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1.
Anticancer Res ; 42(4): 2017-2022, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347023

RESUMO

BACKGROUND/AIM: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. PATIENTS AND METHODS: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI). RESULTS: Of the 28 patients with PFI <6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI >12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI <6 months, 6-12 months, and >12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. CONCLUSION: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Estudos Retrospectivos
2.
BMC Cancer ; 22(1): 508, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524184

RESUMO

BACKGROUND: A high percentage of epithelial ovarian cancers (EOC) express the estrogen receptor (ER), which is an ideal target for endocrine therapy. Letrozole is a proven, potent aromatase inhibitor, extensively tested and used in the treatment of ER positive breast cancer. In addition, it seems a potent drug for patients with heavily pre-treated OC as demonstrated in several distinctive settings. However, it has never been evaluated prospectively in a maintenance setting for ovarian cancer after standard of care. The here proposed trial aims to define a population of EOC patients, who would benefit from the effectiveness of the generic agent letrozole, with little expected toxicity and thus beneficial impact on overall quality of life (QoL). METHODS: In this international multicenter randomized, placebo-controlled phase III trial at clinical centers in Switzerland, Germany and Austria, we plan to include 540 patients with primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low- or high-grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer. Patients are randomized in a 1:1 ratio into two groups: receiving blinded study treatment (letrozole or placebo tablets). When assuming a HR of 0.7, a median PFS of 18 months in the control arm and a median PFS of 25.7 months in the treatment arm, a two-sided alpha level of 5%, 3.5 years recruitment and 1.5 years observation time, we expect 330 events to have occurred within these 5 years in the total cohort yielding a power of 90%. Follow-up data for the whole cohort will be collected for up to 10 years and for the low-grade cancer for up to 12 years. DISCUSSION: The here proposed randomized phase III trial aims to identify patients with EOC in the maintenance setting, who benefit from the effectiveness of the letrozole, by proving its efficacy whilst maintaining a high standard of QoL due to the limited toxicity expected in comparison to the current alternative drugs on the market for this treatment phase. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov under the identifier NCT04111978 . Registered 02 October 2019.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Humanos , Letrozol/uso terapêutico , Estudos Multicêntricos como Assunto , Neoplasias Ovarianas/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Front Endocrinol (Lausanne) ; 13: 871210, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528006

RESUMO

Background: Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy, however, cases with metastatic disease have been described. No data in the literature are available to guide diagnosis and therapy. Methods: We performed a pooled analysis and a systematic review of histopathological-confirmed strumal carcinoid cases published in the literature using the following keywords: "strumal carcinoid of the ovary", "strumal carcinoid case report". A case of strumal carcinoid tumor diagnosed and followed-up at the Medical Oncology Unit of Spedali Civili (Brescia, Italy) was also described and included. Results: Sixty-six eligible publications were identified, providing data from one hundred and seventeen patients, plus a case diagnosed at our institution. At presentation, among the eighty-eight patients with symptomatic disease, 37% of patients suffered from abdominal distention and 49% from pain due to a growing abdominal tumor mass, 37% from constipation (peptide YY was analyzed in only nine of them, resulting above the physiologic range). Surgery was the primary therapy in 99% of the patients. Three patients had metastatic disease at diagnosis and five patients underwent recurrence after radical surgery. Histology at disease recurrence concerned the thyroid component in two patients, the carcinoid component in two patients, both histologies in one patient. Median disease-free survival and overall survival in this series were not attained. Conclusion: Strumal carcinoid of the ovary generally presents a benign behavior and surgery is curative in most cases. However, a small group of patients with this disease can undergo disease recurrence due to both the thyroid and the neuroendocrine (carcinoid) components. A follow-up in radically operated patients is therefore needed, particularly in those with a voluminous disease at diagnosis.


Assuntos
Tumor Carcinoide , Neoplasias Ovarianas , Estruma Ovariano , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Estruma Ovariano/diagnóstico , Estruma Ovariano/patologia , Estruma Ovariano/cirurgia
4.
J Ovarian Res ; 15(1): 52, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35501825

