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1.
Medicine (Baltimore) ; 99(40): e21109, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019380

RESUMO

INTRODUCTION: Carcinoid tumor is one of the most frequent neuroendocrine tumors, and the majority of which are usually observed in the lungs and gastrointestinal tract. The prevalence of ovarian carcinoids is merely 0.1% in ovarian neoplasms and 1% in carcinoid tumors. We described 2 rare cases in our hospital of primary ovarian carcinoid (POC), causing carcinoid syndrome (CS) of the diarrhea, constipation, and carcinoid heart disease. Besides, we also reviewed related literatures about its origin, variant, clinical manifestation, diagnosis methods, pathological features, treatment strategies and prognosis from 2009 to 2019. PATIENT CONCERNS: Case 1 was a 61-year-old postmenopausal woman and presented with diarrhea, abdominal pain, enlargement, bloating and dizziness. Case 2 was a 49-year-old patient who complained of constipation, abdominal pain, bloating, and headache. DIAGNOSIS: Both patients were diagnosed as primary ovarian carcinoid, insular type. INTERVENTIONS: Total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, pelvic lymphadenectomy, and appendectomy without chemotherapy were performed in case 1. Cervix resection, right salpingo-oophorectomy, appendectomy, and pelvic lesion resection with chemotherapy was conducted in case 2. OUTCOMES: Both patients achieved satisfactory treatment effects. The follow-up period was 18 and 17 months in case 1 and case 2, respectively. Case 1 encountered carcinoid heart disease and received percutaneous transluminal coronary angioplasty (PTCA) postoperatively. Case 2 suffered multiple metastases postoperatively. However, after effective treatment, both patients were in good condition during follow-up duration. CONCLUSION: POC is an extraordinarily rare disease, and commonly with a satisfactory outcome. TAH+BSO with or without postoperative chemotherapy has been considered as an acceptable treatment strategy for POC patients.


Assuntos
Tumor Carcinoide/patologia , Neoplasias Ovarianas/patologia , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia , Salpingo-Ooforectomia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia
2.
Medicine (Baltimore) ; 99(40): e22511, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019452

RESUMO

RATIONALE: Granulosa cell tumors (GCTs) are rare, hormonally active sex cord-stromal tumors that generally present as solid unilateral ovarian lesions. It's quite uncommon that they present as pure bilateral ovarian cysts. Histopathology remains the gold standard for making a diagnosis of GCTs. However, as the differential diagnosis is difficult, cystic GCTs are frequently misdiagnosed as benign or other cystic tumors either prior to surgery or during pathologic diagnosis. Accordingly, herein, we describe a fairly rare case of bilateral ovarian cystic GCTs, along with a review of the related literature. PATIENT CONCERNS: A 43-year-old woman presented with abdominal distension and chronic pain since 1 day. The patient had a history of dysmenorrhea. DIAGNOSES: Physical examination revealed palpable bilateral adnexal tumors; ultrasonography revealed cystic and septate masses with a maximum diameter of 7.8 and 10.7 cm, respectively, in the bilateral ovaries. Hormonal analysis revealed that the blood estradiol levels were elevated. Postoperative pathological and immunohistochemical examinations of the surgical specimens revealed a final diagnosis of cystic adult GCTs of the ovaries. INTERVENTIONS: The patient first underwent laparoscopic bilateral ovarian cystectomy. On the basis of the final pathological diagnosis report, abdominal total hysterectomy, bilateral oophoro-salpingectomy, and partial omentectomy were then performed. Microscopic examination revealed that there were no residual CGT cells. The patient's federation international of gynecology and obstetrics (FIGO) Stage was IB period. OUTCOMES: The surgeries were successful. The tumor was a FIGO Stage IB tumor, and the patient did not require any additional treatment. The patient had been followed-up regularly for 2 years after surgery; she did not experience any complications and remained disease-free. LESSONS SUBSECTIONS: Cystic GCTs should be considered in the differential diagnosis if a female patient shows bilateral ovarian cysts. They are extremely rare ovarian malignant tumors that must be differentiated from other ovarian tumors, especially purely cystic tumors and benign cysts. Although pathological and immunohistochemical findings are important for making the diagnosis, the varying histopathological features on microscope make diagnosis difficult, including tumor cells with luteinization or free cell clusters. The current case highlights the importance of physicians being aware of and suspecting cystic CGTs in similar cases, along with knowing the characteristics of GCTs for the diagnosis and differential diagnosis.


