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1.
Acta cir. bras ; 39: e390524, 2024. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1533358

ABSTRACT

Purpose: We aimed to reveal the effects of rosmarinic acid (RA), which has come to the forefront with its antitumor and antioxidant properties in many studies recently in the ovarian adenocarcinoma cell line, on the epidermal growth factor receptor (EFGR) signaling pathway in the presence of doxorubicin (DOX). Methods: Ovarian adenocarcinoma cell line (OVCAR3) and human skin keratinocyte cell line human skin keratinocyte cell line (HaCaT) were used as control. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied to determine the effect of RA and DOX on the proliferation of OVCAR3 and HaCaT cells. Bcl2 expression and epidermal growth factor receptor (EGFR) and western blot analysis were performed to determine the expression levels of the markers. Results: It was determined that RA (IC50 = 437.6 µM) and DOX (IC50 = 0.08 µM) have the ability to inhibit the proliferation of OVCAR3 cells and induce apoptosis in a 72-hour time and dose-dependent manner. Western blot showed that the expression level of Bcl-2 and EGFR in OVCAR3 cells was down-regulated by RA and DOX. Conclusions: Apoptosis in OVCAR3 cells can potentially be induced by RA via the EGFR pathway, and RA may be a potent agent for cancer therapy.


Subject(s)
Ovarian Neoplasms , Adenocarcinoma , Doxorubicin/administration & dosage , ErbB Receptors
2.
Rev. bras. ginecol. obstet ; 45(12): 780-789, Dec. 2023. graf
Article in English | LILACS | ID: biblio-1529912

ABSTRACT

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.


Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.


Subject(s)
Humans , Female , Ovarian Neoplasms , Cytokines , Chemokines , Inflammation
3.
Gac. méd. espirit ; 25(2): [8], ago. 2023.
Article in Spanish | LILACS | ID: biblio-1514158

ABSTRACT

Fundamento: Los linfomas primarios de ovario son poco frecuentes; el 1 % de estos se presenta en ovario y el 1.5 % de los tumores malignos de ovario son linfomas. Los tipos histológicos más frecuentes es el linfoma no Hodgkin difuso de células B grande y el BurKitt; el tratamiento consiste en cirugía combinada con quimioterapia. Objetivo: Reportar un caso de un linfoma no Hodgkin difuso de células B grande primario de ovario. Presentación de caso: Se presentó el caso de una paciente de 39 años de edad, con antecedentes patológicos personales de salud; la cual fue al cuerpo de guardia de ginecología por presentar dolor abdominal difuso que no se aliviaba con analgésicos. En la exploración física presentaba dolor a la palpación superficial y profunda en hipocondrio y fosa ilíaca derecha con masa tumoral palpable. Ecografía hacia proyección anexial derecha se observó una imagen de baja ecogenicidad y en la laparoscopia de urgencia se concluyó como una formación de aspecto tumoral que parecía corresponderse con ovario derecho. Se le realizó una histerectomía con doble anexectomía. El diagnóstico anatomopatológico fue un linfoma no Hodgkin primario de ovario. Conclusiones: La paciente del caso presentado tuvo una clínica oligosintomática y la confirmación de la enfermedad fue a partir de una muestra quirúrgica, lo que expresa que el diagnóstico del linfoma no Hodgkin de células B es difícil y aunque es poco frecuente siempre se debe tener en cuenta en el diagnóstico diferencial de las tumoraciones unilaterales de ovario.


Background: Primary ovarian lymphomas are uncommon, 1% of these malignancies occur in the ovary, and 1.5% of all ovarian malignancies are lymphomas. The most common histologic types are diffuse large B-cell non-Hodgkin's lymphoma and BurKitt's lymphoma; treatment consists of surgery combined with chemotherapy. Objective: To report a case of primary ovarian diffuse large B-cell non-Hodgkin lymphoma. Case presentation: A 39-year-old female case is presented, with a personal pathological history; she went to the gynecology emergency service because she presented diffuse abdominal pain that was not relieved by analgesics. Physical examination revealed superficial and deep pain on palpation in the hypochondrium and right illiac fossa with a palpable tumor mass. Right adnexal ultrasound showed an image of low echogenicity and at the emergency laparoscopy, it was diagnosed as a tumor-like formation that appeared to correspond to the right ovary. She underwent a hysterectomy with double adnexectomy. The anatomopathologic diagnosis was primary ovarian non-Hodgkin's lymphoma. Conclusions: The patient in the presented case had an oligosymptomatic clinical presentation. Confirmation of the disease was obtained from a surgical sample, which means that B-cell non-Hodgkin's lymphoma is difficult to diagnose and although it is uncommon, it should always be considered in the differential diagnosis of unilateral ovarian tumors.


Subject(s)
Ovarian Neoplasms , Lymphoma, Non-Hodgkin , Case Reports , Lymphoma, Large B-Cell, Diffuse
4.
Medisan ; 27(4)ago. 2023. ilus
Article in Spanish | LILACS, CUMED | ID: biblio-1514570

ABSTRACT

Se presenta el caso clínico de una adolescente de 15 años de edad, quien fue asistida en el Hospital Provincial Pediátrico Universitario José Luis Miranda de Villa Clara, remitida desde su área de salud, por presentar dolor pélvico intenso desde hacía 3 días, náuseas y fiebre de 38,5 °C. Luego de realizados el examen clínico y los estudios complementarios pertinentes, se decidió practicar la resección completa del tumor. Durante el procedimiento se tomó muestra para estudio histológico que confirmó la existencia de un tumor del seno endodérmico ovárico, por lo cual fue reintervenida para extirpar el ovario contralateral y el epiplón infiltrados. Posteriormente se indicó poliquimioterapia según el protocolo y la evolución postratamiento fue satisfactoria.


