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1.
Medicine (Baltimore) ; 99(9): e19383, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118786

RESUMO

RATIONALE: Breast metastasis from serous borderline tumor with micro-invasive carcinoma of ovary is a very rare condition. The breast lump as the only clinical presentation is rarely seen in ovarian carcinoma, which may lead to be misdiagnosed, and the mechanism of breast metastasis from ovarian tumors in early stage still needs to be explored. Differentiation from primary breast cancer and extramammary malignancy is crucial because the treatment and prognosis are significantly different. PATIENT CONCERNS: A 33-year-old female presented with a painless, movable, 1.0 × 1.0 cm lump in the upper outer quadrant of the right breast for a month. DIAGNOSES: Breast metastasis of serous borderline tumor with micro-invasive ovarian carcinoma confirmed by pathology and immunohistochemistry. INTERVENTIONS: The patient underwent lumpectomy, bilateral ovarian tumor stripping operation and prophylactic chemotherapy. OUTCOMES: No signs of recurrence have been detected in 1.5 years of follow-up. LESSONS: Distant metastasis may occur in early stage of ovarian carcinoma. It is important to determine the origin of the primary tumor and develop an effective treatment strategy for patients. Imaging findings and pathological diagnostic criteria are important to accurately differentiate between metastasis and primary breast lesions, which may improve the patient's outcomes.


Assuntos
Neoplasias da Mama/diagnóstico , Metástase Neoplásica/diagnóstico , Neoplasias Ovarianas/complicações , Adulto , Neoplasias da Mama/etiologia , Neoplasias da Mama/fisiopatologia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/etiologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Metástase Neoplásica/patologia , Neoplasias Ovarianas/fisiopatologia , Ultrassonografia/métodos
2.
Int J Gynecol Cancer ; 30(2): 227-232, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911537

RESUMO

INTRODUCTION: Poor baseline functional status is associated with adverse surgical outcomes. Additionally, decline in the postoperative setting may result in the delay of additional treatments, impacting overall survival. This study assesses the incidence and risk factors for functional decline following primary ovarian cancer debulking surgery in previously independent women using discharge location as a surrogate. METHODS: All patients with a postoperative diagnosis of ovarian cancer who underwent surgical debulking and had documentation of discharge location were identified using the 2011-2012 American College of Surgeons National Surgical Quality Improvement Program database. Patients were excluded if their baseline functional status was dependent or partially dependent, or if they died before discharge. Discharge destination was dichotomized as home versus non-home. Descriptive data included demographics, comorbidities, and perioperative outcomes. Multivariable logistic regression was used to evaluate the association of clinical and surgical factors on discharge destination. RESULTS: 1786 patients met the criteria for analysis; 120 (6.7%) patients were discharged to non-home. Differences between home and non-home discharges included age (53.2% vs 83.3% ≥60), body mass index (26.5 vs 27.8 median), comorbidities (45.2% vs 64.2% with ≥1), and complications (8.6% vs 30.0% with ≥1, all p<0.05). In multivariable logistic regression analyses, only increasing age and complications were independently associated with discharge to non-home. Those age ≥70 had 9.0 times the risk (95% CI 3.5 to 23.4; p<0.001) as age <50. The presence of one or more postoperative complications carried 4.5 times (95% CI 2.9 to 7.0; p<0.001) the risk of those without complications. 30 day mortality was also increased in patients discharged to non-home. DISCUSSION: 6.7% of previously independent ovarian cancer patients were discharged to non-home following surgery. Major risk factors for non-home include older age, comorbidities, and postoperative complications. Efforts to optimize baseline functional status and minimize surgical complications may improve discharge rates to non-home and postoperative functional status.


Assuntos
Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/cirurgia , Fatores Etários , Idoso , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Modelos Logísticos , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Período Pós-Operatório , Fatores de Risco
3.
J Agric Food Chem ; 68(5): 1326-1336, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31955565

