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1.
Front Immunol ; 13: 1007326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189254

RESUMO

Background: Preclinical trials of immunotherapy in ovarian cancer (OC) have shown promising results. This makes it meaningful to prospectively examine the biological mechanisms explaining the differences in response performances to immunotherapy among OC patients. Methods: Open-accessed data was obtained from the Cancer Genome Atlas and Gene Expression Omnibus database. All the analysis was conducted using the R software. Results: We firstly performed the TIDE analysis to evaluate the immunotherapy response rate of OC patients. The machine learning algorithm LASSO logistic regression and SVM-RFE were used to identify the characteristic genes. The genes DPT, RUNX1T1, PTPRN, LSAMP, FDCSP and COL6A6 were selected for molecular typing. Our result showed that the patients in Cluster1 might have a better prognosis and might be more sensitive to immunotherapy, including PD-1 and CTLA4 therapy options. Pathway enrichment analysis showed that in Cluster2, the pathway of EMT, TNFα/NF-kB signaling, IL2/STAT5 signaling, inflammatory response, KRAS signaling, apical junction, complement, interferon-gamma response and allograft rejection were significantly activated. Also, genomic instability analysis was performed to identify the underlying genomic difference between the different Cluster patients. Single-cell analysis showed that the DPT, COL6A6, LSAMP and RUNX1T1 were mainly expressed in the fibroblasts. We then quantified the CAFs infiltration in the OC samples. The result showed that patients with low CAFs infiltration might have a lower TIDE score and a higher proportion of immunotherapy responders. Also, we found all the characteristic genes DPT, RUNX1T1, PTPRN, LSAMP, FDCSP and COL6A6 were upregulated in the patients with high CAFs infiltration. Immune infiltration analysis showed that the patients in Cluster2 might have a higher infiltration of naive B cells, activated NK cells and resting Dendritic cells. Conclusions: In summary, our study provides new insights into ovarian cancer immunotherapy. Meanwhile, specific targets DPT, RUNX1T1, PTPRN, LSAMP, FDCSP, COL6A6 and CAFs were identified for OC immunotherapy.


Assuntos
Neoplasias Ovarianas , Fator de Transcrição STAT5 , Antígeno CTLA-4 , Carcinoma Epitelial do Ovário , Feminino , Humanos , Imunoterapia , Interferon gama/uso terapêutico , Interleucina-2/uso terapêutico , NF-kappa B , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Receptor de Morte Celular Programada 1 , Proteínas Proto-Oncogênicas p21(ras) , Fator de Necrose Tumoral alfa/uso terapêutico
2.
Anticancer Res ; 42(10): 4945-4954, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36191979

RESUMO

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.


Assuntos
Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Proteína BRCA1/genética , Carcinoma Epitelial do Ovário/genética , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Feminino , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Mutação , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Prognóstico
3.
BMC Surg ; 22(1): 338, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096791

RESUMO

OBJECTIVES: We report the 20-year experience of the largest Australian unit performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer and reflect on learning opportunities. METHODS: A retrospective review of all cases of CRS for ovarian cancer at St George Peritonectomy Unit from Jan 1998 to Jan 2018 was performed. Prospectively collected data include age, stage, histology, disease extent (PCI), completeness of cytoreduction (CC score), HIPEC regime, 30-day surgical morbidity, disease recurrence, and death. Survival was computed using Kaplan-Meier method and analysed using log-rank tests and Cox-proportional hazards models. RESULTS: Forty-one women with advanced ovarian cancer (11 primary stage III/IV, 30 recurrent) underwent CRS, 29 (71%) with HIPEC. Most (68%) had high-volume disease (PCI > 15). In 98%, CC0/CC1 (residual < 2.5 mm) was achieved. Fourteen (34%) had grade 3/4 complications, 1 patient (2%) died within 30 days and 2 patients (5%) died within 90 days. Progression-free and median overall survival was 30.0 and 67.0 months for primary cancer, and 6.7 and 18.1 months for recurrent cancer. Survival was associated with platinum-sensitivity, PCI ≤ 15, and CC score 0, but not HIPEC. CONCLUSION: This study reports outcomes for patients with advanced ovarian cancer patients treated in an Australian centre offering CRS and HIPEC. Whilst survival and morbidity outcomes were good for primary disease, they were poorer than predicted from the literature for cases of recurrent disease. The incorporation of evidence-based predictors of survival and multidisciplinary input are essential to achieve the best survival outcomes.


