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1.
Medicine (Baltimore) ; 99(36): e22029, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899058

RESUMO

This study aims to describe the role of open surgical treatment for focal brainstem gliomas (FBSGs) with the assistance of multimodal neuronavigation and intraoperative neurophysiological monitoring (IOM) in children to investigate the efficacy of microsurgical treatment in pediatric FBSGs. Also the prognostic factors related to the overall survival (OS) of FBSGs to describe the patient and tumor characteristics relevant to prognosis/outcome were focused on. Clinical data of 63 pediatric patients below 16 years of age with FBSGs admitted to the Neurosurgical Unit of Beijing Tiantan Hospital from January 2012 to December 2018 were retrospectively analyzed. All patients underwent initial surgical treatment, followed by magnetic resonance diffusion tensor imaging (DTI), neuronavigation and IOM. Gross or near total resection (GTR or NTR) was achieved in 57/63 (90.5%) cases, and subtotal resection (STR) was achieved in 6/63 (9.5%) cases. Postoperative adjuvant therapy was received by 27/63 (42.9%) cases. Postoperative pathological examination revealed that 36/63 (57.1%) cases had grade I gliomas, 22/63 (34.9%) had grade II, and 5/63 (8.0%) had grade III-IV gliomas according to the WHO classification. The mean Karnofsky score preoperatively was 60, and at the time of follow-up was 90. Consecutively, 6 cases demonstrated disease progression, and 5 of these were deceased. The OS in all patients was 81.2% at 5 years. Histological grade (P < .001) and age at diagnosis (P = .023) showed significant association with prolonged OS. Multimodal neuronavigation and IOM allow very precise intracranial surgery, contributing to a maximally safe resection that might decrease the postoperative disability and mortality rate. This study also showed that pediatric FBSGs were mostly low-grade tumors with excellent surgical outcomes. Consequently, it is suggested that microsurgery can be used to treat FBSGs in children in order to provide better prognosis and survival outcomes.


Assuntos
Neoplasias do Tronco Encefálico/patologia , Glioma/cirurgia , Monitorização Neurofisiológica Intraoperatória/métodos , Neuronavegação/métodos , Adolescente , Quimioterapia Adjuvante , Criança , Pré-Escolar , China/epidemiologia , Imagem de Tensor de Difusão/métodos , Progressão da Doença , Feminino , Glioma/diagnóstico por imagem , Humanos , Lactente , Avaliação de Estado de Karnofsky , Masculino , Microcirurgia/métodos , Gradação de Tumores , Cuidados Pós-Operatórios , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
2.
Clinics (Sao Paulo) ; 75: e1553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32935821

RESUMO

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Glioblastoma/terapia , Recidiva Local de Neoplasia/epidemiologia , Temozolomida/uso terapêutico , Neoplasias Encefálicas/patologia , Brasil/epidemiologia , Quimioterapia Adjuvante , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Estudos Retrospectivos , Sobrevida , Resultado do Tratamento
3.
PLoS Med ; 17(9): e1003292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32970670

