RESUMO
OBJECTIVE: This retrospective analysis of a real-world database of open radical hysterectomy in Japan aimed to reveal the clinicopathological findings and clinical outcomes of low-risk patients with stage IB-IIA cervical cancer. METHODS: A total of 1143 stage IB1, IB2 and IIA1 (reclassified by FIGO 2018 staging system) patients with cervical cancer who underwent radical hysterectomy between January 2004 and December 2008 from the Japanese Gynecologic Oncology Group database were analyzed. Low-risk patients were defined as those without a tumor size exceeding 4 cm, parametrial tumor involvement, deep (outer half) stromal invasion, lymphovascular space invasion or lymph nodal metastasis. RESULTS: 61.2% (772/1262) patients with stage IB1, 32.1% (229/932) with stage IB2 and 16.9% (72/294) of stage IIA1 were classified into the low-risk group. The 5-year overall survival and disease-free survival rates were 98.4 and 93.7%, respectively. Histological classification did not affect the survival rates, but stage IIA cases had significantly lower overall survival and disease-free survival (83.5 and 93.8%, respectively) than stage IB cases. The independent prognostic factors for disease-free survival were older age (â§50), histology, clinical stage and clinical stage as independent prognostic factors for overall survival. Regarding recurrence, older age, non-SCC and stage IIA1 were independent risk factors for local recurrence, but stage IIA1 was the only independent risk factor for distant metastasis. CONCLUSION: We found that stage IIA1 was the strongest risk factor for survival and recurrence of low-risk uterine cervical cancer (FIGO, 2018). In low-risk cases, stage IIA1 should be considered separately from stage IB.
Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Estudos Retrospectivos , Prognóstico , Estadiamento de Neoplasias , Histerectomia , Fatores de RiscoRESUMO
BACKGROUND: Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as large tumor diameter, stromal invasion to the outer half, and lymphovascular space invasion (LVSI). However, the indications and types of adjuvant therapy for the IR group remain controversial. This study aimed to analyze the differences in patient outcomes in the IR group to provide novel insights for tailoring adjuvant therapy. METHODS: Data from 6192 patients with cervical cancer who underwent radical hysterectomy at 116 institutions belonging to the Japanese Gynecologic Oncology Group were reviewed. RESULTS: In total, 1688 patients were classified into the IR group, of whom 37.3% did not receive adjuvant therapy. Conversely, approximately equal proportions of the remaining patients received adjuvant radiotherapy, concurrent chemoradiotherapy, and chemotherapy. Patients with all three risk factors showed worse overall survival than those with one or two risk factors. In addition to LVSI, non-squamous cell carcinoma histology, and vaginal invasion were identified as independent risk factors for both recurrence and mortality in multivariate analyses. Tumor diameter greater than 40 mm and surgical center volume were identified as independent risk factors for recurrence. Stromal invasion to the outer half and ovarian metastasis were identified as independent risk factors for mortality. CONCLUSIONS: This study revealed the significant differences in prognosis in the IR group. The indications for adjuvant therapy should be further studied, focusing on conventional risk factors and other pathological findings.
Assuntos
Histerectomia , Neoplasias do Colo do Útero , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Feminino , Humanos , Japão , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/terapiaRESUMO
BACKGROUND: Treatment strategies based on histological subtypes are unestablished. AIMS: Rethinking the significance of surgery for uterine cervical cancer. METHODS: Using the database of cervical cancer stages IB-IIB with extensive hysterectomy (Federation of Gynecology and Obstetrics [FIGO] 2008) established by the Japanese Gynecologic Oncology Group network, we conducted a clinicopathological study of cervical cancer cases reclassified according to the FIGO 2018 staging. In stage IB (FIGO 2018) cervical cancer patients, there was no significant difference in treatment outcome according to histological type, but in stages IIA, IIB, and IIIC1 (FIGO 2018), the treatment outcome of nonsquamous cell carcinoma was significantly worse than that of squamous cell carcinoma. Considering post-treatment health care, it is important to consider ovarian preservation in young patients with cervical cancer, up to stage IIA (FIGO 2018) for squamous cell carcinoma and stage IB1 (FIGO 2018) for nonsquamous cell carcinoma, after careful evaluation of clinicopathological factors before surgery. DISCUSSION: Locally advanced adenocarcinoma of the cervix is a rare and refractory cancer that has been shown to have low radiosensitivity, and its treatment outcome is still unsatisfactory. A new therapeutic strategy involving multidisciplinary treatment in combination with perioperative chemotherapy at a facility that can provide highly curative surgical treatment is desired. CONCLUSION: Minimally invasive surgery is being introduced for the treatment of early-stage cervical cancer. However, the number of eligible cases should be expanded in a phased manner, based on an objective evaluation of surgical outcomes at the facilities. Omics analysis may be useful to develop a new treatment for human papillomavirus nonrelated cervical cancer, represented by gastric mucinous carcinoma.
Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Histerectomia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVE: The aim of this retrospective analysis is to reveal clinicopathological findings and clinical outcome of patients with stage IB1/IB2 (FIGO 2018) uterine cervical cancer. METHODS: Based on the database of the Japanese Gynecologic Oncology Group, 2194 patients with stage IB1/IB2 (FIGO 2018), who underwent radical hysterectomy between 1/1/2004-12/31/2008, were identified as eligible for this retrospective study. RESULTS: Patients with squamous cell carcinoma had significantly frequent lympho-vascular space invasion than those with non-squamous cell carcinoma in both stage IB1 and IB2 (stage IB1; 29.1% vs. 17.1%, p < 0.0001, stage IB2; 50.5% vs. 39.7%, p = 0.0009). Among 1262 patients with stage IB1, 61.2% (772/1262) were low-risk group, 29.4% (371/1262) were intermediate-risk group (single risk: 23.3%, double risks: 6.1%). Of 932 patients with stage IB2, 32.1% (299/932) were low-risk group, 59.1% (551/932) were intermediate-risk group (single intermediate-risk: 31.0%, double intermediate-risk: 28.1%). Disease-free survival rate and overall survival rate of stage IB1 patients were significantly better than those with stage IB2 (5-year DFS; 94.7% vs. 88.6%, p < 0.001, 5-yrs OS; 98.5% vs. 95.1%, p < 0.001). Stage IB1 Patients with double intermediate-risk showed significantly worse survival than those with single intermediate-risk (5-yrs DFS: 96.1% vs. 84.6%, p < 0.001, 5-yrs OS: 98.9% vs. 93.0%, p = 0.029). Multivariate analysis revealed that double intermediate-risk was the independent prognostic factor in stage IB1, but non-squamous cell carcinoma and intermediate-risk in stage IB2. CONCLUSION: Non-squamous cell carcinoma and intermediate-risk decreased survival in patients with stage IB2, whereas double intermediate-risk was a negative impact on survival in stage IB1.
RESUMO
The impact of histologic subtype on definitive radiotherapy for patients with locally advanced cervical cancer remains unclear. The aim of this retrospective analysis was to assess clinicopathological findings and clinical outcome by histological type in patients with stage IIB-IVA cervical cancer. Ninety-two patients with stage IIB-IVA [International Federation of Gynecology and Obstetrics (FIGO) 2008] cervical cancer, who underwent definitive radiotherapy between 2013 to 2018, were identified as eligible for this study. The clinical information of the eligible patients was obtained from medical records of our hospital. Seventy-eight patients underwent concurrent chemoradiotherapy, and the remaining 14 patients received radiotherapy alone. Of 92 patients, 83 had squamous cell carcinoma (SCC) and 9 had non-SCC histology. Progression-free survival (PFS) rate of patients with non-SCC was significantly worse than of those with SCC (2-year PFS: 62.0% vs. 12.5%, p = 0.0020), but overall survival (OS) rate did not statistically differ between the two subtypes (2-year OS: 82.4% vs. 62.5%, p = 0.2157). Pelvic failure-free (PFF) rate of patients with non-SCC histology was significantly worse than of those with non-SCC (2-year PFF; 88.2% vs. 25.0%, p < 0.0001). In univariate analysis, non-SCC histology was associated with PFS rate, although there was no association with OS rate. In multivariate analysis, non-SCC histology and lymph node metastasis were independent prognostic factors for shorter PFS. In patients with stage IIB-IVA cervical cancer who underwent definitive radiotherapy, patients with non-SCC showed significantly worse PFS rate than those with SCC.
