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1.
Ann Lab Med ; 43(1): 73-81, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36045059

RESUMO

Background: BRCA testing is necessary for establishing a management strategy for ovarian cancer. Several BRCA testing strategies, including germline and somatic testing, are implemented in clinical practice in Korea. We aimed to comparatively evaluate their cost-effectiveness from patients' perspective. Methods: We developed a decision model comprising five BRCA testing strategies implemented in Korea: (1) germline testing first, followed by somatic tumor testing for patients without a germline variant; (2) somatic testing first, followed by germline testing for patients with a variant detected by somatic testing; (3) both germline and somatic testing; (4) germline testing alone; and (5) somatic testing alone, with no testing as the comparator. One-way sensitivity analysis was conducted to test the uncertainty of key parameters. Results: Assuming a willingness-to-pay of $20,000 per progression-free life-year gain (PF-LYG), all five strategies were considered cost-effective. Strategy 4 was the most cost-effective option, with an incremental cost-effectiveness ratio (ICER) of $2,547.7 per PF-LYG, followed by strategy 1, with an ICER of $3,978.4 per PF-LYG. Even when the parameter values were varied within the possible range, the ICERs of all strategies did not exceed the willingness-to-pay threshold. Conclusions: Considering the importance of knowing a patient's BRCA gene status, germline testing first, followed by somatic testing, may be a reasonable option.


Assuntos
Neoplasias Ovarianas , Análise Custo-Benefício , Feminino , Células Germinativas/patologia , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , República da Coreia
2.
World J Surg Oncol ; 20(1): 276, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050693

RESUMO

BACKGROUND AND AIM: Galectins have been recently tackled by many researchers in the field of cancer due to their role in tumorigenesis, disease progression, and metastasis. Thus, they are currently involved in biomarkers research on several types of cancer. In ovarian cancers, few studies were carried out to evaluate galectins expression profiling. Hence, our present study was executed to evaluate the mRNA expression of galectins -1, -3, -4, -8, and -9 in epithelial ovarian cancers. METHODS: Fifty-six tumor samples of ovarian carcinomas were analyzed for mRNA expression using qRT-PCR, and fold-changes were calculated in comparison to tissue samples of 26 women with normal ovaries. RESULTS: The results of the present paper emphasize the importance of galectins as predictors for targeted therapy. LGALS1, LGALS3, LGALS4, LGALS8, and LGALS9 were found to be mostly overexpressed in ovarian carcinoma patients with the following percentage: 78.6%, 92.9%, 66.1%, 87.5%, and 85.7% respectively. Moreover, galectins -3 and -9 were found to be significantly elevated with lymph node metastasis (p = 0.044 and p = 0.011). Also, upregulation of galectin-1 and -9 were statistically significant in stages IIB, IIC, and IIIB (p = 0.002) in FIGO staging. CA19.9 is positively correlated to galectin-4 expression (p = 0.039). CONCLUSION: Our findings strengthen the role of galectins in carcinogenesis, disease progression, and lymphnode metastasis in ovarian carcinomas. And since these galectins are mostly overexpressed, they could be promising markers for targeted therapy to reduce disease progression and metastasis process.


Assuntos
Carcinoma , Galectinas , Neoplasias Ovarianas , Carcinoma/genética , Carcinoma Epitelial do Ovário , Progressão da Doença , Feminino , Galectina 1/genética , Galectina 1/metabolismo , Galectina 3/metabolismo , Galectinas/genética , Galectinas/metabolismo , Humanos , Metástase Linfática , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , RNA Mensageiro/genética
3.
Ceska Gynekol ; 87(4): 255-260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36055785

RESUMO

OBJECTIVE: The aim of this work is to draw attention to the difficulty of differential dia-gnosis of rare adenocarcinoma of the appendix and the histological diversity of ovarian tumors. CASE REPORT: We present a case of a 62-year-old patient sent by an attending gynecologist for the finding of an asymptomatic adnextumor dia-gnosed during a routine preventive examination. Based on preoperative examinations, a malignant ovarian tumor was suspected. Standard surgery was performed including hysterectomy with bilateral adnexectomy, total omentectomy, appendectomy, pelvic and paraaortic lymphadenectomy. Definitive histopathological analysis revealed a secondary ovarian tumor, with the adenocarcinoma of the appendix appearing to be the primary site. CONCLUSION: Up to 25% of all ovarian tumors are secondary metastatic tumors. Appendix neoplasia should be considered in the differential dia-gnosis of right-sided adnextumors. Due to their localization, they can only mimic an ovarian tumor during imaging examinations, or they can be the primary origin of an already metastatic ovary, as in our case.


