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Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis.
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Movimento Celular , Proliferação de Células , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas , Fatores de Transcrição da Família Snail , Humanos , Feminino , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Animais , Proliferação de Células/genética , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Camundongos , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Progressão da Doença , Camundongos Nus , Camundongos Endogâmicos BALB C , Núcleo Celular/metabolismo , PrognósticoRESUMO
PURPOSE: There is still no consensus on the therapeutic strategies for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer (OC). We aim to outline the clinical characteristics and optimal therapeutic strategies of patients with FIGO stage IV OC. METHODS: This single center retrospective study analyzed the clinical features and survival of patients with FIGO stage IV OC that underwent cytoreduction or received at least one course of chemotherapy between January 2014 and December 2020. RESULTS: One hundred and twenty patients were included. Surgery, especially optimal cytoreduction without residual mass improved the overall survival of patients in surgery group (P = .047, HR .432, 95% CI .181-.987). Secondly, the completion of chemotherapy improved median overall survival of patients either with (53.0 months vs 25.0 months, P < .001, HR 7.015, 95% CI 1.372-35.881) or without cytoreduction (43.0 months vs 6.0 months, P = .006, HR 5.969, 95% CI 1.115-31.952). In patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had better survival. CONCLUSIONS: In patients with FIGO stage IV, complete resection of intra-abdominal tumor foci and completion of chemotherapy provided considerable survival benefits to patients with FIGO stage IV OC. Among patients with FIGO stage IVB, those with only extra-abdominal lymph node metastases had a better prognosis.
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Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Humanos , Feminino , Estadiamento de Neoplasias , Estudos Retrospectivos , Metástase Linfática , Neoplasias Ovarianas/patologia , Prognóstico , Carcinoma Epitelial do OvárioRESUMO
The ALPL gene is linked to hypophosphatasia, a rare genetic disease. Owing to the inverse relationships between ALPL expression and both the International Federation of Gynecology and Obstetrics (FIGO) stages and histological grades assigned to patients with serous ovarian cancer (SOC), this study was designed to explore the role and possible mechanisms of ALPL in cell motility of high grade SOC (HGSOC). The effects of ALPL overexpression on migration and invasion were detected in HGSOC cell lines SKOV3 and HEY. Gene ontology analysis for differential genes with ALPL overexpression identified several biological processes, including EMT, correlated with cell motility. Genes potentially implicated in EMT and associated with ALPL were screened using The Cancer Genome Atlas (TCGA) database. The WNT receptor Frizzled2 (FZD2) was identified and its role in HGSOC cell motility and survival was investigated. It was found that forced expression of ALPL could inhibit migration, invasion, and EMT in HGSOC cells. It also reduced the expression of FZD2 and its ligand WNT5A, accompanied by suppressed expression of their downstream target phosphorylated-STAT3 (pSTAT3). These effects were initiated via the FZD2 knockdown using siRNA and reversed by recombinant WNT5A protein. The relationship between FZD2 expression and poor HGSOC patient survival was also investigated. This data supports that ALPL might restrict the function of WNT5A-FZD2-STAT3 axis, a non-canonical WNT pathway for promoting EMT progression, which results in attenuated migration and invasion in HGSOC cells and improves survival in patients with SOC.
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Fosfatase Alcalina/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/patologia , Via de Sinalização Wnt , Linhagem Celular Tumoral , Movimento Celular , Cistadenocarcinoma Seroso/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Humanos , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/metabolismoRESUMO
The abnormal elevation of sulfiredoxin (Srx/SRXN1)-an antioxidant enzyme whose main function is to protect against oxidative stress-has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis. Our study also reveals a significant positive correlation between the expression of Srx and ß-catenin in cervical cancer tissues. Loss-of-function studies demonstrate that Srx knockdown using a lentiviral vector-mediated specific shRNA decreases the migration and invasion capacity in HeLa (human papilloma virus 18 type cervical cancer cell line) and SiHa SiHa (cervical squamous cancer cell line). Notably, the exact opposite effects were observed in gain-of-function experiments in C-33A cells. Mechanistically, downregulation or upregulation of Srx leads to an altered expression of proteins associated with the Wnt/ß-catenin signaling pathway. Furthermore, blockage of the Wnt/ß-catenin signaling pathway contributed to attenuated Srx expression and resulted in significant inhibition of cell migration and invasion in cervical cancer cell lines. Combined, Srx might be an oncoprotein in cervical cancer, playing critical roles in activating the Wnt/ß-catenin signaling pathway; it may therefore be a therapeutic target for cervical cancer.
