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1.
Nanoscale ; 13(34): 14538-14551, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473182

RESUMO

The use of cell-penetrating peptides (CPPs), typically HIV-Tat, to deliver therapeutic genes for cancer treatment is hampered by the inefficient delivery and complicated uptake route of plasmid DNA (pDNA). On the one hand, surface charges, particle size and shape essentially contribute to the endocytosis pathway of Tat/pDNA nanocomplexes, and on the other hand, endogenous cellular factors dominantly determine their intracellular trafficking fate and biological outcome. Recent advances in surfactant-modified nanomaterial and dual molecular imaging technology have offered new opportunities for suicide gene therapy. In this study, we employed the cationic surfactant C16TAB to further condense Tat/pDNA nanocomplexes for improving their delivery efficiency and tested the therapeutic effect of Tat/pDNA/C16TAB (T-P-C) nanoparticles carrying the GCV-converted HSV-ttk suicide gene for ovarian cancer. The cellular endocytosis pathway and underlying signal mechanism of T-P-C nanoparticles were further determined. The obtained T-P-C nanoparticles exhibited a small size, positive surface charge, irregular granular shape and high pDNA encapsulation efficiency. The in vitro experiments showed that T-P-C nanoparticles mainly used the macropinocytosis pathway for uptake in ovarian cancer cells. Their internalization and payload gene expression were controlled by the Arf6 GTPase-dependent, Rab GTPase-activated signal axis. Further in vivo molecular imaging based on DF (Fluc-eGFP)-TF (RFP-Rluc-HSV-ttk) system showed that T-P-C nanoparticles significantly increased the targeted delivery and suicide gene therapy in a mouse model xenografted with human ovarian cancer. More importantly, Arf6-mediated macropinocytosis remarkably enhanced the delivery efficiency and suicide gene therapy effect of T-P-C nanoparticles. Therefore, these C16TAB-condensed Tat/pDNA nanoparticles combined with the dual molecular imaging strategy provides a novel intracellular delivery platform for high-efficient, precise suicide gene therapy of ovarian cancer.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Animais , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Camundongos , Neoplasias Ovarianas/terapia , Plasmídeos , Transfecção
2.
Wiad Lek ; 74(8): 1984-1987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34537754

RESUMO

We review the current research literature on treatment behaviour for neoplasms of the female genital tract during pregnancy. Guidelines for clinical management of cervical cancer, ovarian tumours, and vulvar cancer are presented both regarding gynaecological oncologic treatment and obstetrics. Cervical cancer is the most common malignant tumour of the female genitalia during pregnancy due to the high incidence of this neoplasm in developing countries, including Bulgaria, on the one hand, and on the other, it affects women of reproductive age. Treatment algorithms depending on various factors - gestational age, stage of the disease, tumour lesion size, and presence of pelvic lymph node metastases, are presented. Ovarian tumours are classified into benign, borderline malignant, and malignant tumours. The latter, in turn, are divided into early and advanced stages, as well as epithelial and non-epithelial tumours, which can be detected at different stages of pregnancy.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Feminino , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/terapia , Humanos , Linfonodos , Metástase Linfática , Neoplasias Ovarianas/terapia , Gravidez , Neoplasias do Colo do Útero/terapia
3.
Medicina (B Aires) ; 81(4): 565-573, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34453798

RESUMO

Ovarian cancer represents the third gynecological cancer in frequency in Argentina. There is a lack of information on this pathology in our country regarding the treatment and evolution of patients who suffer it. The aim of this study was to evaluate the perioperative and oncological results in patients with advanced epithelial ovarian tumor. We present a retrospective cohort in which we evaluated disease-free survival and overall survival in patients with epithelial ovarian tumor treated at the Hospital Italiano de Buenos Aires between June 2009 and June 2017. Of 170 patients included in the study, 72 (42.4%) received primary debulking surgery (CCP), while 98 (57.6%) received neoadjuvant therapy and interval surgery (CI). The optimal cyto-reduction rate was 75% and 79% respectively. No differences were found in perioperative outcomes, or in severe complications between the two groups. The median disease-free survival in the CCP group was 2.5 years (95% CI 1.6-3.1) while in the CI group it was 1.4 (95% CI 1.2-1.7) p < 0.001. The median overall survival was 5.8 years in CPP, and 3.5 years in CI. Faced with a meticulous selection by a group of experts, patients with advanced ovarian cancer treated with CCP present better oncological results than those who received neoadjuvant therapy and CI.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Feminino , Hospitais , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Resultado do Tratamento
4.
Biomolecules ; 11(7)2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34356623