Assuntos
Adenocarcinoma , Neoplasias do Apêndice , Apêndice , Neoplasias Ovarianas , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Neoplasias do Apêndice/patologia , Apêndice/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia
4.
Int J Oncol ; 61(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36082820

RESUMO

Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short­term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross­resistance and association with progression­free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment­naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross­resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.


Assuntos
Antineoplásicos , Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Resistência a Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/patologia
5.
BMC Womens Health ; 22(1): 362, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050720

RESUMO

OBJECTIVES: This study was designed to evaluate the specific imaging features of ovarian sclerosing stromal tumor (SST), improve its accuracy as well as the specificity of imaging diagnosing, and prevent overestimation of malignancy to reduce unnecessary surgical procedures. METHODS: Eight patients with magnetic resonance imaging (MRI) and six with computed tomography (CT) images were analyzed in this retrospective observational study. All the cases were confirmed by postoperative pathological examination as those of ovarian SST. Imaging and pathological features were also evaluated. RESULTS: All the 14 masses displayed cystic and solid components with outer surface of tumors contained a capsular and complete smooth rim. Eight tumors of MRI exhibited "lake-island" sign on T2 weighted imaging (T2WI). Two of the 6 CT cases displayed a flaky calcification. One case showed as a multiloculated cystic mass with irregularly thickened septae and the tumor wall. The solid components in other 13 masses were comb- or wheel-like enhanced. After injection of contrast agent, the solid components in 8 cases (57.1%) appeared as early enhancement, whereas the other 6 cases (42.9%) appeared as progressive enhanced, and the cystic components of all the cases had no enhancement in the whole course. Vascular flow signals or/and marked enhancement of the blood vessels were found in 12 lesions (85.7%). Pathological examination demonstrated pseudolobule patterns, round to spindle shaped cells, collagenous areas, edematous hypocellular areas and prominent vasculatures. CONCLUSIONS: The results demonstrated that MRI with "lake-island" signs on T2WI and MRI/CT dynamic enhancement could potentially play a critical role in facilitating appropriate diagnosis preoperatively.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
6.
J Natl Compr Canc Netw ; 20(9): 972-980, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075393

RESUMO

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estados Unidos
7.
BMC Med ; 20(1): 283, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36076202

RESUMO

BACKGROUND: High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. METHOD: We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 BRCA1 germline mutation carriers (BRCA1 carriers) and 3 normal controls with no high-risk history (non-BRCA1 carriers). RESULTS: Exploring the transcriptomes of 19,008 cells, predominantly from BRCA1+ samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of BRCA1+ samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one BRCA1 carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8+ T cell population from BRCA1+ carriers. Among those clonally expanded CD8+ T cells, PD-1 was significantly increased in tubal mucosae of BRCA1+ patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions. CONCLUSION: These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.


Assuntos
Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Proteína BRCA1/genética , Linfócitos T CD8-Positivos/patologia , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Feminino , Células Germinativas/patologia , Humanos , Mutação , Neoplasias Ovarianas/patologia , Transcriptoma/genética
8.
Front Endocrinol (Lausanne) ; 13: 950345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120434