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Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Adulto , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Células HeLa , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Imuno-Histoquímica , Metástase Linfática , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismoRESUMO
OBJECTIVE: Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac. We aimed to study the role of Elmo1 in the malignant migration of ovarian cancer. METHODS: Engulfment and cell motility 1 expression was evaluated in specimens from 93 patients with serous ovarian cancer (SOC) by immunohistochemical staining. Next, Elmo1-RNAi cells were established by validated small interference RNAs. Cell proliferation and cell motility were observed and compared with Dock180-RNAi cells. To confirm their synergetic contribution to forming focal adhesion and activating Rac1, Rac1-GTP level was measured by GST pull-down assay and immunofluorescence was used to observe focal adhesion formation both in Elmo1-RNAi and Dock180-RNAi cells. RESULTS: Engulfment and cell motility 1 was mainly overexpressed in high-grade SOC tissues. Western blot analysis demonstrated that both Elmo1 and Dock180 expressions were hampered in Elmo1-RNAi cells. Compared with the negative control, decreased colony formation and cell invasion were observed in Elmo1-RNAi cells and Dock180-RNAi cells. Consistently, both exhibited reduced Rac1-GTP level and inhibited focal adhesion formation. CONCLUSIONS: Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Adesão Celular , Ciclo Celular , Proliferação de Células , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Feminino , Citometria de Fluxo , Imunofluorescência , Guanosina Trifosfato/metabolismo , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , RNA Interferente Pequeno/genética , Células Tumorais Cultivadas , Proteínas rac de Ligação ao GTP/antagonistas & inibidores , Proteínas rac de Ligação ao GTP/genéticaRESUMO
OBJECTIVE: To observe the clinical efficacy of Camrelizumab in patients with advanced cervical cancer who presented with resistance to initial therapy. METHODS: We retrieved data from 25 patients with advanced (stage IIA2-IV) cervical cancer who were administered a combination salvage therapy with Camrelizumab due to the poor response to initial chemotherapy. The primary outcome was objective response rate (ORR) and disease control rate (DCR), the secondary endpoints included progression-free survival (PFS) and the occurrence of adverse events. To evaluate its long-term effect on PFS, we included 64 patients diagnosed with stage IIA2-IV during the study period, who were responsive to initial radiotherapy or chemotherapy and received conventional therapy as control. RESULTS: Camrelizumab exhibits a high salvage treatment efficacy, with ORR of 80.0% (20/25) and DCR of 88.0% (22/25) in Camrelizumab salvage group (CS group). The PFS in CS group was significantly longer than that in control group. The median follow-up time were 18.1 and 18.3 months in the CS group and the control group, respectively, and neither achieved median PFS. The adverse event (AEs) rates in the CS and control groups were 52.0% (13/25) and 51.6% (33/64), in which the most common adverse events were myelosuppression, cutaneous capillary endothelial proliferation (CCEP), and elevated liver enzymes, and the grade of AEs was less than grade 3 in all patients. CONCLUSION: Camrelizumab demonstrated promising efficacy and safety as the early salvage treatment for patients with advanced cervical cancer.
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Purpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC). Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival. Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1-3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08-3.26, P-value: 0.025) analysis. Residual disease >1cm (HR: 2.69, 95% CI: 1.31-5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13-3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4-16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5-46.5 months). Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.
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OBJECTIVES: To develop a multiparameter magnetic resonance imaging (MRI)-based radiomics approach that can accurately predict the tumor cell proliferation status of serous ovarian carcinoma (SOC). MATERIALS AND METHODS: A total of 134 patients with SOC who met the inclusion and exclusion criteria were retrospectively screened from institution A, spanning from January 2016 to March 2022. Additionally, an external validation set comprising 42 SOC patients from institution B was also included. The region of interest was determined by drawing each ovarian mass boundaries manually slice-by-slice on T2-weighted imaging fat-suppressed fast spin-echo (T2FSE) and T1 with contrast enhancement (T1CE) images using ITK-SNAP software. The handcrafted radiomic features were extracted, and then were selected using variance threshold algorithm, SelectKBest algorithm, and least absolute shrinkage and selection operator. The optimal radiomic scores and the clinical/radiological independent predictors were integrated as a combined model. RESULTS: Compared with the area under the curve (AUC) values of each radiomic signature of T2FSE and T1CE, respectively, the AUC value of the radiomic signature (T1CE-T2FSE) was the highest in the training set (0.999 vs. 0.965 and 0.860). The homogeneous solid component of the ovarian mass was considered the only independent predictor of tumor cell proliferation status among the clinical/radiological variables. The AUC of the radiomic-radiological model was 0.999. CONCLUSIONS: The radiomic-radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can accurately predict tumor cell proliferation status of SOC which has high repeatability and may enable more targeted and effective treatment strategies. CRITICAL RELEVANCE STATEMENT: The proposed radiomic-radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can predict tumor cell proliferation status of SOC which has high repeatability and may guide individualized treatment programs. KEY POINTS: ⢠The radiomic-radiological nomogram may guide individualized treatment programs of SOC. ⢠This radiomic-radiological nomogram showed a favorable prediction ability. ⢠Homogeneous slightly higher signal intensity on T2FSE is vital for Ki-67.