RESUMO

Ovarian cancer is one of the most serious female malignancies worldwide. Despite intensive efforts being made to overcome ovarian cancer, there still remain limited optional treatments for this disease. Nobiletin, a prospective food-derived phytochemical extracted from citrus fruits, has recently been reported to suppress ovarian cancer cells, but the role of pyroptosis in ovarian carcinoma with nobiletin still remains unknown. In this study, we aim to explore the effect of nobiletin on ovarian carcinoma and further expound the underlying mechanisms of nobiletin-induced ovarian cancer cell death. Our results showed that nobiletin could significantly inhibit cell proliferation, induce DNA damage, and also lead to apoptosis by increasing the cleaved poly (ADP-ribose) polymerase (PARP) level of human ovarian cancer cells (HOCCs) in a dose-dependent manner. Moreover, we revealed that nobiletin decreased mitochondrial membrane potential and induced reactive oxygen species (ROS) generation and autophagy of HOCCs, contributing to gasdermin D-/gasdermin E-mediated pyroptosis. Taken together, nobiletin as a functional food ingredient represents a promising new anti-ovarian cancer candidate that could induce apoptosis and trigger ROS-mediated pyroptosis through regulating autophagy in ovarian cancer cells.


Assuntos
Autofagia/efeitos dos fármacos , Flavonas/farmacologia , Neoplasias Ovarianas/fisiopatologia , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo
4.
Adv Gerontol ; 32(4): 530-535, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31800180

RESUMO

Due to the increase in the proportion of elderly women, the prevalence of ovarian cancer is increasing, which requires the search for new methods of its diagnosis. The aim of the work is to analyze the content and informativeness of immunoglobulins and phagocytic activity of peripheral blood to improve the diagnosis of ovarian cancer among elderly women. In 78 patients with ovarian cancer aged 65-70 years immunological and spectrophotometric methods studied phagocytic activity and the level of peripheral blood immunoglobulins. 42 women of the same age with no ovarian cancer served as control. The primary importance of circulating immune complexes, phagocyte migration inhibition index and neutrophil activity index for laboratory diagnosis of ovarian cancer among the elderly was established. The use of highly informative parameters of systemic immunity improves the diagnosis of ovarian cancer in the elderly.


Assuntos
Imunoglobulinas , Neoplasias Ovarianas , Fagocitose , Idoso , Técnicas de Laboratório Clínico , Feminino , Humanos , Imunoglobulinas/sangue , Neutrófilos/metabolismo , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/fisiopatologia
5.
Health Qual Life Outcomes ; 17(1): 185, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856850

RESUMO

BACKGROUND: This study evaluated pre-defined aspects of content validity of the 18-item NCCN FACT-Ovarian Symptom Index (NFOSI-18) and its Disease-Related Symptoms-Physical (DRS-P) subscale, as clinical trial outcome tools for patients with advanced ovarian cancer. METHODS: Twenty-one women (mean age 59.5 years) diagnosed with advanced ovarian cancer completed the NFOSI-18 and participated in a cognitive interview to explore: (1) whether 'pain' and 'cramps' are considered redundant; (2) whether 'fatigue' and 'lack of energy' are overlapping concepts; (3) whether patients consider severity when responding to the item "I am bothered by constipation;" and (4) factors considered when responding to the item "I am sleeping well." Interviews were audio-recorded, transcribed, and analyzed qualitatively. RESULTS: Pain was associated with discomfort, hurt, and life interference; 'cramps' was associated with pain, muscle tightening, and menstrual or digestive issues. Most (81%) considered the items "I have pain" and "I have cramps in my stomach area" to be more different than similar. Participants associated 'fatigue' with intense tiredness and 'lack of energy' with motivation and capability to complete daily activities. Item comparisons revealed a majority (65%) considered the items to be more different than similar. When responding to "I am bothered by constipation," patients indicated constipation severity was related to bother. Finally, patients considered disease, treatment, and other factors when responding to "I am sleeping well." CONCLUSIONS: Findings support content validity of the NFOSI-18 and its DRS-P as originally constructed. We propose an alternative scoring option that excludes the item "I am sleeping well" from the DRS-P when used as a symptom-focused index for clinical research in a regulatory context.