RESUMO

Due to the lack of symptoms and detection biomarkers at the early stage, most patients with ovarian cancer (OC) are diagnosed at an advanced stage and often face chemoresistance and relapse. Hence, defining detection biomarkers and mechanisms of chemoresistance is imperative. A previous report of a cDNA microarray analysis shows a potential association of carnitine O-octanoyltransferase (CROT) with taxane resistance but the biological function of CROT in OC remains unknown. The current study explored the function and regulatory mechanism of CROT on cellular behavior and paclitaxel (PTX)-resistance in OC. We found that CROT was downregulated in OC tissues and PTX-resistant cells. Furthermore, CROT expression was negatively correlated with the prognosis of OC patients. Overexpression of CROT inhibited the OC cell proliferation, migration, invasion, and colony formation, arrested the cell cycle at the G2/M phase, and promoted cell apoptosis. In addition, miR-33a-5p bound directly to the 3'UTR of CROT to negatively regulate the expression of CROT and promoted OC cell growth. Finally, overexpression of CROT decreased the phosphorylation of Smad2, whereas knockdown of CROT increased the nuclear translocation of Smad2 and Smad4, two transducer proteins of TGF-ß signaling, indicating that CROT is a tumor suppressor which mediates OC cell behaviors through the TGF-ß signaling pathway. Thus, targeting the miR-33a-5p/CROT axis may have clinical potential for the treatment of patients with OC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Regiões 3' não Traduzidas , Carnitina , Linhagem Celular Tumoral , DNA Complementar/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Transdução de Sinais , Taxoides/uso terapêutico , Fator de Crescimento Transformador beta
9.
Medicine (Baltimore) ; 101(35): e30105, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107548

RESUMO

Ovarian atypical endometriosis (AE) is a premalignant lesion, and its potential to progress to endometriosis-associated ovarian cancer emphasizes its significance. However, the true risk of malignancy in AE remains unclear. Therefore, this study aimed to investigate the clinical outcomes of ovarian AE after ovarian cystectomy. We retrospectively reviewed the medical records and histopathological reports of 41 patients who had been diagnosed with ovarian AE between January 2011 and April 2020. We reviewed age, obstetric history, age at menarche, preoperative CA 125 level, C-reactive protein level, erythrocyte sedimentation rate, endometriosis stage, mean follow-up duration, postoperative hormonal therapy, and prognosis, including recurrence of endometriosis and malignant transformation. Among 41 patients with pathologically diagnosed ovarian AE, 26 were followed up after cystectomy only. The average follow-up period was 58.27 ± 33.22 months in cystectomy only patients. The mean age of the patients with cystectomy only versus that of patients with endometriosis-associated ovarian carcinoma was 32.73 ± 6.10 versus 48.29 ± 4.35 (P < .01) years. The preoperative CA 125 level was 115.63 ± 219.06 versus 225.75 ± 163.39 (P < .051) U/mL. Patients with endometriosis-associated ovarian carcinoma or other diseases and those who underwent oophorectomy were excluded. After surgery, hormone therapy was administered to 22 of 26 patients, and the remaining 4 patients were followed up without additional treatment. Endometriosis recurrence occurred in 5 patients, 1 of whom underwent second-line laparoscopic ovarian cystectomy. However, no malignant transformations were observed. Ovarian AE has a low possibility of malignant transformation. Conservative treatment is recommended after appropriate ovarian cystectomy, such as enucleation.


Assuntos
Endometriose , Neoplasias Ovarianas , Proteína C-Reativa , Carcinoma Epitelial do Ovário/cirurgia , Cistectomia , Endometriose/complicações , Endometriose/patologia , Endometriose/cirurgia , Feminino , Hormônios , Humanos , Lactente , Neoplasias Ovarianas/patologia , Ovariectomia , Gravidez , Estudos Retrospectivos
10.
JCO Clin Cancer Inform ; 6: e2200034, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36049148

RESUMO

PURPOSE: Although BRCA1/2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS: We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS: We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients (P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION: We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.


Assuntos
Proteína BRCA2 , Informática Aplicada à Saúde dos Consumidores , Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Informática Aplicada à Saúde dos Consumidores/métodos , Feminino , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Processamento de Linguagem Natural , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Encaminhamento e Consulta
11.
Contrast Media Mol Imaging ; 2022: 1032557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072623