Assuntos
Hipertermia Induzida , Neoplasias Ovarianas , Neoplasias Peritoneais , Austrália/epidemiologia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/tratamento farmacológico , Taxa de Sobrevida
4.
Taiwan J Obstet Gynecol ; 61(5): 883-888, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36088062

RESUMO

OBJECTIVE: To illustrate the clinical course of a rare case of recurrent adult granulosa cell tumor (AGCT) and discuss the features and management for recurrences. CASE REPORT: A 56-year-old female was first diagnosed with AGCT in 2008 and had uneventful, regular follow-ups until 2013. Recurrence was suspected and proven by computed tomography-guided biopsy. After undergoing complete cytoreductive surgery (CRS) followed by adjuvant megestrol acetate then leuprolide acetate, another recurrence sprouted at the presacral area in 2017. On both occasions, CRS with no visible residual tumor were attained. The patient has remained in complete remission to date with progestin therapy. CONCLUSION: There are currently no standardized tumor markers, imaging exams, or therapies for managing AGCT recurrences. Whole exome sequencing analysis of our patient suggested possible association with triosephosphate isomerase 1 mutation. Regular follow-ups with at least two types of imaging exams and indefinite hormone therapy are crucial for this patient's remission.


Assuntos
Tumor de Células da Granulosa , Neoplasias Ovarianas , Adulto , Procedimentos Cirúrgicos de Citorredução , Feminino , Tumor de Células da Granulosa/genética , Tumor de Células da Granulosa/terapia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/terapia
5.
J Natl Compr Canc Netw ; 20(9): 972-980, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075393

RESUMO

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estados Unidos
6.
Technol Cancer Res Treat ; 21: 15330338221114497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062718

RESUMO

Cancer is a public health problem that threatens human health. Due to the lack of specific and rapid diagnosis and treatment methods, the 5-year survival rate of patients has not been effectively improved in the past 10 years. Abnormal gene expression is closely related to the occurrence and development of cancer. Cancer diagnosis and treatment methods based on genetic testing have received extensive attention in recent years. It is essential to explore specific and rapid cancer genetic testing methods. Taking ovarian cancer as an example, we reviewed the progress of specific and rapid nucleic acid detection methods related to cancer risk assessment, low-abundance mutation detection, and methylation detection, to provide new strategies and ideas for related research.


Assuntos
Biomarcadores Tumorais , Neoplasias Ovarianas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , Detecção Precoce de Câncer , Feminino , Testes Genéticos/métodos , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
7.
Front Immunol ; 13: 940801, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119108

RESUMO

Limited immunotherapeutic effect in high-grade serous ovarian carcinoma (HGSOC) propels exploration of the mechanics behind this resistance, which may be partly elucidated by investigating characters of cancer-associated fibroblasts (CAFs), a significant population in HGSOC involved in shaping tumor immune microenvironment. Herein, leveraging gene expression data of HGSOC samples from The Cancer Genome Atlas and Gene Expression Omnibus datasets, we suggested that CAFs detrimentally affected the outcomes of HGSOC patients. Subsequently, we performed weighted gene co-expression network analysis (WGCNA) to identify a CAFs-related module and screened out seven hub genes from this module, all of which were positively correlated with the infiltration of immunosuppressive macrophages. As one of the hub genes, the expression of fibrillin 1 (FBN1) and its relevance to CD206 were further verified by immunohistochemistry staining in HGSOC samples. Meanwhile, we extracted genes that correlated well with CAF signatures to construct a CAFscore. The capacity of the CAFscore as an independent prognostic factor was validated by Cox regression analyses, and its relevance to components as well as signals in the tumor immune microenvironment was also investigated. Under the evaluation by the CAFscore, HGSOC patients with relatively high CAFscore had worse outcomes, activated mesenchymal signaling pathways, and immune checkpoint blockade (ICB) resistance signatures, which was consistent with the fact that non-responders in anti-PD-1 treatment cohorts tended to have higher CAFscore. Besides, the possibility of CAFscore to guide the selection of sensitive chemotherapeutic agents was explored. In conclusion, individualized assessment of the CAFscore could uncover the extent of stroma activation and immunosuppression and inform therapeutic strategies to improve the benefit of therapies.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Ovarianas , Fibroblastos Associados a Câncer/metabolismo , Feminino , Fibrilina-1/genética , Fibrilina-1/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Prognóstico , Microambiente Tumoral
8.
Med Oncol ; 39(12): 232, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175774