Assuntos
Neoplasias Ovarianas/psicologia , Qualidade de Vida , Inquéritos e Questionários/normas , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/fisiopatologia
6.
Crit Rev Eukaryot Gene Expr ; 29(2): 161-170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679271

RESUMO

Circular RNA, also called circRNA, is a type of widespread RNA that is mainly derived from the spliceosome, from which DNA is transcribed into messenger RNA (mRNA). CircRNAs are characterized by the formation of a covalently closed continuous loop, and they play a variety of gene regulatory roles. CircRNAs were initially thought to represent splicing errors, but an increasing amount of evidence indicates that they may play significant roles in a variety of human diseases, including cancers, cardiovascular disease, neurological disorders, and pre-eclampsia. Studies have suggested that circRNAs regulate miRNA activity that arises from miRNA-mediated sponge effects. It has been shown that CDR1as acts as a sponge for miR-7 and that a testis-specific circRNA within the sex-determining region of Y (SRY) acts as a sponge for miR-138. Because miR-7 and miR-138 modulate several oncogenes and tumor suppressor genes, the interactions between ciRS-7 and miR-7 and between SRY and miR-138 may play important roles in cancer-related pathways. Hence, currently available data suggest that circRNAs may exert significant effects on diagnoses, prognoses, and therapies in ovarian cancer.


Assuntos
Neoplasias Ovarianas/genética , /metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/terapia , /genética
7.
BMC Complement Altern Med ; 19(1): 273, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638975

RESUMO

BACKGROUND: Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. METHODS: Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. RESULTS: Both the compounds, ST03 and ST08, showed ~ 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). CONCLUSION: Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/fisiopatologia , Movimento Celular/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo
8.
Gynecol Oncol ; 155(1): 126-134, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31416612

RESUMO

OBJECTIVES: Our aim was to investigate the prevalence and potential risk factors for persistent and troublesome physical and psychological symptoms following treatment for ovarian cancer (OC). METHODS: OvQuest is an international, internet-based, cross-sectional questionnaire which explored symptom burden and quality of life (QOL) after treatment for OC. Eligible women were aged 18 and over, diagnosed with OC at least 6 months previously and had received chemotherapy. Self-report data were collected including demographics, diagnosis and treatment, and standardised instruments for treatment-related toxicities, QOL, physical activity (PA) and supportive care needs. RESULTS: The survey included 1360 patients, of whom 421 (31%) had been treated for recurrent OC. 78% reported symptoms of peripheral neuropathy, 60% significant fatigue, 48% mood disturbance and 59% moderate-severe insomnia. Rates of fatigue, mood disorders, neuropathy and insomnia did not differ between women with or without recurrence. The majority of respondents were overweight or obese (high BMI, 59%) and 35% reported low PA. Low PA and high BMI were associated with poorer QOL scores and higher symptom burden across a range of domains. CONCLUSION: Women living after a diagnosis of OC report a substantial and ongoing symptom burden which impacts significantly on their quality of life across multiple domains. The reported associations between obesity, physical inactivity and poor QOL warrant prospective evaluation of lifestyle interventions to improve QOL.


Assuntos
Sobreviventes de Câncer/psicologia , Neoplasias Ovarianas/psicologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Fadiga/etiologia , Fadiga/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/psicologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/psicologia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/terapia , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
9.
J Ovarian Res ; 12(1): 60, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277702

RESUMO

OBJECTIVE: To investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3ß/Snail signaling pathway. METHODS: The expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic, Control siRNA, ATM siRNA, and miR-203a-3p inhibitor + ATM siRNA groups. The biological behaviors of ovarian cancer cells were evaluated by CCK-8, wound healing, and Transwell invasion assays, annexin V-FITC/PI staining and flow cytometry. The levels of Akt/GSK-3ß/Snail pathway-related proteins were assessed by Western blotting. RESULTS: Ovarian cancer tissues showed lower miR-203a-3p levels and higher ATM levels than adjacent normal tissues, both of which were associated with the FIGO stage, grade and prognosis of ovarian cancer. As confirmed by a dual-luciferase reporter gene assay, miR-203a-3p could target ATM. Furthermore, the miR-203a-3p mimic had multiple effects, including the inhibition of the proliferation, invasion and migration of A2780 and SKOV3 cells, the promotion of cell apoptosis, the arrest of the cell cycle at the G1 phase, and the blockage of the Akt/GSK-3ß/Snail signaling pathway. ATM siRNA had similar effects on the biological behaviors of ovarian cancer cells, and these effects could be reversed by a miR-203a-3p inhibitor. CONCLUSION: miR-203a-3p was capable of hindering proliferation, migration, and invasion and facilitating the apoptosis of ovarian cancer cells through its modulation of the Akt/GSK-3ß/Snail signaling pathway by targeting ATM, and therefore it could serve as a potential therapeutic option for ovarian cancer.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Adulto , Idoso , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno , Fatores de Transcrição da Família Snail/genética
10.
Free Radic Res ; 53(8): 882-891, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31290351