RESUMO

Previous studies have revealed that miRNAs participate in the pathogenesis of ovarian cancer; however, whether miR-600 is also involved remains unclear. In this study, we aimed to investigated the role of miR-600 in ovarian cancer progression. Here, miR-600 expression was significantly upregulated in ovarian cancer tissues and stem cells. Functional studies showed that miR-600 promoted ovarian cancer cell stemness, proliferation and metastasis. Mechanistic studies revealed that Kruppel like factor 9 (KLF9) was indicated as the target of miR-600. The luciferase reporter assay suggested that miR-600 directly bound to the 3'-untranslated region of KLF9. Additionally, miR-600 expression was negatively associated with KLF9 expression in human ovarian cancer tissues. Si-KLF9 partially abolished the discrepancy of self-renewal, growth and metastasis capacity between miR-600 knockdown ovarian cancer cells and control cells. In conclusion, our results suggest that miR-600 promotes ovarian cancer cell stemness, proliferation and metastasis via directly downregulating KLF9, and impairing miR-600 levels may be a new treatment strategy for ovarian cancer in the future.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Regiões 3' não Traduzidas , Carcinoma Epitelial do Ovário , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia
9.
Methods Mol Biol ; 2429: 445-454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507180

RESUMO

Identification of serous tubal intraepithelial carcinomas (STIC) in the fallopian tubes of women who are carriers of germ line pathogenic variants in tubo-ovarian cancer predisposition genes (i.e., BRCA1 and BRCA2) has led to the hypothesis that many high-grade serous carcinomas (HGSC) arise from the fimbria of the fallopian tube. However, the primitive (stem and progenitor) tubal epithelial cells that give rise to STIC and HGSC have not been defined. Further, as putative HGSC precursors are discovered at salpingectomy, the natural history of such lesions is truncated at diagnosis. Thus, living cultures of human fallopian tubes suitable for experimental studies are needed to define and characterize the cellular origin of HGSCs and thereby advance the discovery of improved methods to assess risk, develop effective early detection tests and identify novel prevention approaches. Accordingly, patient-derived tissue-organoids and isolated epithelial stem cell derived-organoids generated from average and high-risk patients are vital resources to understand the developmental biology of aging fallopian tubes and pathogenesis of HGSCs. With a vision to boost HGSC prevention research, we have established state-of-the-art protocols for the collection, processing, storage, distribution, and management of fallopian tube tissues. Here we describe the protocol for preparing these organoids, with emphasis on the key steps that require meticulous attention to achieve success.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Células Epiteliais/metabolismo , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/metabolismo , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/metabolismo , Feminino , Humanos , Organoides/metabolismo , Neoplasias Ovarianas/metabolismo
10.
Cell Mol Life Sci ; 79(5): 279, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507203

RESUMO

Translational control is a fundamental mechanism regulating animal germ cell development. Gonadal somatic cells provide support and microenvironment for germ cell development to ensure fertility, yet the roles of translational control in gonadal somatic compartment remain largely undefined. We found that mouse homolog of conserved fly germline stem cell factor Pumilio, PUM1, is absent in oocytes of all growing follicles after the primordial follicle stage, instead, it is highly expressed in somatic compartments of ovaries. Global loss of Pum1, not oocyte-specific loss of Pum1, led to a significant reduction in follicular number and size as well as fertility. Whole-genome identification of PUM1 targets in ovarian somatic cells revealed an enrichment of cell proliferation pathway, including 48 key regulators of cell phase transition. Consistently granulosa cells proliferation is reduced and the protein expression of the PUM-bound Cell Cycle Regulators (PCCR) were altered accordingly in mutant ovaries, and specifically in granulosa cells. Increase in negative regulator expression and decrease in positive regulators in the mutant ovaries support a coordinated translational control of somatic cell cycle program via PUM proteins. Furthermore, postnatal knockdown, but not postnatal oocyte-specific loss, of Pum1 in Pum2 knockout mice reduced follicular growth and led to similar expression alteration of PCCR genes, supporting a critical role of PUM-mediated translational control in ovarian somatic cells for mammalian female fertility. Finally, expression of human PUM protein and its regulated cell cycle targets exhibited significant correlation with ovarian cancer and prognosis for cancer survival. Hence, PUMILIO-mediated cell cycle regulation represents an important mechanism in mammalian female reproduction and human cancer biology.


Assuntos
Neoplasias Ovarianas , Proteínas de Ligação a RNA , Animais , Ciclo Celular/genética , Feminino , Humanos , Mamíferos/metabolismo , Camundongos , Camundongos Knockout , Oócitos/metabolismo , Neoplasias Ovarianas/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Microambiente Tumoral
11.
J Adv Res ; 37: 255-266, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35499043