RESUMO

Ovarian cancer (OC) is one of the most common cancers in women, with a high mortality rate and very few available and effective treatments. Evidence shows that immunotherapy in OC has not been very successful because immune checkpoint blockers have not achieved satisfactory clinical outcomes. On the other hand, as one of the effective treatment approaches, chimeric antigen receptor T-cell (CAR T-cell) therapy has gained a moral position, especially in blood malignancies. Although in solid tumors, CAR T-cell therapy faces various complications and challenges. One of these challenges is selecting the appropriate tumor antigen targeted by CAR T cells, making the selection difficult due to the expression of antigens by tumor cells and normal cells. In addition, the rate of tumor antigen expression and CAR T-cell access to the desired antigen and proper stimulation of CAR T cells can be other important points in antigen selection. This review summarized common tumor antigens and the challenges of selecting them in CAR T cells therapy of OC.


Assuntos
Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Antígenos de Neoplasias , Carcinoma Epitelial do Ovário , Terapia Baseada em Transplante de Células e Tecidos , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia Adotiva , Neoplasias Ovarianas/terapia
9.
Int J Gynecol Cancer ; 32(9): 1153-1163, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36166208

RESUMO

OBJECTIVE: Evaluate the association between time to diagnosis and treatment of advanced ovarian cancer with overall and ovarian cancer specific mortality using a retrospective cross sectional study of a population based cancer registry database. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was searched from 1992 to 2015 for women aged ≥66 years with epithelial ovarian cancer and abdominal/pelvic pain, bloating, difficulty eating, or urinary symptoms within 1 year of cancer diagnosis. Time from presentation to diagnosis and treatment were evaluated as outcomes and covariables. Cox regression models and adjusted Kaplan-Meier curves evaluated 5 year overall and cancer-specific survival. RESULTS: Among 13 872 women, better survival was associated with longer time from presentation to diagnosis (overall survival hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.94 to 0.95; cancer specific survival HR 0.95, 95% CI 0.94 to 0.96) and diagnosis to treatment (overall survival HR 0.94, 95% CI 0.92 to 0.96; cancer specific survival HR 0.93, 95% CI 0.91 to 0.96). There was longer time from presentation to diagnosis in Hispanic women (relative risk (RR) 1.21, 95% CI 1.12 to 1.32) and from diagnosis to treatment in non-Hispanic black women (RR 1.36, 95% CI 1.21 to 1.54), with lower likelihood of survival at 5 years after adjustment for time to diagnosis and treatment among non-Hispanic black women (HR 1.15, 95% CI 1.05 to 1.26) compared with non-Hispanic white women. Gynecologic oncology visit was associated with improved overall (p<0.001) and cancer specific (p<0.001) survival despite a longer time from presentation to treatment (p<0.001). CONCLUSION: Longer time to diagnosis and treatment were associated with improved survival, suggesting that tumor specific features are more important prognostic factors than the time interval of workup and treatment. Significant sociodemographic disparities indicate social determinants of health influencing workup and care. Gynecologic oncologist visits were associated with improved survival, highlighting the importance of appropriate referral for suspected ovarian cancer.