RESUMO

Epithelial ovarian cancer (EOC) is one of the major increasing lethal malignancies of the gynecological tract, mostly due to delayed diagnosis and chemoresistance, as well as its very heterogeneous genetic makeup. Application of high-throughput molecular technologies, gene expression microarrays, and powerful preclinical models has provided a deeper understanding of the molecular characteristics of EOC. Therefore, molecular markers have become a potent tool in EOC management, including prediction of aggressiveness, prognosis, and recurrence, and identification of novel therapeutic targets. In addition, biomarkers derived from genomic/epigenomic alterations (e.g., gene mutations, copy number aberrations, and DNA methylation) enable targeted treatment of affected signaling pathways in advanced EOC, thereby improving the effectiveness of traditional treatments. This review outlines the molecular landscape and discusses the impacts of biomarkers on the detection, diagnosis, surveillance, and therapeutic targets of EOC. These findings focus on the necessity to translate these potential biomarkers into clinical practice.


Assuntos
Biomarcadores Tumorais , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/terapia , Metilação de DNA , DNA de Neoplasias/metabolismo , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia
5.
Eur J Nucl Med Mol Imaging ; 48(10): 3286-3302, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34215923

RESUMO

In most patients with ovarian carcinoma, the diagnosis is reached when the disease is long past the initial stages, presenting already an advanced stage, and they usually have a very bad prognosis. Cytoreductive or debulking surgical procedures, platinum-based chemotherapy and targeted agents are key therapeutic elements. However, around 7 out of 10 patients present recurrent disease within 36 months from the initial diagnosis. The metastatic spread in ovarian cancer follows three pathways: contiguous dissemination across the peritoneum, dissemination through the lymphatic drainage and, although less importantly in this case, through the bloodstream. Radiological imaging, including ultrasound, CT and MRI, are the main imaging techniques in which management decisions are supported, CT being considered the best available technique for presurgical evaluation and staging purposes. Regarding 2-[18F]FDG PET/CT, the evidence available in the literature demonstrates efficacy in primary detection, disease staging and establishing the prognosis and especially for relapse detection. There is limited evidence when considering the evaluation of therapeutic response. This guideline summarizes the level of evidence and grade of recommendation for the clinical indications of 2-[18F]FDG PET/CT in each disease stage of ovarian carcinoma.


Assuntos
Energia Nuclear , Medicina Nuclear , Neoplasias Ovarianas , Feminino , Fluordesoxiglucose F18 , Humanos , Imagem Molecular , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Compostos Radiofarmacêuticos , Estados Unidos
6.
Nat Commun ; 12(1): 4230, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244494

RESUMO

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXß2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXß2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXß2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXß2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Assuntos
Processamento Alternativo , Carcinoma Epitelial do Ovário/genética , Proteínas da Matriz Extracelular/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas da Matriz Extracelular/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Integrina alfaXbeta2/genética , Integrina alfaXbeta2/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Fosforilação/genética , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207103

RESUMO

Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunotherapy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer.


Assuntos
Imunoterapia , Neoplasias Ovarianas/terapia , Medicina de Precisão , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Terapia de Alvo Molecular , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/mortalidade , Medicina de Precisão/efeitos adversos , Medicina de Precisão/métodos , Resultado do Tratamento
8.
Anticancer Res ; 41(7): 3253-3260, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230119

