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1.
Mol Cancer ; 23(1): 162, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39123210

RESUMEN

BACKGROUND: Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction. METHODS: A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1. RESULTS: From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8-NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8-5·6) and 5·6 months (95% CI 3·4-7·0), respectively. CONCLUSIONS: This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resistencia a Antineoplásicos/efectos de los fármacos , Anciano , Adulto , Resultado del Tratamiento , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos
2.
BMC Med ; 22(1): 199, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755585

RESUMEN

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.


Asunto(s)
Antígeno B7-H1 , Biomarcadores de Tumor , Quimioterapia de Mantención , Neoplasias Ováricas , Ftalazinas , Piperazinas , Humanos , Femenino , Ftalazinas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Piperazinas/uso terapéutico , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Quimioterapia de Mantención/métodos , Anciano , Adulto , Estudios Prospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proteína BRCA2/genética , Antineoplásicos/uso terapéutico , Proteína BRCA1/genética , Recombinación Homóloga
3.
Cytotherapy ; 26(2): 210-220, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38127032

RESUMEN

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer. However, key aspects governing the reproducible manufacturing of high-quality DC remain incompletely defined. Here, we show that the time window between leukapheresis and DC manufacturing is critical. METHODS: Transcriptomic profiling by RNA-seq was used to unbiasedly characterize cellular states during each step of DC manufacturing process, and functional assays were used to determine the anti-tumor activities of DC. RESULTS: During preclinical development of a DC-based cytotherapy platform, CUD-002 (NCT05270720), we found that DC quality varied among different batches, even though commonly used DC maturation markers CD80, CD83 and CD86 were indistinguishable. Multivariate analysis indicated that DC quality was negatively associated with the shipping time from the leukapheresis site to the manufacturing center. To investigate the potential effect of shipping time, we stored leukapheresis materials from three donors for 0, 1, 2 or 3 days before DC manufacturing. For each step, we carried out RNA-seq analysis to unbiasedly characterize cellular states. Integrated bioinformatic analyses indicated that longer storage time reduced the expression of several transcription factors to attenuate interferon pathways. CONCLUSIONS: Consistently, we found that 3-day storage of leukapheresis materials significantly lowered the efficiency to generate DC but also impaired DC responses to inflammatory signals, resulting in inferior antigen-presentation and cytotoxic T-cell activities. Thus, we recommend using leukapheresis materials within 48 h to manufacture therapeutic DCs.


Asunto(s)
Leucaféresis , Neoplasias , Humanos , Leucaféresis/métodos , Neoplasias/metabolismo , Inmunoterapia/métodos , Células Dendríticas/fisiología
4.
Arch Biochem Biophys ; 761: 110139, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39242014

RESUMEN

It has been discovered that aberrant expression of RNF113A plays a significant role in various diseases, including esophageal cancer, hepatocellular carcinoma, and X-linked trichothiodystrophy syndrome. Nevertheless, its functional implications in cervical cancer (CC) remain unclear. The objective of this study was to investigate the role of RNF113A in both the development and prognosis of CC. To achieve this objective, a total of sixty cases were included in the follow-up investigation. The findings revealed a significant up-regulation of RNF113A protein in CC tissues compared to paired paracancerous tissues, and a high expression level of RNF113A was strongly associated with malignant phenotypes such as lymph node metastasis, differentiation degree, depth of invasion, and FIGO stage. Meanwhile, RNF113A was found to be an independent prognostic risk factor, with its high expression significantly correlating with a reduced overall survival period in patients. To elucidate the underlying cause and mechanism of the unfavorable prognosis associated with RNF113A, comprehensive functional investigations were conducted both in vitro and in vivo.Interestingly, it was revealed that RNF113A promoted migration and invasion while inhibiting apoptosis of CC cells, thereby contributing to a poor prognosis. Mechanistically, RNF113A regulated the progression and prognosis of CC through the miR197/Prp19/p38Mark signaling pathway. Overall, our findings underscore the potential clinical significance of RNF113A as an unfavorable prognostic factor in CC.