RESUMO

Introduction: The striking imbalance between the ever-increasing amount of nanomedicines and low clinical translation of products has become the focus of intense debate. For clinical translation, the critical issue is to select the appropriate agents and combination regimen for targeted diseases, not to prepare increasingly complex nanoplatforms. Objectives: A safe and efficient platform, α-tocopheryl succinate (α-TOS) married 2D molybdenum disulfide, was devised by a facile method and applied for cooperative imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Methods: A novel platform of PEGylated α-TOS and folic acid (FA) conjugated 2D MoS2 nanoflakes was fabricated  for the cooperative multimode computed tomography (CT)/photoacoustic (PA)/thermal imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Results: The photothermal efficiency (65.3%) of the platform under safe near-infrared irradiation is much higher than that of other photothermal materials reported elsewhere. Moreover, the covalently linked α-TOS renders platform with selective chemotherapy for cancer cells. Remarkably, with these excellent properties, the platform can be used to completely eliminate the solid tumor by safe photothermal therapy, and then kill the residual cancer cells by selective chemotherapy to prevent tumor recurrence. More significantly, barely side effects occur in the whole treatment process. The excellent efficacy and safety benefits in vivo lead to the prominent survival rate of 100% over 91 days. Conclusion: The safe and efficient platform might be a candidate of clinical nanomedicines for multimode theranostics. This study demonstrates an innovative thought in precise nanomedicine regarding the design of next generation of cancer theranostic protocol for potential clinical practice.


Assuntos
Molibdênio , Neoplasias Ovarianas , Dissulfetos , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Fototerapia , Nanomedicina Teranóstica/métodos
12.
Acta Med Okayama ; 76(2): 129-135, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503440

RESUMO

Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann-Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 µg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC.


Assuntos
Neoplasias Ovarianas , Tromboembolia Venosa , Biomarcadores , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Neoplasias Ovarianas/complicações , Prognóstico , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
13.
Radiologia (Engl Ed) ; 64(2): 110-118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35504676

RESUMO

OBJECTIVES: To determine whether there is a significant relationship between the shape of the time-intensity curve on dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of ovarian tumours classified as indeterminate at ultrasonography and the type of lesion (benign, borderline, or malignant) to enable an accurate presurgical diagnosis. MATERIAL AND METHODS: We used dynamic contrast-enhanced MRI to study 68 ovarian tumours that were classified as indeterminate at ultrasonography. We included only cases for which a definitive diagnosis (histologic diagnosis or ≥1 year stability on imaging tests) was available. Each case was classified as benign, borderline, or malignant. To analyse the MRI studies, we marked regions of interest in the lesion and in the myometrium (as a reference). We obtained a curve defined by the relation between the intensity of enhancement and time and classified each tumour according to four predefined curve types. We also analysed semiquantitative parameters. Finally, we compared the results for each of the three groups of tumours. RESULTS: We found significant associations (P<.001) between the curves without early enhancement and benign and borderline lesions as well as between the curves with early enhancement and malignant lesions. Malignant lesions were significantly associated with the semiquantitative enhancement parameters: maximum (P=.002), maximum relative (P=.006), and relative (P=.018). CONCLUSIONS: In ovarian tumours classified as indeterminate at ultrasonography, dynamic contrast-enhanced MRI can be useful for classification as benign, borderline, or malignant because the malignant lesions are significantly associated with early enhancement curves.


Assuntos
Meios de Contraste , Neoplasias Ovarianas , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Ultrassonografia
14.
Radiologia (Engl Ed) ; 64(2): 164-168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35504682

RESUMO

The main objective in the imaging differential diagnosis of an ovarian mass is to establish whether it is cystic or solid; solid lesions are less common. Ovarian fibromatosis is a benign disease of the ovary that is rarely included in the differential diagnosis of solid ovarian lesions. Characteristic features of masses that have a fibrous component are low signal in T1-weighted MRI sequences and especially in T2-weighted MRI sequences. The presence of peripheral fibrotic tissue around the residual ovarian tissue is specific to ovarian fibromatosis; on MRI, this results in marked hypointensity on T2-weighted images that has been dubbed the "black garland sign". This sign, together with slight peripheral enhancement after the administration of contrast material and the preservation of the ovarian architecture, facilitates the diagnosis, making it possible to avoid unnecessary surgical interventions.