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OBJECTIVE: To evaluate the factors that might affect the putative survival benefit from pre-operative neoadjuvant chemotherapy (NAC) in patients with early stage bulky cervical cancer. METHODS: A retrospective review for 304 patients with stage IB(2)/IIA(2) cervical cancer was performed. Two groups were made according to pre-operative NAC or not: NAC group (n=154) and primary surgery group (PST, n=150). Recurrence risks and survival were analyzed. RESULTS: The total response rate was 72.1%. For those NAC-responders, NAC decreased the ratio of lymphovascular space invasion (0 vs. 4.7%, p=0.022; 0 vs. 3.3%, p=0.052), deep stromal invasion (19.8% vs. 53.5%, p=0.000; 19.8% vs. 29.3%, p=0.08), lymph node metastasis (8.1% vs. 25.6%, p=0.004; 8.1% vs. 17.3%, p=0.031), and the need of adjuvant radiotherapy (5.5% vs. 30.2%, p=0.000; 5.4% vs. 15.3%, p=0.012), whereas improve 5-year PFS rate (94% vs. 86%, p=0.041; 94% vs. 80%, p=0.089) and 5-year OS rate (96% vs. 86%, p=0.015; 96% vs. 82%, p=0.05), as compared with non-responders and PST. Multivariate analysis suggested that the response to NAC is an independent prognostic factor of PFS (HR 0.221, 95% CI 0.048-1.022, p=0.053) and OS (HR 0.126, 95% CI 0.016-1.000, p=0.05); as compared, stage IIA disease demonstrates negative impact upon PFS (HR 4.778, 95% CI 1.490-15.317, p=0.009) and OS (HR 4.142, 95% CI 1.258-13.639, p=0.019). CONCLUSION: Responsiveness of NAC before surgery might be an independent prognostic factor for the patients with early stage bulky cervical cancer.
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Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias do Colo do Útero/patologiaRESUMO
Integrin ß1 subunit and its downstream molecules, such as integrin-linked kinase and focal adhesion kinase, are imperative for promotion of cell proliferation, survival and anti-apoptosis in cardiomyocytes by activation of their downstream pro-survival signalling molecules, such as the phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2). As a component of the integrin pathway, C3G (Crk-SH3 domain guanine nucleotide exchange factor) protein may be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes. Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hC3G, a human C3G overexpression eukaryotic recombinant plasmid. Apoptosis, cell proliferation and survival were analysed in the H9C2 cardiomyocytes either treated with hypoxia/reoxygenation (H/R). Human C3G mRNA overexpression significantly elevated C3G protein expression in H9C2 cardiomyocytes whether treated with H/R or not. C3G overexpression promoted proliferation and survival and anti-apoptosis, and attenuated the proliferative and survival inhibition, and apoptosis induced by H/R by activation of its downstream pro-survival signalling molecule, p-ERK1/2. The results suggest that C3G acts as a pro-survival molecule in H9C2 cardiomyocytes by activation of p-ERK1/2.