The case report of a 15-years-old adolescent is presented, who was assisted at José Luis Miranda University Pediatric Provincial Hospital from Villa Clara, referred from her health area due to an intense pelvic pain for 3 days, nausea and fever of 38.5 °C. After carrying out the clinical exam and the pertinent laboratory tests, it was decided to practice the complete tumor resection. During the procedure a sample for histologic study was taken that confirmed the existence of an ovarian yolk sac tumor, reason why she was operated again to extirpate the contralateral ovary and the infiltrated omentum. Later on polychemotherapy was indicated according to the protocol and the post-treatment clinical course was satisfactory.


Subject(s)
Ovarian Neoplasms
5.
Oncología (Guayaquil) ; 33(2): 131-142, 14 de agosto del 2023.
Article in Spanish | LILACS | ID: biblio-1451564

ABSTRACT

Introducción: El índice de irresecabilidad valora la presencia de cuatro variables (masa abdominal palpable, tumor en fondo de saco de Douglas, presencia de líquido ascítico, valor preoperatorio de Ca 125 mayor a 1000 U/ml); previo a la realización de una cirugía citorreductora primaria en pacientes con cáncer de ovario. El objetivo del presente estudio fue realizar una prueba diagnóstica del índice de irresecabilidad con la decisión de realizar citorreducción óptima en pacientes con cáncer de ovario que fueron operadas en un hospital público de referencia nacional en Ecuador en 3 años de estudio. Metodología: En el presente estudio de pruebas diagnósticas, se estudiaron mujeres operadas con cáncer de ovario, en el Hospital de Especialidades Eugenio Espejo (Ecuador) de septiembre del 2016 a septiembre del 2018. Se incluyeron pacientes con citorreducción óptima y subóptima. Se presenta un análisis descriptivo con frecuencias, porcentajes y promedios. Se evaluó la sensibilidad, especificidad, valor predictivo negativo (VPN) y valor predictivo positivo (VPP) del índice de irresecabilidad comparado con la citorreducción. Resultados: Fueron 148 casos analizados. La especificidad del índice fue de 81 %, con un valor predictivo (VP) positivo del 77 % y VP negativo de 68 %. La sensibilidad de la ascitis 85 % y la masa abdominal palpable del 79 %. En las pacientes que presentaron valores de antígeno CA-125 menor a 1000 U/ml, el riesgo de obtener una citorreducción óptima fue OR: 0.15 (IC95% 0.069 ­ 0.307; P: 0.0001); las pacientes que presentaron valores del índice de irresecabilidad entre 1 y 2 puntos versus 3 y 4 fue de OR: 7.04 (IC95% 3.33 -14.87, P: 0.0001). Conclusiones: El Índice de irresecabilidad presentó una capacidad estadísticamente significativa para predecir citorreducción óptima en las pacientes con cáncer ovario operadas en el Hospital de Especialidades Eugenio Espejo.


Introduction: The unresectability index assesses the presence of four variables (palpable abdominal mass, tumor in the fornix of Douglas, presence of ascitic fluid, preoperative Ca 125 value greater than 1000 U/ml); before performing primary cytoreductive surgery in patients with ovarian cancer. The objective of this study was to carry out a diagnostic test of the unresectability index with the decision to perform optimal cytoreduction in patients with ovarian cancer who underwent surgery in a public hospital of national reference in Ecuador in 3 years of study. Methodology: In the present study of diagnostic tests, women operated on for ovarian cancer were studied at the Eugenio Espejo Specialties Hospital (Ecuador) from September 2016 to September 2018. Patients with optimal and suboptimal cytoreduction were included. A descriptive analysis with frequencies, percentages, and averages is presented. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the unresectable index compared with cytoreduction were evaluated. Results: 148 cases were analyzed. The specificity of the index was 81%, with a positive predictive value (PV) of 77% and a negative PV of 68%. The sensitivity of ascites is 85%, and the palpable abdominal mass of 79%. In patients who presented CA-125 antigen values less than 1000 U/ml, the risk of obtaining optimal cytoreduction was OR: 0.15 (95% CI 0.069 - 0.307; P: 0.0001); The patients who presented unresectability index values between 1 and 2 points versus 3 and 4 were OR: 7.04 (95% CI 3.33 -14.87, P: 0.0001). Conclusions: The unresectability index presented a statistically significant capacity to predict optimal cytoreduction in patients with ovarian cancer operated on at the Eugenio Espejo Specialties Hospital.


Subject(s)
Humans , Adult , Ovarian Neoplasms , CA-125 Antigen , Cytoreduction Surgical Procedures , Surgical Procedures, Operative , Predictive Value of Tests
6.
Medicentro (Villa Clara) ; 27(2)jun. 2023.
Article in Spanish | LILACS | ID: biblio-1440529

ABSTRACT

El fibrotecoma ovárico es una neoplasia poco frecuente. Se observa, por lo general, como un tumor sólido unilateral, de tamaño variable, en mujeres premenopáusicas. En su mayoría es benigno y puede ser funcional. En el artículo se describe el diagnóstico y tratamiento de esta rara enfermedad. Se presenta un caso de fibrotecoma ovárico gigante en una paciente adolescente de 18 años de edad, con un embarazo de 34 semanas, a quien se le practicó una cesárea y la exéresis de la lesión, sin complicaciones interoperatorias ni postoperatorias.


Ovarian fibrothecoma is a rare neoplasm. It is usually seen as a unilateral solid tumor of variable size in premenopausal women. It is mostly benign and may be functional. This article describes the diagnosis and treatment of this rare disease. We present an 18-year-old female adolescent patient with a 34-week pregnancy and a giant ovarian fibrothecoma; she underwent a cesarean section and excision of the lesion without intra- or postoperative complications.