RESUMO

To define the role of glutathione peroxidase (GPx) in modulating the oxygen radical-related cytotoxicity of doxorubicin and H2O2 in cells that overexpress P-glycoprotein (Pgp), the GPx activity of NCI/ADR-RES cancer cells was altered by growth in 0.5% serum with (MR-30 subline) or without (MR-0 subline) selenium supplementation. GPx activity increased from 2.2 nmol/min/mg (MR-0) to 22.5 nmol/min/mg (MR-30) when cells were grown in 30-nM selenium, p < .01; the activities of other antioxidant enzymes were unchanged by selenium. By reverse transcriptase polymerase chain reaction, MR-30 and MR-0 cells expressed similar levels of the MDR1, GPx-1, BCL2 and TOP2A mRNA. The IC50 concentration for H2O2 in MR-0 cells was 10-fold lower than in the MR-30 subline, p < .01. Despite identical anthracycline accumulation and efflux in these two lines that expressed equivalent levels of Pgp, the doxorubicin IC50 decreased fivefold in MR-0 versus MR-30 cells, p < .01. Log-linear tumour cell killing by doxorubicin was observed only in selenium-deficient MR-0 cells. Doxorubicin exposure also produced substantially more apoptosis in MR-0 than MR-30 cells; this was not related to the presence of selenium per se. MR-0 cells generated ≈5-times more methane from dimethyl sulfoxide (a measure of reactive oxygen metabolism) than MR-30 cells in the presence of equimolar doxorubicin concentrations (p < .05). These studies suggest that GPx-mediated detoxification of peroxides can modulate the antitumor activity of doxorubicin in the presence of high levels of Pgp.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Apoptose , Doxorrubicina/farmacologia , Glutationa Peroxidase/metabolismo , Neoplasias Ovarianas/enzimologia , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Peróxido de Hidrogênio/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/fisiopatologia , Peróxidos/metabolismo , Células Tumorais Cultivadas
11.
J Environ Sci Health B ; 54(9): 752-757, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271108

RESUMO

Isoquercitrin is a dietary bioflavonoid used as a food supplement. We studied the mechanism underlying its effect in human ovarian cancer cells using OVCAR-3 cell line. Viability, survival, apoptosis, release of human transforming growth factor-ß1 (TGF-ß1) and TGF-ß1 receptor, and intracellular reactive oxygen species (ROS) generation by OVCAR-3 cells were examined after isoquercitrin treatment at concentrations 5, 10, 25, 50, and 100 µg mL-1. AlamarBlue assay revealed that isoquercitrin did not cause any significant change (P > 0.05) in cell viability as compared to control. Apoptotic assay using flow cytometry did not find any significant change (P > 0.05) in the proportion of live, dead and apoptotic cells as compared to control. ELISA also showed that the release of human TGF-ß1 and TGF-ß1 receptor were not significantly (P > 0.05) affected by isoquercitrin as compared to control. Chemiluminescence assay demonstrated that lower concentrations (5, 10, and 25 µg mL-1) were able to exhibit beneficial effects by inhibiting the generation of intracellular ROS. In contrast, elevated concentrations of 50 and 100 µg mL-1 led to oxidative stress (P < 0.05). We concluded that the beneficial effect of isoquercitrin on ovarian cancer cells may be mediated by an antioxidative pathway that involves inhibition of intracellular ROS generation, thereby limiting oxidative stress.


Assuntos
Quercetina/análogos & derivados , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
12.
J Ovarian Res ; 12(1): 56, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208449