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Fator 2 de Liberação do Nucleotídeo Guanina/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Apoptose/genética , Proliferação de Células , Sobrevivência Celular/genética , Citometria de Fluxo , Fator 2 de Liberação do Nucleotídeo Guanina/genética , Humanos , Integrinas/metabolismo , Miócitos Cardíacos/enzimologia , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Coloração e RotulagemRESUMO
INTRODUCTION: To compare the effect of bowel resection vs stripping on the clinical outcomes of patients with FIGO II-IV ovarian cancer. METHODS: We retrospectively analyzed patients with FIGO II-IV ovarian cancer who suffered from bowel involvement and underwent cytoreductive surgery between January 2014 and March 2022. Patients' survival was compared by Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Four hundred and twelve patients were included. 48 patients underwent bowel resection (BR), and 364 patients underwent bowel tumor stripping (BTS). The BR group had longer operative duration, hospital stay, time to post-operative chemotherapy, and more intraoperative bleeding. The median PFS was 37 months (95% CI 12-62) in BTS compared to 25 months (95% CI 10-40) in BR among patients who achieved R0 resection (p = 0.590). Among those with R1 resection, the median PFS in BST was 23 months (95% CI 16-30) and that in BR was 15 months (95% CI 12-18, p = 0.136); moreover, a favorable median PFS was observed in BTS with residual bowel lesions (23 months, 95% CI 14-32), compared to BR (15 months, 95% CI 12-18, p = 0.144). Multivariate analysis indicated that FIGO stage, PCI, cytoreduction time and residual lesions were independent prognostic factors of PFS. CONCLUSION: For patients with FIGO stage II-IV ovarian cancer with bowel implicated, bowel resection is necessary to achieve complete removal to improve the survival. If complete resection was judged unfeasible, cautious decision of bowel resection is required. Neoadjuvant chemotherapy might reduce the ratio of bowel resection for some with mesenteric involvement.
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Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Ovarianas , Intervenção Coronária Percutânea , Humanos , Feminino , Estudos Retrospectivos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/patologia , Estadiamento de NeoplasiasRESUMO
Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells.
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BACKGROUND: Serous ovarian carcinoma (SOC) has the highest morbidity and mortality among ovarian carcinoma. Accurate identification of the probability of suboptimal debulking surgery (SDS) is critical. This study aimed to develop a preoperative prediction nomogram of SDS for patients with SOC. METHODS: A prediction model was established including 205 patients of SOC from institution A, and 45 patients from institution B were enrolled for external validation. Multivariate logistic regression was used to screen independent predictors and establish a nomogram to predict the occurrence of SDS. RESULTS: Multivariate logistic regression demonstrated that the CA-125 level (odds ratio [OR] 8.260, 95% confidence interval [CI] 2.003-43.372), relationship between the sigmoid colon/rectum and ovarian mass (OR 28.701, 95% CI 4.561-286.070), diaphragmatic metastasis (OR 12.369, 95% CI 1.675-274.063), and FIGO stage (OR 32.990, 95% CI 6.623-274.509) were independent predictors for SDS. The area under the curve, concordance index, and 95% CI of the nomogram constructed from the above four factors were 0.951, 0.934, and 0.919-0.982, respectively. The model showed a good fit by the Hosmer-Lemeshow test (training set, p = 0.2475; internal validation set, p = 0.2355; external validation set, p = 0.2707). The external validation proved the reliability of the prediction nomogram. The calibration curve was close to the ideal diagonal line. The decision curve analysis demonstrated a significantly better net benefit. The clinical impact curve indicated good effectiveness in clinical application. CONCLUSION: A prediction nomogram for SDS in patients with SOC provides gynecologists with an accurate and effective tool for appropriate management.
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BACKGROUND AND OBJECTIVES: Primary fallopian tube cancer (PFTC) shares the same diagnostic and management guidelines with epithelial ovarian cancer (EOC). The LION trail raised concerns regarding the role of systematic pelvic and para-aortic lymphadenectomy during debulking surgery. We aimed to evaluate the significance of lymphadenectomy in PFTC survival. METHODS: This retrospective study analyzed the clinical features and survival of patients with PFTC who underwent primary surgery in our center between January 2013 and October 2020. RESULTS: Sixty-one patients diagnosed with PFTC were included in the study. Twenty-five (41.0%, 25/61) were diagnosed with FIGO (International Federation of Gynecology and Obstetrics) stages I/II and 36 (59.0%, 36/61) were diagnosed with stage III/IV. Twenty-nine (47.5%, 29/61) underwent pelvic lymphadenectomy with or without para-aortic lymphadenectomy, among which 12 (41.4%, 12/29) had lymph node metastasis confirmed by postoperative pathology. The mean progression-free survival was 60.4 months in the lymphadenectomy group and 37.8 months in the no-lymphadenectomy group (p = 0.042, HR 0.374, 95% CI 0.145-0.966). CONCLUSIONS: PFTC is often diagnosed earlier and has a better prognosis than EOC. Most patients with PFTC would benefit from lymphadenectomy. However, the extent to which this association translates to a more diverse population needs to be further identified.