5.
Gynecol Oncol ; 191: 165-171, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39447517

RESUMEN

BACKGROUND: Platinum-based chemotherapy with or without bevacizumab is the first-line treatment for patients with recurrent or metastatic cervical cancer (r/mCC), and the treatment options are limited for r/mCC after first-line treatment. Enlonstobart (SG001) is a fully humanized and high-affinity anti-PD-1 immunoglobulin G4 monoclonal antibody. Previous phase Ib study demonstrated that SG001 had a promising efficacy in patients with PD-L1 positive r/mCC. METHODS: In this multicenter, single-arm, open-label, phase II study, eligible patients were ≥ 18 years with PD-L1-positive cervical cancer who had progression on or intolerance to the first-line platinum-based chemotherapy. Patients received SG001 240 mg every two weeks for 24 months or until disease progression, intolerable toxicities, or other study discontinuation criteria were met. The primary endpoint was confirmed objective response rate (ORR) assessed by RECIST version 1.1 by independent review committee. RESULTS: 107 patients were enrolled with median age of 53 years (range 26-72). 64.5 % of patients had a ECOG of 1. After a median follow-up of 14.0 months (range 0.4-21.9), confirmed ORR was 29.0 %, with two complete responses and twenty-nine partial responses. The disease control rate was 54.2 %. Median duration of response was 16.6 months (95 % CI 10.8-NA), median progression free survival was 3.1 months (95 % CI 2.2-6.9). Median overall survival was not reached. 104 patients (97.2 %) experienced at least one treatment emergent adverse events TEAEs, of which 38 patients (35.5 %) had grade 3 or higher TEAEs. The most common treatment-related adverse events were leukopenia (19.6 %), increased aspartate aminotransferase (18.7 %), anemia (17.8 %), increased alanine aminotransferase (15.9 %), hypothyroidism (15.0 %), neutropenia (15.0 %), and hyperthyroidism (11.2 %). CONCLUSION: SG001 monotherapy demonstrated durable anti-tumor activity with acceptable safety in patients with PD-L1 positive r/mCC with progression on or intolerance to the first-line platinum-based chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04886700).

6.
BMC Health Serv Res ; 24(1): 116, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38254152

RESUMEN

BACKGROUND: Patient follow-up is an essential component of hospital management. In the current information era, the patient follow-up scheme is expected to be replaced by Internet technology. This study constructed a cloud follow-up platform for gynecological chemotherapy patients and assessed its cost-effectiveness and patients' feedback. METHODS: A total of 2,538 patients were followed up using a cloud follow-up system between January and October 2021. Prior to this, 690 patients were followed manually via telephone calls. Patients' characteristics, follow-up rate, satisfaction, and session duration were compared between the cloud follow-up and manual follow-up groups. In addition, the read rate of health education materials in the cloud follow-up group was analyzed. RESULTS: General information, including age, education attainment, cancer stage, and disease category, and follow-up rate (cloud: 6,957/7,614, 91.4%; manual: 1,869/2,070, 90.3%; P = 0.13) did not significantly differ between the two groups. The follow-up satisfaction of the cloud follow-up patients was significantly better than that of the manual follow-up group (cloud: 7,192/7,614, 94.5%; manual: 1,532/2,070, 74.0%; P<0.001). The time spent on the follow-up was approximately 1.2 h for 100 patients in the cloud follow-up group and 10.5 h in the manual follow-up group. Multivariate analysis indicated that the cloud follow-up group had significantly greater follow-up satisfaction (odds ratio: 2.239, 95% CI: 1.237 ~ 5.219). Additionally, the average follow-up duration of the cloud follow-up group decreased by 9.287 h (coefficient: -9.287, 95% CI: -1.439~-0.165). The read rate of health education materials was 72.9% in the cloud follow-up group. CONCLUSIONS: The follow-up effect of the cloud follow-up group was not inferior to that of the manual follow-up group. The cloud follow-up was more effective for prevention and control requirements in the post-epidemic era. Cloud follow-up can save medical resources, improve cost-effectiveness, provide sufficient health education resources for patients, and improve their satisfaction.