RESUMO

BACKGROUND: PD-L1 expression levels determined by immunostaining are known to be related to the survival rate and prognosis of patients with various types of cancers, as well as to the therapeutic response to immune checkpoint inhibitors. Recently, the U.S. Food and Drug Administration approved an immune checkpoint inhibitor for the treatment of non-small cell lung cancer along with the clones used for PD-L1 immunostaining to predict the resulting response. In this study, we performed PD-L1 immunostaining of tissue microarrays from ovarian epithelial cancer using SP263, an approved clone, and examined the effect of PD-L1 expression on survival rate and prognosis. METHODS: Tissue microarrays were constructed from ovarian epithelial cancer tissues of 248 patients and PD-L1 immunostaining was performed using the SP263 clone. PD-L1 expression levels in tumor cells, intraepithelial tumor-infiltrating lymphocytes, and stromal tumor-infiltrating lymphocytes were evaluated, and the effect of PD-L1 expression on survival and prognosis was analyzed. RESULTS: PD-L1 was detected in tumor cells as well as intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. It was most frequently expressed in stromal tumor-infiltrating lymphocytes. The Kaplan-Meier curve analysis and log rank test showed that only high stromal PD-L1 expression was associated with increased overall survival in ovarian serous carcinoma. Multivariate and univariate Cox regression analyses revealed that stromal PD-L1 expression was an independent prognostic factor, especially in ovarian serous carcinoma. CONCLUSIONS: PD-L1 immunostaining using SP263 was observed in tumor cells as well as intraepithelial and stromal tumor-infiltrating lymphocytes. PD-L1-expressing stromal tumor-infiltrating lymphocytes were associated with an increased overall survival rate and may serve as a favorable prognostic factor in ovarian cancer, particularly serous carcinoma.


Assuntos
Antígeno B7-H1/metabolismo , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/fisiopatologia , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/fisiopatologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/fisiopatologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Prognóstico , Células Estromais , Taxa de Sobrevida , Adulto Jovem
14.
J Med Case Rep ; 13(1): 181, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31196215

RESUMO

INTRODUCTION: Giant ovarian cysts are rarely described in the literature, owing to the availability of advanced imaging technologies in developed countries leading to early treatment. In resource-limited settings, various factors lead to late presentation. CASE PRESENTATION: We present a case of a 48-year-old black African woman with a giant mucinous cystadenoma who presented to a tertiary hospital with massive abdominal distention 5 years after being referred from a district hospital for the same problem. Surgical management resulted in fatal complications. CONCLUSIONS: The surgical management of these huge tumors is associated with many life-threatening complications. Transvaginal ultrasound should be used in resource-limited settings to delineate ovarian masses. Community health workers must be involved in scouting and follow up of community members with unusual abdominal swellings in developing countries to avoid delays in care.


Assuntos
Parede Abdominal/patologia , Cistadenoma Mucinoso , Gangrena , Neoplasias Ovarianas , Ovariectomia , Complicações Pós-Operatórias , Cistadenoma Mucinoso/patologia , Cistadenoma Mucinoso/fisiopatologia , Cistadenoma Mucinoso/cirurgia , Diagnóstico Tardio , Países em Desenvolvimento , Evolução Fatal , Feminino , Gangrena/etiologia , Gangrena/terapia , Humanos , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias Ovarianas/cirurgia , Ovariectomia/efeitos adversos , Ovariectomia/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Carga Tumoral , Zimbábue
15.
Life Sci ; 232: 116561, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247208

RESUMO

AIMS: The poor prognosis of ovarian cancer is mainly caused by chemotherapy resistance. Studies show that the Bcl-2 inhibitor ABT737 can significantly improve the effect of cisplatin and induce mitochondrial pathway apoptosis. However, the mechanism of ABT737 increases sensitivity to cisplatin by regulating mitochondrial function remains unclear in ovarian cancer cells. Sirt3, as a histone deacetylase, is involved in the regulation of mitochondrial function in cancers. In this study, we intend to explore the mechanistic link between Sirt3 and mitochondrial dysfunction induced by ABT737 and cisplatin in ovarian cancer cells. MAIN METHODS: Apoptosis was examined by flow cytometry following Annexin V and PI staining. Sirt3 activity was assessed using Sirt3 deacetylase fluorometric assay. The mitochondrial membrane potential was examined by flow cytometry following JC-1 staining. Overexpression and knock-down of Sirt3 were confirmed by western blot analysis. Mitochondrial fission/fusion dynamics were detected by immunofluorescence staining or western blot analysis. KEY FINDINGS: Cisplatin accompanied with ABT737 promoted apoptosis and decreased mitochondrial membrane potential. ABT737 enhanced the sensitivity of ovarian cancer cells to cisplatin, which was partly achieved by activating Sirt3 to regulate the mitochondrial fission process. SIGNIFICANCE: This study identified the activation of Sirt3 played an important role in increasing sensitivity of ovarian cancer cells to cisplatin induced by ABT737. Furthermore, Sirt3 might represent a potential therapeutic target for ovarian cancer.


