tumour Biol ; 37(8): 11469-77, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27012551

ABSTRACT

Galectin-3 (Gal-3) has been found to be involved in the tumor progression and chemoresistance of epithelial ovarian cancer (EOC). Some studies have shown that Gal-3 may interact with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, it is unclear whether the effects of Gal-3 on the metastasis and chemosensitivity of EOC are related to NF-κB. In this study, we aimed to explore whether Gal-3 promoted progression and carboplatin resistance in EOC via NF-κB pathway. Plasmid transfection and RNA interference were used to upregulate or downregulate the expression of Gal-3 in ovarian cancer cell lines. Then, the expression of Gal-3 and the protein expressions of phosphorylation NF-κB pathway molecules were further detected by Western blot. Transwell migration assay was employed to detect the effects of Gal-3 on the migration and invasion of ovarian cancer cell lines. After treatment with carboplatin, flow cytometry (FCM) was employed to detect the effects of Gal-3 on carboplatin-induced apoptosis. Immunofluorescence technique was used to examine the translocation of phosphorylated P65 into the nucleus in ovarian cancer cells after the upregulation of Gal-3. After the knockdown of Gal-3 by small interfering RNA (siRNA), the migration and the invasion of cancer cells were significantly inhibited while the apoptosis and the sensitivities to carboplatin increased. Western blot showed reduction in the phosphorylation components of the NF-κB pathway: inhibitor of kappa B (IκB), IκB kinase (IKK), and P65. However, after the Gal-3 upregulation by plasmid transfection, the capabilities of migration and invasion of cancer cells were significantly promoted while the apoptosis and the sensitivities to carboplatin decreased. Immunofluorescence showed increased nuclear translocation of P65. Inhibitors of the NF-κB pathway did not affect the Gal-3 expression level in ovarian cancer cells. Gal-3 may affect the migratory and invasive capabilities of cancer cells as well as the chemosensitiviy to carboplatin in EOC by acting through the NF-κB pathway.


Subject(s)
Drug Resistance, Neoplasm/physiology , Galectin 3/metabolism , NF-kappa B/metabolism , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Signal Transduction/physiology , Apoptosis , Blood Proteins , Blotting, Western , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Female , Fluorescent Antibody Technique , Galectins , Humans , Microscopy, Confocal , Neoplasm Invasiveness/pathology , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Real-Time Polymerase Chain Reaction , Transfection
17.
Zhonghua Yi Xue Za Zhi ; 96(3): 203-6, 2016 Jan 19.
Article in Chinese | MEDLINE | ID: mdl-26879723

ABSTRACT

OBJECTIVE: To investigate the rate of ovarian metastasis and its related factors in patients with cervical adenocarcinoma, and explore whether the ovary should be reserved or not in cervical adenocarcinoma. METHOD: The clinical data of 111 patients with cervical adenocarcinoma who received extensive total hysterectomy plus pelvic lymph node resection in Sun Yat-sen Memorial Hospital and Quanzhou Women's and Children's Hospital from January 2008 to December 2014 were collected and analyzed by single factor χ(2) test and multivariate logistic regression analysis. RESULTS: The median age of the included 111 cases of cervical adenocarcinoma was 44. Sixty-five of the patients were stage Ⅰb1, while 46 were stage Ⅰb2. The single factor analysis indicated that lymph-vascular space invasion(LSVI), lymph node status, interstitial infiltration depth, parametrial involvement and involvement of cervical body junction were associated with ovarian metastasis. Multivariate analysis indicated that LSVI (HR: 47.01, 95% CI: 2.48-890.03, P=0.010) and lymph node status (HR: 23.58, 95% CI: 1.20-463.21, P=0.038) were independent risk factors for ovarian metastasis. CONCLUSIONS: Ovarian metastasis rate of stage Ⅰb cervical adenocarcinoma is low; patients with age less than or equal to 45 years old, negative LSVI, <1/2 cervical stromal invasion, no lymph node metastasis and no cervical body junction involvement can consider preservation of ovary; but these findings still need to be further confirmed by large randomized controlled trials.


Subject(s)
Adenocarcinoma/secondary , Ovarian Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Hysterectomy , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Multivariate Analysis , Neoplasm Staging , Pelvis , Retrospective Studies , Risk Factors
18.
Chin J Cancer ; 34(9): 413-9, 2015 Aug 08.
Article in English | MEDLINE | ID: mdl-26253113

ABSTRACT

BACKGROUND: Occult invasive cervical cancer discovered after simple hysterectomy is not common, radical parametrectomy (RP) is a preferred option for young women. However, the morbidity of RP was high. The aim of our study is to assess the incidence of parametrial involvement in patients who underwent radical parametrectomy for occult cervical cancer or radical hysterectomy for early-stage cervical cancer and to suggest an algorithm for the triage of patients with occult cervical cancer to avoid RP. METHODS: A total of 13 patients with occult cervical cancer who had undergone RP with an upper vaginectomy and pelvic lymphadenectomy were included in this retrospective study. Data on the clinicopathologic characteristics of the cases were collected. The published literature was also reviewed, and low risk factors for parametrial involvement in early-stage cervical cancer were analyzed. RESULTS: Of the 13 patients, 9 had a stage IB1 lesion, and 4 had a stage IA2 lesion. There were four patients with grade 1 disease, seven with grade 2 disease, and two with grade 3 disease. The median age of the entire patients was 41 years. The most common indication for extrafascial hysterectomy was cervical intraepithelial neoplasia 3. Three patients had visible lesions measuring 10-30 mm, in diameter and ten patients had cervical stromal invasions with depths ranging from 4 to 9 mm; only one patient had more than 50% stromal invasion, and four patients had lymph-vascular space invasion (LVSI). Perioperative complications included intraoperative bowel injury, blood transfusion, vesico-vaginal fistula, and ileus (1 case for each). Postoperative pathologic examination results did not show residual disease or parametrial involvement. One patient with positive lymph nodes received concurrent radiation therapy. Only one patient experienced recurrence. CONCLUSIONS: Perioperative complications following RP were common, whereas the incidence of parametrial involvement was very low among selected early-stage cervical cancer patients. Based on these results, we thought that patients with very low-risk parametrial involvement(tumor size ≤ 2 cm, no LVSI, less than 50% stromal invasion, negative lymph nodes) may benefit from omitting RP. Further prospective data are warranted.


Subject(s)
Hysterectomy , Lymph Node Excision , Neoplasms, Unknown Primary , Postoperative Complications , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Adult , Combined Modality Therapy , Female , Humans , Middle Aged , Neoplasm Recurrence, Local , Retrospective Studies , Risk Factors
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