Assuntos
Neoplasias Ovarianas , Tempo para o Tratamento , Idoso , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Estudos Transversais , Feminino , Humanos , Medicare , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Programa de SEER , Estados Unidos/epidemiologia
10.
Int J Mol Sci ; 23(18)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36142437

RESUMO

Current imaging approaches used to monitor tumor progression can lack the ability to distinguish true progression from pseudoprogression. Simultaneous metabolic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) offers new opportunities to overcome this challenge by refining tumor identification and monitoring therapeutic responses to cancer immunotherapy. In the current work, spatial and quantitative analysis of tumor burden were performed using simultaneous [18F]FDG-PET/MRI to monitor therapeutic responses to a novel silicified cancer cell immunotherapy in a mouse model of disseminated serous epithelial ovarian cancer. Tumor progression was validated by bioluminescence imaging of luciferase expressing tumor cells, flow cytometric analysis of immune cells in the tumor microenvironment, and histopathology. While PET demonstrated the presence of metabolically active cancer cells through [18F]FDG uptake, MRI confirmed cancer-related accumulation of ascites and tissue anatomy. This approach provides complementary information on disease status without a confounding signal from treatment-induced inflammation. This work provides a possible roadmap to facilitate accurate monitoring of therapeutic responses to cancer immunotherapies.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Ovarianas , Animais , Feminino , Glucose , Humanos , Imunoterapia , Imageamento por Ressonância Magnética/métodos , Camundongos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Microambiente Tumoral
11.
Clin J Oncol Nurs ; 26(5): 533-542, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36108208

RESUMO

BACKGROUND: In the United States, ovarian cancer remains the deadliest gynecologic cancer because most women are diagnosed with advanced disease. Although early-stage ovarian tumors are considered asymptomatic, women experience symptoms throughout disease. OBJECTIVES: This review identifies ovarian cancer symptom clusters and explores the applicability of the National Institutes of Health Symptom Science Model (NIH-SSM) for prompt symptom recognition and clinical intervention. METHODS: A focused CINAHL® and PubMed® database search was conducted for studies published from January 2000 to May 2022 using combinations of key terms. FINDINGS: The NIH-SSM can guide the delivery of precision-focused interventions that address racial disparities and foster equity in symptom- focused care. Enhanced understanding of symptom biology can support clinical oncology nurses in ambulatory and inpatient settings.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário , Feminino , Humanos , Oncologia , National Institutes of Health (U.S.) , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Síndrome , Estados Unidos
12.
Technol Cancer Res Treat ; 21: 15330338221104565, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35929135

RESUMO

Background: Epithelial ovarian cancer (EOC) remains the leading cause of gynecologic cancer death worldwide due to the high recurrence rate. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality for platinum-sensitive recurrent EOC. The latest studies demonstrate homologous recombination-related (HRR) mutation status increases the sensitivity to platinum-based chemotherapy drugs in EOC. However, the molecular analysis of recurrent EOC patient benefits from HIPEC is unknown. Thus, we aimed to evaluate the efficacy and safety of CRS combined with HIPEC for platinum-sensitive in recurrent EOC with HRR mutation. Methods: This is a phase III randomized controlled clinical trial in patients with platinum-sensitive recurrent EOC. Participants were divided into 2 groups based on the HRR mutation status and randomized to receive CRS + HIPEC. The patients then received periodic chemotherapy and follow-up. Results: The primary objective of this study was to evaluate the effect of CRS + HIPEC compared to CRS alone in patients with a platinum-sensitive recurrent EOC stratified for HRD status. We hypothesize that the addition of HIPEC to CRS improves the progression-free survival (PFS) of platinum-sensitive recurrent EOC patients with HRR mutation compared with patients without HRR mutation. Conclusion: Recurrent EOC has a poor prognosis due to implantation and metastasis in the abdominal cavity. Intraperitoneal chemotherapy reduced seeding by removing free tumor cells. HIPEC utilizes physical and biological properties to significantly increase the clearance rate of tumors. Van Driel WJ et al proposed that HIPEC using platinum-based chemotherapy improves the survival of patients with ovarian cancer. HRR mutation, as a common pathogenic mutation in ovarian cancer, has a predictive effect on the platinum sensitivity of ovarian cancer patients. Whether lobaplatin-based HIPEC will play a greater role in ovarian cancer patients with HRR mutations is currently unknown.