Assuntos
Tumor de Células da Granulosa/patologia , Tumor de Células da Granulosa/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Adulto , Feminino , Humanos , Cistos Ovarianos/patologia , Cistos Ovarianos/cirurgia
3.
Nature ; 585(7826): 603-608, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32939090

RESUMO

Ferroptosis-an iron-dependent, non-apoptotic cell death process-is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers1. The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions2-5. However, precisely how susceptibility to ferroptosis is dynamically regulated remains poorly understood. Here we use genome-wide CRISPR-Cas9 suppressor screens to identify the oxidative organelles peroxisomes as critical contributors to ferroptosis sensitivity in human renal and ovarian carcinoma cells. Using lipidomic profiling we show that peroxisomes contribute to ferroptosis by synthesizing polyunsaturated ether phospholipids (PUFA-ePLs), which act as substrates for lipid peroxidation that, in turn, results in the induction of ferroptosis. Carcinoma cells that are initially sensitive to ferroptosis can switch to a ferroptosis-resistant state in vivo in mice, which is associated with extensive downregulation of PUFA-ePLs. We further find that the pro-ferroptotic role of PUFA-ePLs can be extended beyond neoplastic cells to other cell types, including neurons and cardiomyocytes. Together, our work reveals roles for the peroxisome-ether-phospholipid axis in driving susceptibility to and evasion from ferroptosis, highlights PUFA-ePL as a distinct functional lipid class that is dynamically regulated during cell-state transitions, and suggests multiple regulatory nodes for therapeutic interventions in diseases that involve ferroptosis.


Assuntos
Éteres/metabolismo , Ferroptose , Peroxissomos/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Diferenciação Celular , Linhagem Celular , Éteres/química , Feminino , Edição de Genes , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Peroxidação de Lipídeos , Masculino , Camundongos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Peroxissomos/genética
4.
Medicine (Baltimore) ; 99(39): e22146, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991408

RESUMO

MOGCTs (malignant ovarian germ cell tumors) are rare tumors that mainly affect patients of reproductive age. The aim of this study was to evaluate the fertility and survival outcomes in young women with MOCGTs treated with fertility-sparing surgery (FSS).From 2000 to 2018, data from 28 patients of reproductive age with a diagnosis of MOGCT at the University of Bari were collected. Most received FSS, and in patients treated conservatively, the reproductive outcome and survival were investigated. Data of patient demographics, clinical presentation, oncology marker dosage, staging, type of surgery, histological examination, survival, and reproductive outcome were collected from hospital and office charts. All informed consent was obtained from all patients. The median age was 24 (range: 9-45 years). The majority of the patients had stage IIIC. Twenty-four woman received FSS consisting of unilateral ovariectomy and omentectomy, whereas only 4 women, based on their stage (IIIC), received a radical surgery (hysterectomy with bilateral adnexectomy, lymphadenectomy, and omentectomy). Our study shows that FSS in MOGCTs can produce good results both on reproductive outcomes and on survival. Indeed, in our group, there was only 1 case of exitus as result of recurrence. Furthermore, patients after FSS maintained normal ovarian function and 5 of 5 women who tried to get pregnant succeeded spontaneously. The median follow-up was 90 months (range 3-159).Conservative surgery for MOGCTs should be considered for women of reproductive age who wish to preserve fertility.