RESUMO

BACKGROUND: Identifying stage II patients with colorectal cancer (CRC) at higher risk of progression is a clinical priority in order to optimize the advantages of adjuvant chemotherapy while avoiding unnecessary toxicity. Recently, the intensity and the quality of the host immune response in the tumor microenvironment have been reported to have an important role in tumorigenesis and an inverse association with tumor progression. This association is well established in microsatellite instable CRC. In this work, we aim to assess the usefulness of measures of T-cell infiltration as prognostic biomarkers in 640 stage II, CRC tumors, 582 of them confirmed microsatellite stable. METHODS AND FINDINGS: We measured both the quantity and clonality index of T cells by means of T-cell receptor (TCR) immunosequencing in a discovery dataset (95 patients with colon cancer diagnosed at stage II and microsatellite stable, median age 67, 30% women) and replicated the results in 3 additional series of stage II patients from 2 countries. Series 1 and 2 were recruited in Barcelona, Spain and included 112 fresh frozen (FF, median age 69, 44% women) and 163 formalin-fixed paraffin-embedded (FFPE, median age 67, 39% women) samples, respectively. Series 3 included 270 FFPE samples from patients recruited in Haifa, Northern Israel, as part of a large case-control study of CRC (median age 73, 46% women). Median follow-up time was 81.1 months. Cox regression models were fitted to evaluate the prognostic value of T-cell abundance and Simpson clonality of TCR variants adjusting by sex, age, tumor location, and stage (IIA and IIB). In the discovery dataset, higher TCR abundance was associated with better prognosis (hazard ratio [HR] for ≥Q1 = 0.25, 95% CI 0.10-0.63, P = 0.003). A functional analysis of gene expression on these tumors revealed enrichment in pathways related to immune response. Higher values of clonality index (lower diversity) were not associated with worse disease-free survival, though the HR for ≥Q3 was 2.32 (95% CI 0.90-5.97, P = 0.08). These results were replicated in an independent FF dataset (TCR abundance: HR = 0.30, 95% CI 0.12-0.72, P = 0.007; clonality: HR = 3.32, 95% CI 1.38-7.94, P = 0.007). Also, the association with prognosis was tested in 2 independent FFPE datasets. The same association was observed with TCR abundance (HR = 0.41, 95% CI 0.18-0.93, P = 0.03 and HR = 0.56, 95% CI 0.31-1, P = 0.042, respectively, for each FFPE dataset). However, the clonality index was associated with prognosis only in the FFPE dataset from Israel (HR = 2.45, 95% CI 1.39-4.32, P = 0.002). Finally, a combined analysis combining all microsatellite stable (MSS) samples demonstrated a clear prognosis value both for TCR abundance (HR = 0.39, 95% CI 0.26-0.57, P = 1.3e-06) and the clonality index (HR = 2.13, 95% CI 1.44-3.15, P = 0.0002). These associations were also observed when variables were considered continuous in the models (HR per log2 of TCR abundance = 0.85, 95% CI 0.78-0.93, P = 0.0002; HR per log2 or clonality index = 1.16, 95% CI 1.03-1.31, P = 0.016). LIMITATIONS: This is a retrospective study, and samples had been preserved with different methods. Validation series lack complete information about microsatellite instability (MSI) status and pathology assessment. The Molecular Epidemiology of Colorectal Cancer (MECC) study had information about overall survival instead of progression-free survival. CONCLUSION: Results from this study demonstrate that tumor lymphocytes, assessed by TCR repertoire quantification based on a sequencing method, are an independent prognostic factor in microsatellite stable stage II CRC.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Repetições de Microssatélites/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Estudos de Casos e Controles , Quimioterapia Adjuvante , Neoplasias Colorretais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Instabilidade de Microssatélites , Repetições de Microssatélites/imunologia , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espanha , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
4.
Nat Commun ; 11(1): 4858, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32978382

RESUMO

Overtreatment with cisplatin-based chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC), and currently none of the reported biomarkers for predicting response have been implemented in the clinic. Here we perform a comprehensive multi-omics analysis (genomics, transcriptomics, epigenomics and proteomics) of 300 MIBC patients treated with chemotherapy (neoadjuvant or first-line) to identify molecular changes associated with treatment response. DNA-based associations with response converge on genomic instability driven by a high number of chromosomal alterations, indels, signature 5 mutations and/or BRCA2 mutations. Expression data identifies the basal/squamous gene expression subtype to be associated with poor response. Immune cell infiltration and high PD-1 protein expression are associated with treatment response. Through integration of genomic and transcriptomic data, we demonstrate patient stratification to groups of low and high likelihood of cisplatin-based response. This could pave the way for future patient selection following validation in prospective clinical trials.


