Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 3.229
Filter
1.
J. bras. econ. saúde (Impr.) ; 16(1): 25-64, Abril/2024.
Article in English | LILACS, ECOS | ID: biblio-1555250

ABSTRACT

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.


Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.


Subject(s)
Ovarian Neoplasms , Costs and Cost Analysis , Supplemental Health , Poly(ADP-ribose) Polymerase Inhibitors
2.
Braz. J. Oncol ; 20: e-20230437, 20240101.
Article in English | LILACS | ID: biblio-1554109

ABSTRACT

Borderline ovarian tumors typically exhibit indolent behavior and boast a favorable prognosis; however, a subset of patients experiences disease recurrence and progression to low-grade ovarian carcinoma. The complex biology underlying these phenomena has been illuminated through molecular analyses. KRAS and BRAF mutations have emerged as recurrent ?ndings in borderline ovarian tumors. Speci?cally, KRAS mutations have been linked to a higher risk of recurrence and progression to low-grade ovarian carcinoma, while BRAF mutations seem to confer a protective e?ect, inducing a senescent state that mitigates the likelihood of progression. In this comprehensive review, we explore the biology and the molecular pro?le of borderline ovarian tumors, shedding light on recent discoveries that have enriched our comprehension. Additionally, we discuss the current state of borderline ovarian tumors management. Surgery remains the cornerstone of treatment. While cytotoxic therapies role is limited so far, molecular characterization emphasizes the imminent potential for personalized therapeutic approaches.


Os tumores borderline de ovário geralmente exibem comportamento indolente e apresentam prognóstico favorável; no entanto, um subconjunto de pacientes apresenta recorrência da doença e progressão para carcinoma de ovário de baixo grau. A biologia complexa subjacente a estes fenômenos foi iluminada através de análises moleculares. Mutações KRAS e BRAF surgiram como achados recorrentes em tumores borderline de ovário. Especificamente, as mutações KRAS têm sido associadas a um maior risco de recorrência e progressão para carcinoma de ovário de baixo grau, enquanto as mutações BRAF parecem conferir um efeito protetor, induzindo um estado senescente que mitiga a probabilidade de progressão. Nesta revisão abrangente, exploramos a biologia e o perfil molecular dos tumores borderline de ovário, lançando luz sobre descobertas recentes que enriqueceram nossa compreensão. Além disso, discutimos o estado atual do manejo de tumores borderline de ovário. A cirurgia continua sendo o pilar de tratamento. Embora o papel das terapias citotóxicas seja limitado até o momento, a caracterização molecular enfatiza o potencial iminente para abordagens terapêuticas personalizadas.


Subject(s)
Ovarian Neoplasms , Gynecologic Surgical Procedures , Urogenital Neoplasms , Varicocele
3.
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
4.
Article in English | WPRIM | ID: wpr-1013465

ABSTRACT

Background@#Ovarian, fallopian tube, and peritoneal cancer patients with advanced-stage diagnosis or recurrences spread to the peritoneal surface of the abdomen. Hyperthermic intraperitoneal chemotherapy (HIPEC) can penetrate and eradicate tumors that are microscopic up to those with a diameter of 2.5 cm from the peritoneal surface following cytoreductive surgery (CRS). @*Objectives@#The study aimed to determine the efficacy and safety of CRS with HIPEC versus CRS alone for patients with epithelial ovarian, fallopian tube, and peritoneal cancer. @*Materials and Methods@#This retrospective cohort study included 50 patients (20 patients underwent CRS + HIPEC, while 30 patients underwent CRS alone). Records of these patients from January 2014 to June 2020 were reviewed, tabulated, and analyzed.@*Results@#The difference in recurrence rate between CRS with HIPEC and CRS alone was not statistically significant (50% vs. 43%, P = 0.774). The median time to recurrence was 10 and 9 months, respectively (P = 0.636). Five percent in the HIPEC group succumbed to the disease, while 13% died in the CRS alone group (P = 0.636). More post-operative complications were noted in the HIPEC group (45% vs. 10%, P = 0.007), but among these, only 2 cases had grade 3 to 4 complications (10%). The addition of HIPEC in the management of these patients resulted in a longer operative time (360 vs. 240 min, P < 0.001) and postoperative hospital stay (8 vs. 6 days, P = 0.026). There were no intra- or peri-operative mortalities in both groups.@*Conclusion@#CRS with HIPEC and CRS alone showed similar time to recurrence and recurrence rate. CRS with HIPEC had low risk of grade 3-4 complications and may still be considered as a treatment option for advanced, progressive, and recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.