Subject(s)
Ovarian Neoplasms , Pregnancy , Adolescent Medicine
7.
J. bras. econ. saúde (Impr.) ; 15(1): 52-58, Abril/2023.
Article in English, Portuguese | LILACS, ECOS | ID: biblio-1437941

ABSTRACT

Objetivo: Avaliar o impacto orçamentário do tratamento com iPARP como primeira linha de manutenção, comparado ao tratamento-padrão a partir de evidências de mundo real sob a perspectiva de um hospital público referência em oncologia no Rio de Janeiro. Métodos: Foi aplicada uma análise de impacto orçamentário para estimar a introdução das tecnologias iPARP, olaparibe e niraparibe, em comparação com o cenário referência, utilizando dados de eficácia e evidências de mundo real, e considerando os custos globais de tratamento da doença em cinco anos. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa, CAAE: 95157018.9.0000.5274. Resultados: A análise demonstrou que o cenário referência apresentou um impacto orçamentário no valor de R$ 3.578.768,04 em cinco anos. No cenário alternativo, o custo incremental do olaparibe chegou a ser 23,8% maior, comparado ao niraparibe, atingindo um custo de R$ 23.736.459,20 versus R$ 18.076.951,81, respectivamente. Os parâmetros que apresentaram maior impacto nas análises para a tecnologia olaparibe foram a difusão da tecnologia e o preço do medicamento. Contudo, para o niraparibe, os parâmetros de maior impacto foram a duração do tratamento, a difusão da tecnologia e a dose utilizada, demonstrando maior suscetibilidade de variação. Conclusão: Os iPARP no tratamento de pacientes com carcinoma de ovário avançado, apesar de apresentarem custo incremental de aproximadamente R$ 23 milhões em cinco anos, apontam para uma potencial redução de custos associados à progressão da doença.


Objective: Assess the budgetary impact of treatment with iPARP as a first line of maintenance, compared to standard treatment based on real-world evidence from the perspective of a public hospital reference in oncology at Rio de Janeiro. Methods: A budget impact analysis was applied to estimate the introduction of iPARP, olaparib and niraparib technologies, compared to the reference scenario, using efficacy data and real-world evidence, and considering the global costs of treating the disease in five years. This study was approved by the Research Ethics Committee, CAAE: 95157018.9.0000.5274. Results: The analysis showed that the reference scenario presented a budgetary impact of R$ 3,578,768.04 in five years. In the alternative scenario, the incremental cost of olaparib reached 23.8% higher compared to niraparib, reaching a cost of R$ 23,736,459.20 versus R$ 18,076,951.81, respectively. The parameters that had the greatest impact on the analyzes for the olaparib technology were technology diffusion and drug price. However, for niraparib, the parameters with the greatest impact were the duration of treatment, the diffusion of the technology and the dose used, demonstrating greater susceptibility to variation. Conclusion: iPARP in the treatment of patients with advanced ovarian carcinoma, despite having an incremental cost of approximately R$ 23 million in five years, point to a potential reduction in costs associated with disease progression.


Subject(s)
Ovarian Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Analysis of the Budgetary Impact of Therapeutic Advances
8.
Oncología (Guayaquil) ; 33(1): 49-57, 4 de Abril 2023.
Article in Spanish | LILACS | ID: biblio-1427639

ABSTRACT

Introducción: La supervivencia del cáncer de ovario se aproxima al 50%, sin embargo, varía en función de los distintos factores pronósticos, siendo el principal la extensión de la enfermedad al diagnóstico. El objetivo del presente estudio fue establecer la supervivencia global y libre de enfermedad en un centro de referencia para el tratamiento de cáncer de ovario en Quito, Ecuador. Métodos: El presente estudio longitudinal, se realizó en el Hospital Metropolitano de Quito, de enero del 2008 a diciembre del 2018. Se incluyeron mujeres con cáncer de ovario. Se registraron variables demográficas, número de embarazos, comorbilidades, diagnóstico histológico, tiempo de evolución, tratamiento recibido, estadío de la enfermedad, progresión, recaídas, período libre de enfermedad y mortalidad. La muestra fue no probabilística. Se realiza un análisis descriptivo y un análisis de supervivencia. Resultados: Participaron 84 pacientes. La edad en 20 casos (23.8%) < 50 años, en 29 casos (34.5%) de 50 a 59 años y en 35 casos (41.7%) > 60 años. El 60.7 % con 1 a 3 embarazos, el 23.8% nunca se embarazo y el 15.5 % con > 4 embarazos, sin relación con la mortalidad. El tipo histológico más prevalente fue el carcinoma epitelial en 56 casos (66.6%). La media de tiempo de recaída fue 56.8 meses y de tiempo de sobrevida fue de 87.7 meses. La supervivencia a los 5 años fue del 62% y a los 10 años del 55%. La supervivencia fue menor en mayores de 60 años y con estadios IIB, IIC, IIIA y IIIC. Conclusión: En este estudio la mortalidad se modificó por el estadío clínico, el tiempo de evolución y la edad de las pacientes con cáncer de ovario.