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Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Estudos RetrospectivosRESUMO
PURPOSE: To explore the utility of CTE in the evaluation of bowel invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer. METHODS: This observational study included 73 patients who received CTE before operation between September 2019 and December 2021. Two radiologists reviewed CTE images, focusing on the sites and depth of bowel involvement. Based on the findings during surgical exploration, we evaluated the diagnostic power, like sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+ LR), and negative likelihood ratio (- LR) of CTE. Additionally, the characteristic images of bowel involvement on CTE corresponding to surgical findings were shown in the study. RESULTS: The rate of macroscopic bowel invasion in this cohort was 49.31% (36/73), of which eight patients had small bowel involvement, 17 patients had colon involvement and 27 patients had sigmoid-rectum involvement. CTE detected bowel invasion in the small intestine with a sensitivity, specificity, PPV, NPV, and accuracy of 87.50%, 92.31%, 58.33%, 98.36%, 91.78%; for colon, the statistics were 58.82%, 96.43%, 83.33%, 88.52%, 87.67% and for sigmoid-rectum 62.96%, 82.61%, 68.00%, 79.17%, 75.34%, respectively. CONCLUSION: CTE appeared a preferable diagnostic power on the small bowel and colon invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer.
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Doença de Crohn , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Doença de Crohn/diagnóstico , Feminino , Humanos , Intestino Delgado , Neoplasias Ovarianas/diagnóstico por imagem , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodosRESUMO
Adaptor protein Crk and CrkL were thought to be closely related because both consist of one SH2 and two SH3 domains and share 60% homology with the highest identity within their functional domains. Their functions were most presumed to be in part, if not all, redundant. And both were suggested to be implicated in carcinogenesis. In this study, both Crk and CrkL presented with much higher expression in ovarian cancer tissues than those in normal and benign ovarian tissues. However, in contrast with CrkL, high Crk expression displayed close association with advanced stages and high-grade diseases. Furthermore, the differential binding selectivity of Crk and CrkL to their downstream partners Dock 180 and C3G was demonstrated in ovarian cancer cell line SKOV3 through coimmunoprecipitation. Additionally, Crk-knockdown cells presented with changed morphology, reduced growth, and cell invasion but remained viable. In contrast, all CrkL-knockdown cells could not survive over time, gradually detaching from the bottom of plastic dish. In conclusion, these two highly homologous proteins hold features that allow for the differential association with each binding molecules, thereby activating different signaling pathways and being involved in diverse roles in ovarian cancer.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-crk/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Sequência de Bases , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Proteínas Nucleares/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-crk/genéticaRESUMO
Objective: To determine the predictive value of cytokeratin 19 (CK19) for evaluating the safety of ovarian preservation in patients with endometrial cancer (EC). Methods: Five hundred and seventeen EC patients hospitalized from November 2010 to June 2016 were reviewed retrospectively. Pre-operative tumor biomarkers including CA125, HE4, CK19, and CA19-9 were obtained. Predictive biomarkers associated with ovarian metastasis were selected using univariate and multivariate Logistic regression. The cut-off values were determined by receiver operating characteristic (ROC) curves. Kaplan-Meier method and Cox multivariate regression model was used to perform survival analysis. Results: Among clinical parameters and biomarkers included, age > 65, type II EC, CA125 ≥ 35 u/ml, CK19 > 3.3 ng/ml, and myometrial invasion ≥ 50% depth appeared as significant predictors of the risk of ovarian involvement in univariable logistic analysis. In multivariable analysis, CK19 > 3.3 ng/ml (OR = 11.541, 95%CI: 1.968-67.668, P = 0.007) and Type II EC (OR = 8.336, 95%CI: 1.456-47.722, P = 0.017) were independent risk predictors of ovarian metastasis in pre-menopausal women. In pre-menopausal women with Type I EC (n = 142), CK19 level could satisfactorily predict the risk of ovarian metastasis (AUC = 0.860, 95%CI: 0.792-0.912, P < 0.001), and when the cut-off point was set as 2.45 ng/ml, the negative predictive value and negative likelihood ratio were 99% and 0.19, with the maximum Youden index of 0.598. Conclusions: The present study advocates the necessity of incorporating serum CK19 measurement into the pre-operative evaluation of EC, especially as extension of current standard approach with ovarian preservation counseling.
