Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.202
Filtrar
Más filtros

Intervalo de año de publicación
1.
BMC Complement Med Ther ; 24(1): 145, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575994

RESUMEN

BACKGROUND: Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. METHODS: The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. RESULTS: Ginger significantly reduced the m6A level of OC cells SKOV3. The 3'UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. CONCLUSIONS: Ginger inhibits ovarian cancer cells' SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.


Asunto(s)
Neoplasias Ováricas , Zingiber officinale , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Metilación de ARN , Antígeno B7-H1 , Claudinas
2.
Molecules ; 29(5)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38474556

RESUMEN

Chemotherapy is a well-established method for treating cancer, but it has limited effectiveness due to its high dosage and harmful side effects. To address this issue, researchers have explored the use of photothermal agent nanoparticles as carriers for precise drug release in vivo. In this study, three different sizes of polydopamine nanoparticles (PDA-1, PDA-2, and PDA-3) were synthesized and evaluated. PDA-2 was selected for its optimal size, encapsulation rate, and drug loading rate. The release of the drug from PDA-2@TAX was tested at different pH and NIR laser irradiation levels. The results showed that PDA-2@TAX released more readily in an acidic environment and exhibited a high photothermal conversion efficiency when exposed to an 808 nm laser. In vitro experiments on ovarian cancer cells demonstrated that PDA-2@TAX effectively inhibited cell proliferation, highlighting its potential for synergistic chemotherapy-photothermal treatment.


Asunto(s)
Hipertermia Inducida , Indoles , Nanopartículas , Neoplasias Ováricas , Polímeros , Quercetina/análogos & derivados , Humanos , Femenino , Fototerapia/métodos , Hipertermia Inducida/métodos , Neoplasias Ováricas/tratamiento farmacológico , Doxorrubicina/farmacología
3.
Curr Oncol ; 31(2): 660-671, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38392042

RESUMEN

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.


Asunto(s)
Hipertermia Inducida , Neoplasias Ováricas , Neoplasias Peritoneales , Femenino , Humanos , Paclitaxel/uso terapéutico , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Seguimiento , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía
4.
Curr Treat Options Oncol ; 25(3): 313-329, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38270801

RESUMEN

OPINION STATEMENT: In our clinical practice, we have shifted away from the use of adjuvant normothermic intraperitoneal (IP) chemotherapy, particularly following the publication of GOG 252. Our decision is rooted in the accumulating evidence indicating a lack of demonstrable superiority, alongside the recognized toxicities and logistical challenges associated with its administration. This strategic departure is also influenced by the rising utilization of maintenance therapies such as bevacizumab and PARP inhibitors, which present viable alternatives for improving patient outcomes. Our utilization of hyperthermic IP chemotherapy (HIPEC) is currently reserved for a specific cohort of patients, mirroring the patient population studied in the OVHIPEC-1 trial. Specifically, our HIPEC protocol applies to patients presenting with newly diagnosed stage IIIC high-grade epithelial ovarian cancer who are deemed ineligible for primary debulking surgery. Patients must exhibit at least stable disease with neoadjuvant platinum-based chemotherapy, maintain a favorable performance status (ECOG score 0-1), possess good nutritional reserves (with no evidence of protein-calorie malnutrition and an albumin level exceeding 3.5), and not have chronic kidney disease. When HIPEC is planned, it is administered at the time of interval debulking surgery, contingent upon the attainment of optimal surgical outcomes (< 1 cm of residual disease). Our HIPEC protocol adheres to the original OVHIPEC-1 trial guidelines, employing cisplatin at a dosage of 100 mg/m2. We administer at least two antiemetics, antihistamines, and sodium thiosulfate to mitigate known side effects. Postoperatively, patients are admitted to the general surgical floor, reserving the intensive care unit for those in critical condition. We follow Enhanced Recovery After Surgery principles, incorporating early ambulation and feeding into our postoperative care strategy. We have encountered encouraging results with this approach, with most patients having largely uncomplicated postoperative courses and resuming adjuvant chemotherapy within 3 to 4 weeks of surgery.