Assuntos
Preservação da Fertilidade/métodos , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/patologia , Adulto Jovem
5.
Anticancer Res ; 40(10): 5517-5527, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988875

RESUMO

BACKGROUND/AIM: Drug resistance is a significant cause of high mortality in ovarian cancer (OC) patients. The reverse transcriptase inhibitor azidothymidine (AZT) has been utilized as a treatment for tumors, but its role in OC treatment has not been revealed. The aim of the present in vitro study was to examine the influence of AZT on the growth of human OC cells and the involved proteins. MATERIALS AND METHODS: The proliferation, cell cycle distribution, extent of apoptosis, mitotic index, and terminal restriction fragment length were examined in three OC cell lines, CaOV3, TOV112D, and TOV21G, treated with AZT. RESULTS: AZT inhibited growth of the TOV21G and CaOV3 cell lines by regulating cell cycle distribution. Specifically, AZT caused G2/M phase arrest on TOV21G cells and S phase arrest on CaOV3 cells. In addition, AZT treatment induced up-regulation of p21 and p16 in the TOV21G and CaOV3 cell line, respectively. CONCLUSION: AZT inhibited cell proliferation in serous and clear cell OC via the regulation of cell cycle distribution.


Assuntos
Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Zidovudina/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
6.
Anticancer Res ; 40(10): 5601-5609, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988884

RESUMO

BACKGROUND/AIM: Since pathways involving LRRC17 are related to the survival of patients with various cancers, we analyzed LRRC17 as a prognostic gene in serous ovarian cancer. MATERIALS AND METHODS: Data were collected from Gene Expression Omnibus (GSE9891, GSE13876, and GSE26712) and The Cancer Genome Atlas (TCGA). We performed survival analyses using C statistics, area under the curve, survival plot with optimal cutoff level, and cox proportional regression. Zebrafish embryos were used as an in vivo model. RESULTS: The prognosis of patients with high LRRC17 expression was poorer than that of patients with low LRRC17 expression. Multivariate regression analysis showed that LRRC17 expression, age, and stage were independently related with survival. Knockdown of lrrc17 reduced survival rate and delayed development in zebrafish embryos. We also found that lrrc17 is important for cell viability by protecting from p53-dependent apoptosis. CONCLUSION: LRRC17 could be a prognostic gene in ovarian cancer as it regulates cancer cell viability through the p53 pathway.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ovarianas/genética , Proteínas/genética , Proteína Supressora de Tumor p53/genética , Idoso , Apoptose/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico
7.
Anticancer Res ; 40(10): 5631-5639, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988887

RESUMO

BACKGROUND/AIM: DNA damage response (DDR), wherein p21 is a cell fate determinant, is a potential cancer therapeutic target. Molecular expression during DDR was explored in ovarian clear-cell carcinoma (CCC). MATERIALS AND METHODS: CHK1, CHK2, TP53 and p21 expression in DDR was examined using immunostaining in surgical sections of CCC (n=22). Molecular alterations in two types of CCC cell lines, JHOC-5 and JHOC-9, were investigated using western blot analysis. RESULTS: Expression of DDR-associated molecules was noted in most patients. While high p21 expression was found in half of the patients, the remaining patients exhibited low p21 expression. Treatment with UC2288, a p21 inhibitor, attenuated proliferation of both cell lines, more prominently in JHOC-9, resulting in reduced viability and subsequent apoptosis. CONCLUSION: p21 Inhibitor induced cell death in cells with high p21 expression, suggesting that p21 suppression can be a therapeutic strategy to treat patients with CCC.


Assuntos
Quinase 1 do Ponto de Checagem/genética , Quinase do Ponto de Checagem 2/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Neoplasias Ovarianas/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Dano ao DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia
8.
Anticancer Res ; 40(10): 5869-5875, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988917

RESUMO

BACKGROUND/AIM: We aimed to identify differences in cytoreduction rates and procedures performed in patients with advanced ovarian cancer undergoing primary (PDS) or interval debulking surgery (IDS). PATIENTS AND METHODS: Data were collected prospectively on 110 consecutive patients from June 2016 to Mar 2020. RESULTS: Forty-nine patients (44.5%) underwent diaphragmatic peritonectomy (34 in PDS and 15 in IDS, p=0.005), while 38 (34.5%) underwent large bowel resection (29 in PDS and 9 in IDS, p<0.001). Complete cytoreduction was achieved in 39 patients in PDS and 29 in IDS (65% vs. 58%, p=0.22). Longer operations with more blood loss and extended hospital stay were performed in the PDS group. Ten patients (9.1%) experienced severe complications and in eight patients (7.2%) chemotherapy was delayed. CONCLUSION: More bowel resections and diaphragmatic stripping were performed in the PDS group. End surgical results were similar between groups, with a trend for more complete cytoreduction in PDS.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/cirurgia , Ovário/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ovário/patologia
9.
Medicine (Baltimore) ; 99(36): e22100, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899091