Asunto(s)
Epidemias , Ginecología , Humanos , Estudios de Seguimiento , Escolaridad , Educación en Salud
7.
Lab Invest ; 103(11): 100234, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37574009

RESUMEN

Coinfection with multiple high-risk human papillomavirus (hrHPV) is frequently observed in cervical specimens; however, the clinical significance of concomitant multiple hrHPV infections is poorly understood, and the published results remain inconsistent. A retrospective study at a tertiary care institution was performed, evaluating Tellgenplex human papillomavirus (HPV) 27 genotyping or YanengBio HPV 23 genotyping results and immediate cervical histologic diagnosis (within 6 months after HPV genotyping), between November 2015 and October 2022. Among 49,299 cases with hrHPV genotyping and histologic diagnosis, 24,361 cases were diagnosed as cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma. Among women with cervical squamous lesions, 86.5% (21,070/24,361) had hrHPV infections, and concomitant multiple hrHPV infections accounted for 24.7% of hrHPV-positive cases (5210/21,070). The hrHPV-positive rates in these cervical squamous lesions increased progressively with disease severity; however, the percentages of concomitant multiple hrHPV infection rates among hrHPV-positive cases decreased significantly with increasing degree of squamous abnormalities. There was no increased detection rate of CIN3+ (CIN3 and squamous cell carcinoma) in cases with concomitant 2 or 3 hrHPV genotype infections when compared with those with corresponding single hrHPV infections. Conversely, some combinations of multiple hrHPV infections demonstrated a decrease in the detection rates of CIN3+ lesions. In this large cohort, our results demonstrated that multiple hrHPV infections do not carry an increased risk for developing CIN3+ lesions when compared to the corresponding single-genotype infection. The reduced risk of CIN3+ in women infected with some combinations of hrHPV genotypes compared to those with single-genotype infections supports the concept of intergenotypic competition of hrHPV genotypes in cervical squamous lesions.


Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Virus del Papiloma Humano , Estudios Retrospectivos , Incidencia , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/complicaciones , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/patología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Papillomaviridae/genética , Genotipo
8.
BMC Med ; 21(1): 376, 2023 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-37775744

RESUMEN

BACKGROUND: The effect of the combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor in cancer treatment is unclear. We assessed the oral combination of fuzuloparib, a PARP inhibitor, and apatinib, a VEGFR2 inhibitor for treating advanced ovarian cancer (OC) or triple-negative breast cancer (TNBC). METHODS: This dose-escalation and pharmacokinetics-expansion phase 1 trial was conducted in China. We used a standard 3 + 3 dose-escalation design, with 7 dose levels tested. Patients received fuzuloparib orally twice daily, and apatinib orally once daily. The study objectives were to determine the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics, preliminary efficacy, and efficacy in relation to germline BRCA mutation (gBRCAmut). RESULTS: Fifty-two pre-treated patients were enrolled (30 OC/22 TNBC). 5 (9.6%) patients had complete response, 14 (26.9%) had partial response, and 15 (28.8%) had stable disease. Objective response rate (ORR) and disease control rate were 36.5% (95% CI 23.6-51.0) and 65.4% (95% CI 50.9-78.0), respectively. At the highest dose level of fuzuloparib 100 mg plus apatinib 500 mg, the ORR was 50.0% (4/8; 95% CI 15.7-84.3); this dose was determined to be the RP2D. Patients with gBRCAmut had higher ORR and longer median progression-free survival (PFS) than those with gBRCAwt, both in OC (ORR, 62.5% [5/8] vs 40.9% [9/22]; PFS, 9.4 vs 6.7 months) and TNBC (ORR, 66.7% [2/3] vs 15.8% [3/19]; PFS, 5.6 vs 2.8 months). Two dose-limiting toxicities occurred: grade 4 febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). Maximum tolerated dose was not reached. The most common treatment-related grade ≥ 3 toxicities in all patients were hypertension (19.2%), anaemia (13.5%), and decreased platelet count (5.8%). Exposure of apatinib increased proportionally with increasing dose ranging from 250 to 500 mg, when combined with fuzuloparib 100 mg. CONCLUSIONS: Fuzuloparib plus apatinib had acceptable safety in patients with advanced OC or TNBC. Fuzuloparib 100 mg bid plus apatinib 500 mg qd was established as the RP2D. With the promising clinical activity observed, this combination is warranted to be further explored as a potential alternative to chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03075462 (Mar. 9, 2017).