Asunto(s)
Hipertermia Inducida , Neoplasias Ováricas , Humanos , Femenino , Quimioterapia Intraperitoneal Hipertérmica , Hipertermia Inducida/métodos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Cisplatino/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Terapia Combinada
5.
Int J Gynecol Cancer ; 34(4): 574-580, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38242546

RESUMEN

OBJECTIVES: The modeled CA-125 elimination constant K (KELIM) is a pragmatic early marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy before interval surgery. The primary objective of this study was to assess the prognostic value of KELIM regarding the feasibility of complete surgery, and secondary objectives were to assess the prognostic value of KELIM for the risk of a platinum resistant relapse, progression free survival, and overall survival. METHODS: The study was based on a retrospective cohort of 284 patients treated for an advanced serous high grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV, with neoadjuvant chemotherapy, followed by interval surgery, in a comprehensive cancer center. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. The KELIM predictive value regarding the tumor radiological response rate, likelihood of complete surgery, risk of subsequent platinum resistant relapse, progression free survival, and overall survival were assessed with univariate and multivariate tests. RESULTS: In 232 patients, KELIM was an independent and major predictor of the probability of complete surgery and survival. The final logistic regression model, including KELIM (odds ratio (OR) 0.36, 95% confidence interval (CI)0.16 to 0.73, p=0.006) and complete surgery (no vs yes, OR 0.29, 95% CI 0.15 to 0.53, p<0.001), highlighted the complementary impact of chemosensitivity and surgical outcome relative to the complete surgery. In the multivariate analysis, KELIM and complete surgery were significantly associated with a lower risk of early relapse. In the case of an unfavorable KELIM, when surgical efforts allowed complete cytoreduction, median overall survival was similar to that reported in the case of a favorable KELIM (46.3 months (range 34.6-60.3) vs 46.5 months (range 40.6-68.7), respectively). CONCLUSION: Primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during neoadjuvant chemotherapy, is a major parameter to consider for decision making regarding interval surgery. Complementary to the RECIST score and laparoscopy, this non-invasive tool, available online, helps tailor the interval surgery strategy according to patient tumor chemosensitivity.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias Ováricas , Humanos , Femenino , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Terapia Neoadyuvante , Antígeno Ca-125 , Recurrencia , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Adyuvante
6.
Mol Biol Rep ; 51(1): 118, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38227082

RESUMEN

BACKGROUND: Ovarian cancer is one of the most lethal gynecological cancers among women worldwide. Cisplatin (Cis) is an effective chemotherapeutic agent used to treat several types of cancer. Silymarin (SLM) is an extract of medicinal plant Silybum marianum (milk thistle) with anti-inflammatory, anti-angiogenesis, antioxidant, and anticancer properties used alone or in combination with other drugs. OBJECTIVE: This study aimed to explore the effects of co-treatment with SLM and Cis on A2780 human ovarian cancer cell lines. METHODS: In this study, A2780 cells were treated with various concentrations of SLM and Cis, separately and in combination. Cell cytotoxicity, scratch, clonogenic, and flow-cytometry assays were accomplished to estimate cell viability, migration, colony formation, and apoptosis, respectively. Real-time PCR was utilized to determine the expression levels of miR-155 and miR-27a. RESULTS: SLM significantly reduced the proliferation of A2780 cells in a concentration- and time-dependent manner. Combination treatment with SLM and Cis was more potent than either single treatment in reducing viability, suppressing migration, inhibiting colony formation, and promoting the induction of apoptosis. Additionally, gene expression analysis revealed a significant decline in the expression levels of miR-155 and miR-27a in response to all separate and combined treatments, and co-treatment was more effective than individual treatments in altering miRNAs expression. CONCLUSION: Based on our findings, SLM boosts the anticancer activity of Cis and mitigates its side effects. Thus, the co-treatment of SLM and Cis can be proposed as a promising therapeutic strategy for further investigation.