Assuntos
Adenocarcinoma , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
Although the addition of bevacizumab to platinum-based combination chemotherapy has been recommended as a standard regimen for patients with advanced or recurrent cervical cancer, there is no clear evidence regarding the effectiveness of bevacizumab monotherapy as salvage chemotherapy. This study prospectively examined the efficacy and safety of switching from platinum-based chemotherapy combined with bevacizumab to single maintenance therapy in patients with advanced or recurrent cervical cancer. Patients were first treated with standard combination chemotherapy. However, if chemotherapy was discontinued because of an adverse event, bevacizumab monotherapy was continued for patients who agreed to participate in this study and provided written informed consent. The study protocol was approved by the Independent Review Board of Tohoku University School of Medicine (reception number 2017-1-540). A total of 15 patients (median age of 55 years, range 33-69 years) participated in this study. The median number of cycles of bevacizumab single maintenance administration was 8, and the main reasons for discontinuation were disease progression and adverse events. Bevacizumab single maintenance therapy had a disease control rate of 53.3% (CR 40%, PR 6.7%, SD 6.7%). The most frequent grade 3/4 clinical adverse events were proteinuria (5/15) and hypertension (4/15). No treatment-related deaths occurred. Bevacizumab single maintenance therapy was effective as salvage chemotherapy in patients with advanced or recurrent cervical cancer, and the safety profile was generally consistent with those reported in previous studies of bevacizumab monotherapy.
Assuntos
Neoplasias do Colo do Útero , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Projetos Piloto , Platina/uso terapêutico , Estudos Prospectivos , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
Pelvic lymphadenectomy is generally performed to treat early-stage cervical cancer, and pelvic ± para-aortic lymphadenectomy is performed in patients with endometrial cancer confined to the uterus. However, systematic lymphadenectomy is frequently associated with sequelae including lymphocele, lymphedema and cellulitis. The sentinel lymph node concept has been recently applied in the management of patients with gynecological cancer, with the goal of avoiding systematic lymphadenectomy and its associated postoperative complications. In this review, we examine and summarize the recently expanding body of literature and discuss sentinel lymph node navigation during surgery in patients with cervical and endometrial cancer. Current data suggest that sentinel node navigation surgery (SNNS) appears to be feasible for detecting lymph node metastasis compared with systematic lymphadenectomy in patients with early-stage cervical or endometrial cancer. The non-inferiority of long-term prognosis through omission of systematic lymphadenectomy has not been proven by randomized trial, but SNNS decreases lymphatic complications related to systematic lymphadenectomy. Further studies are needed to clarify the necessity of additional systematic lymphadenectomy and/or adjuvant therapy in cases with isolated tumor cells or micrometastasis in SLNs.
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Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias do Colo do Útero/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/efeitos adversos , Neoplasias do Colo do Útero/cirurgiaRESUMO
Spontaneous hemoperitoneum in pregnancy (SHiP) has mainly been discussed in the context of endometriosis. With hormonal changes and enlargement of the uterus during pregnancy, tumors can also increase the chance of rupture and consequent SHiP. We report a case of a 30-year-old primiparous woman presented with sudden-onset intraabdominal hemorrhage at 34 weeks' gestation. The source of bleeding was rupture of a perivascular epithelioid cell neoplasm on the left round ligament of the uterus. The pregnancy ended with an uncomplicated, full-term, vaginal delivery. We performed an additional post-partum surgery to resect the left round ligament and transposition of the right ovary. In cases of SHiP, the possibility of a nonendometriosis origin should be considered. Preoperative imaging and histologic examinations of bleeding lesions are crucial for managing SHiP.