RESUMO

Epithelial ovarian cancer is the second most common malignancy of the female genital tract, with approximately 7,400 new cases annually in Germany. With 5,500 deaths per year, ovarian cancer is the leading gynecologic cause of death. Epithelial ovarian cancer is characterized by morphologic heterogeneity with 4 molecular biological subtypes (immunoreactive-like, differentiated-like, proliferative-like, mesenchymal-like) with different prognosis. Significantly improved survival is achieved by optimal debulking with no residual disease (R0). Systematic lymphonodectomy of clinical negative lymph nodes has no effect on overall survival in advanced ovarian cancer. Interval debulking in advanced ovarian cancer after three cycles of neoadjuvant chemotherapy with carboplatin/paclitaxel is controversial. Standard chemotherapy for advanced ovarian cancer consists of six cycles of carboplatin AUC5 and paclitaxel 175 mg/m2, in a three-week cycle. Intraperitoneal chemotherapy is not a standard therapy. Anti-hormonal therapy with an aromatase inhibitor plays a minor role in therapy of both low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC). A major achievement in ovarian cancer therapy has been the results of the SOLO-1 trial, in which olaparib as a first line maintenance monotherapy resulted in an overall 70% lower risk of disease progression in patients with advanced Breast Cancer Gene (BRCA)-mutated ovarian cancer.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada/métodos , Feminino , Alemanha , Humanos , Terapia Neoadjuvante/métodos
9.
Int J Nanomedicine ; 16: 4351-4369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234430

RESUMO

Purpose: Multifunctional nanoparticles with targeted therapeutic function and diagnostic-imaging are of great interest in the domain of precision therapy. NIR laser responsive nanoparticles (PLGA-PEG-FA encapsulating Bi2S3, PFP, and Dox (designed as FBPD NPs)) are synthesized for ovarian cancer targeted combination therapy with CT/PA dual-modal imaging guidance (PA: photoacoustic; CT: X-ray computed tomography). Methods and Results: The FBPD NPS prepared by the double emulsification method revealed excellent dispersity, great stability, outstanding optical properties. The temperature of FBPD NPs increased rapidly after laser irradiation, inducing liquid-to-gas conversion of perfluoropentane (PFP), and promoting the release of Dox up to 86.7%. These FBPD NPs demonstrated their outstanding imaging capability for both PA and CT imaging both in vitro and in vivo, providing the potential for therapeutic guidance and monitoring. Assisted by folic acid, these nanoparticles could highly enrich in ovarian tumor tissue and the accumulation peaked at 3 h after intravenous administration. The desirable photothermal-conversion efficiency of the nanoparticles combined with chemotherapy achieved highly efficient therapy, which was demonstrated both in vitro and in vivo. Conclusion: We successfully constructed multifunctional theranostic FBPD NPs for highly efficient PTT/chemotherapy combined therapy with dual CT/PA imaging guidance/monitoring. The unique nanoparticles with multiple abilities pave an emerging way toward precise treatment of ovarian cancer.


Assuntos
Raios Infravermelhos , Lasers , Nanopartículas/uso terapêutico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Técnicas Fotoacústicas , Tomografia Computadorizada por Raios X , Animais , Terapia Combinada , Feminino , Ácido Fólico/química , Humanos , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química
10.
Anticancer Res ; 41(7): 3649-3656, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230163

RESUMO

BACKGROUND/AIM: Postoperative pancreatic fistula after distal pancreatectomy represents the most frequent procedure-related complication; however, a standard treatment is currently not available. CASE REPORT: We herein report a case of postoperative pancreatic fistula after distal pancreatectomy and splenectomy in a patient affected by a platinum-sensitive ovarian cancer recurrence. The 59-year-old patient developed a pancreatic fistula on postoperative day 4. An endoscopic transgastric double-pigtail drainage was placed on postoperative day 13. The patient was discharged after 5 days and referred to adjuvant medical treatment. A month later, computed tomography revealed complete resolution of the fistula, the drainage was removed, and the patient continued chemotherapy. She recovered uneventfully at a 3-month follow-up. CONCLUSION: EUS-guided drainage is a viable option in the management of postoperative pancreatic fistula, which can lead to a rapid resolution of peripancreatic fluid collections and to initiation of adjuvant chemotherapy with the slightest delay in ovarian cancer patients.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/terapia , Fístula Pancreática/cirurgia , Fístula Pancreática/terapia , Drenagem/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatectomia/métodos , Período Pós-Operatório , Esplenectomia/métodos
11.
J Egypt Natl Canc Inst ; 33(1): 16, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241710