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , China , Mutación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética
9.
J Med Virol ; 95(1): e28302, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36369778

RESUMEN

Our aim was to conduct a large epidemiologic analysis of the distribution of human papilloma virus (HPV) genotypes associated with cervical neoplasias and cancers at a major Chinese gynecologic center. The pathologic database was searched for cervical histopathologic diagnoses with prior HPV genotyping from liquid cervical cytology specimens obtained ≤6 months before biopsy. HPV testing was performed by using the Tellgenplex HPV27 or YanengBio HPV23 genotyping assays. A total of 40 352 cases meeting study criteria were identified. High risk human papillomavirus (hrHPV) was detected in 94.1% of squamous cancers compared to in only 83.3% of cervical adenocarcinomas. The prevalence of multiple HPV infections was highest in cervical intraepithelial neoplasia 1 (CIN1) (33.8%) and decreased with increasing severity of squamous lesions. The distribution of HPV genotypes was similar between CIN1 and histopathologic-negative cases. HPV16 was one of the three most common hrHPV genotypes before all histopathologic abnormalities, ranging from 72.0% for cervical cancers, 38.7% for CIN2/3/AIS, 13.1% for CIN1, and 9.1% for biopsy-negative cases. HPV16 and HPV18 accounted for over 87.2% of detected hrHPV genotypes for all glandular intraepithelial neoplastic lesions and cancers, whereas squamous lesions did not show this pattern. 80.3% of cervical cancers were associated with genotypes covered by HPV16/18 vaccines and 89.6% with genotypes covered by 9-valent vaccination.


Asunto(s)
Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Virus del Papiloma Humano , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/complicaciones , Papillomavirus Humano 18/genética , Displasia del Cuello del Útero/epidemiología , Papillomaviridae/genética , Genotipo , Carcinoma de Células Escamosas/complicaciones
10.
Cytotherapy ; 25(2): 210-219, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36443171

RESUMEN

BACKGROUND AIMS: Dendritic cell (DC)-based immunotherapy is a promising approach to treat cancer; however, there is no consensus on the manufacturing processes. Cell type heterogeneity in products manufactured by various methods is understudied and may elicit safety concerns from the regulatory perspective. METHODS: We characterized the cell type composition of a recently developed DC vaccine, CUD-002, consisting of DCs loaded with mRNA encoding personalized tumor neoantigens (NCT05270720). RESULTS: Using single-cell transcriptomic analysis as an unbiased approach, we found that >80% cells in the final product were DCs and the rest primarily comprised myelocytes and lymphocytes. Subsequent fluorescence-activated cell sorting analyses confirmed these cellular identities. These results indicate that unintended cells originate from leukapheresis, the first step of the manufacturing process, and thus likely safe. Consistently, no overt toxicity or tumorigenicity was observed in mice inoculated with CUD-002. CONCLUSIONS: Considering that leukapheresis is a widely used procedure for collecting diverse peripheral blood cell types to manufacture various cytotherapies, this study establishes a workflow to analyze and address regulatory considerations on cell type heterogeneity.


Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Vacunas , Animales , Ratones , Vacunas contra el Cáncer/genética , Células Dendríticas , Inmunoterapia/métodos , Neoplasias/terapia , Análisis de Secuencia de ARN , Vacunas/metabolismo , Estudios Clínicos como Asunto
11.
J Obstet Gynaecol Res ; 49(2): 479-486, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36328803

RESUMEN

INTRODUCTION: Singleton normal fetus with partial hydatidiform mole (PHM) pregnancy is a rare phenomenon. No previous reports have investigated the risk factors of gestational trophoblastic neoplasia (GTN) progression following this condition. METHODS: We retrospectively enrolled cases of singleton normal fetuses with PHM pregnancies at West China Second University Hospital, Sichuan University, from 2005 to 2017. Other cases were identified from PubMed databases during 1975 to 2021 for the cohort study. Cox proportional hazards models were applied to evaluate risk factors for GTN progression based on the patient's clinical characteristics. RESULTS: Overall, 36 cases of singleton normal fetuses with PHM pregnancies were enrolled. After a median follow-up of 4.0 (0.8-12.0) months, nine (25.0%) patients progressed to GTN. Gestational age at pregnancy termination (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.78-0.99, p = 0.032), hyperthyroidism (HR 5.75; 95% CI, 1.16-28.50, p = 0.032), and reasons for pregnancy termination (medical indications vs. patients' choice; HR 0.25; 95% CI, 0.06-0.99, p = 0.049) were significantly correlated with GTN progression. Area under the receiver operating characteristic curve (AUC) of gestational age at pregnancy termination to predict non-progression to GTN was 0.784 (95% CI, 0.615-0.903, p < 0.001). A clinically significant cutoff value, that is, gestational age of 24 weeks, was determined by comprehensively considering the cutoff values of AUC and clinical significance of gestational age. CONCLUSIONS: Compared to gestational age of pregnancy termination <24 weeks, ≥24 weeks was a protective factor for GTN. Therefore, there is enough evidence to continue pregnancy, except for uncontrolled severe complications, without increasing the risk of GTN progression.