Assuntos
Fibroma , Cistos Ovarianos , Neoplasias Ovarianas , Meios de Contraste , Feminino , Fibroma/diagnóstico por imagem , Humanos , Neoplasias Ovarianas/diagnóstico por imagem
15.
N C Med J ; 83(3): 221-228, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35504701

RESUMO

BACKGROUND The average lifetime risk of breast cancer for an American woman is 12.5%, but individual risks vary significantly. Risk modeling is a standard of care for breast cancer screening and prevention with recommended tools to stratify individual risks based on age, family history, breast density, and a host of other known risk factors. Because of a lack of resources rurally, we have not consistently met this standard of care within all of North Carolina.METHODS We implemented a quality improvement project to assess the risk for breast cancer by gathering data on community risks. We implemented an evidence-based tool (Tyrer-Cuzick) for quantifying risk within a mostly rural population of Eastern North Carolina and developed customized services for women meeting elevated-risk definition. These services included additional imaging for elevated-risk women and a risk-reduction program. We also assessed genetic risks for hereditary breast and ovarian cancer in our at-risk population using National Comprehensive Cancer Network (NCCN) guidelines based on family history and added local genetics extenders to help test more women. We analyzed data regularly using Plan-Do-Study-Act methods to improve outcomes over 1 year.RESULTS We screened a population of 4500 women at a community hospital over a 1-year period for their individual lifetime cancer risk and genetic risk. Breast cancer risk was quantitated at the time of mammography, and women were stratified into 3 groups for risk management. Within our screening population, 6.3% of women were at high risk (defined by a lifetime breast cancer risk greater than or equal to 20%) and another 8.1% were above-average risk (defined by a lifetime breast cancer risk of 15%-20%). These women (14.4%) could potentially benefit from additional risk-management strategies. Additionally, 20% of all unaffected women within a typical screening population of Eastern North Carolina met NCCN guidelines for hereditary breast cancer and ovarian cancer testing independent of their cancer risk score. Using a model of targeted intervention within a population with elevated risks can be helpful in improving outcomes.LIMITATIONS This population within Eastern North Carolina is mostly rural and represents a potentially biased population, as it involves older women undergoing annual mammography. It may not be broadly applicable to the entire population based on age, geography, and other risks.CONCLUSIONS This model for improving cancer risk assessment and testing at a small community hospital in Eastern North Carolina was successful and addressed a community need. We discovered a high rate of increased-risk women who can benefit from individualized risk management, and a higher percentage of women who potentially benefit from genetic testing. These higher cumulative risks may in part explain some of the disparities seen for breast-cancer-specific outcomes in some parts of the state.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Humanos , Masculino , Mamografia , North Carolina/epidemiologia , Fatores de Risco
16.
Methods Mol Biol ; 2451: 49-58, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35505009

RESUMO

Numerous cancer models have been developed to investigate the effects of mechanical stress on the biology of cells. Here we describe a protocol to fabricate a perfusion model to culture 3-dimensional (3D) ovarian cancer nodules under constant flow. The modular design of this model allows for a wide range of treatment regimens and combinations, including PDT and chemotherapy. Finally, methods for a number of readouts are detailed, allowing researchers to investigate a variety of biological and cytotoxic parameters related to mechanical stress and therapeutic modalities.


Assuntos
Antineoplásicos , Neoplasias Ovarianas , Fotoquimioterapia , Antineoplásicos/farmacologia , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Perfusão/métodos
17.
Methods Mol Biol ; 2451: 175-183, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35505018

RESUMO

Advanced ovarian cancer is the most serious among gynecological malignancies and is associated with 35% five-year overall survival. Surgery is the first therapeutic indication, and the absence of remaining macroscopic lesions is the most important prognostic factor. However, tumor dissemination over the whole abdominal cavity largely contributes to the difficulty of complete surgical resection. Consequently, any therapeutic approach that may complete surgical resection should improve patient survival. Considering that some sites are not suitable for surgery because of their close location to vital organs, intraoperative photodynamic therapy (ioPDT) appears to be a complementary therapeutic approach to surgery to obtain the lowest residual disease.Relevant in vivo cancer models that closely resemble human ovarian cancer are essential for preclinical research of alternative antitumor therapeutic strategies. Thus, we propose a comprehensive protocol to set up an orthotopic ovarian xenograft in mice leading to peritoneal carcinomatosis that could be harnessed for antitumor therapeutic application and evaluation.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Fotoquimioterapia , Animais , Carcinoma Epitelial do Ovário , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Triazenos
18.
Methods Mol Biol ; 2451: 185-201, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35505019

RESUMO

Tumor-targeted and -activatable photosensitizer delivery platforms are creating new opportunities to develop photodynamic therapy (PDT) of metastatic disease. This is possible by confining the activity of the photosensitizing chemical (i.e., the PDT agent) to the tumor in combination with diffuse near-infrared light irradiation for wide-field treatment. This chapter outlines protocols and research tools for preclinical development of light-activated therapies of cancer metastases using advanced-stage ovarian cancer as a model system. We also describe an in vivo molecular imaging approach that uniquely enables tracking intraperitoneal micrometastatic burden and responses to treatment using fluorescence microendoscopy.