RESUMO

TYMP1 is a cancer driver in several human malignancies. However, its significance in ovarian cancer (ovarian carcinoma) remains uncertain. This research aims to understand the TYMP1's role in ovarian carcinoma carcinogenesis and cisplatin (DDP) resistance and its molecular ovarian marchionesses. Circ TYMP1 overexpression in ovarian carcinoma samples led to an accelerated tumor stage. Bioinformatics identified miR-182A-3p as the TYMP1's target transcript. Circ TYMP1 functioned as a sponge for miR-182A-3p, lowering its inhibitory effect on TGF1B. Downregulating circ TYMP1 decreased A2780-Res cell proliferation, invasion, and death resistance. Malignant ovarian carcinoma cells recovered following miR-182A-3p downregulation. TGF1B overexpression boosted A2780-Res cell proliferation, aggression, and cisplatin resistance while reducing Smad2/3 phosphorylation. TYMP1 sequesters miR-182A-3p and promotes TGF1B in ovarian carcinoma, boosting carcinogenesis and cisplatin resistance. This might lead to novel ovarian carcinoma treatments.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Circular , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosforilação , RNA Circular/genética , Proteína Smad2/metabolismo , Proteína Smad3 , Fator de Crescimento Transformador beta1
12.
Tumour Biol ; 44(1): 171-185, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093649

RESUMO

BACKGROUND: Hereditary ovarian cancers (HOC) represent about 23% of ovarian cancer (OC) cases: they are most frequently related to germline mutations in the BRCA genes. OBJECTIVE: We aimed to compare CA125/HE4 serum levels and Computed Tomography (CT) features at time of ovarian cancer (OC) diagnosis in two populations: BRCA mutant and BRCA wild-type (WT) OC, and to investigate the relationship between this laboratory and radiological biomarker and BRCA mutation status. METHODS: This retrospective study included 60 newly diagnosed OC patients with FIGO stage IIIC-IV disease, tested for BRCA1/2 germline mutation status of which preoperative CT scan and serum tumor marker assay were available. RESULTS: The median level of CA125 (708 U/mL) was significantly higher (p < 0.002) in BRCA1/2 mutated patients than in WT patients (176 U/mL), whereas the median level of HE4 (492 pmol/L) was significantly higher (p < 0.002) in WT than in BRCA-mutated patients (252 pmol/L). BRCA mutation carriers showed a higher incidence of bilateral ovarian masses (p = 0.0303) characterized by solid structures (p < 0.00001), higher peritoneal tumor load, macronodular implants >2 cm (p = 0.000099), increased frequency of lymphadenopathies (p = 0.019), and metastasis (p = 0.052) compared to patients with BRCA WT. CONCLUSIONS: Tumor markers and CT patterns may help in identifying BRCA mutation status in OC directing patients towards a personalized treatment.


Assuntos
Antígeno Ca-125 , Neoplasias Ovarianas , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fenótipo , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Comput Math Methods Med ; 2022: 9398823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110573

RESUMO

Objective: To determine the effectiveness of comprehensive nursing in the care of ovarian carcinoma (OC) patients treated with paclitaxel (PTX) plus nedaplatin (NDP). Methods: The research population comprised 180 advanced OC patients who received treatment in the Shaanxi Cancer Hospital between November 2018 and November 2021. The enrolled cases were assigned to two groups based on different nursing plans: an observation group (OG) with 100 cases treated with comprehensive nursing and a control group (CG) with 80 cases intervened by conventional nursing. Intergroup comparisons were performed to identify statistical significance in terms of the following parameters: serum NGF, TK1, and CA15-3 levels; VAS, SAS, and SDS scores; nursing compliance; incidence of adverse reactions; and nursing satisfaction. Results: Compared with CG, OG showed the following: (1) lower posttreatment NGF, TK1, and CA15-3 levels; (2) lower scores of SAS and SDS; (3) higher nursing compliance; and (4) lower incidence of adverse reactions and higher nursing satisfaction after nursing. Conclusions: Comprehensive nursing far outperformed conventional nursing in the care of advanced OC patients treated with PTX plus NDP, which is worth popularizing.


Assuntos
Neoplasias Ovarianas , Paclitaxel , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Fator de Crescimento Neural/uso terapêutico , Compostos Organoplatínicos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/uso terapêutico
14.
J Exp Clin Cancer Res ; 41(1): 277, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114548

RESUMO

Ovarian cancer (OC) is a heterogeneous malignancy with various etiology, histopathology, and biological feature. Despite accumulating understanding of OC in the post-genomic era, the preclinical knowledge still undergoes limited translation from bench to beside, and the prognosis of ovarian cancer has remained dismal over the past 30 years. Henceforth, reliable preclinical model systems are warranted to bridge the gap between laboratory experiments and clinical practice. In this review, we discuss the status quo of ovarian cancer preclinical models which includes conventional cell line models, patient-derived xenografts (PDXs), patient-derived organoids (PDOs), patient-derived explants (PDEs), and genetically engineered mouse models (GEMMs). Each model has its own strengths and drawbacks. We focus on the potentials and challenges of using these valuable tools, either alone or in combination, to interrogate critical issues with OC.