RESUMO

Intraperitoneal (IP) chemotherapy is believed to prolong the survival of patients with advanced ovarian cancer after primary debulking surgery. However, there is little knowledge about IP chemotherapy in the setting of neoadjuvant chemotherapy, and there are contradictory conclusions about adjuvant IP chemotherapy. Here, we evaluated the feasibility of neoadjuvant and adjuvant IP chemotherapy in patients with advanced epithelial ovarian cancer (AEOC).We retrospectively reviewed the data of 114 patients with AEOC who received neoadjuvant chemotherapy followed by laparoscopic conservative interval debulking surgery (NACT + LIDS) in our institution from January 1, 2009 to December 31, 2017.The median overall survival (OS) was 56 months and the median disease-free interval (DFI) was 14 months for the entire study population. Neoadjuvant IP chemotherapy cycles were crucial for the treatment of no gross residual (R0) disease (hazard ratio [HR] = 0.446, 95% confidence interval [CI] = 0.245-0.811), which was independently associated with OS of the entire study population (HR = 9.589, 95% CI = 3.911-23.507). In addition, residual disease and body mass index (BMI) were the prognostic factors for DFI (HR = 6.022, 95% CI = 3.632-9.986; HR = 1.085, 95% CI = 1.012-1.163). However, adjuvant IP cycles along with BMI were the determining factors for DFI in the R0 group (HR = 0.703, 95% CI = 0.525-0.941; HR = 1.130, 95% CI = 1.025-1.247), and were associated with OS in the R0 group (HR = 0.488, 95% CI = 0.289-0.824). The OS and DFI Kaplan-Meier curves stratified by adjuvant IP chemothearpy cycles within the R0 group were statistically significant (P = .024 and P = .033, respectively).Our results showed improvement in patients with AEOC in terms of survival, thus suggesting the feasibility of neoadjuvant and adjuvant IP chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Índice de Massa Corporal , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Infusões Parenterais , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos
10.
Anticancer Res ; 40(9): 5255-5261, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878814

RESUMO

BACKGROUND/AIM: Treatment of recurrent platinum-resistant ovarian cancer remains challenging due to the development of resistance to chemotherapy. Cabazitaxel is a new taxane that has demonstrated beneficial effect in prostate cancer patients resistant to docetaxel. Therefore, it could be anticipated to possibly also have an effect on chemotherapy resistant ovarian cancer. PATIENTS AND METHODS: Twenty-six patients with chemotherapy-resistant epithelial ovarian cancer, fallopian tube or peritoneal cancer were treated with cabazitaxel at a dose of 25 mg/m2 (on day 1 of each 3-week cycle), until progression or inacceptable toxicity, between September 2015 and April 2018. The fraction of patients without progression after three months of treatment was the primary endpoint. Prophylaxis with granulocyte colony-stimulating factor (G-CSF) was prescribed to all patients. RESULTS: The median number of cabazitaxel infusions was 4 (range=1-18). In general, cabazitaxel was well-tolerated. The fraction of patients alive and without progression after 3 months of treatment was 54% (14/26). The response rate was 46% (12/26) according to the Gynecological Cancer Intergroup (GCIG) criteria for CA125. Partial response (PR), evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST), was found in 4/26 patients (15%). By intention-to-treat analysis, the median progression-free survival (PFS) was 3.9 months (95% CI=1.9-4.4) using the combination of CA125 or RECIST (whichever came first), while the median overall survival (OS) was 8.4 months (95% CI=5.1-11.0). CONCLUSION: Cabazitaxel holds promise as a drug in recurrent platinum-resistant ovarian cancer. It demonstrated efficacy and in general, the toxicity was manageable.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Qualidade de Vida , Recidiva , Retratamento , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
11.
Anticancer Res ; 40(9): 5285-5290, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878818