Subject(s)
Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Ovarian Neoplasms
5.
Article in Chinese | WPRIM | ID: wpr-1012305

ABSTRACT

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.


Subject(s)
Female , Humans , Retrospective Studies , Gonadal Dysgenesis, 46,XY/surgery , Gonadoblastoma/surgery , Neoplasms, Germ Cell and Embryonal/surgery , Ovarian Neoplasms/pathology
6.
Evid. actual. práct. ambul. (En línea) ; 27(1): e007093, 2024. tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1552247

ABSTRACT

Introducción. Si bien contamos con recomendaciones basadas en la evidencia en contra de realizar tamizaje de cáncer ovárico con ecografía transvaginal debido a que aumenta el riesgo de resultados falsamente positivos y de cascadas diagnósticas, sin disminuir la mortalidad por esta enfermedad, su solicitud en mujeres sanas es frecuente. Sin embargo, no conocemos la magnitud de la implementación de esta práctica, que constituye un cuidado de bajo valor. Objetivo. Documentar el sobreuso de ecografías transvaginales realizadas en forma ambulatoria en un hospital universitario privado de Argentina. Métodos. Estudio de corte transversal de una muestra aleatoria de ecografías realizadas en forma ambulatoria durante 2017 y 2018. Mediante revisión manual de las historias clínicas, la solicitud de cada ecografía fue clasificada como apropiada cuando algún problema clínico justificaba su realización, o inapropiada cuando había sido realizada con fines de control de salud o por una condición clínica sin indicación de seguimiento ecográfico. Resultados. De un total de 1.997 ecografías analizadas, realizadas a 1.954 mujeres adultas (edad promedio 50 años),1.345 (67,4 %; intervalo de confianza [IC] 95 % 65,2 a 69,4) habían sido solicitadas en el contexto de un control de saludo sin un problema asociado en la historia clínica y otras 54 (8,3 %; IC 95 % 6,3 a 10,7), por condiciones de salud para las que no hay recomendaciones de realizar seguimiento ecográfico. Conclusiones. Esta investigación documentó una alta proporción de sobre utilización de la ecografías transvaginales en nuestra institución. Futuras investigaciones permitirán comprender los motivos que impulsan esta práctica y ayudarán a diseñar intervenciones para disminuir estos cuidados de bajo valor. (AU)


Background. Although we have evidence-based recommendations against screening for ovarian cancer with transvaginalultrasound because it increases the risk of false positive results and diagnostic cascades without reducing mortality from this disease, its request in healthy women is frequent. However, we do not know the magnitude of the implementation of this practice, which constitutes low-value care. Objective. To document the overuse of transvaginal ultrasounds performed on an outpatient basis in a private university hospital in Argentina. Methods. Cross-sectional study of a random sample of outpatient ultrasounds performed during 2017 and 2018. Through a manual review of the medical records, the request for each ultrasound was classified as appropriate when a clinical problem justified its performance or inappropriate when it was carried out for health control purposes or for a clinical condition that had no indication for ultrasound follow-up. Results. Of a total of 1997 ultrasounds analyzed, performed on 1954 adult women (average age 50 years), 1,345 (67.4 %;95 % confidence interval [CI] 65.2 to 69.4) had been requested in the context of a health check-up or without a documented problem in the medical history that would support its performance, and another 54 (8.3 %; 95 % CI 6.3 to 10.7), for health conditions for which there are no treatment recommendations to perform ultrasound follow-up. Conclusions. This research documented a high proportion of overuse of transvaginal ultrasound in our institution. Future research will allow us to understand the reasons that drive this practice and will help design interventions to reduce thislow-value care. (AU)