RESUMO
PURPOSE: To observe the feasibility and efficacy of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA) in refractory lymphatic leakage following lymphadenectomy among patients with gynecological cancers. PATIENTS AND METHODS: Ten cases with post-operative massive lymphatic leakage were collected, in which patients failed to respond to conservative treatment. Topical PA-MSHA injection of a single dose (2mL) was performed through drainage tube or transvaginal catheter into pelvic or peritoneal cavity. Drainage volumes and side effects were recorded. RESULTS: The incidence of refractory lymphatic leakage following pelvic and para-aortic lymphadenectomy was 2.44% (10/409). All ten patients (100%) had quick recovery and were discharged within 72 hours. Among them, one patient (10%) experienced fever and six patients (60%) experienced abdominal pain, one of which was moderate and relieved by routine analgesic treatment. During 11 (6-38) months of follow-up time, no long-term side effect was observed. CONCLUSION: Topical injection of PA-MSHA of a single dose appears a feasible and effective treatment for refractory post-operative lymphatic leakage.
RESUMO
Small GTPases, particularly the Rho family, are key regulators of cell motility and migration. Dock180 was well known for the main target of signal adaptor protein Crk and acted as a guanine-nucleotide exchange factor for small GTPase Rac1. In the present study, Dock180 was found to combine primarily with CrkI other than CrkII, and its association with Elmo1 was also demonstrated in ovarian cancer cell SKOV3. To evaluate the role of Dock180 in human ovarian cancer cell, we performed RNAi-mediated knockdown of Dock180 in SKOV3 cells using small interfering RNA expression vector. In Dock180 knockdown cells, we found that Elmo1 expression and Rac1 activity were decreased simultaneously. By contrast, the expressions of both another Crk-combining molecule C3G and Rap1 activity were observed to increase obviously. Accordingly, all Dock180 knockdown cells present with evident change in cell morphology, reduced cell proliferation, and attenuated cell migration. Taken together, these results suggest that signal transfer of Crk/Dock180/Rac1 is implicated in actin cytoskeleton reorganization and thus in the cell proliferation, motility, invasion, and of human ovarian cancer cell line SKOV3.
Assuntos
Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-crk/fisiologia , Transdução de Sinais/fisiologia , Proteínas rac de Ligação ao GTP/fisiologia , Proteínas rac1 de Ligação ao GTP/fisiologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Complexo Shelterina , Proteínas de Ligação a Telômeros/fisiologiaRESUMO
OBJECTIVE: To investigate the safety and efficacy of ultrasound ablation in treatment of uterine fibroids. METHODS: Ninety-nine patients with 117 leiomyomas in total treated by Haifu JC focused ultrasound tumor therapeutic system were enrolled in prospective and non-randomized clinical trial in First Affiliated Hospital of Chongqing Medical University and Academy of Military Medical Sciences. Ultrasound ablation was performed guided by real-time ultrasonography under conscious sedation for single session. All patients were followed up at 6 months after treatment. On the day of treatment and after 1 month, patients were given by magnetic resonance imaging (MRI) exam to evaluate the effect of fibroids ablation. At 3 and 6 months after treatment, the ratio of ablated area and volume reduction of fibroids more than 50% were evaluated by MRI exam again. The symptoms improvements were evaluated by uterine fibroid symptom (UFS) and complications were analyzed by guideline of society of international radiation (SIR). RESULTS: The average ablated area ratio of the target fibroid was (76 ± 24)%. The average reduction in fibroid volume determined by MRI at 3 and 6 months after treatment was (45 ± 21)% and (59 ± 26)%. Which were significantly decreased than those before treatment (P < 0.05). At 6 months after treatment, 84.6% (99/117) of patients showed more than 50% volume reduction, the rate of improved symptom score was 92% (66/72). All patients could resume normal daily activities at 2 hours after treatment. The adverse reactions of SIR C-D included delayed hospitalization, repeat treatment and increased level of nursing. E-F included permanent sequelae and death. In this study, no adverse reactions of C-F were recorded. Common complications (SIR A-B, only observation or simple management without sequelae) were 35% (35/99). Four cases with adverse reactions B of SIR were found, including 2 cases with skin burning of degree II and 2 cases with febrile, they were administered by symptomatic therapy and changing dressing. The other adverse reaction A of SIR included sorness of buttock, vaginal discharge, dysuria and painful urination, they were only suggested by follow-up. CONCLUSION: It was efficacy and safe that ultrasound ablation as a single strategy were used in treatment of uterine fibroids.