RESUMO

BACKGROUND: P D-L1 is expressed in tumor cells and plays a crucial role in tumor immune escape. Tumor-infiltrating lymphocytes (TILs) as CD8 T cells contribute to reduced tumor growth. Few studies investigated the prognostic effect of PD-L1 and CD8 TILs in ovarian high-grade serous carcinoma (HGSC). In the present study, we analyzed the expression of PD-L1 and CD8 TILs in HGSC by immunohistochemistry, and results were correlated to prognosis. It was carried on 54 cases of ovarian HGSC who attended the Oncology Centre, Mansoura University, Egypt, from 2012 till 2019. RESULTS: Nearly 60% of cases showed positive PD-L1 expression in tumor cells. Regarding the clinicopathological characteristics, higher PD-L1 expression was found among patients with residual tumor (82.4%) compared to patients with no residual tumor (54.5%), with marginal statistical significance (p 0.07). PD-L1 was significantly associated with CD8 TILs expression. Higher PD-L1 expression was found among tumors with low expression of CD8 TILs with statistically significant difference (p≤0.001). Disease-free survival (DFS) was significantly lower among the group with positive expression of PD-L1 compared to the group with negative expression of PD-L1 (p 0.01), while overall survival (OS) was not associated with PD-L1 expression. On the other hand, the overall survival (OS) in patients with high CD8 expression was significantly higher than patients with low CD8 expression (p 0.043), while DFS was not significantly different among both CD8 TILS groups. CONCLUSIONS: PD-L1 and CD8 TILs may become a promising therapeutic target for patients with ovarian HGSC. More studies are needed to further validate their prognostic effect. Precise identification of patients who will benefit from PD-L1 checkpoint blockade and TILs adaptive immunotherapy is mandatory.


Assuntos
Antígeno B7-H1 , Linfócitos T CD8-Positivos/imunologia , Carcinoma , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Ovarianas/terapia , Adulto , Antígeno B7-H1/análise , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma/mortalidade , Carcinoma/terapia , Egito , Feminino , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/química , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Prognóstico , Receptor de Morte Celular Programada 1 , Análise de Sobrevida
12.
J Obstet Gynaecol Res ; 47(9): 3339-3351, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34219334

RESUMO

AIM: To evaluate the clinico-pathologic features, treatment options, prognostic factors, and survival outcomes of malignant struma ovarii based on a systematic literature review in association with our case study. METHODS: A systematic review of the medical literature was performed to identify articles about malignant struma ovarii from January 1983 until July 2020. We evaluated 178 cases. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) of the entire cohort was 72.5% and 91%, respectively. In univariate analysis, younger age (<43 years), whole strumal cyst diameter >95 mm, presence of a histologic type other than papillary classic-type thyroid carcinoma within the tumor and lymphovascular space invasion were related to poor PFS. Patients who received radioactive iodine ablation (RIA) before the treatment failure had significantly higher PFS than those who did not receive RIA (94.9% vs. 64.8%, p = 0.041, respectively). In univariate analysis, PFS was significantly higher in patients who underwent gynecologic surgery followed by thyroidectomy and RIA compared with those who had surgical treatment only (94.5% vs. 64.3%, p = 0.05, respectively). However, this result could not be identified as an independent prognostic factor in multivariate analysis (p = 0.207). Younger age and absence of capsular involvement were related to significantly increased OS. Histologic type was the only independent prognostic factor for PFS (hazard ratio: 3.30, 95% confidence interval: 1.122-9.748; p = 0.030) CONCLUSION: The most common histologic subtype was the papillary classic type. The presence of a histologic type other than the classic papillary thyroid carcinoma within the tumor was an independent adverse prognostic factor.


Assuntos
Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Adulto , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/terapia , Estruma Ovariano/diagnóstico , Estruma Ovariano/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia
13.
Biochim Biophys Acta Rev Cancer ; 1876(1): 188584, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34157315

RESUMO

An emerging role of long non-coding RNAs (lncRNAs) in tumor progression has been revealed in the last decade. Through interactions with nucleic acids and proteins, lncRNAs could act as enhancers, scaffolds or decoys for a number of oncoproteins and tumor suppressors. The aberrant lncRNA expression or mutations are often associated with changes in a variety of cellular processes, including proliferation, stress response and cell death. Here, we will focus on the tumor-associated lncRNAs in ovarian cancer according to their contribution to cancer hallmarks, such as intense proliferation, cell death resistance, altered energy metabolism, invasion and metastasis, and immune evasion. Moreover, the potential clinical implications of lncRNAs and their significance for the diagnosis, prognosis and therapy of ovarian cancer will be discussed.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Sistemas CRISPR-Cas , Resistencia a Medicamentos Antineoplásicos , Feminino , Edição de Genes , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Humanos , Oligonucleotídeos Antissenso/uso terapêutico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , RNA Longo não Codificante/genética , Transdução de Sinais
14.
Expert Rev Clin Pharmacol ; 14(9): 1065-1074, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34080491