Asunto(s)
Enfermedad Trofoblástica Gestacional , Mola Hidatiforme , Neoplasias Uterinas , Femenino , Embarazo , Humanos , Lactante , Estudios Retrospectivos , Estudios de Cohortes , Neoplasias Uterinas/epidemiología , Enfermedad Trofoblástica Gestacional/epidemiología , Factores de Riesgo , Feto
12.
Eur Radiol ; 32(10): 6850-6858, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35579712

RESUMEN

OBJECTIVES: Cancer chemotherapy potentially increases the risk of myocardial ischemia. This study assessed myocardial microvascular function by cardiac magnetic resonance (CMR) first-pass perfusion in patients treated with chemotherapy for gynecologic malignancies. METHODS: A total of 81 patients treated with chemotherapy for gynecologic malignancies and 39 healthy volunteers were prospectively enrolled and underwent CMR imaging. Among the patients, 32 completed CMR follow-up, with a median interval of 6 months. The CMR sequences comprised cardiac cine, rest first-pass perfusion, and late gadolinium enhancement. RESULTS: There were no significant differences in the baseline characteristics between the patients and normal controls (all p > 0.05). Compared with the normal controls, the patients had a lower myocardial perfusion index (PI) (13.62 ± 2.01% vs. 12% (11 to 14%), p = 0.001) but demonstrated no significant variation with an increase in the number of chemotherapy cycles at follow-up (11.79 ± 2.36% vs. 11.19 ± 2.19%, p = 0.234). In multivariate analysis with adjustments for clinical confounders, a decrease in the PI was independently associated with chemotherapy treatment (ß = - 0.362, p = 0.002) but had no correlation with the number of chemotherapy cycles (r = - 0.177, p = 0.053). CONCLUSION: Myocardial microvascular dysfunction was associated with chemotherapy treatment in patients with gynecologic malignancies, and can be assessed and monitored by rest CMR first-pass perfusion. KEY POINTS: • Chemotherapy was associated with but did not aggravate myocardial microvascular dysfunction in patients with gynecologic malignancies. • Rest CMR first-pass perfusion is an ideal modality for assessing and monitoring alterations in myocardial microcirculation during chemotherapy treatment.


Asunto(s)
Cardiomiopatías , Neoplasias de los Genitales Femeninos , Imagen de Perfusión Miocárdica , Medios de Contraste , Circulación Coronaria , Femenino , Gadolinio , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Humanos , Imagen por Resonancia Cinemagnética , Espectroscopía de Resonancia Magnética , Imagen de Perfusión Miocárdica/métodos , Perfusión , Valor Predictivo de las Pruebas
13.
Arch Gynecol Obstet ; 305(4): 929-935, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34542678

RESUMEN

OBJECTIVE: The aim of this study was to investigate the diagnosis, treatment, and prognosis of patients with brain metastases from gestational trophoblastic neoplasia (GTN) in the real world. METHODS: Analyzing the clinicopathological characteristics, treatment process, and prognosis of 14 GTN patients with brain metastases admitted to the West China Second University Hospital between January 2006 and December 2020. RESULTS: The median FIGO prognostic score was 15 points (range 11-21 points), with 12 cases having 13 points or more (extremely high risk). All patients received combination chemotherapy. The first-line regimen included 5-Fluorouracil, dactinomycin, and intrathecal methotrexate (5-FU + KSM + intrathecal MTX), and etoposide + methotrexate + actinomycin D/cyclophosphamide and vincristine (EMA-CO). Two patients died during the early period after diagnosis of brain metastases. A further patient with GTN Stage III failed to achieve a negative serum ß human chorionic gonadotropin (hCG) after receiving chemotherapy in another hospital. Ten months after self-discontinuation of treatment, the disease progressed and she was admitted to our hospital with suspected liver and brain metastases, after which she abandoned treatment and was lost to follow-up. Among the remaining 11 patients, one relapsed once and two relapsed three times. Aside from the two patients who died and the one who was lost to follow-up, the remaining 11 patients had a median follow-up time of 89 months (range 35-148 months) and all achieved complete remission. CONCLUSION: The overall survival rate of the patients in the present study was 78.57% through combination chemotherapy, symptomatic treatment, and co-treatment with brain radiotherapy for some patients. Enhancing the understanding of this disease and standardizing treatment are key to improving the overall survival rate of GTN patients with brain metastases.