Assuntos
Neoplasias Ovarianas , Animais , Carcinoma Epitelial do Ovário/patologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Organoides , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
15.
J Ovarian Res ; 15(1): 104, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114551

RESUMO

BACKGROUND: Ovarian malignant mesoderm mixed tumor (OMMMT) is a rare clinical entity. To provide reference for the treatment and prognosis of OMMMT, we analyzed the clinical features, pathology and molecular biology characteristic of published cases. METHODS: The English and Chinese reported cases of OMMMT were selected from PubMed, Clinical Trials.gov and CNKI database from 2000 to December 15th, 2021 following the PRISMA guidelines. RESULTS: A total of 63 literatures including 199 OMMMT cases were included. The average age of patients at diagnosis was 56.46 years, the highest incidence age was 60-65 years, and 82% of them were menopausal women. Most patients were diagnosed in FIGO III stage (59.64%). The most common symptom of OMMMT was abdominal pain (60.5%). 61.6% of patients were accompanied by ascites, while ascites was not associated with metastatic tumor and local recurrence. The CA125 of 88.68% patients increased. The most common reported carcinomatous component and sarcomatous component were serous adenocarcinoma (44.96%) and chondrosarcoma (24.81%), respectively. Initial treatment included surgery (94.97%) and taxanes-based (55.10%) or platinum-based (85.71%) chemotherapy regimens. The median survival time of patients was 20 months. Heterologous sarcoma component did not shorten life expectancy. The optimal ovarian tumor cell debulking surgery (OOTCDS), radiotherapy and chemotherapy could significantly prolong the median survival time of patients. Furthermore, platinum drugs could significantly prolong the survival time after comparing various chemotherapy schemes. Besides, the combination of platinum and taxanes was therapeutically superior to the combination of platinum and biological alkylating agents. CONCLUSION: The OOTCDS and platinum-based chemotherapy regimen can improve the prognosis of OMMMT. Targeted therapy might become a new research direction in the future. Since the elderly patients are the majority, the toxicity of new drugs on the elderly patients is more noteworthy.


Assuntos
Carcinoma , Neoplasias Ovarianas , Idoso , Alquilantes/uso terapêutico , Feminino , Humanos , Mesoderma/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Taxoides/uso terapêutico
16.
J Ovarian Res ; 15(1): 103, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088429

RESUMO

BACKGROUND: Ubiquitin-binding enzyme E2T (UBE2T), a member of the E2 family of the ubiquitin-proteasome pathway, is associated with tumorigenesis of varioustumours; however, its role and mechanism in ovarian cancer remain unclear. RESULTS: Our study revealed that UBE2T is highly expressed in ovarian cancer; this high expression was closely related to poor prognosis. Immunohistochemistry was used to validate the high expression of UBE2T in ovarian cancer. This is the first study to demonstrate that UBE2T expression is higher in ovarian cancer with BRCA mutation. Moreover, we demonstrated that UBE2T gene silencing significantly inhibited ovarian cancer cell proliferation and invasion. The epithelial-mesenchymal transition (EMT) of ovarian cancer cells and phosphatidylinositol 3 kinase/protein kinase B (PI3K-AKT) pathway were significantly inhibited. Adding the mechanistic target of rapamycin activator MHY1485 activated the PI3K-AKT pathway and significantly restored the proliferative and invasive ability of ovarian cancer cells. Furthermore, a tumorigenesis experiment in nude mice revealed that tumour growth on mice body surface and tumour tissue EMT were significantly inhibited after UBE2T gene silencing. CONCLUSIONS: This study demonstrated that UBE2T regulates EMT via the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer. Moreover, UBE2T may interact with BRCA to affect ovarian cancer occurrence and development. Hence, UBE2T may be a valuable novel biomarker for the early diagnosis and prognosis and treatment of ovarian cancer. Further, UBE2T inhibition may be effective for treating ovarian cancer.