Subject(s)
Humans , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Ovarian Neoplasms/prevention & control , Vagina/diagnostic imaging , Ultrasonography/statistics & numerical data , Medical Overuse/statistics & numerical data , Low-Value Care , Ovarian Neoplasms/diagnostic imaging , Argentina , Mass Screening , Simple Random Sampling , Cross-Sectional Studies , Electronic Health Records , Medical Overuse/prevention & control
7.
J. bras. econ. saúde (Impr.) ; 15(3): 172-177, Dezembro/2023.
Article in English, Portuguese | LILACS, ECOS | ID: biblio-1553985

ABSTRACT

Objetivo: Estimar o custo da sequência de tratamento considerando as terapias com niraparibe e bevacizumabe, respectivamente, como terapias de manutenção de 1L e 2L para pacientes com câncer de ovário (CO) epitelial com deficiência de recombinação homóloga (HRD) e BRCA selvagem (BRCAwt) em um horizonte temporal de cinco anos, sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo de sobrevida particionado com três transições de estados de saúde, considerando os seguintes regimes em 1L e 2L, respectivamente: carboplatina + paclitaxel seguido de terapia de manutenção com niraparibe; carboplatina + gencitabina + bevacizumabe seguido pela continuação de bevacizumabe. As posologias em bula e as curvas de sobrevida livre de progressão dos respectivos estudos pivotais em cada uma das linhas terapêuticas foram utilizadas na análise, e o custo de tratamento foi calculado a partir da lista oficial de preços de medicamentos da CMED de abril de 2023. Resultados: O custo em 1L e 2L foi de BRL 868.830 e BRL 403.407, totalizando BRL 1.272.237 em um horizonte temporal de cinco anos, com 2,28 e 0,52 anos de vida livre de progressão, respectivamente, na 1L e 2L, com o total de 2,8 anos. Conclusões: O resultado da análise de custo de sequência de tratamento de câncer de ovário HRD/BRCAwt apresentou um custo total estimado de BRL 1.272.237, com 2,8 anos de vida livre de progressão. Essa análise contribui no entendimento dos custos e da eficácia esperada com o uso da terapia de manutenção de niraparibe em 1L e bevacizumabe em 2L em um horizonte temporal de cinco anos.


Objective: To estimate the cost of the treatment sequence, considering the maintenance therapies niraparib and bevacizumab, respectively, as maintenance therapies in 1L and 2L for patients with epithelial ovarian cancer with homologous recombination deficiency (HRD) and BRCA wild-type (BRCAwt) over a 5-year time horizon from the perspective of the Brazilian supplementary health system. Methods: A partitioned survival model was developed with three health state transitions, considering the following regimens in the 1L and 2L, respectively: carboplatin + paclitaxel followed by maintenance therapy with niraparib; carboplatin + gemcitabine + bevacizumab followed by the continuation of bevacizumab. The product's label and progression-free survival curves from the respective pivotal studies in each of the therapeutic lines were used in the analysis and the cost of treatment was calculated using as a reference the official CMED drug price list from April 2023. Results: The cost in 1L and 2L was BRL 868,830 and BRL 403,407, totaling BRL 1,272,237 over a 5-year period, with 2.28 and 0.52 years of progression-free survival, respectively in 1L and 2L, with a total of 2.8 years. Conclusions: The result of the analysis of the cost of the treatment sequence of ovarian cancer HRD/BRCAwt presented an estimated total cost of 1,272,237 with 2.8 year of progression-free survival. This analysis contributes to understand the expected cost and effectiveness with the use of maintenance therapy niraparib in 1L and bevacizumab in 2L over a 5-year time horizon.