Assuntos
Antineoplásicos , Hipertermia Induzida , Neoplasias Ovarianas , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Recombinação Homóloga , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Platina , Taxa de Sobrevida
13.
Front Immunol ; 13: 951143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990626

RESUMO

Chimeric antigen receptor (CAR) T cells have emerged as a powerful immunotherapeutic tool against certain hematological malignancies but a significant proportion of patients either do not respond or they relapse, sometimes as a result of target antigen loss. Moreover, limited clinical benefit has been reported for CAR therapy against epithelial derived solid tumors. A major reason for this is the paucity of solid tumor antigens identified to date that are broadly, homogeneously and stably expressed but not found on healthy tissues. To address this, here we describe the development and evaluation of CAR T cells directed against N-glycoslylated ganglioside monosialic 3 (NGcGM3). NGcGM3 derives from the enzymatic hydroxylation of N-acetylneuraminic acid (NAc) GM3 (NAcGM3) and it is present on the surface of a range of cancers including ovarian, breast, melanoma and lymphoma. However, while NAcGM3 is found on healthy human cells, NGcGM3 is not due to the 7deletion of an exon in the gene encoding for the enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH). Indeed, unlike for most mammals, in humans NGcGM3 is considered a neoantigen as its presence on tumors is the result of metabolic incorporation from dietary sources. Here, we have generated 3 CARs comprising different single chain variable fragments (scFvs) originating from the well-characterized monoclonal antibody (mAb) 14F7. We show reactivity of the CAR T cells against a range of patient tumor fragments and we demonstrate control of NGcGM3+ SKOV3 ovarian tumors in the absence of toxicity despite the expression of CMAH and presence of NGcGM3+ on healthy tissues in NSG mice. Taken together, our data indicate clinical potential for 14F7-based CAR T cells against a range of cancers, both in terms of efficacy and of patient safety.


Assuntos
Gangliosídeo G(M3) , Neoplasias Ovarianas , Animais , Feminino , Gangliosídeo G(M3)/metabolismo , Humanos , Imunoterapia Adotiva , Mamíferos/metabolismo , Camundongos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/terapia , Linfócitos T
14.
Colloids Surf B Biointerfaces ; 218: 112766, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35994990

RESUMO

Ovarian cancer (OC) is considered fifth-deadliest cancer globally responsible for high mortality in women. As the conventional therapeutic and diagnostic approaches are ineffective in increasing the survival rates of advanced staged patients by more than 5 years, OC has resulted in high morbidity and mortality rates over the last two decades. As a result, there is a dire need for innovative treatment approaches to address the issues. RNAi and nanotechnology can be considered the most appropriate strategies that can be used to improve OC therapy and help circumvent the chemo-resistance. siRNA is considered highly successful in facilitating the knockdown of specific genes on entering the cytosol when administered in-vivo via inhibiting the mRNA expression responsible for translation of those specific genes through the mechanism called RNA interference (RNAi). However, the primary barrier of utmost importance in the clinical efficacy of employed siRNA for the treatment of OC is the systemic distribution to the targeted site from the administration site. As a result, nanoparticles are constructed to carry the siRNA molecules inside them to the targeted site by preventing serum degradation and enhancing the serum stability of administered siRNA. The present review assesses the developments made in the polymeric-based nanoparticle siRNA delivery for targeting particular genes involved in the prognosis of ovarian cancers and surpassing the chemo-resistance and thus improving the therapeutic potentials of administered agents.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/terapia , Polímeros/metabolismo , Interferência de RNA , RNA Mensageiro , RNA Interferente Pequeno
15.
JCO Clin Cancer Inform ; 6: e2200035, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35985004