Asunto(s)
Neoplasias Encefálicas , Enfermedad Trofoblástica Gestacional , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/secundario , Gonadotropina Coriónica Humana de Subunidad beta , Ciclofosfamida/uso terapéutico , Dactinomicina/uso terapéutico , Femenino , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Enfermedad Trofoblástica Gestacional/patología , Humanos , Metotrexato/uso terapéutico , Embarazo , Estudios Retrospectivos
14.
J Obstet Gynaecol ; 42(5): 830-837, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35148230

RESUMEN

To verify the role of consolidation chemotherapy after concurrent chemoradiotherapy for bulky and locally advanced cervical cancer, a meta-analysis was performed. Based on articles published up to Jun 2020 a literature search in PubMed, EMBASE and Cochrane Library was conducted to identify eligible studies. A total of 4 articles consisting of 1659 patients were enrolled. The pooled results revealed that overall survival (OS) of patients treated with consolidation chemotherapy after concurrent chemoradiotherapy (CCRT + CT) was significantly superior to concurrent chemoradiotherapy (CCRT) alone (HR = 0.78, 95% CI: 0.69-0.88, p < .0001). The meta-analysis reviewed that the progression-free survival rate (PFS) of patients treated with CCRT + CT was significantly superior to CCRT alone (HR = 0.80, 95% CI: 0.73-0.87, p < .00001). The pooled results revealed a significant reduction of local recurrence rate for the CCRT + CT group (RR = 0.66, 95% CI: 0.55-0.79, p < .00001). The pooled meta-analysis also showed a significant reduction of distant recurrence rate for the CCRT + CT group (RR = 0.55, 95% CI: 0.44-0.69, p < .00001). The pooled results of grade 3/4 bone marrow suppression were calculated as OR and presented with a 95% CI (OR = 15.85; 95% CI: 9.48, 26.5, p < .00001), indicating patients who received CCRT + CT are more likely to suffer 3/4 bone marrow suppression than those treated with CCRT alone. In conclusion, patients who received chemoradiation with consolidation chemotherapy showed a significantly longer PFS, longer OS, lower local recurrence rate and distant recurrence rate compared to traditional concurrent chemoradiotherapy.Impact statementWhat is already known on this subject? Since CCRT was recommended as the standard treatment for cervical cancer, there was still a 20-30% chance of local recurrence, and 18-25% of distant recurrence for cervical cancer patients. Aiming to completely eradicate potential undetected micrometastases, consolidation chemotherapy came into the area of interest. We conducted a meta-analysis to verify the role of consolidation chemotherapy in cervical cancer.What do the results of this study add? The addition of consolidation CT resulted in a longer overall survival rate (OS) and progression-free survival rate (PFS), mainly due to control of local and distant relapses, especially the latter one. Toxicity followed consolidation CT increased but still clinically manageable.What are the implications of these findings for clinical practice and/or further research? In the future, we need more clinical studies with high quality to verify the role of consolidation CT in cervical cancer, and further to optimise the criteria for it.


Asunto(s)
Quimioterapia de Consolidación , Neoplasias del Cuello Uterino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Quimioterapia de Consolidación/métodos , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Supervivencia sin Progresión , Neoplasias del Cuello Uterino/patología
15.
Gynecol Oncol ; 160(1): 175-181, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33250205