Assuntos
Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Biomarcadores Tumorais , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Metilação de DNA , Tratamento Farmacológico , Instabilidade Genômica , Humanos , Mutação , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Transcriptoma , Neoplasias da Bexiga Urinária/patologia
5.
Bone Joint J ; 102-B(10): 1392-1398, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32993346

RESUMO

AIMS: There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence? METHODS: A total of 114 patients with a sacral GCT who underwent nerve-sparing surgery at our hospital between July 2005 and August 2017 were reviewed. The rate of local recurrence was determined, and Kaplan-Meier survival analysis carried out to evaluate the mean recurrence-free survival. Possible risks factors including demographics, tumour characteristics, adjuvant therapy, operation, and laboratory indices were analyzed using univariate analysis. Variables with p < 0.100 in the univariate analysis were further considered in a multivariate Cox regression analysis to identify the risk factors. RESULTS: The rate of local recurrence of sacral GCT treated with nerve-sparing surgery was 28.95% (33/114). Multivariate Cox regression analysis showed that large tumour size (> 8.80 cm) (hazard ratio (HR) 3.16; 95% confidence interval (CI) 1.27 to 7.87; p = 0.014), high neutrophil-to-lymphocyte ratio (NLR) (> 2.09) (HR 3.13; 95% CI 1.28 to 7.62; p = 0.012), involvement of a sacroiliac joint (HR 3.09; 95% CI 1.06 to 9.04; p = 0.039), and massive intraoperative blood loss (> 1,550 ml) (HR 2.47; 95% CI 1.14 to 5.36; p = 0.022) were independent risk factors for local recurrence. CONCLUSION: Patients with a sacral GCT who undergo nerve-sparing surgery have a local recurrence rate of 29%. Large tumour size, high NLR, involvement of a sacroiliac joint, and massive intraoperative blood loss are independent risk factors. Cite this article: Bone Joint J 2020;102-B(10):1392-1398.


Assuntos
Tumor de Células Gigantes do Osso/cirurgia , Recidiva Local de Neoplasia/patologia , Sacro/cirurgia , Adulto , Quimioterapia Adjuvante , Curetagem , Feminino , Tumor de Células Gigantes do Osso/patologia , Humanos , Monitorização Neurofisiológica Intraoperatória , Masculino , Estudos Retrospectivos , Fatores de Risco , Sacro/patologia
6.
Medicine (Baltimore) ; 99(39): e22250, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991420

RESUMO

It is unclear whether the use of antibiotics is related to the efficacy of gemcitabine plus nab-paclitaxel (GnP). Therefore, we investigated the association between the use of antibiotics and efficacy of GnP.We conducted a retrospective single center study from January 2014 to December 2018 in Hokkaido University Hospital.Ninety-nine patients were eligible for the study. Thirty-seven used antibiotics (U) and 62 did not use antibiotics (NU) during GnP therapy. In the U group, 15 patients used ß-lactam antibiotics, 21 used new quinolones, and 1 used carbapenem. The median progression-free survival was 5.8 and 2.7 months (hazards ratio [HR] .602, 95% confidence interval [CI] .391-.928, P = .022) and the median overall survival was 11.0 and 8.4 months (HR .768, 95% CI .491-1.202, P = .248) in the U and not use antibiotics groups, respectively. Antibiotic use (HR .489, 95% CI .287-.832, P = .008) and locally advanced pancreatic cancer (HR 1.808, 95% CI 1.051-3.112, P = .032) were independent prognostic factors for progression-free survival.Antibiotic use was associated with a higher efficacy of GnP, and therefore, it may be employed as a novel treatment strategy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/uso terapêutico , Antibacterianos/uso terapêutico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica , Estudos de Casos e Controles , Quimioterapia Adjuvante/métodos , Desoxicitidina/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 99(35): e21721, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871890

RESUMO

The aim of this study was to provide an innovative nomogram to predict the risk of >2 positive nodes in patients fulfilling the Z0011 criteria with 1-2 sentinel lymph nodes (SLNs) only retrieved.From 2007 to 2017, at the Breast Unit of ICS Maugeri Hospital 271 patients with 1-2 macrometastatic SLNs, fulfilling the Z0011 criteria, underwent axillary dissection and were retrospectively reviewed.A mean of 1.5 SLNs per patient were identified and retrieved. One hundred eighty-seven (69.0%) had 1-2 positive nodes, and 84 (31.0%) had >2 metastatic nodes. Independent predictors of axillary status were: positive SLNs/retrieved SLNs ratio (odds ratio [OR] 10.95, P = .001), extranodal extension (OR 5.51, P = .0002), and multifocal disease (OR 2.9, P = .003). A nomogram based on these variables was constructed (area under curve after bootstrap = 0.74).The proposed nomogram might select those patients fulfilling the Z0011 criteria, with 1-2 SLNs harvested, in whom a high axillary tumor burden is expected, aiding to guide adjuvant treatments.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Primárias Múltiplas/patologia , Nomogramas , Linfonodo Sentinela/patologia , Idoso , Antineoplásicos Hormonais/uso terapêutico , Área Sob a Curva , Axila , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Metástase Linfática , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Carga Tumoral
8.
Anticancer Res ; 40(10): 5765-5776, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988904