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Hemoperitônio/etiologia , Neoplasias de Células Epitelioides Perivasculares/complicações , Complicações Neoplásicas na Gravidez/patologia , Ligamentos Redondos/patologia , Neoplasias Uterinas/complicações , Útero/irrigação sanguínea , Adulto , Feminino , Idade Gestacional , Hemoperitônio/patologia , Humanos , Neoplasias de Células Epitelioides Perivasculares/patologia , Gravidez , Ruptura Espontânea/etiologia , Ruptura Espontânea/patologia , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: Several studies have reported that retinoic acid (RA) might be used to treat malignancies. The effects of RA are mediated by the RA receptor (RAR), and RARα/RARß especially acts as a tumor suppressor. However, little is known about its role in human endometrial cancer. MATERIALS AND METHODS: In this study, we examined the effects of all-trans RA (ATRA) on progression of human endometrial cancer cell line, RL95-2 and Hec1A. We then examined the expression of RARα and RARß in 50 endometrial cancer tissues by using immunohistochemistry. RESULTS: We found inhibitory effects of ATRA on cell proliferation, apoptosis, and migration in RL95-2 cells, but not in Hec1A cells. RARα or RARß knockdown individually could not cancel out the inhibition of cell proliferation by ATRA in RL95-2 cells, but simultaneous knockdown of RARα and RARß could block its effect on proliferation. RARα and RARß knockdown dose dependently reduced the inhibition of migration by ATRA, but the effect was more pronounced with RARß knockdown than with RARα knockdown. We confirmed that RARß gene was directly regulated by ATRA in microarray and real-time reverse transcription polymerase chain reaction. Furthermore, the RARß agonist (BMS453) significantly suppressed proliferation of RL95-2 cells. In immunohistochemical analysis, RARα expression was positively correlated with tumor grade, and RARß showed the opposite tendency in endometrial cancer. CONCLUSIONS: Retinoic acid might have multiple antitumor effects, and RARß may be a potent therapeutic target in RA treatment for endometrial cancers.
Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Receptores do Ácido Retinoico/metabolismo , Tretinoína/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Terapia de Alvo Molecular , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/deficiência , Receptores do Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/biossíntese , Receptor alfa de Ácido Retinoico/deficiência , Receptor alfa de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/metabolismoRESUMO
Primary osteosarcoma of the uterine cervix is extremely rare. Only 20 cases have been reported, 19 of which originated in the uterine corpus. We report a case of primary uterine cervical osteosarcoma with pulmonary metastasis in a 30-year-old nulligravida woman. The initial diagnosis was carcinosarcoma of the uterine cervix, as detected by cervical cytology and biopsy analysis. We performed a total hysterectomy, bilateral salpingo-oophorectomy and colostomy without macroscopic residual tumors in the abdominal cavity, but pelvic recurrent tumors appeared 14 days postoperatively. Both recurrent and metastatic tumors were effectively reduced by combination therapy of adriamycin with ifosfamide; however, the patient died as a result of of disease progression nine months after her first visit to our department.
Assuntos
Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/patologia , Osteossarcoma/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Osteossarcoma/terapia , Neoplasias do Colo do Útero/terapiaRESUMO
BACKGROUND: Uterine leiomyosarcoma (LMS) and undifferentiated endometrial sarcoma (UES) are rare, aggressive malignancies. Both are treated similarly; however, few chemotherapy agents are effective. Recently, the combination of gemcitabine (900 mg/m(2), days 1 and 8) plus docetaxel (100 mg/m(2), day 8) with granulocyte colony-stimulating factor (G-CSF, 150 µg/m(2), days 9-15) has been shown to have activity in LMS. In Japan, neither prophylactic G-CSF at a dose of 150 µg/m(2) nor docetaxel at a dose of 100 mg/m(2) are approved for use. For this reason, we evaluated the combination of 900 mg/m(2) gemcitabine plus 70 mg/m(2) docetaxel regimen without prophylactic G-CSF support in advanced or recurrent LMS and UES in Japanese patients. METHODS: Eligible women with advanced or recurrent LMS and UES were treated with 900 mg/m(2) gemcitabine on days 1 and 8, plus 70 mg/m(2) docetaxel on day 8, every 3 weeks. The primary endpoint was overall response rate, defined as a complete or partial response. RESULTS: Of the eleven women enrolled, 10 were evaluated for a response. One complete response and 2 partial responses were observed (30 %) with an additional 4 (40 %) having stable disease. Mean progression-free survival was 5.4 months (range 1.3-24.8 months), and overall survival was 14 months (range 5.3-38.4 months). Grade 4 neutropenia was the major toxicity (50 %). The median number of cycles was 5 (range 2-18). Twenty-two cycles (44 %) employed G-CSF. CONCLUSION: The gemcitabine plus docetaxel regimen without prophylactic G-CSF support was tolerable and highly efficacious in Japanese patients with advanced or recurrent LMS and UES.