Introduction: Survival from ovarian cancer is close to 50%; however, it varies depending on the different prognostic factors, the main one being the extent of the disease at diagnosis. The objective of this study was to establish overall and disease-free survival in a reference center for the treatment of ovarian cancer in Quito, Ecuador. Methods: The present longitudinal study was carried out at the Metropolitan Hospital of Quito from January 2008 to December 2018. Women with ovarian cancer were included. Demographic variables, number of pregnancies, comorbidities, histological diagnosis, evolution time, treatment received, disease stage, progression, relapses, disease-free period, and mortality were recorded. The sample was non-probabilistic. A descriptive analysis and a survival analysis are performed. Results: 84 patients participated. Age in 20 cases (23.8%) <50 years, in 29 cases (34.5%) from 50 to 59 years, and in 35 cases (41.7%) >60 years. 60.7% with 1 to 3 pregnancies, 23.8% never got pregnant, and 15.5% with > 4 pregnancies without relation to mortality. The most prevalent histological type was epithelial carcinoma in 56 cases (66.6%). The mean time to relapse was 56.8 months, and the survival time was 87.7 months. Survival at 5 years was 62%, and at 10 years, 55%. Survival was lower in those over 60 years of age and with stages IIB, IIC, IIIA, and IIIC. Conclusion: In this study, mortality was modified by the clinical stage, the time of evolution, and the age of the patients with ovarian cancer.


Subject(s)
Humans , Female , Adult , Ovarian Neoplasms , Survival Analysis , Mortality Registries , Progression-Free Survival
9.
Chinese Journal of Oncology ; (12): 424-432, 2023.
Article in Chinese | WPRIM | ID: wpr-984739

ABSTRACT

Objective: To investigate the cytomorphological and immunocytochemical features of tumor cells in the ascites of ovarian plasmacytoma (SOC). Methods: Specimens of serous cavity effusions were collected from 61 tumor patients admitted to the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2015 to July 2021, including ascites from 32 SOC, 10 gastrointestinal adenocarcinomas, 5 pancreatic ductal adenocarcinomas, 6 lung adenocarcinomas, 4 benign mesothelial hyperplasia and 1 malignant mesothelioma patients, pleural effusions from 2 malignant mesothelioma patients and pericardial effusion from 1 malignant mesothelioma. Serous cavity effusion samples of all patients were collected, conventional smears were made through centrifugation, and cell paraffin blocks were made through centrifugation of remaining effusion samples. Conventional HE staining and immunocytochemical staining were applied to observe and summarize cytomorphological characteristics and immunocytochemical characteristics. The levels of serum tumor markers carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected. Results: Of the 32 SOC patients, 5 had low-grade serous ovarian carcinoma (LGSOC) and 27 had high-grade serous ovarian carcinoma (HGSOC). 29 (90.6%) SOC patients had elevated serum CA125, but the difference was not statistically significant between them and patients with non-ovarian primary lesions included in the study (P>0.05); The serum CEA was positive in 9 patients with gastrointestinal adenocarcinoma and 5 patients with lung adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.001); The serum CA19-9 was positive in 5 patients with gastrointestinal adenocarcinoma and 5 patients with pancreatic ductal adenocarcinoma, and the positive rate was higher than that in SOC patients (P<0.05). The serum CA125, CEA and CA19-9 were within the normal range in 4 patients with benign mesothelial hyperplasia. LGSOC tumor cells were less heterogeneous and aggregated into small clusters or papillary pattern, and psammoma bodies could be observed in some LGSOC cases. The background cells were fewer and lymphocytes were predominant; the papillary structure was more obvious after making cell wax blocks. HGSOC tumor cells were highly heterogeneous, with significantly enlarged nuclei and varying sizes, which could be more than 3-fold different, and nucleoli and nuclear schizophrenia could be observed in some cases; tumor cells were mostly clustered into nested clusters, papillae and prune shapes; there were more background cells, mainly histiocytes. Immunocytochemical staining showed that AE1/AE3, CK7, PAX-8, CA125, and WT1 were diffusely positively expressed in 32 SOC cases. P53 was focally positive in all 5 LGSOCs, diffusely positive in 23 HGSOCs, and negative in the other 4 HGSOCs. Most of adenocarcinomas of the gastrointestinal tract and lung had a history of surgery, and tumor cells of pancreatic ductal adenocarcinoma tend to form small cell nests. Immunocytochemistry can assist in the differential diagnosis of mesothelial-derived lesions with characteristic "open window" phenomenon. Conclusion: Combining the clinical manifestations of the patient, the morphological characteristics of the cells in the smear and cell block of the ascites can provide important clues for the diagnosis of SOC, and the immunocytochemical tests can further improve the accuracy of the diagnosis.


Subject(s)
Female , Humans , Carcinoembryonic Antigen , Ascites , CA-19-9 Antigen , Mesothelioma, Malignant/diagnosis , Hyperplasia , Adenocarcinoma/pathology , Cystadenocarcinoma, Serous/diagnosis , Biomarkers, Tumor , Carcinoma, Ovarian Epithelial , Diagnosis, Differential , Ovarian Neoplasms/pathology , Carbohydrates
10.
Chinese Journal of Oncology ; (12): 322-329, 2023.
Article in Chinese | WPRIM | ID: wpr-984725

ABSTRACT

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.