Asunto(s)
MicroARNs , Neoplasias Ováricas , Silimarina , Femenino , Humanos , Cisplatino/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Silimarina/farmacología , Línea Celular Tumoral , Proliferación Celular , Apoptosis , MicroARNs/genética
7.
Mini Rev Med Chem ; 24(4): 440-452, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37587814

RESUMEN

In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo. Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches.


Asunto(s)
Curcumina , MicroARNs , Neoplasias Ováricas , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Polifenoles/farmacología , Polifenoles/uso terapéutico , Resveratrol , Curcumina/farmacología , Quercetina/farmacología , Genisteína , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética
8.
Comb Chem High Throughput Screen ; 27(1): 157-167, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37366364

RESUMEN

BACKGROUND: Ovarian cancer (OC) is a commonly diagnosed female cancer around the world. The Chinese herbal medicine Brucea Javanica has an anti-cancer effect. However, there is no relevant report on whether Brucea Javanica is effective in treating OC, and the corresponding mechanism is also unknown. OBJECTIVE: This study was projected to excavate the active components and underpinned molecular mechanisms of Brucea Javanica in treating ovarian cancer (OC) through network pharmacology combined with in vitro experiments. METHODS: The essential active components of Brucea Javanica were selected using the TCMSP database. The OC-related targets were selected by GeneCards, intersecting targets were obtained by Venn Diagram. The core targets were obtained through the PPI network and Cytoscape, and the key pathway was gained through GO and KEGG enrichment analyses. Meanwhile, docking conformation was observed as reflected by molecular docking. MTT, colony formation assay and flow cytometer (FCM) analysis were performed to determine cell proliferation and apoptosis, respectively. Finally, Levels of various signaling proteins were evaluated by western blotting. RESULTS: Luteolin, ß-sitosterol and their corresponding targets were selected as the essential active components of Brucea Javanica. 76 intersecting targets were obtained by Venn Diagram. TP53, AKT1, and TNF were obtained through the PPI network and Cytoscape, and the key pathway PI3K/AKT was gained through GO and KEGG enrichment analyses. A good docking conformation was observed between luteolin and AKT1. Luteolin could hinder A2780 cell proliferation, induce cell apoptosis and enhance the inhibition of the PI3K/AKT pathway. CONCLUSION: It was verified in vitro that luteolin could hinder OC cell proliferation and activate the PI3K/AKT pathway to lead to apoptosis.


Asunto(s)
Medicamentos Herbarios Chinos , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Luteolina/farmacología , Farmacología en Red , Brucea javanica , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/farmacología
9.
Technol Health Care ; 32(2): 1135-1148, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37781832

RESUMEN

BACKGROUND: Although the prognosis of ovarian cancer can be significantly improved through standardized surgery and chemotherapy, 70% of epithelial ovarian cancer (EOC) patients would suffer from drug resistance and recurrence during the long chemotherapy cycle. OBJECTIVE: To explore the impact of a training mode based on the integration of virtual reality technology and mindfulness on anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy. METHOD: Through virtual reality technology, a mindfulness training software was designed and developed, and a mindfulness training mode based on virtual reality technology was constructed. Using a self-controlled design, 48 ovarian cancer patients undergoing chemotherapy who were hospitalized in a tertiary hospital in Beijing from August 2022 to May 2023 were conveniently selected as the research subjects. The patients were subjected to four weeks of mindfulness training based on virtual reality technology, and the acceptance of the mindfulness training mode using virtual reality technology was evaluated. The Hospital Anxiety and Depression Scale (HADS) and Cancer Related Fatigue Scale (CRF) were used to evaluate the anxiety, depression, and fatigue of patients before and after intervention. RESULTS: The virtual reality based mindfulness training mode includes four functional modules: personalized curriculum, intelligent monitoring, emotion tracking, and Funny Games. 48 patients had a high acceptance score (139.21 ± 10.47), and after using mindfulness training mode based on virtual reality technology, anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy were significantly reduced, with a statistically significant difference (p< 0.001). CONCLUSION: Ovarian cancer patients during chemotherapy have a high acceptance of virtual reality based mindfulness training mode. The application of this mode can reduce the psychological problems of anxiety, depression, and cancer-related fatigue in ovarian cancer patients during chemotherapy, and is worth promoting and using.