Assuntos
Desoxicitidina/análogos & derivados , Leiomiossarcoma/tratamento farmacológico , Sarcoma do Estroma Endometrial/tratamento farmacológico , Taxoides/administração & dosagem , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Docetaxel , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Estudos de Viabilidade , Feminino , Fator Estimulador de Colônias de Granulócitos/genética , Humanos , Japão , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Sarcoma do Estroma Endometrial/genética , Sarcoma do Estroma Endometrial/patologia , Taxoides/efeitos adversos , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia , GencitabinaRESUMO
The 2018 International Federation of Gynecology and Obstetrics (FIGO) revision to the staging criteria for uterine cervical cancer adopted pathological staging for patients who underwent surgery. We investigated the correlation between clinicopathological factors and prognosis in patients with high-risk factors in accordance with the FIGO 2018 staging criteria by analyzing a real-world database of 6,192 patients who underwent radical hysterectomy at 116 institutions belonging to the Japan Gynecologic Oncology Group. A total of 1,392 patients were categorized into the high-risk group. Non-squamous cell carcinoma histology, regional lymph node metastasis, pT2 classification, and ovarian metastasis were identified as independent risk factors for mortality. Based on pathological findings, 313, 1003, and 76 patients were re-classified into FIGO 2018 stages IIB, IIIC1p, and IIIC2p, respectively. Patients with stage IIIC2p disease showed worse prognoses than those with stage IIB or IIIC1p disease. In patients with stage IIIC1p disease, overall survival was significantly better if their tumors were localized in the uterine cervix, except for single lymph node metastasis, with a 5-year overall survival rate of 91.8%. This study clarified the heterogeneity of the high-risk group and provided insights into the feasibility of upfront radical hysterectomy for a limited number of patients harboring high-risk factors.
Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Estadiamento de Neoplasias , Metástase Linfática , Prognóstico , Histerectomia , Estudos RetrospectivosRESUMO
Platinum sensitivity is an important prognostic factor in patients with ovarian cancer. Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a core member of the nucleosome remodeling and deacetylase complex, which functions as a chromatin remodeler. Emerging evidence indicates that CHD4 could be a potential therapeutic target for cancer therapy. The purpose of this study was to clarify the role of CHD4 in ovarian cancer and investigate its therapeutic potential focusing on platinum sensitivity. In an analysis of the Cancer Genome Atlas ovarian cancer dataset, CHD4 gene amplification was associated with worse overall survival. CHD4 mRNA expression was significantly higher in platinum-resistant samples in a subsequent clinical sample analysis, suggesting that CHD4 overexpression conferred platinum resistance to ovarian cancer cells, resulting in poor patient survival. In concordance with these findings, CHD4 knockdown enhanced the induction of apoptosis mediated by cisplatin in ovarian cancer cells TOV21G and increased cisplatin sensitivity in multiple ovarian cancer cells derived from different subtypes. However, CHD4 knockdown did not affect the expression of RAD51 or p21, the known targets of CHD4 in other cancer types that can modulate platinum sensitivity. Knockdown and overexpression assays revealed that CHD4 positively regulated the expression of multi-drug transporter MDR1 and its coding protein p-glycoprotein. In addition, a first-in-class CHD4/SMARCA5 inhibitor ED2-AD101 showed synergistic interactions with cisplatin. Our findings suggest that CHD4 mediates platinum sensitivity by modulating MDR1 expression in ovarian cancer. Further, CHD4 suppression has a potential to be a novel therapeutic strategy in combination with platinum agents.