RESUMO

BACKGROUND/AIM: Chemotherapy with additional bevacizumab is the standard treatment for primary and recurrent ovarian cancer. We aimed to investigate the clinical utility and safety of bevacizumab when used in combination with chemotherapy after disease progression. PATIENTS AND METHODS: This retrospective, observational study recruited patients treated for recurrent ovarian cancer from 2014 to 2016. We evaluated the effects of bevacizumab with chemotherapy in patients whose disease had progressed following treatment with bevacizumab. We assessed progression-free survival and adverse events. RESULTS: Thirty-three patients received post-progression treatment with bevacizumab. The median progression-free survival was 8.7 months (95% confidence interval=5.5-11). The progression-free survival was compared pre- and post-progression treatment, and was longer in platinum-resistant than platinum-sensitive cases after treatment (p=0.06). The most common non-hematological toxicity was proteinuria. The incidence of serious adverse events was low. CONCLUSION: Continuous administration of bevacizumab may be beneficial for ovarian cancer patients after disease progression.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Recidiva , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(38): e22297, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957389

RESUMO

RATIONALE: Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome. PATIENT CONCERNS: A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly. DIAGNOSIS: The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis. INTERVENTIONS: Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated. OUTCOMES: The patient has been free from recurrence for 5 years. LESSONS: Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/terapia , Salpingo-Ooforectomia/métodos , Teratoma/terapia , Bleomicina/uso terapêutico , Criança , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Gradação de Tumores , Recidiva Local de Neoplasia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Síndrome , Teratoma/diagnóstico por imagem , Teratoma/patologia
13.
Medicine (Baltimore) ; 99(34): e21841, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846831

RESUMO

RATIONALE: Ovarian microcystic stromal tumor is a relatively rare tumor type, which is characterized by morphology with microcyst structure, solid cellular areas, and hyalinized fibrous stroma. The most reported tumors were stage I with good prognosis. PATIENT CONCERNS: We report a case of a 33-year-old woman with primary ovarian microcystic stromal tumor with significant bizarre nuclei. We describe the clinical, histopathological, and immunohistochemical findings and review the English literatures. So far, as we know, the patient presented here is a rare case of ovarian microcystic stromal tumor with prominent bizarre nuclei accounting for about 50% of the tumor cells. DIAGNOSES: She was diagnosed with ovarian microcystic stromal tumor with significant bizarre nuclei. INTERVENTIONS: The right ovarian tumor was resected laparoscopically on October 19, 2018. OUTCOMES: Up to now, the patient is free of disease at 19 months of follow-up. LESSONS: This is a rare case of ovarian microcystic stromal tumor with obvious bizarre nuclei. This report will contribute to expand the morphological spectrum of ovarian microcystic stromal tumor.


Assuntos
Núcleo Celular/patologia , Neoplasias Ovarianas/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia , beta Catenina/metabolismo , Adulto , Assistência ao Convalescente , Biomarcadores Tumorais/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica/métodos , Laparoscopia/métodos , Resultado do Tratamento
14.
Zhonghua Fu Chan Ke Za Zhi ; 55(8): 521-528, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32854476

RESUMO

Objective: To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy ("rolling carpet" surgery) in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality. Methods: From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent "rolled carpet" CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of "rolled carpet" CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of "rolling carpet" CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups. Results: (1) Clinicopathological features: the age of patients in "rolling carpet" CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the "rolled carpet" CRS group, all patients (100%, 30/30) were performed optimal CRS, reaching completeness of cytoreduction score (CC score), named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients (77%, 23/30) reached CC-0 score, 5 cases (17%, 6/30) reached CC-1 score, 2 cases (7%, 2/30) reached CC-2 score, and there were statistical significance between the two groups (P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the "rolled carpet" CRS group and the traditional CRS groups (P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion: It is safe and feasible to perform "rolled carpet" CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Hipertermia Induzida , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Peritônio/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
15.
Zhonghua Fu Chan Ke Za Zhi ; 55(8): 529-534, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32854477

RESUMO

Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ,included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: (1) PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC (type Ⅱ) than those of low-grade (type Ⅰ) and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Recidiva Local de Neoplasia/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Receptor de Morte Celular Programada 1 , RNA Mensageiro/genética
16.
BMJ ; 370: m2614, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32732303

RESUMO

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.