RESUMEN

PURPOSE: Maintenance therapy with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib provided a substantial progression-free survival (PFS) benefit compared with placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (BRCAm) who were in clinical complete or partial response following platinum-based chemotherapy in the Phase III SOLO1 global study. This led to the approval of maintenance olaparib in China, USA, EU, Japan and other countries, in the newly diagnosed setting. This separate China cohort of the SOLO1 study investigated the efficacy and safety of maintenance olaparib within the Chinese population. PATIENTS AND METHODS: In this double-blind, multicentre study, patients were randomized 2:1 to receive oral olaparib tablets (300 mg twice daily) or placebo. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). RESULTS: Of the 64 randomized patients, 44 received olaparib and 20 placebo. Olaparib reduced the risk of disease progression or death by 54% compared with placebo (HR 0.46, 95% Cl 0.23-0.97; median PFS was not reached in the olaparib arm vs 9.3 months in the placebo arm). The most common AEs in the olaparib arm were nausea (63.6 vs 25.0% with placebo), anaemia (59.1 vs 15.0%) and leukopenia (54.5 vs 20.0%). Grade ≥3 AEs were experienced by 56.8% of olaparib patients and 30.0% of placebo patients. CONCLUSIONS: Results in the SOLO1 China cohort support the use of olaparib as maintenance treatment for Chinese patients with newly diagnosed advanced ovarian cancer who have a BRCAm and are in complete or partial response after platinum-based chemotherapy.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Pueblo Asiatico/genética , China , Estudios de Cohortes , Método Doble Ciego , Femenino , Mutación de Línea Germinal , Humanos , Quimioterapia de Mantención , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos
16.
Oncologist ; 25(1): 19-e10, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31439812

RESUMEN

LESSONS LEARNED: Pharmacokinetics characteristics of niraparib in Chinese patients were similar to those in white patients. Niraparib could be well tolerated by Chinese patients, and adverse events were manageable in this study. Population pharmacokinetics analysis indicated that baseline body weight had a modest impact on pharmacokinetics parameters of niraparib; however, it was not considered clinically important. BACKGROUND: This randomized, open-label, single-arm, phase I study was designed to investigate the pharmacokinetics (PK) and safety of niraparib in Chinese patients with epithelial ovarian cancer. METHODS: Eligible patients were randomized in a 1:1:1 ratio to receive 100, 200, or 300 mg of niraparib once daily. PK parameters were analyzed after single and multiple dose administrations. RESULTS: Thirty-six Chinese patients were enrolled in total. Niraparib was rapidly absorbed after administration, and median time-to-peak (Tmax ) was 3 hours. The long terminal elimination half-life (T1/2 ∼ 35 hours) supports once-daily dosing regimen. The exposure to niraparib showed linear and dose-proportional pharmacokinetics, whereas other PK parameters such as Tmax , T1/2 , and accumulation ratio were dose independent. Population PK analysis indicated that there was no effect of race on niraparib PK parameters, whereas baseline body weight had a modest impact on niraparib exposure. Grade 3/4 treatment-emergent adverse events (TEAEs; reported in ≥10% of patients) included platelet count decreased (a total of five patients who were all from the 300-mg group) and neutrophil count decreased. The TEAEs were manageable after dose modification. CONCLUSION: The PK profile of niraparib in Chinese patients is consistent with that in white patients. Niraparib is safe and well tolerated in Chinese patients with ovarian cancer.


Asunto(s)
Indazoles/farmacocinética , Indazoles/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Piperidinas/farmacocinética , Piperidinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Femenino , Humanos , Masculino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología
17.
Cancer ; 125(7): 1030-1037, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30748006

RESUMEN

We conducted a systematic review of the epidemiology of high-risk human papillomavirus (HPV) infections in mainland Chinese women to provide a general profile for the application and subsequent effectiveness evaluation of HPV vaccines. The PubMed, Web of Science, Medline (Ovid), China National Knowledge Infrastructure, and Wanfang databases were used for the literature search. The epidemiological studies published from January 2000 to June 2018 on high-risk HPVs in mainland Chinese women were investigated to systematically evaluate their epidemiological status. A total of 198 eligible studies were included. The results of meta-analysis showed that the overall infection rate of high-risk HPVs in mainland Chinese women was 19.0% (95% confidence interval [CI], 17.1%-20.9%), and the top 5 subtypes with the highest infection rates were 16, 52, 58, 53, and 18. The overall infection rates of cervical intraepithelial neoplasia I (CINI), CINII+, and cervical cancer patients were 59.6% (95% CI, 52.7%-66.4%), 84.8% (95% CI, 81.2%-88.5%), and 89.9% (95% CI, 86.6%-93.1%), respectively. The high-risk HPV infections and common subtypes in women of various ages in various regions were different, and the high-risk HPVs and subtypes in cervical cancer patients in various regions were also different. In conclusion, we systematically analyzed the HPV infections in women who live on the Chinese mainland. The epidemiology of high-risk HPVs in mainland Chinese women is basically consistent with that for the rest of the world. The HPV vaccines currently licensed in China could cover the major prevalent high-risk HPV subtypes in China, providing a basis for the development of a cervical cancer screening strategy and vaccine implementation in China.