RESUMO

BACKGROUND/AIM: We evaluated the safety, feasibility, and preliminary efficacy of Wilms tumor gene 1 (WT1) peptide and Mucin 1 (MUC1)-pulsed dendritic cell (DC) (WT1/MUC1-DC) vaccination as an adjuvant immunotherapy for surgically resectable pancreatic ductal adenocarcinoma (PDA) patients. PATIENTS AND METHODS: Eligible patients were administered WT1/MUC1-DC vaccination at least seven times every 2 weeks with concomitant adjuvant chemotherapy after surgical resection of PDA. RESULTS: Ten patients were enrolled and no Grade 2 or higher toxicities were associated with DC vaccination. The estimated overall survival (OS) and relapse-free survival (RFS) at 3-years from the time of surgical resection were 77.8% and 35.0%, respectively. Immunohistochemical analysis suggested a possible relationship between induction of WT1-specific cytotoxic T lymphocyte after DC vaccination and higher infiltration of CD3/CD4/CD8 lymphocytes in tumor tissues. CONCLUSION: WT1/MUC1-DC vaccination in the adjuvant setting was safe and well-tolerated in PDA patients after tumor resection. A large-scale prospective study is warranted to evaluate the clinical benefit of this modality.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Mucina-1/genética , Proteínas WT1/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante/métodos , Células Dendríticas/imunologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Mucina-1/uso terapêutico , Proteínas WT1/uso terapêutico
9.
Anticancer Res ; 40(10): 5869-5875, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988917

RESUMO

BACKGROUND/AIM: We aimed to identify differences in cytoreduction rates and procedures performed in patients with advanced ovarian cancer undergoing primary (PDS) or interval debulking surgery (IDS). PATIENTS AND METHODS: Data were collected prospectively on 110 consecutive patients from June 2016 to Mar 2020. RESULTS: Forty-nine patients (44.5%) underwent diaphragmatic peritonectomy (34 in PDS and 15 in IDS, p=0.005), while 38 (34.5%) underwent large bowel resection (29 in PDS and 9 in IDS, p<0.001). Complete cytoreduction was achieved in 39 patients in PDS and 29 in IDS (65% vs. 58%, p=0.22). Longer operations with more blood loss and extended hospital stay were performed in the PDS group. Ten patients (9.1%) experienced severe complications and in eight patients (7.2%) chemotherapy was delayed. CONCLUSION: More bowel resections and diaphragmatic stripping were performed in the PDS group. End surgical results were similar between groups, with a trend for more complete cytoreduction in PDS.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/cirurgia , Ovário/cirurgia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ovário/patologia
10.
Anticancer Res ; 40(9): 4819-4828, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878770

RESUMO

Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is standard treatment for locally advanced cervical cancer. Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative approach, especially for patients with stage Ib2-IIb disease. This review analyzes the most commonly used combination regimens in this clinical setting and the randomized trials comparing chemo-surgery versus definitive radiotherapy or CCRT. The combination of paclitaxel plus ifosfamide plus cisplatin (TIP regimen) obtained the highest rates of optimal pathological response, associated with elevated hematological toxicity. In a recent phase II study, a dose-dense regimen consisting of weekly paclitaxel plus carboplatin for 9 cycles has achieved optimal pathological response rates similar to those of TIP with better toxicity profile. Further studies are strongly warranted to better define the optimal regimen for the patients selected to receive NACT followed by radical surgery.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia , Terapia Neoadjuvante , Prognóstico , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia
11.
Anticancer Res ; 40(9): 4869-4874, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878774