Assuntos
Antineoplásicos/uso terapêutico , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Montagem e Desmontagem da Cromatina/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Ovarianas/patologiaRESUMO
Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual's current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/sangue , Metaboloma , Neoplasias Ovarianas/sangue , Toxinas Biológicas/sangue , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Feminino , Humanos , Metabolômica , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Prognóstico , Toxinas Biológicas/metabolismo , Uremia/metabolismoRESUMO
The purpose of this study was to reveal treatment outcomes and toxicity after pelvic intensity-modulated radiotherapy (IMRT) for postoperative uterine cervical cancer of Japanese patients. Consecutive patients who were treated with pelvic IMRT for postoperative cervical cancer in our institute were retrospectively analyzed. Relapse-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator, and log-rank tests were used to compare differences. From the database, 62 patients were identified. The pathology was squamous cell carcinoma in 44 patients and other pathology in 18 patients. Of the 62 patients, 35 had high-risk prognostic factors and 27 patients had intermediate-risk prognostic factors. The prescribed radiation doses were 50 Gy in 25 fractions for 58 patients and 50.4 Gy in 28 fractions for 4 patients. One patient received a vaginal cuff boost. Chemotherapy was administered in 36 patients. During the median follow-up period of 50.9 months, there was no locoregional failure. Six patients in the high-risk group relapsed, but none of the patients in the intermediate-risk group relapsed (P = 0.02). The 3-year OS and RFS rates were 98.2% and 90.9%, respectively. Significant factors related to RFS were squamous cell carcinoma pathology (P = 0.02), pathological T stage (P = 0.04), surgical margin status (P < 0.01) and multiple lymph nodes metastases (P < 0.01). Grade 3 or more toxicity occurred in 6 patients. Four patients had obstruction of the intestine, and 2 patients had stenosis of the urinary tract. In clinical practice, the use of pelvic IMRT for postoperative cervical cancer of Japanese patients showed a low rate of toxicity without decreasing the efficacy.
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Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Radioterapia de Intensidade Modulada , Radioterapia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Japão , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgiaRESUMO
Quantum chemical calculations are necessary to develop advanced emitter materials showing thermally-activated delayed fluorescence (TADF) for organic light-emitting diodes (OLEDs). However, calculation costs become problematic when more accurate functionals were used, therefore it is judicious to use a multimethod approach for efficiency. Here we employed combinatorial chemistry in silico to develop the deep blue TADF materials with a new concept of homo-junction design. The homo-junction materials containing TADF candidates designed by calculation were synthesized and analyzed. We found that these materials showed the emission from charge transfer (CT) state, and the clear delayed emission was provided in solid state. Because the homo-junction TADF materials showed three exponential decayed emission in solid state, we employed novel four-state kinetic analysis.
RESUMO
Leptomeningeal metastasis (LM) is rarely observed in gynecologic cancers. As gadolinium-enhanced magnetic resonance imaging (Gd-MRI) is highly effective for diagnosing LM, the aim of this study is to describe the clinical behaviors and outcomes of LM patients who were diagnosed by Gd-MRI. After securing institutional review board approvals, we retrospectively reviewed patient records. Eight patients were found to have LM from gynecological malignancies. Primary tumors included three ovarian cancers, one tubal cancer, one peritoneal cancer, two endometrial cancers, and one cervical cancer. Gd-MRI of the brain and the spine is indicated as the high-priority inspection for the diagnosis of this devastating complication.
Assuntos
Encéfalo/diagnóstico por imagem , Neoplasias dos Genitais Femininos/patologia , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/secundário , Adulto , Idoso , Feminino , Gadolínio , Humanos , Aumento da Imagem , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Blast furnace slag (BFS), a high-volume byproduct resulting from iron-making processes, can be considered as a low-cost and abundant precursor for preparing layered double hydroxide (LDH) compounds. Here we demonstrate that a Ca-based LDH compound (hydrocalumite) synthesized from waste BFS through facile two-step procedures and its derivatives work as useful heterogeneous base catalysts for multiple chemical reactions including the Knoevenagel condensation, oxidation of alkylaromatics with O(2), transesterification, and cycloaddition reaction of epoxides with atmospheric CO(2). Structures were verified by using XRD and thermogravimetric analysis. The surface basicity and coordination geometry of the active metal species that substantially affect the catalytic activity were investigated by CO(2)-temperature programmed desorption (TPD) and X-ray absorption fine structure (XAFS) measurements, respectively. These characterization results revealed that the slag-derived impurity elements, such as Fe, Ti, and Mn, effectively act either as active sites or as catalyst promoters in particular reactions and that the kind of guest counter anion (Cl(-) or NO(3)(-)) also plays a key role for achieving high catalytic efficiencies. In any reaction, the catalyst was easily separated by filtration and recyclable in multiple catalytic runs with retention of its activity and fine selectivity, irrespective of its considerable impurity level. It is believed that the slag-made hydrocalumite can replace existing LDH catalysts as a low-cost alternative and potentially contribute to sustainable chemical processes.