Assuntos
Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Animais , Carcinogênese/genética , Carcinógenos , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinas
17.
In Vivo ; 36(5): 2453-2460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099140

RESUMO

BACKGROUND/AIM: The 2014 International Federation of Gynecology and Obstetrics (FIGO) classification subdivides patients with stage IIIA1 ovarian, fallopian tube, and peritoneal cancers by the greatest dimension of metastatic lymph node without supporting evidence. This study aimed to assess the validity of this subdivision. PATIENTS AND METHODS: A retrospective single-institution cohort study was performed in patients with ovarian, fallopian tube, or peritoneal cancer from 2009 to 2020. We compared outcomes between patients diagnosed with IIIA1(i) (metastasis ≤10 mm in the greatest dimension) and IIIA1(ii) (metastasis >10 mm in the greatest dimension). RESULTS: Of the 895 patients, 46 (5.1%) were classified as stage IIIA1, 20 as IIIA1(i), and 26 as IIIA1(ii). In stage IIIA1(ii), there were significantly more cases of serous carcinoma (p<0.001), and the number of positive nodes and lymph node ratio were significantly higher than those in stage IIIA1(i) (p=0.001, p=0.002). Five-year progression-free survival was 68.7% in patients with stage IIIA1(i) cancer and 58.1% in those with stage IIIA1(ii) (p=0.58). Five-year overall survival was 83.1% in patients with stage IIIA1(i) cancer and 80.2% in those with stage IIIA1(ii) (p=0.44). Among other patient characteristics and pathologic findings, there were no prognostic factors for patients with stage IIIA1 cancer. CONCLUSION: In this retrospective cohort study, further classification of FIGO stage IIIA1 cancer was not significantly associated with patient outcomes.


Assuntos
Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Neoplasias Peritoneais , Estudos de Coortes , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Retrospectivos
18.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077477

RESUMO

Most patients with epithelial ovarian cancers (EOCs) are at advanced stages (stage III-IV), for which the recurrence rate is high and the 5-year survival rate is low. The most effective treatment for advanced diseases involves a debulking surgery followed by adjuvant intravenous chemotherapy with carboplatin and paclitaxel. Nevertheless, systemic treatment with intravenous chemotherapeutic agents for peritoneal metastasis appears to be less effective due to the poor blood supply to the peritoneal surface with low drug penetration into tumor nodules. Based on this reason, hyperthermic intraperitoneal chemotherapy (HIPEC) emerges as a new therapeutic alternative. By convection and diffusion, the hyperthermic chemotherapeutic agents can directly contact intraperitoneal tumors and produce cytotoxicity. In a two-compartment model, the peritoneal-plasma barrier blocks the leakage of chemotherapeutic agents from peritoneal cavity and tumor tissues to local vessels, thus maintaining a higher concentration of chemotherapeutic agents within the tumor tissues to facilitate tumor apoptosis and a lower concentration of chemotherapeutic agents within the local vessels to decrease systemic toxicity. In this review, we discuss the molecular and cellular mechanisms of HIPEC actions and the effects on EOCs, including the progression-free survival (PFS), disease-free survival (DFS) and overall survival (OS). For primary advanced ovarian cancers, more studies are agreeing that patients undergoing HIPEC have better surgical and clinical (PFS; OS) outcomes than those not, although one study reported no differences in the PFS and OS. For recurrent ovarian cancers, studies have revealed better DFS and OS in patients undergoing HIPEC than those in patients not undergoing HIPEC, although one study reported no differences in the PFS. HIPEC appears comparable to traditional intravenous chemotherapy in treating advanced EOCs. Overall, HIPEC has demonstrated some therapeutic benefits in many randomized phase III trials when combined with the standard cytoreductive surgeries for advanced EOCs. Nevertheless, many unknown aspects of HIPEC, including detailed mechanisms of actions, along with the effectiveness and safety for the treatment of EOCs, warrant further investigation.