Subject(s)
Ovarian Neoplasms , Costs and Cost Analysis , Supplemental Health , Poly(ADP-ribose) Polymerase Inhibitors
8.
Rev. méd. hondur ; 91(2): 131-134, jul.-dic. 2023. ilus
Article in Spanish | LILACS, BIMENA | ID: biblio-1552020

ABSTRACT

Introducción: La tuberculosis peritoneal es una enfermedad reemergente, de evolución insidiosa y arduo diagnós- tico. La afectación peritoneal tiene una baja incidencia, afectando por igual ambos sexos figurando entre edades de 35 a 45 años. El alto índice de sospecha debe ser un factor importante en el diagnóstico precoz, para que una vez establecido, se pueda iniciar el tratamiento y disminuir las tasas de morbimortalidad. Descripción del caso clínico: Paciente de 26 años, con clínica inespecífica; dolor abdominal, ascitis y fiebre. Fue ingresada por servicio de medicina interna para abordaje etiológico de ascitis, posteriormente fue abordada como sospecha de cáncer de ovario, se presentó al servicio de cirugía quienes determinaron practicarle laparotomía y cuya biopsia intraoperatoria reporto hallazgos su- gestivos de tuberculosis peritoneal. Conclusión: La tuberculosis peritoneal es una enfermedad poco frecuente, las manifestaciones clínicas pueden sugerir la presencia de una enfermedad tumoral; la sospecha clínica es baja y en muchas ocasiones el diagnóstico es incidenta...(AU)


Subject(s)
Humans , Female , Adult , Ovarian Neoplasms , Peritonitis, Tuberculous/diagnosis , Radiography/methods , Communicable Diseases, Emerging
9.
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
10.
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
11.
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
12.
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
13.
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
14.
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
15.
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
16.
Biol. Res ; 56: 3-3, 2023. ilus, tab, graf
Article in English | LILACS | ID: biblio-1420301

ABSTRACT

BACKGROUND: Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. METHODS: and materials In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. RESULTS: Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. CONCLUSIONS: The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.


Subject(s)
Humans , Female , Ovarian Neoplasms/drug therapy , Curcumin/pharmacology , Cell Movement , Apoptosis , Matrix Metalloproteinase 2/pharmacology , Cell Line, Tumor , Cell Proliferation , Oxaliplatin/pharmacology
17.
Health sci. dis ; 24(1): 77-81, 2023. figures, tables
Article in French | AIM | ID: biblio-1411351

ABSTRACT

Introduction. Les cancers gynécologiques constituent un problème majeur de santé publique dans le monde. L'objectif de cette étude était de déterminer la fréquence des cancers gynécologiques en pratique oncologique à Lomé et d'en étudier les aspects épidémiologiques et histo-cliniques. Méthodes. Il s'agitd'une étude rétrospective et descriptive portant sur tous les cancers gynécologiques reçus en oncologie entre le 1erJanvier 2016 et le 31 Décembre 2021. Résultats. Au total 202 cas de cancers gynécologiques ont été enregistrés. L'âge moyen des patientes était de 54 ans avec des extrêmes de 20 et 88 ans. Les cancers les plus fréquents étaient le cancer du col utérin (n=88; 43,6%), du corps utérin (n= 57; 28,3%) et de l'ovaire (n= 35; 17,4%). Le carcinome épidermoïde était le type histologique le plus fréquent dans le cancer du col (n= 86; 97,7%) tandis que les cancers du corps de l'utérus étaient majoritairement des adénocarcinomes (n=46 ; 80,7 %). Tous les cancers de la vulve et du vagin étaient des carcinomes épidermoïdes et la majorité des cancers de l'ovaire était des tumeurs épithéliales (n=29 ; 82,9%). Les deux-tiers des patients o été diagnostiqué à un stade avancé (stade III et IV) (n=134 ; 66,3%). Conclusion. Les cancers gynécologiques sont fréquents dans notre pratique et majoritairement diagnostiqués à un stade tardif. Cette étude souligne la nécessité d'une détection précoce de ces affections afin d'améliorer le pronostic des patientes.