Asunto(s)
Atención Plena , Neoplasias Ováricas , Realidad Virtual , Humanos , Femenino , Depresión/etiología , Depresión/terapia , Ansiedad/etiología , Ansiedad/terapia , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/tratamiento farmacológico , Fatiga/etiología , Fatiga/terapia , Fatiga/psicología
10.
Biomed Pharmacother ; 170: 116016, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38128180

RESUMEN

BACKGROUND: Ovarian cancer (OC) is the most lethal gynecological malignancy. Frequent peritoneal dissemination is the main cause of low survival rate. Guizhi-Fuling Wan (GZFL) is a classical traditional Chinese herbal formula that has been clinically used for treating ovarian cancer with good outcome. However, its therapeutic mechanism for treating OC has not been clearly elucidated. PURPOSE: We aim to elucidate the potential mechanisms of GZFL in treating OC with a focus on STAT3 signaling pathway. METHODS: In vivo efficacy of GZFL was assessed using an OC xenograft mouse model. Proteomics analysis in OC cells and RNA-seq analysis in mice tumors were performed to fully capture the translational and transcriptional signature of GZFL. Effects of GZFL on proliferation, spheroid formation and reactive oxygen species (ROS) were assessed using wildtype and STAT3 knockout OC cells in vitro. STAT3 activation and transcription activity, hypoxia and EMT-related protein expression were assessed to validate the biological activity of GZFL. RESULTS: GZFL suppresses tumor growth with a safety profile in mice, while prevents cell growth, spheroid formation and accumulates ROS in a STAT3-dependent manner in vitro. GZFL transcriptionally and translationally affects genes involved in inflammatory signaling, EMT, cell migration, and cellular hypoxic stress response. In depth molecular study confirmed that GZFL-induced cytotoxicity and EMT suppression in OC cells are directly corelated to inhibition of STAT3 activation and transcription activity. CONCLUSION: Our study provides the first evidence that GZFL inhibits OC progression through suppressing STAT3-EMT signaling. These results will further support its potential clinical use in OC.


Asunto(s)
Neoplasias Ováricas , Proteómica , Humanos , Ratones , Femenino , Animales , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Línea Celular Tumoral , Factor de Transcripción STAT3/metabolismo
11.
In Vitro Cell Dev Biol Anim ; 59(10): 739-746, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38038884

RESUMEN

Epigallocatechin gallate (EGCG), a bioactive component in tea, displays broad anti-cancer effects. Our study was designed to evaluate the anti-cancer effects of EGCG on ovarian cancer and explored the underlying molecular mechanisms. To evaluate the in vitro inhibitory effects of EGCG against ovarian cancer, MTT assay, colony formation assay, apoptosis assay, and wound healing assay, were performed. Besides, the inhibitory effects of EGCG on tumor growth in the xenograft animal model were evaluated by measuring tumor volume and tumor weight. Moreover, Western blotting and qPCR were used to evaluate the levels of target genes and proteins. Treatment with EGCG inhibited cell migration and cell survival, and promoted cell apoptosis in A2780 and SKOV3 cells. Interestingly, treatment with EGCG inhibited the tumor growth in the xenograft animal model. The mechanistic study revealed that treatment with EGCG induced the activation of FOXO3A and suppressed the expression of c-Myc both in vitro and in vivo. Our findings demonstrate that EGCG suppress ovarian cancer cell growth, which may be due to its regulation on FOXO3A and c-Myc.