Subject(s)
Humans , Female , Receptors, Chimeric Antigen/genetics , Carcinoma, Non-Small-Cell Lung , CD8-Positive T-Lymphocytes , Interleukin-2/pharmacology , Tumor Necrosis Factor-alpha , Cell Line, Tumor , HEK293 Cells , Lung Neoplasms , Ovarian Neoplasms , Immunotherapy, Adoptive
11.
Philippine Journal of Pathology ; (2): 9-12, 2023.
Article in English | WPRIM | ID: wpr-984487

ABSTRACT

INTRODUCTION@#Ovarian cancer is one of the leading causes of mortality in women. In 2020, 5,395 (6.2%) of diagnosed malignancies in females were ovarian in origin. It also ranked second among gynecologic malignancies after cervical cancer. The prevalence in Asian /Pacific women is 9.2 per 100,000 population. Increased mortality and poor prognosis in ovarian cancer are caused by asymptomatic growth and delayed or absent symptoms for which about 70% of women have an advanced stage (III/IV) by the time of diagnosis. The most associated gene mutations are Breast Cancer gene 1 (BRCA1) which is identified in chromosome 17q21 and Breast Cancer gene 2 (BRCA2) identified in chromosome 13. Both proteins function in the double-strand DNA break repair pathway especially in the large framework repair molecules. Olaparib is a first-line drug used in the management of ovarian cancer. It targets affected cells by inhibition of poly (ADP-ribose) polymerase (PARP) activity which induces synthetic lethality in mutated BRCA1/2 cancers by selectively targeting tumor cells that fail to repair DNA double-strand breaks (DSBs).@*OBJECTIVE@#The study aims to determine the prevalence of pathogenic somatic mutations in BRCA1 and BRCA2 among patients diagnosed of having ovarian cancer, to characterize the identified variants into benign/ no pathogenic variant identified, variant of uncertain significance (VUS), and pathogenic, and to determine the relationship of specific mutations detected with histomorphologic findings and clinical attributes.@*METHODOLOGY@#Ovarian cancer tissues available at the St. Luke’s Medical Center Human Cancer Biobank and formalin-fixed paraffin-embedded (FFPE) tissue blocks diagnosed as ovarian cancer from the year 2016 to 2020 were included. Determination of the prevalence of somatic BRCA1 and BRCA2 mutations using Next Generation Sequencing (NGS).@*RESULTS@#A total of 60 samples were processed, and three samples were excluded from the analysis due to an inadequate number of cells. In the remaining 57 samples diagnosed ovarian tumors, pathogenic BRCA1/2 variants were identified in 10 (17.5%) samples. Among the BRCA1/2 positive samples, 3 (5.3%) BRCA1 and 7 (12.3%) BRCA2 somatic mutations were identified.@*CONCLUSION@#Identification of specific BRCA1/2 mutations in FFPE samples with NGS plays a big role in the management of ovarian cancer, particularly with the use of targeted therapies such as Olaparib. The use of this drug could provide a longer disease-free survival for these patients. Furthermore, we recommend that women diagnosed with ovarian cancer should be subjected to genetic testing regardless of the histologic subtypes or clinical features. Lastly, genetic testing should be done along with proper genetic counseling, especially for patients who are susceptible to these mutations.


Subject(s)
Ovarian Neoplasms
12.
Chinese Journal of Pathology ; (12): 678-682, 2023.
Article in Chinese | WPRIM | ID: wpr-985757

ABSTRACT

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.


Subject(s)
Female , Humans , Young Adult , Adult , Nestin , Ki-67 Antigen , Immunohistochemistry , Ovarian Neoplasms/pathology , Teratoma/pathology
13.
Chinese Journal of Obstetrics and Gynecology ; (12): 368-377, 2023.
Article in Chinese | WPRIM | ID: wpr-985660

ABSTRACT

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.


Subject(s)
Female , Humans , Cancer-Associated Fibroblasts/pathology , Carcinoma, Ovarian Epithelial , Ovarian Neoplasms/pathology , Prognosis , STAT3 Transcription Factor/metabolism , Drug Resistance, Neoplasm
14.
Chinese Journal of Oncology ; (12): 64-73, 2023.
Article in Chinese | WPRIM | ID: wpr-969807

ABSTRACT

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/β-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/β-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.


Subject(s)
Female , Humans , Carcinoma, Ovarian Epithelial , Receptor, PAR-2 , Ovarian Neoplasms/pathology , Prognosis , RNA, Messenger/metabolism
15.
Chinese Medical Sciences Journal ; (4): 130-137, 2023.
Article in English | WPRIM | ID: wpr-981601

ABSTRACT

Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.


Subject(s)
Female , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Carcinoma, Small Cell/pathology , Carcinoma, Ovarian Epithelial , Ovarian Neoplasms/therapy , Prognosis
16.
Rev. Bras. Cancerol. (Online) ; 69(4)out-dez. 2023.
Article in Portuguese | LILACS, SES-SP | ID: biblio-1512909

ABSTRACT

Introdução: Struma ovarii é um tipo raro de tumor ovariano composto por mais de 50% de tecido tireoidiano. Representa apenas 1% dos tumores sólidos do ovário e 3% dos subtipos dermoides, com a maioria dos casos de curso benigno. Geralmente afeta mulheres entre a terceira e a quinta décadas de vida, sendo muitas vezes assintomático ou com sinais inespecíficos. A síndrome de pseudo-Meigs, caracterizada por ascite e derrame pleural, pode estar presente, dificultando o diagnóstico. Relato do caso: Mulher, 43 anos, com desconforto abdominal, dor pélvica e dispneia crônica. A tomografia identificou massa sólido-cística na pelve e ascite moderada, além de derrame pleural à direita. A ressonância magnética confirmou as alterações e, desse modo, suspeitou-se de tumor maligno ovariano. O marcador sérico tumoral CA-125 estava elevado. A paciente foi submetida a uma laparotomia exploradora que resultou em salpingo-oforectomia bilateral. A análise histopatológica do espécime confirmou o diagnóstico de struma ovarii em ovário esquerdo e teratoma cístico maduro à direita. Conclusão: Os níveis elevados de CA-125 podem ser encontrados em casos de struma ovarii, tornando-o diagnóstico diferencial nas neoplasias ovarianas malignas, especialmente quando associado à síndrome de pseudo-Meigs. Nesse sentido, embora raro, o tumor deve ser considerado uma possibilidade durante investigação clínica de massas ovarianas com apresentações atípicas. Os exames de imagem podem auxiliar, mas a confirmação é estabelecida pela análise microscópica. O tratamento consiste na ressecção cirúrgica simples, e o desaparecimento dos sintomas acontece em seguida, sendo de bom prognóstico