Assuntos
Neoplasias Ovarianas , Fotoquimioterapia , Carcinoma Epitelial do Ovário , Feminino , Humanos , Raios Infravermelhos , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
19.
Korean J Radiol ; 23(5): 539-547, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35506527

RESUMO

OBJECTIVE: To investigate the association between functional tumor burden of peritoneal carcinomatosis (PC) derived from diffusion-weighted imaging (DWI) and overall survival in patients with advanced ovarian carcinoma (OC). MATERIALS AND METHODS: This prospective study was approved by the local research ethics committee, and informed consent was obtained. Fifty patients (mean age ± standard deviation, 57 ± 12 years) with stage III-IV OC scheduled for primary or interval debulking surgery (IDS) were recruited between June 2016 and December 2021. DWI (b values: 0, 400, and 800 s/mm²) was acquired with a 16-channel phased-array torso coil. The functional PC burden on DWI was derived based on K-means clustering to discard fat, air, and normal tissue. A score similar to the surgical peritoneal cancer index was assigned to each abdominopelvic region, with additional scores assigned to the involvement of critical sites, denoted as the functional peritoneal cancer index (fPCI). The apparent diffusion coefficient (ADC) of the largest lesion was calculated. Patients were dichotomized by immediate surgical outcome into high- and low-risk groups (with and without residual disease, respectively) with subsequent survival analysis using the Kaplan-Meier curve and log-rank test. Multivariable Cox proportional hazards regression was used to evaluate the association between DWI-derived results and overall survival. RESULTS: Fifteen (30.0%) patients underwent primary debulking surgery, and 35 (70.0%) patients received neoadjuvant chemotherapy followed by IDS. Complete tumor debulking was achieved in 32 patients. Patients with residual disease after debulking surgery had reduced overall survival (p = 0.043). The fPCI/ADC was negatively associated with overall survival when accounted for clinicopathological information with a hazard ratio of 1.254 for high fPCI/ADC (95% confidence interval, 1.007-1.560; p = 0.043). CONCLUSION: A high DWI-derived functional tumor burden was associated with decreased overall survival in patients with advanced OC.


Assuntos
Neoplasias Ovarianas , Neoplasias Peritoneais , Idoso , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/terapia , Estudos Prospectivos , Carga Tumoral
20.
Sci Rep ; 12(1): 7494, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523936

RESUMO

Ovarian cancer is one of the lethal gynecologic cancers. Chemoresistance is an essential reason for treatment failure and high mortality. Emerging evidence connects epithelial-mesenchymal transition (EMT) like changes and acquisition of chemoresistance in cancers. Including EMT, DNA methylation influences cellular processes. Here, EMT-like changes were investigated in cisplatin-resistant A2780 ovarian cancer cells (A2780cis), wherein role of DNA methylation in some EMT genes regulations was studied. Cell viability assay was carried out to test the sensitivity of A2780, and A2780cis human cancer cell lines to cisplatin. Differential mRNA expression of EMT markers using qPCR was conducted to investigate EMT like changes. CpG methylation role in gene expression regulation was investigated by 5-azacytidine (5-aza) treatment. DNA methylation changes in EMT genes were identified using Methylscreen assay between A2780 and A2780cis cells. In order to evaluate if DNA methylation changes are causally underlying EMT, treatment with 5-aza followed by Cisplatin was done on A2780cis cells. Accordingly, morphological changes were studied under the microscope, whereas EMT marker's gene expression changes were investigated using qPCR. In this respect, A2780cis cell line has maintained its cisplatin tolerance ability and exhibits phenotypic changes congruent with EMT. Methylscreen assay and qPCR study have revealed DNA hypermethylation in promoters of epithelial adhesion molecules CDH1 and EPCAM in A2780cis compared to the cisplatin-sensitive parental cells. These changes were concomitant with gene expression down-regulation. DNA hypomethylation associated with transcription up-regulation of the mesenchymal marker TWIST2 was observed in the resistant cells. Azacytidine treatment confirmed DNA methylation role in regulating gene expression of CDH1, EPCAM and TWIST2 genes. A2780cis cell line undergoes EMT like changes, and EMT genes are regulated by DNA methylation. To that end, a better understanding of the molecular alterations that correlate with chemoresistance may lead to therapeutic benefits such as chemosensitivity restoration.


Assuntos
Ilhas de CpG , Metilação de DNA , Transição Epitelial-Mesenquimal , Neoplasias Ovarianas , Azacitidina/metabolismo , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo
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