Introduction. Gynecological cancers are an important public health problem worldwide. The objective of this study was to describe the epidemiological, clinical, and histopathological features of gynecological cancer in clinical oncology practice in Lomé. Methods. This was a retrospective study of histopathological confirmed gynecological malignancies conducted in the department of oncology from January 2016 to December 2021. Results. A total of 202 cases were identified. The mean age of patients was 54years [range20-88years]. The most common gynecological malignancy was cervical cancer (n=88 ; 43.6%), followed by uterine corpus cancer (n= 57 ; 28.3%) and ovarian cancer (n= 35 ; 17.4%). The most common histopathological diagnosis of cervical cancer was squamous cell carcinoma (n= 86 ; 97.7%) while most corpus uterine cancers were endometrioid adenocarcinoma (n= 46 ; 80.7 %). Vulval and vagina cancers were squamous cell carcinoma and the majority of ovarian cancers were epithelial tumours (n= 29 ; 82.9%). Two-thirds of patients were diagnosed at the advanced stage (stage III et IV) (n= 134 ; 66.3%). Conclusion. Gynecologic cancers are common in our practice. This study emphasizes the necessity of early detection of these diseases to improve prognostic and patient survival


Subject(s)
Ovarian Neoplasms , Uterine Neoplasms , Vaginal Neoplasms , Carcinoma, Squamous Cell , Vulvar Neoplasms
19.
Article in Chinese | WPRIM | ID: wpr-1012300

ABSTRACT

Objective: To investigate the clinical significance of endothelin A receptor (ETAR) expression in high-grade serous ovarian carcinoma (HGSOC). To design ETAR carboxyl terminal (ETAR-C) amino acids derived polypeptide and to study the inhibitory effect on ovarian epithelial carcinoma cells in vitro. Methods: (1) A total of 126 patients who received surgical treatment and were diagnosed with HGSOC by postoperative pathological examination in Central Hospital of Xuzhou from January 1, 2007 to December 31, 2017 were selected. All patients had completed clinicopathological data and follow-up data. Cancer tissue samples were collected and ETAR mRNA expression in HGSOC tissues was detected by reverse transcript-PCR. The clinical significance was analyzed. (2) ETAR-C fusion polypeptide was designed based on the sequence of carboxyl terminal amino acids of ETAR, expressed and purified in vitro. The effects of ETAR-C fusion polypeptide on migration and invasion ability of ovarian cancer SKOV3 and CAOV3 cells were detected by scratch test and invasion test, respectively. The effect of ETAR-C fusion polypeptide on chemosensitivity of cisplatin-resistant ovarian cancer SKOV3/cDDP and CAOV3/cDDP cells was determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The effect of ETAR-C fusion polypeptide on β-arrestin-1 expression in ovarian cancer SKOV3 and CAOV3 cells was detected by western blot. Results: (1) The relative expression level of ETAR mRNA in HGSOC tissues was 18.6±5.1. Patients with HGSOC were divided into high ETAR mRNA expression (n=76) and low ETAR mRNA expression (n=50) with 61.7% as cut-off value analyzed by X-Tile software. High expression of ETAR mRNA was significantly correlated with abdominal water volume, platinum drug resistance, and cancer antigen 125 (CA125) value in HGSOC patients (all P<0.05), but was not related to the age of patients with HGSOC and the size of postoperative residual lesions (all P>0.05). The 5-year progression free survival rates were 18.4% and 28.0%, and the 5-year overall survival rates were 38.2% and 52.0% in HGSOC patients with high and low ETAR mRNA expression respectively, there were statistically significant differences (P=0.046, P=0.034). (2) The results of scratch test and invasion test showed that the scratch healing rate and cell invasion rate of SKOV3 or CAOV3 cells treated with endothelin-1 (ET-1) and ET-1+ETAR-C were respectively compared, and the differences were statistically significant (all P<0.05). MTT assay showed that the inhibition rates of ETAR-C fusion polypeptide treated in SKOV3/cDDP and CAOV3/cDDP cells were significantly higher than those of control cells after the addition of 4, 6, 8, 10, 12, and 24 μg/ml cisplatin (all P<0.05). Western blot analysis showed that the relative expression levels of β-arrestin-1 in SKOV3 or CAOV3 cells treated with ET-1 and ET-1+ETAR-C were 1.85±0.09 and 1.13±0.09 (SKOV3 cells), 2.14±0.15 and 1.66±0.12 (CAOV3 cells), respectively. The differences were statistically significant (all P<0.05). Conclusions: The prognosis of HGSOC patients with high expression of ETAR mRNA is significantly worse than those with low expression of ETAR mRNA. ETAR might be a new target for HGSOC treatment. The ETAR-C fusion polypeptide that interferes with the interaction of ETAR and β-arrestin-1 has good inhibitory effect on ovarian cancer cells in vitro, and might have clinical application potential.