Introduction: Struma ovarii is a rare type of ovarian tumor composed of more than 50% of thyroid tissue. It represents only 1% of solid ovarian tumors and 3% of dermoid subtypes, with the majority of cases following a benign course. It typically affects women between the third and fifth decades of life and often remains asymptomatic or presents with nonspecific signs. pseudo-Meigs syndrome, characterized by ascites and pleural effusion, may be present, complicating the diagnosis. Case report: A 43-year-old woman presented with abdominal discomfort, pelvic pain, and chronic dyspnea. A CT scan identified a solid-cystic pelvic mass, moderate ascites, and right-sided pleural effusion. Magnetic resonance imaging (MRI) confirmed the findings, raising suspicion of malignant ovarian tumor. The serum tumor marker CA-125 was elevated. The patient underwent exploratory laparotomy, resulting in bilateral salpingo-oophorectomy. Histopathological analysis of the specimen confirmed the diagnosis of struma ovarii in the left ovary and mature cystic teratoma in the right ovary. Conclusion: Elevated CA-125 levels can be found in cases of struma ovarii, posing a differential diagnosis challenge with malignant ovarian neoplasms, especially when associated with pseudo-Meigs syndrome. Therefore, although rare, it should be considered as a possibility during clinical investigation of ovarian masses with atypical presentations. Imaging studies can assist, but confirmation is established through microscopic analysis. Treatment involves simple surgical resection, and symptom disappearance follows, with favorable prognosis.


Introducción: El struma ovarii es un tipo raro de tumor ovárico compuesto por más del 50% de tejido tiroideo. Representa solo el 1% de los tumores ováricos sólidos y el 3% de los subtipos dermoides, siendo en su mayoría benigno. Típicamente afecta a mujeres entre la tercera y quinta década de vida y a menudo permanece asintomático o presenta signos inespecíficos. El síndrome de pseudo-Meigs, caracterizado por ascitis y derrame pleural, puede estar presente, complicando el diagnóstico. Informe del caso: Una mujer de 43 años consultó por malestar abdominal, dolor pélvico y disnea crónica. La tomografía identificó una masa pélvica sólido-quística, ascitis moderada y derrame pleural en el lado derecho. La resonancia magnética confirmó los hallazgos, levantando sospechas de un tumor ovárico maligno. El marcador tumoral sérico CA-125 estaba elevado. La paciente fue sometida a una laparotomía exploratoria, resultando en salpingo-ooforectomía bilateral. El análisis histopatológico de la muestra confirmó el diagnóstico de struma ovarii en el ovario izquierdo y teratoma quístico maduro en el ovario derecho. Conclusión: Los niveles elevados de CA-125 pueden encontrarse en casos de struma ovarii, lo que lo convierte en diagnóstico diferencial con neoplasias ováricas malignas, especialmente cuando se asocia con el síndrome de pseudo-Meigs. Por lo tanto, aunque sea raro, se debe considerar como una posibilidad durante la investigación clínica de masas ováricas con presentaciones atípicas. Los estudios por imágenes pueden ayudar, pero la confirmación se establece mediante análisis microscópico. El tratamiento implica la resección quirúrgica simple y los síntomas desaparecen después, con un pronóstico favorable.


Subject(s)
Ovarian Neoplasms , Struma Ovarii , CA-125 Antigen
17.
Rev. Bras. Cancerol. (Online) ; 69(4): e-044214, out-dez. 2023.
Article in English | LILACS, SES-SP | ID: biblio-1523327

ABSTRACT

Introduction: Approximately 10% of breast cancer cases are attibutable to germinative mutations in susceptibility genes, including BRCA1, BRCA2 and others. The National Comprehensive Cancer Network (NCCN) recommends screening women with breast cancer for mutations in BRCA1/2 in defined scenarios. However, these genetic tests are unavailable at the Brazilian Public Health System (SUS). Objective: This study aimed to characterize women with breast cancer and define the criteria for performing BRCA1/2 test. Method: Quantitative, descriptive, analytic, and retrospective study. Medical records of women diagnosed by SUS with breast cancer between January 2016 and December 2018 were analyzed through the software JAMOVI (version 2.3 - 2022). Results: A total of 245 women were diagnosed. According to NCCN guidelines, 97 women met the criteria for performing BRCA1/2 test, with mean age of 47 years old, predominantly white (90,7%), with comorbidities (55.6%), premenopausal (59.8%), diagnosed in early stages 0 - IIb (68.2%) and 48.4% had familial history of breast cancer. Most frequent histology and molecular subtype was invasive ductal carcinoma (87.2%) and luminal type (59.8%). Conclusion: A significant number of women diagnosed by SUS had indication for BRCA1/2 test. These women are younger, had fewer comorbidities, not menopausal, and differ in terms of the molecular subtype when compared with those without indication for performing the test