RESUMO

PURPOSE: Novel distress screening approaches using electronic patient-reported outcome (ePRO) measurements are critical for the provision of comprehensive quality community cancer care. Using an ePRO platform, the prevalence of psychosocial factors (distress, post-traumatic growth, resilience, and financial stress) affecting quality of life in ovarian cancer survivors (OCSs) was examined. METHODS: A cross-sectional OCS sample from the National Ovarian Cancer Coalition-Illinois Chapter completed web-based clinical, sociodemographic, and psychosocial assessment using well-validated measures: Hospital Anxiety/Depression Scale-anxiety/depression, Post-traumatic Growth Inventory, Brief Resilience Scale, comprehensive score for financial toxicity, and Functional Assessment of Cancer Therapy-Ovarian (FACT-O/health-related quality of life [HRQOL]). Correlational analyses between variables were conducted. RESULTS: Fifty-eight percent (174 of 300) of OCS completed virtual assessment: median age 59 (range 32-83) years, 94.2% White, 60.3% married/in domestic partnership, 59.6% stage III-IV, 48.8% employed full-time/part-time, 55.2% had college/postgraduate education, 71.9% completed primary treatment, and median disease duration 6 (range < 1-34) years. On average, OCS endorsed normal levels of anxiety (mean ± standard deviation = 6.9 ± 3.8), depression (4.1 ± 3.6), mild total distress (10.9 ± 8.9), high post-traumatic growth (72.6 ± 21.5), normal resilience (3.7 ± 0.72), good FACT-O-HRQOL (112.6 ± 22.8), and mild financial stress (26 ± 10). Poor FACT-O emotional well-being was associated with greater participant distress (P < .001). Partial correlational analyses revealed negative correlations between FACT-O-HRQOL and anxiety (r = -0.65, P < .001), depression (r = -0.76, P < .001), and total distress (r = -0.92, P < .001). Yet, high FACT-O-HRQOL was positively correlated with post-traumatic coping (r = 0.27; P = .006) and resilience (r = 0.63; P < .001). CONCLUSION: ePRO assessment is feasible for identification of unique psychosocial factors, for example, financial toxicity and resilience, affecting HRQOL for OCS. Future investigation should explore large-scale, longitudinal ePRO assessment of the OCS psychosocial experience using innovative measures and community-based advocacy populations.


Assuntos
Sobreviventes de Câncer , Neoplasias Ovarianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Eletrônica , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/terapia , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida/psicologia
17.
JCI Insight ; 7(18)2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-35972817

RESUMO

BACKGROUNDNew therapeutic combinations to improve outcomes of patients with ovarian cancer are clearly needed. Preclinical studies with ribociclib (LEE-011), a CDK4/6 cell cycle checkpoint inhibitor, demonstrate a synergistic effect with platinum chemotherapy and efficacy as a maintenance therapy after chemotherapy. We tested the safety and initial efficacy of ribociclib in combination with platinum-based chemotherapy in recurrent ovarian cancer.METHODSThis phase I trial combined weekly carboplatin and paclitaxel chemotherapy with ribociclib, followed by ribociclib maintenance in patients with recurrent platinum-sensitive ovarian cancer. Primary objectives were safety and maximum tolerated dose (MTD) of ribociclib when given with platinum and taxane chemotherapy. Secondary endpoints were response rate (RR) and progression-free survival (PFS).RESULTSThirty-five patients were enrolled. Patients had a mean of 2.5 prior lines of chemotherapy, and 51% received prior maintenance therapy with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab. The MTD was 400 mg. The most common adverse events included anemia (82.9%), neutropenia (82.9%), fatigue (82.9%), and nausea (77.1%). The overall RR was 79.3%, with a stable disease rate of 18%, resulting in a clinical benefit rate of 96.6%. Median PFS was 11.4 months. RR and PFS did not differ based on the number of lines of prior chemotherapy or prior maintenance therapy.CONCLUSIONThis work demonstrates that the combination of ribociclib with chemotherapy in ovarian cancer is feasible and safe. With a clinical benefit rate of 97%, this work provides encouraging evidence of clinical efficacy in patients with recurrent platinum-sensitive disease.TRIAL REGISTRATIONClinicalTrials.gov NCT03056833.FUNDINGThis investigator-initiated trial was supported by Novartis, which provided drugs and funds for trial execution.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Carboplatina/efeitos adversos , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/terapia , Paclitaxel/uso terapêutico , Platina , Purinas
18.
Clin. transl. oncol. (Print) ; 24(8): 1542–1548, agosto 2022.
Artigo em Inglês | IBECS | ID: ibc-206242