RESUMO

BACKGROUND/AIM: In the present study, we evaluated the efficacy of adjuvant administration of oral recombinant methioninase (o-rMETase) against recurrence and metastasis in a 4T1 murine breast-cancer syngeneic model. MATERIALS AND METHODS: 4T1 cells were orthotopically implanted into the 2nd mammary fat pad of BALB/c mice. The 4T1 orthotopic syngeneic models were randomized into 2 groups after primary tumor resection: untreated control and o-rMETase (100 units, oral, daily, 2 weeks). RESULTS: The frequency and extent of local recurrence were reduced by o-rMETase. The number of individual cancer cells and metastatic nodules on the lung surface was significantly lower in the o-rMETase-treated mice than the untreated control mice. CONCLUSION: Adjuvant o-rMETase inhibited local recurrence and lung metastasis after primary tumor resection.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/tratamento farmacológico , Administração Oral , Animais , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Esquema de Medicação , Feminino , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/cirurgia , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Medicine (Baltimore) ; 99(36): e22100, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899091

RESUMO

Intraperitoneal (IP) chemotherapy is believed to prolong the survival of patients with advanced ovarian cancer after primary debulking surgery. However, there is little knowledge about IP chemotherapy in the setting of neoadjuvant chemotherapy, and there are contradictory conclusions about adjuvant IP chemotherapy. Here, we evaluated the feasibility of neoadjuvant and adjuvant IP chemotherapy in patients with advanced epithelial ovarian cancer (AEOC).We retrospectively reviewed the data of 114 patients with AEOC who received neoadjuvant chemotherapy followed by laparoscopic conservative interval debulking surgery (NACT + LIDS) in our institution from January 1, 2009 to December 31, 2017.The median overall survival (OS) was 56 months and the median disease-free interval (DFI) was 14 months for the entire study population. Neoadjuvant IP chemotherapy cycles were crucial for the treatment of no gross residual (R0) disease (hazard ratio [HR] = 0.446, 95% confidence interval [CI] = 0.245-0.811), which was independently associated with OS of the entire study population (HR = 9.589, 95% CI = 3.911-23.507). In addition, residual disease and body mass index (BMI) were the prognostic factors for DFI (HR = 6.022, 95% CI = 3.632-9.986; HR = 1.085, 95% CI = 1.012-1.163). However, adjuvant IP cycles along with BMI were the determining factors for DFI in the R0 group (HR = 0.703, 95% CI = 0.525-0.941; HR = 1.130, 95% CI = 1.025-1.247), and were associated with OS in the R0 group (HR = 0.488, 95% CI = 0.289-0.824). The OS and DFI Kaplan-Meier curves stratified by adjuvant IP chemothearpy cycles within the R0 group were statistically significant (P = .024 and P = .033, respectively).Our results showed improvement in patients with AEOC in terms of survival, thus suggesting the feasibility of neoadjuvant and adjuvant IP chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Índice de Massa Corporal , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Infusões Parenterais , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos
13.
Medicine (Baltimore) ; 99(36): e22148, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899102

RESUMO

BACKGROUND: Oesophageal cancer (OC) is the sixth leading cause of cancer death worldwide. Despite the improvement of therapeutic methods in recent years, the prognosis of OC remains unsatisfactory. Kang-ai injection, a kind of traditional Chinese herbal medicine, has been widely applied as a promising adjunctive drug for OC. In this study, we aimed to summarize the efficacy and safety of Kang-ai injection for patients with advanced OC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: Relevant randomized controlled trials and high-quality prospective cohort studies were searched from PubMed, Web of Science, Medline, Cochrane Library, Google Scholar, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Scientific Journal Database and Wanfang Database. Papers in English or Chinese published from their inception to August 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, disease control rate, overall survival, disease-free survival, quality of life, immune function and adverse events, were systematically evaluated. Stata 14.0 and Review Manager 5.3 were used for data synthesis, subgroup analysis, sensitivity analysis, meta regression, and risk of bias assessment. RESULTS: The results of this study will be published in a peer-reviewed journal, or presented the findings at a relevant conference. CONCLUSION: Our study will draw an objective conclusion of the effects of Kang-ai injection combined with conventional treatment for advanced OC and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for OC patients. INPLASY REGISTRATION NUMBER: INPLASY202080019.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Quimioterapia Adjuvante , China , Intervalo Livre de Doença , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa , Análise de Sobrevida
14.
Nat Commun ; 11(1): 4498, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908142