Assuntos
Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/patologia , Modelos Logísticos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Calibragem , Tratamento Conservador , Neoplasias das Tubas Uterinas/terapia , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Ovariectomia , Estudos Prospectivos , Medição de Risco/métodos , Ultrassonografia , Adulto Jovem
17.
Medicine (Baltimore) ; 99(30): e20387, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791659

RESUMO

RATIONALE: Ovarian small cell carcinoma of hypercalcemic type (OSCCHT) is a relatively rare and highly fatal gynecological malignancy of unknown histogenesis, affecting mainly girls and young women. OSCCHT occurring during pregnancy is an uncommon event, and preoperative diagnosis of this malignancy is much more difficult in pregnant than non-pregnant women. The aim of this study was to describe a rare case of primary OSCCHT in a pregnant woman and to review the current literature. PATIENT CONCERNS: Here we present a case of OSCCHT in a 21-year-old patient in the 32nd week of gestation, who had abdominal pain and irregular vaginal bleeding for 5 hours. Because placental abruption, stillbirth, and hemorrhagic shock were suspected, she subsequently underwent diagnostic laparotomy. During the hysterotomy delivery and exploratory laparotomy, we found a dead fetus in the uterus and a large tumor mass arising from her left ovary. Plasma-based detection showed that the patient had a slightly elevated parathyroid hormone (PTH) level and normal serum calcium. After surgery, her serum PTH levels returned to normal. DIAGNOSIS AND INTERVENTIONS: The patient was initially treated with surgery. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, as well as the following additional procedures: appendectomy, sigmoidectomy, debulking of extra-ovarian tumor, lymph node dissection, and peritoneal biopsies. The patient, who was in the third trimester of pregnancy, was diagnosed with OSCCHT that was confirmed to be Stage III. She was recommended chemotherapy after surgery, but she declined chemotherapy. OUTCOMES: Unfortunately, the patient died 5 months after surgery. LESSONS: OSCCHT is a very rare and highly aggressive tumor type. The clinical symptoms of this tumor are nonspecific, and pathological examination remains the gold standard for diagnosis. Most patients are diagnosed with advanced stage disease and do not respond to chemotherapy. The prognosis of OSCCHT is generally poor, and no treatment guidelines are available as yet. For pregnant woman, OSCCHT is especially harmful to the mother and may indirectly lead to the death of the fetus.


Assuntos
Carcinoma de Células Pequenas/patologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Complicações Neoplásicas na Gravidez/patologia , Feminino , Humanos , Gravidez , Adulto Jovem
18.
Nat Commun ; 11(1): 4184, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826889

RESUMO

Oncogenic processes exert their greatest effect by targeting regulators of cell proliferation. Studying the mechanism underlying growth augmentation is expected to improve clinical therapies. The ovarian tumor (OTU) subfamily deubiquitinases have been implicated in the regulation of critical cell-signaling cascades, but most OTUs functions remain to be investigated. Through an unbiased RNAi screen, knockdown of OTUD5 is shown to significantly accelerate cell growth. Further investigation reveals that OTUD5 depletion leads to the enhanced transcriptional activity of TRIM25 and the inhibited expression of PML by altering the ubiquitination level of TRIM25. Importantly, OTUD5 knockdown accelerates tumor growth in a nude mouse model. OTUD5 expression is markedly downregulated in tumor tissues. The reduced OTUD5 level is associated with an aggressive phenotype and a poor clinical outcome for cancers patients. Our findings reveal a mechanism whereby OTUD5 regulates gene transcription and suppresses tumorigenesis by deubiquitinating TRIM25, providing a potential target for oncotherapy.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Predisposição Genética para Doença/genética , Células HEK293 , Xenoenxertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Knockout , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Interferência de RNA , Transdução de Sinais , Transcriptoma , Ubiquitinação
19.
Int J Nanomedicine ; 15: 5561-5571, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801704