RESUMO

Introduction: Small-bowel involvement in patients with ovarian cancer has been strongly correlated with the possibility of cytoreduction and thus with survival. The main objective of this study was to evaluate the prognostic significance of small-bowel involvement in patients undergoing optimal-complete interval cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).Methods: We included a series of patients diagnosed with stage IIIC-IVA (pleural effusion) high-grade serous epithelial ovarian cancer and in whom CRS + HIPEC was indicated after neoadjuvant systemic chemotherapy (NACT). The study period extended from January 2008 to January 2020, with a minimum follow-up of 12 months from the inclusion of the last patient. A multivariate analysis using Cox regression allowed us to identify the variables that were independently related to disease-free survival.Results: A total of 144 patients were selected, 13 (9%) of whom were excluded from the analysis, because their disease was considered unresectable. The study included a series of 131 patients with a median age of 62 years (34-79 years) and a median Peritoneal Cancer Index (PCI) calculated during surgery of 9 (1-35). The median PCI of bowel areas 9-12 (SB-PCI) was 3 (1-10). Performance of a CC-1 cytoreduction (HR: 1.93, 95% CI: 1.02-3.64, p = 0.042) and SB-PCI greater than 3 (HR: 2.25, 95%CI: 1.13-4.48, p = 0.21) were independent factors associated with shorter disease-free survival.Conclusion: Small-bowel involvement, even in patients with a macroscopically complete resection, showed a correlation with worse prognostic outcomes and could be considered as a variable in the postoperative management of these patients. (AU)


Assuntos
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/terapia , Hipertermia Induzida , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/terapia , Estudos Retrospectivos , Taxa de Sobrevida
19.
Int Immunopharmacol ; 110: 109052, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35978506

RESUMO

Ovarian cancer (OC) is the seventh most common malignancy in women globally. This type of cancer can occur at any age, but it is more frequent in women over 50 and is usually diagnosed late. Despite platinum-based chemotherapy and optimal cytoreductive surgery, OC cells tend to metastasize, and patients with OC experience recurrent relapses and poor prognosis. Therefore, the emergence of novel therapies is essential for treating these patients. On the other hand, it has been shown that the tumor microenvironment (TME) and its components play an important role in the pathogenesis of OC. One of these components is cancer-associated fibroblast (CAF), which is involved in the growth and development of tumor cells by inducing tumor cells growth, proliferation, angiogenesis and inhibiting anti-tumor responses. Due to the importance of these cells in the TME, various therapeutic approaches such as direct targeting of CAFs, reprogramming of CAFs, and CAF-associated genes and molecules targeting have been suggested for OC treatment. This review summarizes the role of CAFs in the pathogenesis of OC and therapeutic approaches based on the mentioned therapeutic approaches.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Ovarianas , Fibroblastos Associados a Câncer/patologia , Proliferação de Células , Feminino , Humanos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Microambiente Tumoral
20.
Gynecol Oncol ; 167(1): 115-122, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36031452

RESUMO

OBJECTIVE: Germline genetic testing is increasingly offered to patients with epithelial ovarian cancer by non-genetic healthcare professionals, so called mainstream genetic testing. The aim of this study was to evaluate the effect of implementing a mainstream genetic testing pathway on the percentage of newly diagnosed patients with epithelial ovarian cancer to whom genetic testing was offered and the genetics-related healthcare costs. METHODS: The possible care pathways for genetic counseling and testing and their associated costs were mapped. Patient files from all newly diagnosed patients with epithelial ovarian cancer before (March 2016 - September 2017) and after (April 2018 - December 2019) implementing our mainstream genetic testing pathway were analyzed. Based on this analysis, the percentage of newly diagnosed patients to whom genetic testing was offered was assessed and genetics-related healthcare costs were calculated using a healthcare payer perspective based on a Diagnosis-Related Group financing approach. RESULTS: Within six months after diagnosis, genetic testing was offered to 56% of patients before and to 70% of patients after implementation of our mainstream genetic testing pathway (p = 0.005). Genetics-related healthcare costs decreased from €3.511,29 per patient before implementation to €2.418,41 per patient after implementation of our mainstream genetic testing pathway (31% reduction, p = 0.000). CONCLUSION: This study shows that mainstream genetic testing leads to a significantly higher proportion of newly diagnosed patients with epithelial ovarian cancer being offered germline genetic testing. In addition, it significantly reduces genetics-related healthcare costs per patient.


Assuntos
Testes Genéticos , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/genética , Feminino , Aconselhamento Genético , Células Germinativas , Custos de Cuidados de Saúde , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia
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