RESUMO

The androgen receptor (AR) is the master regulator of prostate cancer (PCa) development, and inhibition of AR signalling is the most effective PCa treatment. AR is expressed in PCa cells and also in the PCa-associated stroma, including infiltrating macrophages. Macrophages have a decisive function in PCa initiation and progression, but the role of AR in macrophages remains largely unexplored. Here, we show that AR signalling in the macrophage-like THP-1 cell line supports PCa cell line migration and invasion in culture via increased Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) signalling and expression of its downstream cytokines. Moreover, AR signalling in THP-1 and monocyte-derived macrophages upregulates IL-10 and markers of tissue residency. In conclusion, our data suggest that AR signalling in macrophages may support PCa invasiveness, and blocking this process may constitute one mechanism of anti-androgen therapy.


Assuntos
Macrófagos/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Idoso , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Anilidas/farmacologia , Anilidas/uso terapêutico , Biópsia , Buffy Coat/citologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Quimioterapia Adjuvante , Técnicas de Cocultura , Intervalo Livre de Doença , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/prevenção & controle , Nitrilos/farmacologia , Nitrilos/uso terapêutico , Intervalo Livre de Progressão , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Procedimentos Cirúrgicos Robóticos , Transdução de Sinais/imunologia , Análise de Célula Única , Células THP-1 , Compostos de Tosil/farmacologia , Compostos de Tosil/uso terapêutico
15.
Medicine (Baltimore) ; 99(33): e20875, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871972

RESUMO

BACKGROUND: To systematically evaluate the efficacy and safety of sotagliflozin (SOTA) adjuvant therapy for type 1 diabetes mellitus (T1DM). METHODS: Through April 2019, the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure databases were electronically searched to identify randomized controlled trials exploring SOTA adjuvant therapy for T1DM. Strict screening and quality evaluations of the obtained literature were performed independently by 2 researchers. Outcome indexes were extracted, and a meta-analysis of the data was performed using Revman 5.3 software. RESULTS: A total of 7 randomized controlled trials were included. The meta-analysis results showed that compared with the patients in the placebo group, the patients in the SOTA group had a lower hemoglobin A1c (mean difference [MD] = -0.28, 95% confidence interval [CI] [-0.34, -0.22], P < .01), lower total daily insulin use (MD = -8.89, 95% CI [-11.64, -6.13], P < .01), faster weight loss (MD = -3.03, 95% CI [-3.79, -2.26], P < .01), better fasting blood glucose and 2-hour postprandial blood glucose control (MD = -0.75, 95% CI [-1.04, -0.45], P < .01; MD = -2.42, 95% CI [-3.17, -1.67], P < .01), and a higher rate of well-controlled glucose levels (relative risk = 1.75, 95% CI [1.55, 1.99], P < .01), while no significant difference in the incidence of severe hypoglycemic events was found between the SOTA and placebo groups (risk difference [RD] = -0.01, 95% CI [-0.02, 0.00], P = .13). The incidence of diabetic ketoacidosis was higher in the SOTA group than in the placebo group (RD = 0.03, 95% CI [0.02, 0.04], P < .01). The incidence of genital mycotic infection was higher in the SOTA group than in the placebo group (RD = 0.06, 95% CI [0.05, 0.08], P < .01). No significant difference in the incidence of urinary tract infections was detected between the SOTA group and the placebo group (RD = 0.00, 95% CI [-0.01, 0.01], P = 0.97). CONCLUSIONS: SOTA is a potential drug for the treatment of T1DM and is effective for controlling blood sugar. The main adverse reactions to SOTA are genital mycotic infections and diabetic ketoacidosis. We must further assess the severity of diabetic ketoacidosis caused by SOTA.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicosídeos/efeitos adversos , Glicosídeos/uso terapêutico , Transportador 1 de Glucose-Sódio/efeitos adversos , Transportador 1 de Glucose-Sódio/uso terapêutico , Quimioterapia Adjuvante , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Zhonghua Yi Xue Za Zhi ; 100(34): 2682-2688, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-32921017