Subject(s)
Female , Humans , Amino Acids/therapeutic use , beta-Arrestins/therapeutic use , Cell Line, Tumor , Cisplatin/pharmacology , Clinical Relevance , Ovarian Neoplasms/pathology , Receptor, Endothelin A/therapeutic use , RNA, Messenger/metabolism
20.
Article in Chinese | WPRIM | ID: wpr-1012299

ABSTRACT

Objective: To investigate the cytotoxic effects of induced pluripotent stem (iPS) cells of anti-mesothelin (MSLN)-chimeric antigen receptor natural killer (CAR-NK) cells (anti-MSLN-iCAR-NK cells) on ovarian epithelial cancer cells. Methods: Twenty cases of ovarian cancer patients who underwent surgical treatment at Henan Provincial People's Hospital from September 2020 to September 2021 were collected, and 20 cases of normal ovarian tissues resected during the same period due to other benign diseases were also collected. (1) Immunohistochemistry and immunofluorescence were used to verify the expression of MSLN protein in ovarian cancer tissues. (2) Fresh ovarian cancer tissues were extracted and cultured to obtain primary ovarian cancer cells. Recombinant lentiviral vectors targeting anti-MSLN-CAR-CD244 were constructed and co-cultured with iPS cells to obtain anti-MSLN-iCAR cells. These cells were differentiated into anti-MSLN-iCAR-NK cells using cytokine-induced differentiation method. The cell experiments were divided into three groups: anti-MSLN-iCAR-NK cell group, natural killer (NK) cell group, and control group. (3) Flow cytometry and live cell staining experiment were used to detect the apoptosis of ovarian cancer cells in the three groups. (4) Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), granzyme B (GZMB), perforin 1 (PRF1), interleukin (IL)-6, and IL-10 in the three groups of ovarian cancer cells. Results: (1) Immunohistochemistry analysis showed that a positive expression rate of MSLN protein in ovarian cancer tissues of 65% (13/20), while normal ovarian tissues had a positive rate of 30% (6/20). The comparison between the two groups was statistically significant (χ2=4.912, P=0.027). Immunofluorescence analysis revealed that the positive expression rate of MSLN protein in ovarian cancer tissues was 70% (14/20), while normal ovarian tissues had a positive rate of 30% (6/20). The comparison between the two groups was statistically significant (χ2=6.400, P=0.011). (2) Flow cytometry analysis showed that the apoptotic rate of ovarian cancer cells in the anti-MSLN-iCAR-NK cell group was (29.27±0.85)%, while in the NK cell group and control group were (8.44±0.34)% and (6.83±0.26)% respectively. There were statistically significant differences in the comparisons between the three groups (all P<0.01). Live cell staining experiment showed that the ratio of dead cells to live cells in the anti-MSLN-iCAR-NK cell group was (36.3±8.3)%, while in the NK cell group and control group were (5.4±1.4)% and (2.0±1.3)% respectively. There were statistically significant differences in the comparisons between the three groups (all P<0.001). (3) ELISA analysis revealed that the expression levels of IFN-γ, TNF-α, GZMB, PRF1, IL-6, and IL-10 in ovarian cancer cells of the anti-MSLN-iCAR-NK cell group were significantly higher than those in the NK cell group and the control group (all P<0.05). Conclusion: The anti-MSLN-iCAR-NK cells exhibit a strong killing ability against ovarian cancer cells, indicating their potential as a novel immunotherapy approach for ovarian cancer.


Subject(s)
Humans , Female , Carcinoma, Ovarian Epithelial/metabolism , Ovarian Neoplasms/metabolism , Interleukin-10/pharmacology , Induced Pluripotent Stem Cells/metabolism , Iron-Dextran Complex/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Cell Line, Tumor , Killer Cells, Natural , Interleukin-6
SELECTION OF CITATIONS
SEARCH DETAIL