RESUMO

Purpose: Platinum/paclitaxel-based chemotherapy is the strategy for ovarian cancer, but chemoresistance, inherent or acquired, occurs and hinders therapy. Therefore, further understanding of the mechanisms of drug resistance and adoption of novel therapeutic strategies are urgently needed. Methods: In this study, we report that sphingosine-1-phosphate receptor-1 (S1PR1)-mediated chemoresistance for ovarian cancer. Then we developed nanoparticles with a hydrophilic PEG2000 chain and a hydrophobic DSPE and biodegradable CaP (calcium ions and phosphate ions) shell with pH sensitivity as a delivery system (CaP-NPs) to carry BAF312, a selective antagonist of S1PR1 (BAF312@CaP-NPs), to overcome the cisplatin (DDP) resistance of the ovarian cancer cell line SKOV3DR. Results: We found that S1PR1 affected acquired chemoresistance in ovarian cancer by increasing the phosphorylated-signal transduction and activators of transcription 3 (P-STAT3) level. The mean size and zeta potential of BAF312@CaP-NPs were 116 ± 4.341 nm and -9.67 ± 0.935 mV, respectively. The incorporation efficiency for BAF312 in the CaP-NPs was 76.1%. The small size of the nanoparticles elevated their enrichment in the tumor, and the degradable CaP shell with smart pH sensitivity of the BAF312@CaP-NPs ensured the release of BAF312 in the acidic tumor niche. BAF312@CaP-NPs caused substantial cytotoxicity in DDP-resistant ovarian cancer cells by downregulating S1PR1 and P-STAT3 levels. Conclusion: We found that BAF312@CaP-NPs act as an effective and selective delivery system for overcoming S1PR1-mediated chemoresistance in ovarian carcinoma by inhibiting S1PR1 and P-STAT3.


Assuntos
Azetidinas/administração & dosagem , Compostos de Benzil/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Receptores de Esfingosina-1-Fosfato/genética , Azetidinas/farmacocinética , Compostos de Benzil/farmacocinética , Fosfatos de Cálcio/química , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fosforilação/efeitos dos fármacos , Polietilenoglicóis/química , Fator de Transcrição STAT3/metabolismo , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Receptores de Esfingosina-1-Fosfato/metabolismo
20.
DNA Cell Biol ; 39(10): 1767-1778, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32833542

RESUMO

N1-methyladenosine (m1A) is an important post-transcriptional modification in RNA, and plays critical roles in cellular functions. However, the relationship between m1A regulators and clinical significance of gynecological cancers remains unknown. In this study, we systematically analyzed RNA-seq and clinical data from several public database. Cell proliferation and migration assays were performed to verify the function of the m1A writer TRMT10C in cancer cells. We observed genetic alterations and dysregulated expressions of m1A regulators in gynecological cancer samples. We demonstrated that several m1A regulators could serve as prognostic biomarkers for gynecological cancer patients. The high correlations among the expression of m1A, N6-methyladenosine (m6A), and 5mC regulators were also revealed. Gene set enrichment analysis indicated that the mechanism of TRMT10C in regulating tumorigenesis was related to a variety of cancer-related pathways. Moreover, silencing TRMT10C suppressed the proliferation, colony formation, and migration of ovarian cancer and cervical cancer cells. In summary, our results highlight the importance of m1A regulators in regulating oncogenesis, and indicate that targeting specific m1A regulators might be a potential therapeutic strategy for gynecological cancers.


Assuntos
Biomarcadores Tumorais/genética , Metiltransferases/genética , Neoplasias Ovarianas/genética , Neoplasias do Colo do Útero/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Células HeLa , Humanos , Metiltransferases/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
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