RESUMO

Objective: The aim of present study was to investigate the influence of genetic variation of programmed death-ligand 1 (PD-L1) on the prognosis of patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Methods: This study was designed as a retrospective analysis, and a total of 278 patients with postoperative NSCLC who received platinum-based adjuvant chemotherapy from January 2012 to December 2018 in the Department of Respiratory Medicine of the First affiliated Hospital of Zhengzhou University were included in this study. Biological specimens of the patients were collected during hospitalization. Recurrence status and adverse reactions were evaluated in the hospital during adjuvant chemotherapy. Survival data of the patients were obtained through telephone follow-up after completing the fixed cycle of adjuvant chemotherapy. DNA extracted from the collected hematological specimens was genotyped for PD-L1 gene polymorphism. Additionally, postoperative cancer tissue specimens from 68 patients were collected for RNA extraction in order to perform the PD-L1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis. Results: Prognostic results indicated that the median disease-free survival (DFS) of the 278 patients with NSCLC was 3.2 years and the median overall survival (OS) was 4.9 years. The prevalence of -1813G>C polymorphism were: GG genotype 173 cases (62.23%), GC genotype 92 cases (33.09%), CC genotype 13 cases (4.68%), the minor allele frequency was 0.21, the distribution of the three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.864). In view of the rare frequency of CC genotype, GC and CC genotype were merged in the following analysis. The survival analysis results of the two genotype groups suggested that the median DFS of patients with GG and GC/CC genotype was 2.7 and 4.0 years, which was statistically significant (P=0.013). Furthermore, the median OS of patients with GG and GC/CC was 4.0 and 5.4 years respectively, which was statistically significant as well (P=0.009). However, the safety analysis failed to find the significant association between the polymorphism and adverse events (P>0.05). Interestingly, expression analysis of RNA extracted from cancer tissues specimens indicated that the PD-L1 mRNA expression of the patients with GG genotype were significantly higher than those of the GC/CC genotype (3.67±0.65 vs 2.69±0.78, P<0.001). Conclusion: The prognosis of patients with postoperative non-small cell lung cancer who received platinum-based adjuvant chemotherapy is influenced by -1813G>C polymorphism of PD-L1 gene.


Assuntos
Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Quimioterapia Adjuvante , Humanos , Neoplasias Pulmonares/genética , Recidiva Local de Neoplasia , Platina/uso terapêutico , Prognóstico , Estudos Retrospectivos
17.
Medicine (Baltimore) ; 99(33): e21498, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871996

RESUMO

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Lipídeos/sangue , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
18.
Medicine (Baltimore) ; 99(31): e21281, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756108

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has gradually drawn the attention of clinicians as an alternative for Primary Liver Cancer (PLC), is based on the theory of syndrome differentiation. However, owing to the lack of evidence-based medical evidence, the authors designed this protocol to evaluate TCM's effectiveness and safety. METHODS: Seven electronic databases will be searched from inception to Aug. 2020. Two of us will independently identify randomized controlled trials, extract the data and assess the risk of bias. The meta-analysis will be conducted with the Review Manager 5.3 software according the heterogeneity of eligible studies. Further, we will use the grading of recommendations assessment, development, and evaluation to evaluate the evidence quality. RESULTS: This study will demonstrate an evidence-based review of TCM for PLC. CONCLUSION: The study will provide clear evidence to assess the effectiveness and side effects of TCM for PLC. TRIAL REGISTRATION NUMBER: PROSPERO CRD 42020173748.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Quimioterapia Adjuvante , Humanos , Medicina Tradicional Chinesa
19.
Medicine (Baltimore) ; 99(31): e21375, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756126