Asunto(s)
Proteína Forkhead Box O3 , Ácido Gálico , Neoplasias Ováricas , , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Apoptosis/efectos de los fármacos , Humanos , Línea Celular Tumoral , Femenino , Animales , Ratones , Ratones Desnudos , Ratones Endogámicos BALB C , Movimiento Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Supervivencia Celular , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Proteína Forkhead Box O3/metabolismo , Xenoinjertos , Té/química
14.
Curr Oncol ; 30(12): 10272-10282, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38132382

RESUMEN

Combining interval cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in advanced epithelial ovarian carcinoma (EOC). Although limited, growing evidence regarding carboplatin-based HIPEC highlights its potential. This retrospective study included all patients with advanced primary high-grade serous ovarian cancer who underwent interval CRS combined with carboplatin-based HIPEC at our Canadian tertiary care center between 2014 and 2020. We identified 40 patients with a median age of 61 years. The median peritoneal cancer index was 13 and complete cytoreduction was achieved in 38 patients (95%). Median hospital stay was 13 days and there were four admissions to the intensive care unit (10%) and six readmissions (15%). Severe adverse events occurred in eight patients (20%) and there was no perioperative death. Recurrence was seen in 33 patients (82%) with a median DFS of 18.0 months and a median overall survival of 36.4 months. Multivariate analyses showed that age, peritoneal cancer index, completeness of cytoreduction, occurrence of severe complications, and bowel resection did not significantly impact DFS or OS in our cohort. Interval CRS combined with carboplatin-based HIPEC for advanced primary EOC is associated with acceptable morbidity and oncological outcomes. Larger studies are required to determine the long-term outcomes.


Asunto(s)
Hipertermia Inducida , Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Persona de Mediana Edad , Carboplatino/uso terapéutico , Quimioterapia Intraperitoneal Hipertérmica , Procedimientos Quirúrgicos de Citorreducción , Terapia Combinada , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Canadá , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía
15.
Medicine (Baltimore) ; 102(51): e36656, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38134066

RESUMEN

The mortality rate of ovarian cancer is the highest among gynecological cancers, posing a serious threat to women health and life. Scutellaria barbata D. Don (SBD) can effectively treat ovarian cancer. However, its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of SBD in the treatment of ovarian cancer using network pharmacology, and to verify the experimental results using human ovarian cancer SKOV3 cells. The Herb and Disease Gene databases were searched to identify common targets of SBD and ovarian cancer. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind SBD. Finally, the molecular docking and main possible pathways were verified by experimental studies. Cell proliferation, the mRNA expression level of key genes and signaling pathway were all investigated and evaluated in vitro. A total of 29 bioactive ingredients and 137 common targets in SBD were found to inhibit ovarian cancer development. The active ingredients identified include quercetin, luteolin, and wogonin. Analysis of the PPI network showed that AKT1, VEGFA, JUN, TNF, and Caspase-3 shared centrality among all target genes. The results of the KEGG pathway analysis indicated that the cancer pathway, PI3K-Akt signaling pathway, and MAPK signaling pathways mediated the effects of SBD against ovarian cancer progression. Cell experiments showed that quercetin, luteolin, and wogonin inhibited the proliferation and clone formation of SKOV3 cells and regulated mRNA expression of 5 key genes by inhibiting PI3K/Akt signaling pathway. Our results demonstrate that SBD exerted anti-ovarian cancer effects through its key components quercetin, luteolin and wogonin. Mechanistically, its anti-cancer effects were mediated by inhibition of the PI3K/Akt signaling pathways. Therefore, SBD might be a candidate drug for ovarian cancer treatment.


Asunto(s)
Medicamentos Herbarios Chinos , Neoplasias Ováricas , Femenino , Humanos , Farmacología en Red , Luteolina/farmacología , Luteolina/uso terapéutico , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Quercetina , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , ARN Mensajero
16.
Front Endocrinol (Lausanne) ; 14: 1277155, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38027211