Assuntos
Compostos de Bifenilo/farmacologia , Nitrofenóis/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Sirtuína 3/metabolismo , Sulfonamidas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/metabolismo , Cisplatino/farmacologia , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Neoplasias Ovarianas/fisiopatologia , Ovário/metabolismo , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Nutrients ; 11(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234395

RESUMO

Among all gynaecological neoplasms, ovarian cancer has the highest rate of disease-related malnutrition, representing an important risk factor of postoperative mortality and morbidity. Hence, the importance of finding effective nutritional interventions is crucial to improve ovarian cancer patient's well-being and survival. This systematic review of randomized controlled trials (RCTs) aims at assessing the effects of nutritional interventions on clinical outcomes such as overall survival, progression-free survival, length of hospital stay (LOS), complications following surgery and/or chemotherapy in ovarian cancer patients. Three electronic bibliographic databases (MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials) were used to conduct a systematic literature search based on fixed inclusion and exclusion criteria, until December 2018. A total of 14 studies were identified. Several early postoperative feeding interventions studies (n = 8) were retrieved mainly demonstrating a reduction in LOS and an ameliorated intestinal recovery after surgery. Moreover, innovative nutritional approaches such as chewing gum intervention (n = 1), coffee consumption (n = 1), ketogenic diet intervention (n = 2) or fruit and vegetable juice concentrate supplementation diet (n = 1) and short-term fasting (n = 1) have been shown as valid and well-tolerated nutritional strategies improving clinical outcomes. However, despite an acceptable number of prospective trials, there is still a lack of homogeneous and robust endpoints. In particular, there is an urgent need of RCTs evaluating overall survival and progression-free survival during ovarian oncology treatments. Further high-quality studies are warranted, especially prospective studies and large RCTs, with more homogeneous types of intervention and clinical outcomes, including a more specific sampling of ovarian cancer women, to identify appropriate and effective nutritional strategies for this cancer, which is at high risk of malnutrition.


Assuntos
Desnutrição/dietoterapia , Estado Nutricional , Neoplasias Ovarianas/dietoterapia , Feminino , Humanos , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
17.
Int J Mol Sci ; 20(12)2019 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-31234549

RESUMO

High grade serous ovarian cancer (HGSOC) is the most common and aggressive ovarian cancer subtype with the worst clinical outcome due to intrinsic or acquired drug resistance. Standard treatment involves platinum compounds. Cancer development and chemoresistance is often associated with an increase in histone deacetylase (HDAC) activity. The purpose of this study was to examine the potential of HDAC inhibitors (HDACi) to increase platinum potency in HGSOC. Four HGSOC cell lines with different cisplatin sensitivity were treated with combinations of cisplatin and entinostat (class I HDACi), panobinostat (pan-HDACi), or nexturastat A (class IIb HDACi), respectively. Inhibition of class I HDACs by entinostat turned out superior in increasing cisplatin potency than pan-HDAC inhibition in cell viability assays (MTT), apoptosis induction (subG1), and caspase 3/7 activation. Entinostat was synergistic with cisplatin in all cell lines in MTT and caspase activation assays. MTT assays gave combination indices (CI values) < 0.9 indicating synergism. The effect of HDAC inhibitors could be attributed to the upregulation of pro-apoptotic genes (CDNK1A, APAF1, PUMA, BAK1) and downregulation of survivin. In conclusion, the combination of entinostat and cisplatin is synergistic in HGSOC and could be an effective strategy for the treatment of aggressive ovarian cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Ovarianas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular , Cistadenocarcinoma Seroso/enzimologia , Cistadenocarcinoma Seroso/fisiopatologia , Sinergismo Farmacológico , Feminino , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases , Humanos , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/fisiopatologia , Panobinostat/farmacologia , Panobinostat/uso terapêutico , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(1): 116-120, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31102366

RESUMO

Chemotherapy resistance is one of the biggest challenges in treatment of ovarian cancer. Mounting evidence shows that the exosomes shedding from tumor cells are considered to be involved in chemotherapy resistance of ovarian cancer by enhanced exosomal export of drugs, transferring RNAs or proteins and interfering with the bioactivity of therapeutic anti-tumor antibodies. In this review, we display the correlation between exosomes and chemotherapy resistance of ovarian cancer, the mechanism of exosomes involved in chemotherapy resistance of ovarian cancer, and discuss the potential clinical values of exosomes in chemotherapy resistance of ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário , Exossomos , Neoplasias Ovarianas , Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/fisiopatologia , Resistencia a Medicamentos Antineoplásicos , Exossomos/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/fisiopatologia
19.
Gulf J Oncolog ; 1(29): 83-86, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30956200