RESUMO

INTRODUCTION: Epithelial ovarian cancer (EOC) remains the most lethal of gynecological cancers. Sarcopenia and low Skeletal Muscle Radiodensity (SMD) are highly prevalent in EOC. Cross sectional imaging via MRI and CT are considered the gold standard for quantification of muscle mass and muscle density. Skeletal Muscle Index (SMI) and SMD-based thresholds for sarcopenia in EOC vary significantly and specific EOC thresholds for sarcopenia have not been defined. AREAS COVERED: Sarcopenia and low SMD are highly prevalent in EOC affecting between 11-68% and 21-35% of women, respectively. SMD may be a better prognostic biomarker in ovarian cancer than SMI. Reduced SMI and SMD may also influence the risk of postoperative complications but further studies are required. There is increasing evidence that sarcopenia increases during neoadjuvant chemotherapy. EXPERT COMMENTARY: Prehabilitation studies in surgical oncology indicate encouraging results, such as, maintenance of SMI, reduced length of stay and surgical complication rates, improved health-related quality of life and functional capacity. Early identification of body composition abnormalities would permit targeted intervention prior to, and after surgery. Cross-sectional imaging is routinely used for staging and surveillance of EOC patients and hence assessment of body composition abnormalities is possible and an underutilized resource.


Assuntos
Carcinoma Epitelial do Ovário/terapia , Músculo Esquelético/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Composição Corporal/fisiologia , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Músculo Esquelético/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Qualidade de Vida , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Resultado do Tratamento
15.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066508

RESUMO

Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5'-Aminolevulinic acid (5'-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.


Assuntos
Fluordesoxiglucose F18/uso terapêutico , Neoplasias Ovarianas/terapia , Fotoquimioterapia , Radiação , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linhagem Celular Tumoral , Feminino , Injeções Intraperitoneais , Camundongos Endogâmicos BALB C
16.
Int J Mol Sci ; 22(11)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070369

RESUMO

Folate receptor beta (FRß) is a folate binding receptor expressed on myeloid lineage hematopoietic cells. FRß is commonly expressed at high levels on malignant blasts in patients with acute myeloid leukemia (AML), as well as on M2 polarized tumor-associated macrophages (TAMs) in the tumor microenvironment of many solid tumors. Therefore, FRß is a potential target for both direct and indirect cancer therapy. We demonstrate that FRß is expressed in both AML cell lines and patient-derived AML samples and that a high-affinity monoclonal antibody against FRß (m909) has the ability to cause dose- and expression-dependent ADCC against these cells in vitro. Importantly, we find that administration of m909 has a significant impact on tumor growth in a humanized mouse model of AML. Surprisingly, m909 functions in vivo with and without the infusion of human NK cells as mediators of ADCC, suggesting potential involvement of mouse macrophages as effector cells. We also found that TAMs from primary ovarian ascites samples expressed appreciable levels of FRß and that m909 has the ability to cause ADCC in these samples. These results indicate that the targeting of FRß using m909 has the potential to limit the outgrowth of AML in vitro and in vivo. Additionally, m909 causes cytotoxicity to TAMs in the tumor microenvironment of ovarian cancer warranting further investigation of m909 and its derivatives as therapeutic agents in patients with FRß-expressing cancers.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Receptor 2 de Folato , Imunoterapia , Leucemia Mieloide Aguda , Proteínas de Neoplasias , Neoplasias Ovarianas , Animais , Células CHO , Cricetulus , Feminino , Receptor 2 de Folato/antagonistas & inibidores , Receptor 2 de Folato/imunologia , Células HL-60 , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Células THP-1 , Ensaios Antitumorais Modelo de Xenoenxerto
17.
BMJ Case Rep ; 14(6)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127502