Asunto(s)
Infecciones por Papillomavirus/epidemiología , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Distribución por Edad , China/epidemiología , Detección Precoz del Cáncer , Femenino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/uso terapéutico , Prevalencia , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virología
18.
Mol Carcinog ; 58(12): 2286-2296, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31545000

RESUMEN

Differentiation antagonizing non-protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and cell lines. The functional role of DANCR in tumor angiogenesis was revealed by the following methods: CD31 staining of ovarian tumor tissues, matrigel-plug assay tissues, HUVEC-related tube formation assay, and invasion assay. Enzyme-linked immunosorbent assay, Western blotting, luciferase assay, and rescue experiments were used to investigate the underlying mechanisms of DANCR-regulating angiogenesis. DANCR was upregulated in ovarian malignant tissues and ovarian cancer cells. Knockdown of DANCR efficiently impaired ovarian tumor growth through inhibition of tumor angiogenesis. Furthermore, the conditional culture medium from DANCR-knockdown ovarian cells significantly inhibited tube formation and invasion of HUVEC in vitro. Mechanistic investigation indicated that vascular endothelial growth factor A (VEGF-A, VEGF) plays a crucial role during DANCR inhibition of tumor angiogenesis in ovarian cancer. Further results demonstrated that miR-145 is the direct binding target of DANCR during regulation of VEGF expression and tumor angiogenesis in ovarian cancer cells. Collectively, DANCR plays a promotional role in tumor angiogenesis in ovarian cancer through regulation of miR-145/VEGF axis. Therefore, DANCR may be a novel therapy target for ovarian cancer.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neovascularización Patológica/genética , Neoplasias Ováricas/genética , ARN Largo no Codificante/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Ratones , Neovascularización Patológica/metabolismo , Neoplasias Ováricas/irrigación sanguínea , Neoplasias Ováricas/terapia , Interferencia de ARN , Tratamiento con ARN de Interferencia/métodos , Carga Tumoral/genética , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
20.
Int J Gynecol Cancer ; 27(8): 1650-1657, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28692638

RESUMEN

OBJECTIVE: Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing ovarian cancer and enhanced sensitivity to platinum-containing agents and PARP (poly[ADP-ribose] polymerase) inhibitors. BRCA mutations in Asian patients are poorly understood compared with other populations. We aimed to investigate gBRCAm prevalence and characteristics in Chinese ovarian cancer patients. METHODS: We conducted the first nationwide multicenter gBRCAm prevalence study in China. Eight hundred twenty-six unselected ovarian cancer patients from 5 clinical centers were enrolled and tested for gBRCAm status. Medical data including age, family history, previous treatments, clinical diagnosis, histopathologic diagnosis, tumor grade, platinum sensitivity, and CA-125 test result were reviewed and collected. RESULTS: Prevalence rate or gBRCAm was determined as 28.5%, with 20.8% of patients harboring BRCA1 mutation and 7.6% harboring BRCA2 mutation. The group had a higher percentage of high-grade serous (73.0%), late-stage (III and IV [85.5%]) patients and a younger median age at diagnosis (52 years) compared with other reported studies. Twnety-seven BRCA1 and 17 BRCA2 mutations have not been reported previously in public databases or the literature. Statistically significant correlations were observed between gBRCAm status and family history (P < 0.001), gBRCAm status, and tumor stage (P = 0.02). A numerical higher prevalence of gBRCAm in patients with high-grade serous histopathology (30.9%), platinum-sensitive phenotype (34%), and late-line chemotherapy was observed. CONCLUSIONS: Germline BRCA1/2 mutations is common in Chinese ovarian cancer patients. This study implies that all ovarian patients should be tested for gBRCAm status regardless of family history and histopathology.


Asunto(s)
Pueblo Asiatico/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Mutación de Línea Germinal , Neoplasias Ováricas/genética , Adulto , Anciano , Pueblo Asiatico/estadística & datos numéricos , China/epidemiología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/epidemiología , Prevalencia
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