RESUMO

Ovarian mucinous cystadenomas are cystic neoplasms lined by mucin-producing epithelial cells. They are mostly benign (80%) and frequently asymptomatic at early stages. The average diameter of ovarian mucinous cystadenomas ranges from 15 to 30 cm. Herein, we report the case of a giant benign ovarian mucinous cystadenoma in a 53-year-old postmenopausal woman. The patient presented with a very huge pelvi-abdominal distention that started ten months ago and was progressively increasing in size. It was associated with on-off abdominal pain, nausea and urinary retention. The case was discussed with a multidisciplinary team. Subsequently, the patient was consented for exploratory laparotomy. The origin of the mass was identified to be the right ovary, and right salpingo-oophorectomy was done. The resected mass measured 73x51x42 cm and weighed 108 kg. The left ovary had a multilocular mass of 15 cm in diameter, and left salpingo-oophorectomy was successively performed. There was no ascites. Histopathological examination confirmed the diagnosis of bilateral benign mucinous cystadenoma. At a postoperative 9-month follow-up in the outpatient clinic, the patient showed up in good condition without evidence of recurrence. To the best of our knowledge, we report the largest benign ovarian cyst in Saudi Arabia, and one of the largest (probably the third) in the English medical literature. It is technically feasible to manage an extremely large-sized benign mass with satisfactorily perioperative outcomes. This should be done through a multidisciplinary approach that demands an orchestrated collaboration between different specialists to yield an optimized perioperative care.


Assuntos
Cistadenoma Mucinoso/fisiopatologia , Neoplasias Ovarianas/fisiopatologia , Cistadenoma Mucinoso/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia
20.
Int J Gynecol Cancer ; 29(3): 585-592, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30833444

RESUMO

OBJECTIVE: There are limited data on clinical outcomes of patients with advanced-stage epithelial ovarian cancer who require ostomy formation at the time of either primary cytoreductive surgery or interval cytoreductive surgery. The objective of this study was to evaluate patients undergoing bowel surgery and ostomy formation after primary or interval surgery. METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV epithelial ovarian cancer who underwent cytoreductive surgery between January 2010 and December 2014 were identified retrospectively. Patients with non-epithelial histology, low-grade serous histology or incomplete medical records were excluded. Demographic and clinical data were collected and analyzed. Age, stage, co-morbidity index, pre-operative CA125, pre-operative albumin, and Aletti surgical complexity score were included in a multivariable logistic regression model to assess independent associations with ostomy formation. RESULTS: A total of 554 patients were included in the study. Of these, 261 (47%) underwent primary cytoreduction and 293 (53%) underwent interval cytoreduction. Patients undergoing primary surgery were more likely to undergo bowel resection, compared with interval surgery patients (37.2% vs 14%, p<0.001). Of the 139 (25.1%) patients who underwent bowel surgery, 25 (18%) underwent ostomy formation (11 ileostomies and 14 colostomies). Rates of ostomy formation were similar between the groups (6.1% primary vs 3.1% interval, p=0.10). Patients undergoing ostomy formation were more likely to have longer mean operative time (335 vs 229 min, p<0.001) and undergo small and large bowel resections at the time of cytoreductive surgery (44% vs 14%, p<0.001). Multivariate analysis revealed that a high surgical complexity score was associated with ostomy formation. Of the patients who underwent ostomy formation, 13 (43.3%) underwent stoma reversal including 11 ileostomies and two colostomies. Median time to ostomy reversal was 7 months. CONCLUSION: Bowel surgery is more common among patients undergoing primary surgery as compared with interval surgery, but this does not result in an increased risk of ostomy formation.


Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Colectomia/métodos , Procedimentos Cirúrgicos de Citorredução/métodos , Estomia/métodos , Neoplasias Ovarianas/cirurgia , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/fisiopatologia , Feminino , Humanos , Intestinos/fisiopatologia , Intestinos/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/fisiopatologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
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