RESUMO

Struma ovarii (SO) is a rare ovarian teratoma containing abundant mature thyroid tissue. Malignant transformation is even less common and distant metastasis is documented in about 5%-10%. The time from diagnosis of primary SO to metastatic disease varies. As malignant SO is rare, there are no uniform diagnostic criteria or treatment guidelines. Management is usually extrapolated from that of thyroid malignancy. We report a patient who relapsed 12 years from the initial diagnosis and metastasised to the lungs 5 years after the first recurrence. Our patient was treated with total thyroidectomy followed by radioactive iodine, and retreated on progression in the lungs. The tumour harboured high microsatellite instability and treatment with programmed cell death protein 1 inhibitor was initiated. This case shows the long latency of SO with the rare phenomenon of metastasis. It also highlights the importance of molecular testing for rare cancers such as this.


Assuntos
Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Instabilidade de Microssatélites , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Estruma Ovariano/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/terapia
19.
JCO Glob Oncol ; 7: 1032-1066, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34185571

RESUMO

PURPOSE: To provide expert guidance to clinicians and policymakers in three resource-constrained settings on diagnosis and staging of adult women with ovarian masses and treatment of patients with epithelial ovarian (including fallopian tube and primary peritoneal) cancer. METHODS: A multidisciplinary, multinational ASCO Expert Panel reviewed existing guidelines, conducted a modified ADAPTE process, and conducted a formal consensus process with additional experts. RESULTS: Existing sets of guidelines from eight guideline developers were found and reviewed for resource-constrained settings; adapted recommendations from nine guidelines form the evidence base, informing two rounds of formal consensus; and all recommendations received ≥ 75% agreement. RECOMMENDATIONS: Evaluation of adult symptomatic women in all settings includes symptom assessment, family history, and ultrasound and cancer antigen 125 serum tumor marker levels where feasible. In limited and enhanced settings, additional imaging may be requested. Diagnosis, staging, and/or treatment involves surgery. Presurgical workup of every suspected ovarian cancer requires a metastatic workup. Only trained clinicians with logistical support should perform surgical staging; treatment requires histologic confirmation; surgical goal is staging disease and performing complete cytoreduction to no gross residual disease. In first-line therapy, platinum-based chemotherapy is recommended; in advanced stages, patients may receive neoadjuvant chemotherapy. After neoadjuvant chemotherapy, all patients should be evaluated for interval debulking surgery. Targeted therapy is not recommended in basic or limited settings. Specialized interventions are resource-dependent, for example, laparoscopy, fertility-sparing surgery, genetic testing, and targeted therapy. Multidisciplinary cancer care and palliative care should be offered.Additional information can be found at www.asco.org/resource-stratified-guidelines. It is ASCO's view that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.


Assuntos
Neoplasias Ovarianas , Adulto , Antígeno Ca-125 , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Terapia Neoadjuvante , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia
20.
J Womens Health (Larchmt) ; 30(6): 769-781, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34128688

RESUMO

Evidence shows that treatment by gynecologic oncologists (GOs) increases overall survival among women with ovarian cancer. However, specific strategies for institutions and community-based public health programs to promote treatment by GOs are lacking. To address this, we conducted a literature review to identify evidence-based and promising system- and environmental-change strategies for increasing treatment by GOs, in effort to ensure that all women with ovarian cancer receive the standard of care. We searched for English-language literature published from 2008 to 2018. We used PubMed, PubMed Central, OVID, and EBSCO for peer-reviewed literature and Google and Google Scholar for gray literature related to increasing receipt of care by GOs among ovarian cancer patients. Numerous suggested and proposed strategies that have potential to increase treatment by GOs were discussed in several articles. We grouped these approaches into five strategic categories: increasing knowledge/awareness of role and importance of GOs, improving models of care, improving payment structures, improving/increasing insurance coverage for GO care, and expanding or enhancing the GO workforce. We identified several strategies with the potential for increasing GO care among ovarian cancer patients, although currently there is little evidence regarding their effectiveness across US populations. Public health programs and entities that measure delivery of quality health care may pilot the strategies in their populations. Certain strategies may work better in certain environments and a combination of strategies may be necessary for any one entity to increase GO ovarian cancer care. Findings, lessons learned, and recommendations from implementation projects would inform community and public health practice.


Assuntos
Oncologistas , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Feminino , Humanos , Neoplasias Ovarianas/terapia , Qualidade da Assistência à Saúde
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