Assuntos
Antineoplásicos , Hipertermia Induzida , Neoplasias Ovarianas , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia
19.
BMC Cancer ; 22(1): 965, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085013

RESUMO

BACKGROUND: To evaluate the impact of intraoperative hypotension and hemodynamic instability on survival outcomes in patients with high-grade serous ovarian carcinoma (HGSOC). METHODS: We retrospectively identified patients with HGSOC, who underwent primary or interval debulking surgery between August 2013 and December 2019. We collected anesthesia-related variables, including the arterial blood pressure measurements (at 1-min intervals) during the surgery of patients. The cumulative duration of mean arterial blood pressure (MAP) readings under 65 mmHg and two performance measurements (median performance error [MDPE] and wobble) were calculated. We investigated associations between the factors indicating hemodynamic instability and prognosis. RESULTS: In total, 338 patients were included. Based on the cumulative duration of MAP under 65 mmHg, we divided patients into two groups: ≥30 min and <30 min. The progression-free survival (PFS) was worse in the ≥30 min group (n = 107) than the <30 min group (n = 231) (median, 18.2 vs. 23.7 months; P = 0.014). In multivariate analysis adjusting for confounders, a duration of ≥30 min of MAP under 65 mmHg was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.376; 95% CI, 1.035-1.830; P = 0.028). Shorter PFS was observed in the group with a MDPE <-4.0% (adjusted HR, 1.351; 95% CI, 1.024-1.783; P = 0.033) and a wobble ≥7.5% (adjusted HR, 1.445; 95% CI, 1.100-1.899; P = 0.008). However, no differences were observed in overall survival. CONCLUSION: This study suggests that the three intraoperative variables for hemodynamic instability, cumulative duration of MAP <65 mmHg, MDPE, and wobble, might be novel prognostic biomarkers for disease recurrence in patients with HGSOC.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Feminino , Hemodinâmica , Humanos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos
20.
BMC Cancer ; 22(1): 967, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36085021

RESUMO

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological cancer due to the recurrence of drug-resistance. Cancer initiating cells (CICs) are proposed to be responsible for the aggressiveness of OC. The rarity and difficulty of in vitro long-term cultivation of CICs challenge the development of CIC-targeting therapeutics. Reprogramming cancer cells into induced cancer initiating cell (iCICs) could be an approach to solve these. Several inducible CICs have been acquired by activating the expression of stemness genes in different cancer cells. However, few reports have demonstrated the feasibility in OC. METHODS: Patients with primary OC receiving surgery were enrolled. Tumor tissue were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunohistochemistry (IHC) staining to investigate the association of stemness markers with overall survival (OS). An high-grade serous ovarian cancer (HGSOC) cell line, OVCAR-3 was reprogrammed by transducing Yamanaka four factors OCT4, SOX2, KLF4 and MYC (OSKM) to establish an iOCIC model, iOVCAR-3-OSKM. CIC characteristics of iOVCAR-3-OSKM were evaluated by RT-PCR, sphere formation assay and animal experiments. Drug-resistance and migration ability were accessed by dye-efflux activity assay, MTT assay and migration assay. Gene profile was presented through RNA-sequencing. Lineage differentiation ability and organoid culture were determined by in vitro differentiation assays. RESULTS: In OC patients, the co-expression of multiple stem-related transcription factors (OCT4, SOX2, and NANOG) was associated with worse OS. iOVCAR-3-OSKM cells generated by reprogramming successfully exhibited stemness characteristics with strong sphere-forming and tumorigenesis ability. iOVCAR-3-OSKM cells also showed malignant potential with higher drug resistance to chemodrug, Paclitaxel (PTX) and migration ability. iOVCAR-3-OSKM was maintainable and expandable on feeder-dependent culture condition, it also preserved ovarian lineage differentiation abilities, which could well differentiate into OC cells with CK-7 and CA125 expressions and develop into an organoid mimic poor prognostic OC histological feature. CONCLUSIONS: The establishment of iOVCAR-3-OSKM not only allows us to fill the gap in the information on induced CICs in OC but also provides a potential strategy to develop personalized CICs and organoid models for treating OC in the near future.


Assuntos
Neoplasias Ovarianas , Animais , Apoptose , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Feminino , Humanos , Modelos Teóricos , Organoides/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
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