RESUMO

BACKGROUND: Poststroke depression is one of the common complications of clinical cerebrovascular diseases. It is commonly seen in 3 to 6 months after the onset of stroke. The incidence rate is 22% to 75%. The patient not only has depression-related emotional symptoms, but also are accompanied by autonomic nervous disorders and other physical symptoms. It will also delay the recovery time of patients' neurological function, cognitive function, and limb function due to different degrees of depression, and even further aggravate the mortality and risk of accidental death of cerebrovascular disease. In recent years, Chinese patent medicine combined with western medicine has been widely used in the treatment of this disease. Many clinical practices have proved that the adjuvant treatment of pure Chinese herbal medicine can effectively alleviate the poststroke depression state and reduce the neurological deficits. The author has sorted out the relevant literature and data analysis to screen out the seven most representative and commonly used Chinese patent medicine preparations in clinical treatment of poststroke depression, which have certain clinical comparability when the dosage form and syndrome type are relatively unified. The network meta-analysis method is used to select the best clinical treatment plan, so as to provide reference value and evidence-based medicine evidence for the clinical optimization of drug selection. METHODS: Using computer retrieval technology, comprehensive retrieval of CNKI, VIP, CBM, and WANFANG Chinese electronic database and the Cochrane Library, PubMed, Web of Science and EMBASE foreign electronic database. Search the clinical randomized controlled trials of these 7 kinds of Chinese patent medicines for adjuvant treatment of poststroke depression, and set a period of time is from the establishment of the database to May 31, 2020. The 3 authors will screen the literatures that meets the inclusion criteria, extract the data independently according to the predesigned rules, and evaluate the literature quality and bias risk of the included research according to the Cochrane 5.1 manual standard. R and the Aggregate Data Drug Information System software were used for data consolidation and network meta-analysis to evaluate the ranking probability of all interventions. RESULTS: This network meta-analysis and probability ranking will identify the best Chinese patent medicine adjuvant treatment for poststroke depression. CONCLUSION: This study will provide systematic evidence-based medicine evidence for Chinese patent medicine adjuvant treatment for poststroke depression, and help clinicians, patients with poststroke depression and decision-makers to make more effective, safer, and economic optimal treatment plan in the decision-making process. PROSPERO REGISTRATION NUMBER: CRD42020164543.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Acidente Vascular Cerebral/psicologia , Quimioterapia Adjuvante/métodos , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
20.
Medicine (Baltimore) ; 99(30): e21337, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791732

RESUMO

This study aim is to enhance the understanding, diagnosis and treatment of desmoplastic small round cell tumor (DSRCT) and to determine what factors can affect survival of the disease in China.We report here 8 patients with DSRCT in our center who received a variety of treatment methods. By reviewing the literature published from Chinese database (CNKI, WANGFAN, VIP, CBM, CMCC) in 2000 to 2015 with the terms of "dsrct", "desmoplastic" and "small round-cell tumor",104 eligible cases of DSRCT(including 8 cases in our hospital) were retrospectively analyzed.Among the 104 patients, Median age was 24 years with a range of 15 to 54 years. The main primary tumor site was the abdomen and/or pelvis in 92/104 patients (88.5%). Only 25% of patients had localized disease. Most of the patients had received adjuvant chemotherapy (87.5%) and 76.9% patients had not experienced adjuvant radiotherapy. One-fourth of the patients underwent grossly complete surgical resection, and 33.7% and 41.3% patients received no surgery and incomplete surgical resection, respectively. Median overall survival for all patients was 26 months (95% CI: 20.29-31.71). Multivariate analysis revealed that Metastatic status (HR: 2.327, 95% CI: 1.136-4.768, P = .021), Surgical patterns (HR: 0.673, 95% CI: 0.487-0.928, P = .016), and Adjuvant chemotherapy (HR: 0.337, 95% CI: 0.167-0.678, P = .002) were significant independent prognostic factors for longer overall survival. It was noteworthy that CD99 were significantly associated with OS (P = .002).Here, we identified the prognostic factors which may facilitate risk-adapted treatments for this rare DSRCT group, which should be further investigated.


Assuntos
Abdome/patologia , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Tumor Desmoplásico de Pequenas Células Redondas/terapia , Pelve/patologia , Procedimentos Cirúrgicos Operatórios/tendências , Antígeno 12E7/metabolismo , Adulto , Quimioterapia Adjuvante , China/epidemiologia , Terapia Combinada , Tumor Desmoplásico de Pequenas Células Redondas/metabolismo , Tumor Desmoplásico de Pequenas Células Redondas/mortalidade , Humanos , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida
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