Introdução: Aproximadamente 10% dos casos de câncer de mama são atribuíveis a mutações germinativas em genes de suscetibilidade, incluindo BRCA1 e BRCA2. A National Comprehensive Cancer Network (NCCN) recomenda a triagem de mulheres com câncer de mama para mutações em BRCA1/2 em cenários definidos. No entanto, esses testes genéticos não estão disponíveis no Sistema Único de Saúde (SUS). Objetivo: Caracterizar as mulheres com câncer de mama e definir os critérios para realização do teste BRCA1/2. Método: Estudo quantitativo, descritivo, analítico e retrospectivo. Foram analisadosprontuários de mulheres com diagnóstico de câncer de mama pelo SUS entre janeiro de 2016 e dezembro de 2018, por meio do software JAMOVI (versão 2.3 - 2022). Resultados: Foram diagnosticadas 245 mulheres. De acordo com as diretrizes da NCCN, 97 mulheres atenderam aos critérios para realizar o teste BRCA1/2, com idade média de 47 anos, predominantemente brancas (90,7%), com comorbidades (55,6%), na pré-menopausa (59,8%), diagnosticadas nos estágios iniciais 0 - IIb (68, 2%), e 48,4% tinham histórico familiar de câncer de mama. A histologia e o subtipo molecular mais frequentes foram carcinoma ductal invasivo (87,2%) e tipo luminal (59,8%). Conclusão: Considerando os critérios da NCCN, um número significativo de mulheres diagnosticadas pelo SUS teve indicação para realização do teste BRCA1/2. Essas mulheres são mais jovens, têm menos comorbidades, estão em período pré-menopausa mais frequentemente e diferem quanto ao subtipo molecular quando comparadas àquelas sem indicação de realização do exame. Palavras-chave: neoplasias da mama; neoplasias ovarianas; síndrome hereditária de câncer de mama e ovário; genes, BRCA1


Introducción: Aproximadamente el 10% de los casos de cáncer de mama son atribuibles a mutaciones germinales en genes de susceptibilidad, incluidos BRCA1 y BRCA2. La National Comprehensive Cancer Network (NCCN) recomienda la detección de mutaciones BRCA1/2 en mujeres con cáncer de mama en entornos definidos. Sin embargo, estas pruebas genéticas no están disponibles en el Sistema Único de Salud (SUS). Objetivo: Caracterizar mujeres con cáncer de mama y definir los criterios para la realización de la prueba BRCA1/2. Método: Estudio cuantitativo, descriptivo, analítico y retrospectivo. Las historias clínicas de las mujeres diagnosticadas con cáncer de mama entre enero de 2016 y diciembre de 2018, usuarias del SUS, fueron analizadas mediante el software JAMOVI (versión 2.3 - 2022). Resultados: 245 mujeres fueron diagnosticadas. Según las pautas de NCCN, 97 mujeres cumplieron con los criterios para someterse a la prueba BRCA1/2. Las mujeres con indicación para la prueba tenían un promedio de edad de 47 años, eran predominantemente blancas (90,7%), con comorbilidades (55,6%), premenopáusicas (59,8%), diagnosticadas en estadios tempranos 0 - IIb (68,2%) y 48,4% tenía antecedentes familiares de cáncer de mama. Los subtipos histológicos y moleculares más frecuentes fueron el carcinoma ductal invasivo (87,2%) y el tipo luminal (59,8%). Conclusión: Considerando los criterios de la NCCN, un número significativo de mujeres, usuarias del SUS, fueron designadas para hacer la prueba BRCA1/2. Estas mujeres son más jóvenes, tienen menos comorbilidades, están en el periodo de la premenopausia con mayor frecuencia y difieren en el subtipo molecular en comparación con aquellas sin orden de realizarse la prueba


Subject(s)
Humans , Female , Ovarian Neoplasms , Breast Neoplasms , Genes, BRCA1 , Hereditary Breast and Ovarian Cancer Syndrome
18.
Rev. Bras. Cancerol. (Online) ; 69(4)out-dez. 2023.
Article in English, Spanish, Portuguese | LILACS, SES-SP | ID: biblio-1537337

ABSTRACT

Struma ovarii is a rare type of ovarian tumor composed of more than 50% of thyroid tissue. It represents only 1% of solid ovarian tumors and 3% of dermoid subtypes, with the majority of cases following a benign course. It typically affects women between the third and fifth decades of life and often remains asymptomatic or presents with nonspecific signs. pseudo-Meigs syndrome, characterized by ascites and pleural effusion, may be present, complicating the diagnosis. Case report: A 43-year-old woman presented with abdominal discomfort, pelvic pain, and chronic dyspnea. A CT scan identified a solid-cystic pelvic mass, moderate ascites, and right-sided pleural effusion. Magnetic resonance imaging (MRI) confirmed the findings, raising suspicion of malignant ovarian tumor. The serum tumor marker CA-125 was elevated. The patient underwent exploratory laparotomy, resulting in bilateral salpingo-oophorectomy. Histopathological analysis of the specimen confirmed the diagnosis of struma ovarii in the left ovary and mature cystic teratoma in the right ovary. Conclusion: Elevated CA-125 levels can be found in cases of struma ovarii, posing a differential diagnosis challenge with malignant ovarian neoplasms, especially when associated with pseudo-Meigs syndrome. Therefore, although rare, it should be considered as a possibility during clinical investigation of ovarian masses with atypical presentations. Imaging studies can assist, but confirmation is established through microscopic analysis. Treatment involves simple surgical resection, and symptom disappearance follows, with favorable prognosis