RESUMEN

In this study, response of ovarian cells (human granulosa cell line HGL5, and human adenocarcinoma cell line OVCAR-3) to short-term pomegranate peel extract (PPE) treatment (for 24 hours in cell culture) was evaluated in vitro. Quantitative and qualitative screening of polyphenols revealed punicalagins α and ß as major polyphenolic components. Total phenolic content (TPC) was 93.76 mg GAE/g d.w. with a high antioxidant activity of 95.30 mg TEAC/g d.w. In OVCAR-3, PPE treatment inhibited the metabolic activity, and increased cyclin-dependent kinase 1 (CDKN1A, p21) level at the highest dose, but not in HGL5. Flow cytometry analysis could not detect any significant difference between proportions of live, dead, and apoptotic cells in both cell lines. Reactive oxygen species (ROS) revealed an antioxidant effect on HGL5, and a prooxidant effect by stimulating ROS generation in OVCAR-3 cells at the higher doses of PPE. However, in contrast to HGL5, PPE treatment decreased release of growth factors - TGF-ß2 and EGF at the highest dose, as well as their receptors TGFBR2 and EGFR in OVCAR-3 cells. PPE also influenced steroidogenesis in granulosa cells HGL5 by stimulating 17ß-estradiol secretion at higher doses. In conclusion, the present study highlighted the bioactive compounds in pomegranate peels and the possible mechanisms of action of PPE, shedding light on its promising role in ovarian cancer (chemo)prevention and/or management.


Asunto(s)
Neoplasias Ováricas , Granada (Fruta) , Humanos , Femenino , Apoptosis , Especies Reactivas de Oxígeno , Neoplasias Ováricas/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Línea Celular Tumoral , Antioxidantes/farmacología , Antioxidantes/uso terapéutico
17.
Int J Gynecol Cancer ; 33(12): 1957-1965, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38011988

RESUMEN

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option for epithelial ovarian cancer following cytoreductive surgery. The intraperitoneal spread of the disease makes the peritoneal cavity an ideal target for drug delivery. HIPEC has shown promising results in improving overall survival in epithelial ovarian cancer patients when performed during interval cytoreductive surgery. Recent studies have provided level 1 evidence supporting increased overall survival in stage III ovarian cancer patients treated with HIPEC during interval cytoreduction. Meta-analyses have further confirmed the survival improvement in women receiving HIPEC. Despite its inclusion in guidelines, many centers have been hesitant to implement HIPEC programs due to perceived obstacles, such as increased morbidity, cost, and resource requirements. Studies have shown that morbidity rates are acceptable in selected patients, and the addition of HIPEC to cytoreductive surgery is cost effective. Therefore, the main barrier to implementing HIPEC programs is related to resource requirements and logistics, but with proper preparation, these challenges can be overcome. Establishing a successful HIPEC program requires institutional support, a knowledgeable and dedicated team, adequate resources and equipment, and proper training and audit. This review aims to provide evidence based information to guide the development of successful HIPEC programs, including preoperative, anesthetic, and surgical considerations. It also reviews the different equipment and protocols for the perfusion and common postoperative events.


Asunto(s)
Neoplasias de los Genitales Femeninos , Hipertermia Inducida , Neoplasias Ováricas , Femenino , Humanos , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Terapia Combinada , Neoplasias de los Genitales Femeninos/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida/métodos , Canadá/epidemiología , Procedimientos Quirúrgicos de Citorreducción/métodos , Tasa de Supervivencia
18.
Cell Metab ; 35(11): 2044-2059.e8, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37890478

RESUMEN

Amino acid metabolism has been actively investigated as a potential target for antitumor therapy, but how it may alter the response to genotoxic chemotherapy remains largely unknown. Here, we report that the depletion of fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the final step of tyrosine catabolism, reduced chemosensitivity in epithelial ovarian cancer (EOC). The expression level of FAH correlated significantly with chemotherapy efficacy in patients with EOC. Mechanistically, under genotoxic chemotherapy, FAH is oxidized at Met308 and translocates to the nucleus, where FAH-mediated tyrosine catabolism predominantly supplies fumarate. FAH-produced fumarate binds directly to REV1, resulting in the suppression of translesion DNA synthesis (TLS) and improved chemosensitivity. Furthermore, in vivo tyrosine supplementation improves sensitivity to genotoxic chemotherapeutics and reduces the occurrence of therapy resistance. Our findings reveal a unique role for tyrosine-derived fumarate in the regulation of TLS and may be exploited to improve genotoxic chemotherapy through dietary tyrosine supplementation.