Struma ovarii é um tipo raro de tumor ovariano composto por mais de 50% de tecido tireoidiano. Representa apenas 1% dos tumores sólidos do ovário e 3% dos subtipos dermoides, com a maioria dos casos de curso benigno. Geralmente afeta mulheres entre a terceira e a quinta décadas de vida, sendo muitas vezes assintomático ou com sinais inespecíficos. A síndrome de pseudo-Meigs, caracterizada por ascite e derrame pleural, pode estar presente, dificultando o diagnóstico. Relato do caso: Mulher, 43 anos, com desconforto abdominal, dor pélvica e dispneia crônica. A tomografia identificou massa sólido-cística na pelve e ascite moderada, além de derrame pleural à direita. A ressonância magnética confirmou as alterações e, desse modo, suspeitou-se de tumor maligno ovariano. O marcador sérico tumoral CA-125 estava elevado. A paciente foi submetida a uma laparotomia exploradora que resultou em salpingo-oforectomia bilateral. A análise histopatológica do espécime confirmou o diagnóstico de struma ovarii em ovário esquerdo e teratoma cístico maduro à direita. Conclusão: Os níveis elevados de CA-125 podem ser encontrados em casos de struma ovarii, tornando-o diagnóstico diferencial nas neoplasias ovarianas malignas, especialmente quando associado à síndrome de pseudo-Meigs. Nesse sentido, embora raro, o tumor deve ser considerado uma possibilidade durante investigação clínica de massas ovarianas com apresentações atípicas. Os exames de imagem podem auxiliar, mas a confirmação é estabelecida pela análise microscópica. O tratamento consiste na ressecção cirúrgica simples, e o desaparecimento dos sintomas acontece em seguida, sendo de bom prognóstico.


El struma ovarii es un tipo raro de tumor ovárico compuesto por más del 50% de tejido tiroideo. Representa solo el 1% de los tumores ováricos sólidos y el 3% de los subtipos dermoides, siendo en su mayoría benigno. Típicamente afecta a mujeres entre la tercera y quinta década de vida y a menudo permanece asintomático o presenta signos inespecíficos. El síndrome de pseudo-Meigs, caracterizado por ascitis y derrame pleural, puede estar presente, complicando el diagnóstico. Informe del caso: Una mujer de 43 años consultó por malestar abdominal, dolor pélvico y disnea crónica. La tomografía identificó una masa pélvica sólido-quística, ascitis moderada y derrame pleural en el lado derecho. La resonancia magnética confirmó los hallazgos, levantando sospechas de un tumor ovárico maligno. El marcador tumoral sérico CA-125 estaba elevado. La paciente fue sometida a una laparotomía exploratoria, resultando en salpingo-ooforectomía bilateral. El análisis histopatológico de la muestra confirmó el diagnóstico de struma ovarii en el ovario izquierdo y teratoma quístico maduro en el ovario derecho. Conclusión: Los niveles elevados de CA-125 pueden encontrarse en casos de struma ovarii, lo que lo convierte en diagnóstico diferencial con neoplasias ováricas malignas, especialmente cuando se asocia con el síndrome de pseudo-Meigs. Por lo tanto, aunque sea raro, se debe considerar como una posibilidad durante la investigación clínica de masas ováricas con presentaciones atípicas. Los estudios por imágenes pueden ayudar, pero la confirmación se establece mediante análisis microscópico. El tratamiento implica la resección quirúrgica simple y los síntomas desaparecen después, con un pronóstico favorable.


Subject(s)
Ovarian Neoplasms , Struma Ovarii , CA-125 Antigen
19.
China Journal of Chinese Materia Medica ; (24): 2222-2232, 2023.
Article in Chinese | WPRIM | ID: wpr-981353

ABSTRACT

The present study aimed to explore the main active components and underlying mechanisms of Marsdenia tenacissima in the treatment of ovarian cancer(OC) through network pharmacology, molecular docking, and in vitro cell experiments. The active components of M. tenacissima were obtained from the literature search, and their potential targets were obtained from SwissTargetPrediction. The OC-related targets were retrieved from Therapeutic Target Database(TTD), Online Mendelian Inheritance in Man(OMIM), GeneCards, and PharmGKB. The common targets of the drug and the disease were screened out by Venn diagram. Cytoscape was used to construct an "active component-target-disease" network, and the core components were screened out according to the node degree. The protein-protein interaction(PPI) network of the common targets was constructed by STRING and Cytoscape, and the core targets were screened out according to the node degree. GO and KEGG enrichment analyses of potential therapeutic targets were carried out with DAVID database. Molecular docking was used to determine the binding activity of some active components to key targets by AutoDock. Finally, the anti-OC activity of M. tenacissima extract was verified based on SKOV3 cells in vitro. The PI3K/AKT signaling pathway was selected for in vitro experimental verification according to the results of GO function and KEGG pathway analyses. Network pharmacology results showed that 39 active components, such as kaempferol, 11α-O-benzoyl-12β-O-acetyltenacigenin B, and drevogenin Q, were screened out, involving 25 core targets such as AKT1, VEGFA, and EGFR, and the PI3K-AKT signaling pathway was the main pathway of target protein enrichment. The results of molecular docking also showed that the top ten core components showed good binding affinity to the top ten core targets. The results of in vitro experiments showed that M. tenacissima extract could significantly inhibit the proliferation of OC cells, induce apoptosis of OC cells through the mitochondrial pathway, and down-regulate the expression of proteins related to the PI3K/AKT signaling pathway. This study shows that M. tenacissima has the characteristics of multi-component, multi-target, and multi-pathway synergistic effect in the treatment of OC, which provides a theoretical basis for in-depth research on the material basis, mechanism, and clinical application.


Subject(s)
Humans , Female , Marsdenia , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Ovarian Neoplasms/genetics , Databases, Genetic , Plant Extracts , Drugs, Chinese Herbal/pharmacology
20.
Chinese Medical Journal ; (24): 1098-1110, 2023.
Article in English | WPRIM | ID: wpr-980838

ABSTRACT

BACKGROUND@#Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer.@*METHODS@#LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 ( SNAI2 ) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo . Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2 .@*RESULTS@#AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo . miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis.@*CONCLUSION@#AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.


Subject(s)
Animals , Mice , Humans , Female , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Ovarian Neoplasms/metabolism , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Snail Family Transcription Factors/metabolism
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