Asunto(s)
ADN , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Daño del ADN , Tirosina/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Fumaratos
20.
Rev Med Inst Mex Seguro Soc ; 61(4): 420-426, 2023 Jul 31.
Artículo en Español | MEDLINE | ID: mdl-37535978

RESUMEN

Background: Currently, epithelial ovarian cancer is diagnosed in advanced stages (EC IIIC) in 75-80% of cases worldwide. In this group of patients treatment with neoadjuvant chemotherapy is started, followed by interval cytoreduction of residual disease and even require peritonectomy with application of hyperthermic intraperitoneal chemotherapy (HIPEC). Objective: To identify the overall survival and progression-free survival associated with peritonectomy, in patients with peritoneal carcinomatosis secondary to ovarian cancer treated in the oncology gynecology service from January 2009 to January 2019 at the UMAE Hospital de Oncología Centro Médico Nacional Siglo XXI. Material and methods: Observational, descriptive, cross-sectional, retrospective study, information was obtained from the clinical file of patients treated with peritonectomy with the use of hyperthermic intraperitoneal chemotherapy in the gynecological oncology service from January 2009 to January 2019 at the UMAE Hospital de Oncología Centro Médico Nacional Siglo XXI. Results: Information was obtained from a total of 36 patients (n=100%), 36.1% received intraperitoneal chemotherapy and 63.8% underwent cytoreduction without the application of intraoperative chemotherapy. The most frequently used drug was cisplatin followed by mitomycin. There was no statistical significance when comparing both groups, however there was a trend in favor of the use of intraoperative chemotherapy by obtaining a greater number of months in terms of overall survival. Conclusion: Peritonectomy with hyperthermic intraperitoneal chemotherapy is an option in selected patients with advanced stage ovarian cancer in primary and recurrent surgery, as well as in patients with platinum-resistant ovarian cancer.


Introducción: en la actualidad, el cáncer de ovario epitelial se diagnostica en etapas avanzadas (EC IIIC) en 75-80% de los casos a nivel mundial. En este grupo de pacientes se inicia el tratamiento con quimioterapia neoadyuvante, seguida de citorreducción de intervalo de la enfermedad residual e incluso requieren de peritonectomía con aplicación de quimioterapia intraperitoneal hipertérmica (HIPEC). Objetivo: identificar la sobrevida global y sobrevida libre de progresión asociada a la realización de peritonectomía, en pacientes con carcinomatosis peritoneal secundario a cáncer de ovario tratadas en el servicio de Ginecología Oncológica de enero de 2009 a enero de 2019 en el Hospital de Oncología Centro Médico Nacional Siglo XXI (CMN SXXI). Material y métodos: estudio observacional, descriptivo, transversal, retrospectivo, se obtuvo información del expediente clínico de pacientes tratados con peritonectomía con uso de quimioterapia intraperitoneal hipertérmica en el servicio de Ginecología Oncológica de enero de 2009 a enero de 2019 en el Hospital de Oncología CMN SXXI. Resultados: se obtuvo información de un total de 36 pacientes (n = 100%), el 36.1% recibió quimioterapia intraperitoneal y al 63.8% se les realizó citorreducción sin la aplicación de quimioterapia intraoperatoria. El fármaco utilizado con mayor frecuencia fue el cisplatino seguido por mitomicina. No hubo significancia estadística al comparar ambos grupos, sin embargo hubo una tendencia a favor del uso de quimioterapia intraoperatoria al obtener un mayor número de meses en cuanto a sobrevida global. Conclusión: la peritonectomía con quimioterapia intraperitoneal hipertérmica es una opción en pacientes seleccionados de cáncer de ovario en etapa avanzada en cirugía primaria y recurrente, así mismo en paciente con cáncer de ovario platino-resistentes.


Asunto(s)
Hipertermia Inducida , Neoplasias Ováricas , Humanos , Femenino , Quimioterapia Intraperitoneal Hipertérmica , Procedimientos Quirúrgicos de Citorreducción , Estudios Retrospectivos , Estudios Transversales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Terapia Combinada , Tasa de Supervivencia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA