RESUMO
The perioculomotor (pIII) region of the midbrain was postulated as a sleep-regulating center in the 1890s but largely neglected in subsequent studies. Using activity-dependent labeling and gene expression profiling, we identified pIII neurons that promote non-rapid eye movement (NREM) sleep. Optrode recording showed that pIII glutamatergic neurons expressing calcitonin gene-related peptide alpha (CALCA) are NREM-sleep active; optogenetic and chemogenetic activation/inactivation showed that they strongly promote NREM sleep. Within the pIII region, CALCA neurons form reciprocal connections with another population of glutamatergic neurons that express the peptide cholecystokinin (CCK). Activation of CCK neurons also promoted NREM sleep. Both CALCA and CCK neurons project rostrally to the preoptic hypothalamus, whereas CALCA neurons also project caudally to the posterior ventromedial medulla. Activation of each projection increased NREM sleep. Together, these findings point to the pIII region as an excitatory sleep center where different subsets of glutamatergic neurons promote NREM sleep through both local reciprocal connections and long-range projections.
Assuntos
Hipotálamo/metabolismo , Mesencéfalo/metabolismo , Neurônios/metabolismo , Fases do Sono/fisiologia , Animais , Colecistocinina/metabolismo , Hipotálamo/citologia , Mesencéfalo/citologia , Camundongos , Camundongos Transgênicos , Neurônios/citologia , OptogenéticaRESUMO
BACKGROUND: The combination of anti-programmed death 1 (PD-1) inhibitors and tyrosine kinase inhibitors is an effective treatment strategy in endometrial cancer. We aimed to explore the efficacy and safety of camrelizumab plus apatinib as an alternative therapeutic option in patients with previously treated endometrial cancer. METHODS: This single-arm Simon's two-stage phase II trial was conducted at the Fudan University Shanghai Cancer Center. Patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy were screened for potential participation. Eligible patients were treated with intravenous camrelizumab (200 mg d1 q2w) and oral apatinib (250 mg qd) every 4 weeks. The primary end point was the objective response rate (ORR) per RECIST v1.1 in the intention-to-treat principle. RESULTS: Between January 20, 2020, and October 14, 2022, 36 patients (29 with microsatellite stability/mismatch repair proficient [MSS/pMMR] tumors; two with microsatellite instability-high/mismatch repair deficient [MSI-H/dMMR] tumors) were enrolled and treated. The confirmed ORR was 44.4% (95% CI: 27.9, 61.9) and the disease control rate was 91.7% (95% CI: 77.5, 98.2). The median duration of response was 9.3 (95% CI: 4.3, not reached) months, the median progression-free survival was 6.2 (95% CI: 5.3, 11.1) months, and the median overall survival was 21.0 (95% CI: 13.4, not reached) months during a median follow-up of 14.2 (interquartile range: 10.3, 27.6) months. Treatment-related adverse events of grade 3 or 4 occurred in 20 (55.6%) patients, with the most common being increased γ-glutamyl transferase (27.8%), alanine aminotransferase (16.7%) and aspartate aminotransferase (13.9%), and hypertension (11.1%). No treatment-related death occurred. CONCLUSIONS: Camrelizumab plus apatinib showed promising antitumor activity with manageable toxicity in patients with advanced or recurrent endometrial cancer who had failed at least one prior systemic therapy. The findings of this study support further investigation of camrelizumab plus apatinib as an alternative therapeutic option, especially for patients with MSS/pMMR tumors. TRIAL REGISTRATION: This trial was retrospectively registered with ChiCTR.org.cn, number ChiCTR2000031932.
Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias do Endométrio , Piridinas , Humanos , Feminino , Pessoa de Meia-Idade , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Idoso , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagemRESUMO
OBJECTIVE: The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer (EC) was released with incorporating histology, lympho-vascular space invasion, and molecular classification together. Our objective is to further explore the clinical utility and prognostic significance of the 2023 FIGO staging system in China. METHODS: A retrospective analysis was conducted for patients who received standard surgeries and underwent genetic testing using multigene next-generation sequencing (NGS) panels between December 2018 and December 2023 at Fudan University Shanghai Cancer Center, Shanghai, China. The genomic and clinical data of all patients were analyzed, and stages were determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 547 patients were enrolled in the study. After the restaged by the FIGO 2023 staging system, stage shifts occurred in 147/547 (26.9%) patients. In patients with early stages in FIGO 2009 (stage I-II), 63 cases were rearranged to IAmPOLEmut and 53 cases to IICmp53abn due to the molecular classification of POLEmut and p53abn. Altogether 345 cases were in stage I, 107 cases in stage II, 69 cases in stage III, and 26 cases in stage IV according to the FIGO 2023 staging criteria. For stage I diseases, the 3-year PFS rate was 92.7% and 95.3% in 2009 and 2023 FIGO staging systems, respectively. The 3-year PFS of stage II in 2023 FIGO was lower than that of FIGO 2009 (3-year PFS: 85.0% versus 90.9%), especially in substage IIC and IICmp53abn. Three cases (12%) of stage IIIA in FIGO 2009 were shifted to stage IA3 FIGO 2023, with 3-year PFS rates of 90.9% versus 100%, respectively. In NGS analysis, the most prevalent gene alterations were observed in PTEN and PIK3CA. CONCLUSION: The FIGO 2023 staging system was proved to be a good predictor of survival for EC patients with enhanced precision compared to FIGO 2009. Predominant stage shifts were observed in early-stage diseases. Distinct gene alterations of different subtypes may help to explore more accurate target therapies.
Assuntos
Neoplasias do Endométrio , Estadiamento de Neoplasias , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , China/epidemiologia , Idoso , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Prognóstico , Idoso de 80 Anos ou mais , Estimativa de Kaplan-Meier , Mutação , População do Leste AsiáticoRESUMO
PURPOSE: With an increase in the number of young and middle-aged colorectal cancer (CRC) patients with stoma, understanding their perception about return to work (RTW) in the early postoperative period can guide medical professionals to provide appropriate rehabilitation strategies, which can eventually improve patients' readiness for return to work (RRTW) and enable them to achieve final rehabilitation. The present study aimed to investigate the RTW-related perceptions and considerations of young and middle-aged CRC patients with stoma after surgery. METHODS: From 2021 to 2022, we conducted a basic interpretive qualitative study involving semi-structured interviews with 17 CRC patients with stoma in two grade 3A hospitals in China. This study was based on the RRTW model. Data collection was continued until data saturation was reached, and all data were transcribed verbatim and analyzed by Colaizzi's phenomenological method. RESULTS: The following three key themes were identified: (1) self-efficacy; (2) decision balance; and (3) change process. Eight subthemes were formulated that were included within the respective main themes. CONCLUSION: In light of the current low self-efficacy and unsatisfactory willingness of patients with stoma about RTW, we suggest that medical staff should implement cognitive intervention and supportive interventions to improve self-efficacy, actively enhance the motivation of patients for RTW, and simultaneously resolve the pertinent difficulties; this could help patients to accept the positive change process and enable their successful transition from a change process to RTW.
Assuntos
Neoplasias Colorretais , Retorno ao Trabalho , Pessoa de Meia-Idade , Humanos , Retorno ao Trabalho/psicologia , Motivação , Pesquisa Qualitativa , Neoplasias Colorretais/cirurgia , PercepçãoRESUMO
OBJECTIVE: This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. METHODS: In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. RESULTS: 33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. CONCLUSION: Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.
Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Carcinoma Epitelial do Ovário , Indóis/uso terapêuticoRESUMO
This study determined the relationship between mental distress and professional commitment among medical postgraduate students, and the roles of psychological capital as a mediator and the supervisor-postgraduate relationship as a moderator. This cross-sectional study recruited 836 medical postgraduate students from eight medical universities and the medical college of comprehensive universities in Guangdong Province, China. Participants were assessed through questionnaires, which covered demographic items, the supervisor-postgraduate relationship scale, the psychological capital questionnaire, the symptom checklist - 90 (SCL -90), and the professional commitment scale. We used descriptive statistics to describe demographics and mental distress and professional commitment scores. Pearson's analysis was used to identify correlations between the variables and the SPSS PROCESS macro was performed to confirm mediating and moderating effects of psychological capital and the supervisor-postgraduate relationship. Mental distress was negatively related with professional commitment (r = -0.262, p < 0.01) and psychological capital (r = -0.442, p < 0.01). Psychological capital was positively associated with professional commitment (r = 0.486, p < 0.01). The confidence interval (CI) suggested that psychological capital mediated the relationship between mental distress and professional commitment (95% CI, -0.198 to - 0.143), and the supervisor-postgraduate relationship had a moderate role between psychological capital and professional commitment (95% CI, 0.069 to -0.212). Hence, educators may refer to these findings to improve professional commitment level among medical postgraduate students.
Assuntos
População do Leste Asiático , Transtornos Mentais , Estudantes de Medicina , Humanos , Estudos Transversais , Inquéritos e Questionários , Estudantes de Medicina/psicologiaRESUMO
Background: Epigenetic regulation by promoter methylation-mediated silencing of cancer-related microRNAs plays vital roles in tumorigenesis. MiR-192-5p promotes tumor progression in various human cancers with conflicting biological effects. However, its expression levels and biological functions in endometrial carcinoma (EC) have not been reported. Methods: The methylation status of miR-192-5p in tissue samples and cell lines, was examined using bisulfite sequencing PCR. miR-192-5p expression was also measured. EC cell lines transfected with specifically designed vectors overexpressing miR-192-5p, its target gene ALX1 or both, were constructed. Tumorigenicity of these cell lines were examined by in vitro and in vivo experiments. Dual-luciferase reporter assay were employed to verify the target of miR-192-5p. Results: The promoter region of miR-192-5p gene was highly methylated and its expression significantly repressed in EC samples. Moreover, a higher level of promoter methylation as well as a lower expression of miR-192-5p, was significantly associated with advanced Federation of Gynecology and Obstetrics stage and shorter disease-free survival in patients with curatively resected EC. Functional studies demonstrated that miR-192-5p overexpression inhibited in vitro tumor progression, in vivo tumorigenicity and the expression of several oncoproteins that was highly related to epithelial-to-mesenchymal transition. ALX1 was verified as a direct target of miR-192-5p and demonstrated to mediate the tumor-suppressive function of miR-192-5p. Conclusion: miR-192-5p is a tumor suppressor miRNA that is epigenetically silenced by promoter methylation and may serve as a potential prognostic biomarker in EC.
Assuntos
Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , MicroRNAs/metabolismo , Idoso , Animais , Linhagem Celular Tumoral , Metilação de DNA , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Endométrio/patologia , Endométrio/cirurgia , Epigênese Genética , Feminino , Humanos , Camundongos , MicroRNAs/genética , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Interferência de RNA , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: This study aimed to evaluate the risk factors of recurrence and invasive disease in patients with extramammary Paget's disease of the vulva (EPDV). METHODS: We performed a retrospective analysis of patients who were initially diagnosed with EPDV in Fudan University Shanghai Cancer Center between May 2006 and March 2019. RESULTS: Thirty-eight patients were initially diagnosed with EPDV in our institution. Among them, 29 had intraepithelial EPDV, 8 had intraepithelial EPDV with stromal invasion, and 1 had an underlying vulvar adenocarcinoma. In total, 8 (21%) patients had 12 recurrences. Of these eight patients, four had one recurrence, while other four had two recurrences. Intraepidermal EPDV recurred nine times, while intraepidermal EPDV with invasive disease recurred thrice. The first and second recurrence intervals were 62.1 (9-146) months and 22 (15-28) months, respectively. The rate of invasive disease was 23.7% (9/38) for primary EPDV and 25% (3/12) for recurrent ones. We determined that the presence of invasive disease was associated with a history of more than 10 years (p = 0.02) and inversely correlated with positive margins (p = 0.037), However, invasive disease had no statistical relations with age (p = 0.438), recurrence (p = 0.642), and lesion diameter (p = 0.08). CONCLUSIONS: EPDV with a history of more than 10 years was associated with invasive disease. Close and long-term follow-up are recommended to identify those who require further treatment.
Assuntos
Adenocarcinoma/patologia , Doença de Paget Extramamária/patologia , Neoplasias Vulvares/patologia , Adenocarcinoma/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Doença de Paget Extramamária/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Vulvares/epidemiologiaRESUMO
OBJECTIVE: To identify the predictors of coexisting adnexa malignancy (CAM) before surgery for patients with G1/G2 endometrioid endometrial cancer (EEC). METHODS: Patients with G1/G2 EEC who received surgery in Fudan University Shanghai Cancer Center from 1996 to 2017 were enrolled. Univariate and multivariate logistic regression were performed to identify the predictors for CAM, and the nomogram was constructed and evaluated the discrimination and calibration. RESULTS: Among the 1511 patients in the study cohort, 66 (4.4%) coexisted adnexa malignancy (51 metastatic and 15 synchronous primaries). In the univariate logistic regression analysis, CA125 level (>35 U/ml), histologic grades, myometrial invasion depth in magnetic resonance imaging (MRI), adnexal involvement in MRI/surgical exploration (SEP) were found to be significant predictors for CAM (P < .001, 0.047, 0.011, <0.001, respectively). The multivariate analysis demonstrated that high CA125 level (P < .001; OR: 2.945; 95%CI: 1.700-5.101), deep myometrial invasion (P = .011; OR: 2.194; 95%CI: 1.200-4.011), and suspected adnexal involvement in MRI/SEP (P < .001; OR: 11.524; 95%CI: 6.726-19.744) were independent predictors for CAM (AUC = 0.786). In 338 patients with MMR results, eighty-seven (25.7%) were detected MSI-high. There were 5.7% (5/87) patients diagnosed with CAM in the MSI-high group compared with 4.4% (11/251) in the MSS group. CONCLUSIONS: A nomogram with pre- and intra-operative factors was constructed to predict CAM in G1/G2 EEC patients, which may help clinicians in decision-making for ovarian preservation for these patients.
Assuntos
Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Neoplasias Primárias Múltiplas/patologia , Nomogramas , Neoplasias Ovarianas/patologia , Antígeno Ca-125/sangue , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-IdadeRESUMO
Electroacupuncture (EA) can improve myocardial ischemia (MI) injury; nevertheless, the mechanism is not entirely clear. And there were disagreements about whether the effect of EA at acupoint in disease-affected meridian is better than EA at acupoint in non-affected meridian and sham acupoint. Here, we showed that the effect of EA at Neiguan (PC6) is better than EA at Hegu (LI4) and sham acupoint in affecting RPP and ECG, increasing ATP and ADO production, decreasing AMP production, and upregulating the mRNA expression levels of A1AR, A2aAR, and A2bAR; knockdown of A1AR or A2bAR reversed the effect of EA at PC6 in alleviating MI injury; knockdown of A2aAR had no influence on the cardiac protection of EA at PC6; thus, the cardioprotective effect of EA at PC6 needs A1AR and A2bAR, instead of A2aAR; considering that the cardio protection of adenosine receptor needs activation of other adenosine receptors, one of the reasons may be that after silence of A1AR or A2bAR, EA at PC6 could not impact the expression levels of the other two adenosine receptors, and after silence of A2aAR, EA at PC6 could impact the expression levels of A1AR and A2bAR. These results suggested that EA at PC6 may be a potential and effective treatment for MI by activation of A1AR and A2bAR.
Assuntos
Eletroacupuntura , Isquemia Miocárdica/terapia , Receptores Purinérgicos P1/metabolismo , Animais , Feminino , Masculino , Isquemia Miocárdica/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
As inherited genetic alterations are important etiological factors causing endometrial cancer (EC), our study aimed to outline the ethnic-related prevalence and the associated clinical and biological characteristics of germline mutations in cancer predisposition genes in Chinese EC patients. One hundred ninety-eight Chinese EC patients were screened for germline mutations in a panel of cancer susceptibility genes using next-generation sequencing combined with multiplex ligation-dependent probe amplification. First, we found that among patients under 50 years of age, 26% (18/69) carried germline genetic mutations, all involving mismatch repair (MMR) genes except for one mutation affecting BRCA1. Second, when we focused on Lynch syndrome (LS) with additional selected patients, 45 were identified to carry pathogenic mutations in MMR genes, with a higher frequency found in MSH2 and MSH6. We found that age at onset, personal and familial history together with immunohistochemical assay results were the most useful criteria for the diagnosis of LS although limitations in routine practice and the sensitivity and specificity of each parameter should be taken into account. One pathogenic mutation in the PALB2 gene was detected in a patient with no breast cancer in her family. Interestingly, we identified a family carrying pathogenic variant in both PMS2 and BRCA1 genes with distinct clinical phenotypes. Multigene panel testing should be recommended to patients based on their clinical information and tumor phenotype. Our study also showed the genetic complexity in EC, which requires further investigations.
Assuntos
Neoplasias do Endométrio/genética , Mutação em Linhagem Germinativa , Adulto , Povo Asiático/genética , China/epidemiologia , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etnologia , Feminino , Genes BRCA1 , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND: Elevated blood pressure (hypertension) affects about one billion people worldwide. It is important as it is a major risk factor for stroke and myocardial infarction. However, it remains a challenge for the medical profession as many people with hypertension have blood pressure (BP) that is not well controlled. According to Traditional Chinese Medicine theory, acupuncture has the potential to lower BP. OBJECTIVES: To assess the effectiveness and safety of acupuncture for lowering blood pressure in adults with primary hypertension. SEARCH METHODS: We searched the Hypertension Group Specialised Register (February 2017); the Cochrane Central Register of Controlled Trials (CENTRAL) 2017, Issue 2; MEDLINE (February 2017); Embase (February 2017), China National Knowledge Infrastructure (CNKI) (January 2015), VIP Database (January 2015), the World Health Organisation Clinical Trials Registry Platform (February 2017)and ClinicalTrials.gov (February 2017). There were no language restrictions. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared the clinical effects of an acupuncture intervention (acupuncture used alone or add-on) with no treatment, a sham acupuncture or an antihypertensive drug in adults with primary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies according to inclusion and exclusion criteria. They extracted data and assessed the risk of bias of each trial, and telephoned or emailed the authors of the studies to ask for missing information. A third review author resolved disagreements. Outcomes included change in systolic blood pressure (SBP), change in diastolic blood pressure (DBP), withdrawal due to adverse effects, and any adverse events. We calculated pooled mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes using a fixed-effect or random-effects model where appropriate. MAIN RESULTS: Twenty-two RCTs (1744 people) met our inclusion criteria. The RCTs were of variable methodological quality (most at high risk of bias because of lack of blinding). There was no evidence for a sustained BP lowering effect of acupuncture; only one trial investigated a sustained effect and found no BP lowering effect at three and six months after acupuncture. Four sham acupuncture controlled trials provided very low quality evidence that acupuncture had a short-term (one to 24 hours) effect on SBP (change) -3.4 mmHg (-6.0 to -0.9) and DBP -1.9 mmHg (95% CI -3.6 to -0.3). Pooled analysis of eight trials comparing acupuncture with angiotensin-converting enzyme inhibitors and seven trials comparing acupuncture to calcium antagonists suggested that acupuncture lowered short-term BP better than the antihypertensive drugs. However, because of the very high risk of bias in these trials, we think that this is most likely a reflection of bias and not a true effect. As a result, we did not report these results in the 'Summary of findings' table. Safety of acupuncture could not be assessed as only eight trials reported adverse events. AUTHORS' CONCLUSIONS: At present, there is no evidence for the sustained BP lowering effect of acupuncture that is required for the management of chronically elevated BP. The short-term effects of acupuncture are uncertain due to the very low quality of evidence. The larger effect shown in non-sham acupuncture controlled trials most likely reflects bias and is not a true effect. Future RCTs must use sham acupuncture controls and assess whether there is a BP lowering effect of acupuncture that lasts at least seven days.
Assuntos
Terapia por Acupuntura , Hipertensão/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: The adjuvant treatment of high-risk endometrial cancer (HREC) remains controversial. This prospective phase-II clinical trial was conducted to evaluate the adjuvant concurrent chemoradiotherapy followed by chemotherapy in patients with HREC. METHODS: Altogether 122 patients were enrolled between January 2007 and January 2013, in which 112 were analyzable. The inclusion criteria included endometrioid endometrial cancer of histological grade 3 and with greater than 50% myometrial invasion, cervical stromal invasion, pelvic and/or para-aortic lymph node metastases; non-endometrioid endometrial cancer; no residual disease and distant metastases. Pelvic radiation was administered with cisplatin on days 1 and 28. Para-aortic radiation was administered with confirmed para-aortic lymph node metastases, and vaginal afterloading brachytherapy with cervical stromal invasion after total hysterectomy. Four courses of paclitaxel and carboplatin (PC) or cisplatin, cyclophosphamide and epirubicin (CEP) were administered at three-week interval after radiation. RESULTS: Ninety-six patients (85.7%) completed the planned treatment. Treatment discontinuation was the result of toxicity (5/112, 4.5%), disease progression (8/112, 7.1%), and patients refusal (3/112, 2.7%). There was no life-threatening toxicity. Twenty-five (22.3%) patients recurred, in which 4 cases recurred in the field of radiation, and 13 (11.6%) patients died of endometrial cancer during follow-up. The estimated five-year progression-free survival and overall survival were 73% and 84%, respectively. Adverse effects were less common in patients who received PC than CEP (p=0.001). CONCLUSIONS: This regimen demonstrated acceptable toxicity and good survival outcomes despite a preponderance (62.5%) of late stage disease. PC showed less adverse effects than CEP. A well designed randomized trial is under development. CLINICAL TRIAL ID: https://clinicaltrials.gov/: 070148-7.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adulto , Idoso , Braquiterapia , Carboplatina/administração & dosagem , Quimiorradioterapia Adjuvante , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Epirubicina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The human embryonic stem cells (hESCs) serve as a self-renewable, genetically-healthy, pluripotent and single source of all body cells, tissues and organs. Therefore, it is considered as the good standard for all human stem cells by US, Europe and international authorities. In this study, the standard and healthy human mesenchymal progenitors, ligament tissues, cardiomyocytes, keratinocytes, primary neurons, fibroblasts, and salivary serous cells were differentiated from hESCs. The human cellular health-safety of NaF, retinoic acid, 5-fluorouracil, dexamethasone, penicillin G, adriamycin, lead acetate PbAc, bisphenol A-biglycidyl methacrylate (Bis-GMA) were evaluated selectively on the standardized platforms of hESCs, hESCs-derived cardiomyocytes, keratinocytes, primary neurons, and fibroblasts. The evaluations were compared with those on the currently most adopted cellular platforms. Particularly, the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endothelial cells (HUVECs) were evaluated. The RESULTS showed that the standardized hESCs cellular platforms provided more sensitivity and accuracy for human cellular health-safety evaluation.
Assuntos
Células-Tronco Embrionárias Humanas/citologia , Testes de Toxicidade , Diferenciação Celular , Fibroblastos/citologia , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Miócitos Cardíacos/citologia , Neurônios/citologiaRESUMO
BACKGROUND: While peripheral neuropathy is a common side effect of platinum-based chemotherapy, central nervous system (CNS) toxicity, such as encephalopathy or seizures, appears to be rare. This manuscript describes the only reported case of nonconvulsive status epilepticus associated with cisplatin in a cervical cancer patient who does not have other underlying medical conditions. CASE PRESENTATION: The patient is a 54-year-old Chinese female with recurrent stage IIIB moderately differentiated squamous cell carcinoma of the cervix who was being treated with cisplatin and topotecan. During the sixth cycle of this regimen, the patient presented with mental status changes. While imaging and laboratory values were within normal limits, the patient's EEG revealed nonconvulsive status epilepticus. After appropriate intervention, she made a complete recovery with no further seizures. The patient currently remains on antiepileptic therapy, but is no longer receiving cisplatin. CONCLUSION: Patients who present with new onset seizures should primarily be evaluated for underlying medical conditions. Among patients who are suspected to have CNS side effects associated with platinum use, we recommend avoidance of platinum agents in future chemotherapeutic regimens. Although rare, providers should be aware of the potential for CNS toxicity associated with this drug class.
Assuntos
Cisplatino/efeitos adversos , Estado Epiléptico/patologia , Topotecan/efeitos adversos , Neoplasias do Colo do Útero/tratamento farmacológico , Cisplatino/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/patologia , Estado Epiléptico/induzido quimicamente , Topotecan/administração & dosagem , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The aim of this study was to evaluate the survival benefit of radical surgery with additional extensive upper abdominal procedures (EUAS) for the treatment of stage IIIC and IV ovarian cancer with bulky upper abdominal disease (UAD). METHODS: An observational study was conducted between 2009 and 2012 involving two different surgical teams. Team A was composed of the "believers" in EUAS and Team B the "non-believers" in EUAS. Patients were divided into a radical surgery group (EUAS group) or a standard surgery group (non-EUAS group) according to whether or not they had received EUAS. All patients underwent primary cytoreductive surgery with the goal of optimal debulking (≤ 1 cm); this was reviewed in the pelvis, middle abdomen, and upper abdomen. The baseline for the two groups was optimal cytoreduction in both the pelvis and middle abdomen. Progression-free survival (PFS) was evaluated. RESULTS: Radical surgery was performed in 70.7% (82/116) and 12.7% (30/237) of the patients by Teams A and B, respectively. The study groups had similar clinicopathologic characteristics. The median PFS and OS were significantly improved in the radical surgery group, compared with standard surgery groups (PFS: 19.5 vs. 13.3 months, HR: 0.61; 95% CI: 0.46-0.80, P < 0.001; OS: not reached vs. 39.3 months, HR: 0.47; 95% CI: 0.30-0.72, P < 0.001). Positive predictors of complete cytoreduction were treatment with neoadjuvant chemotherapy, improved American Society of Anesthesiologists performance status, and the absence of bowel mesenteric carcinomatosis. CONCLUSIONS: Radical surgery lengthens the PFS and overall survival times of ovarian cancer patients with bulky UAD. However, a well-designed randomized trial is needed to confirm the present results.
Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Neoplasias Ovarianas/cirurgia , Abdome/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
OBJECTIVE: The aim of this study was to determine the impact of neoadjuvant chemotherapy (NACT) on survival in patients with bulky stage IIIC and IV epithelial ovarian cancer. METHODS: Between January 2009 and December 2012, 408 patients with ovarian cancer with extensive upper abdominal disease were reviewed. On the basis of the cycle number of NACT, patients were divided into 2 groups, namely, primary debulking surgery (PDS) group, which included the patients who received no more than 1 cycle of NACT; and neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) group, which included the patients who received more than 1 cycle of NACT. All patients underwent cytoreductive surgery with the goal of optimal outcome (≤1 cm). Progression-free survival and overall survival were evaluated. RESULTS: There was no difference in surgical outcomes between PDS and NACT-IDS group, which was evaluated with either complete cytoreduction (41/376, 10.9% vs 6/32, 18.8%) or optimal cytoreduction (201/376, 53.5% vs 18/32, 56.2%). The median survival was 43.0 and 27.3 months in the PDS group and NACT-IDS group, with an estimated 5-year survival of 36% and 31%, respectively (P = 0.032; hazard ratio, 0.59; 95% confidence interval, 0.36-0.95). Complete cytoreduction, without bowel mesenteric carcinomatosis, and no more than 1 cycle of NACT were associated with lengthened survival by the multivariate analysis (P = 0.012, 0.025, and 0.036, respectively). CONCLUSIONS: Neoadjuvant chemotherapy was associated with poor survival of patients with bulky stage IIIC and IV ovarian cancer. A well-designed randomized trial with a better quality control of surgical procedures is needed to confirm the results.
Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma Mucinoso/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Electroacupuncture (EA) is reported to be an effective treatment for obesity, but its mechanism is unclear. This study aimed to investigate the relationship between hypothalamic LKB1-AMPK-ACC signaling and EA. METHODS: Fifty male Sprague-Dawley rats were divided into two groups fed either chow (chow-fed group) or high-fat diet (HF group). After 4 weeks of feeding, obese rats in the HF group (defined as weighing 20% or more than rats in the chow-fed group) were randomly allocated into an EA or Diet-induced obesity (DIO) group. The EA group was given EA on bilateral ST25-ST36 for 4 weeks, while the DIO group received no further intervention. Body weight of the chow-fed, DIO, and EA groups were measured weekly. mRNA and protein levels of the hypothalamic LKB1-AMPK-ACC signaling pathway were detected using real-time (RT)-PCR and western blot, respectively. RESULTS: After 4 weeks of EA treatment, the weight growth trend of rats in the EA group was inhibited compared with those in the DIO group. RT-PCR and western blotting showed that EA upregulated the transcription of Adenosine 5'-monophosphate-activated protein kinase α2 (AMPKα2), promoted protein expression of Liver kinase B1 (LKB1) and AMPKα1, and inhibited acetyl-CoA carboxylase (ACC) protein expression in the hypothalamus. CONCLUSIONS: This study suggests that hypothalamic LKB1-AMPK-ACC signaling plays an important role in EA treatment for obesity.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica , Eletroacupuntura , Proteínas Serina-Treonina Quinases/metabolismo , Aumento de Peso/fisiologia , Quinases Proteína-Quinases Ativadas por AMP , Animais , Masculino , Obesidade , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Salvage cytoreductive surgery (SCR) has been shown to improve the survival of cancer patients. This study aimed to determine the survival benefits of SCR for recurrent endometrial cancer in Chinese population. METHODS: Between January 1995 and May 2012, 75 Chinese patients with recurrent endometrial cancer undergoing SCR were retrospectively analyzed. RESULTS: 43 patients (57.3%) had R0 (no visible disease), 15 patients (20.0%) had R1 (residual disease ≤1 cm), and 17 (22.7%) had R2 (residual disease >1 cm) Resection. 35 patients (46.7%) had single, and 40 (53.3%) had multiple sites of recurrence. The median survival time was 18 months, and 5-year overall survival (OS) rate were 42.0%. Multivariate analysis showed that residual disease ≤1 cm and high histology grade were significantly associated with a better OS. The size of the largest recurrent tumors (≤6 cm), solitary recurrent tumor, and age at recurrence (≤56 years old) were associated with optimal SCR. CONCLUSION: Optimal SCR and high histology grade are associated with prolonged overall survival for patients with recurrent endometrial cancer. Patients with young age, tumor size < 6 cm, and solitary recurrent tumor are more likely to benefit from optimal cytoreductive surgery.
Assuntos
Povo Asiático , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Terapia de Salvação/métodos , Adulto , Idoso , Neoplasias do Endométrio/mortalidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical animal studies. However, the clinical benefits of propofol in this context are subject to debate. We conducted a systematic search across eight databases to identify all relevant animal studies investigating the preventive effects of propofol on MIRI until October 30, 2023. We assessed the methodological quality of the included studies using SYRCLE's bias risk tool. Statistical analysis was performed using STATA 15.1. The primary outcome measures analyzed in this study were myocardial infarct size (IS) and myocardial injury biomarkers. This study presents a comprehensive analysis of 48 relevant animal studies investigating propofol's preventive effects on MIRI. Propofol administration demonstrated a reduction in myocardial IS and decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI). Moreover, propofol improved myocardial function parameters (+dp/dtmax, -dP/dtmax, LVEF, LVFS), exhibited favorable effects on inflammatory markers (IL-6, TNF-α) and oxidative stress markers (SOD, MDA), and reduced myocardial cell apoptotic index (AI). These findings suggest propofol exerts cardioprotective effects by reducing myocardial injury, decreasing infarct size, and improving heart function. However, the absence of animal models that accurately represent comorbidities such as aging and hypertension, as well as inconsistent administration methods that align with clinical practice, may hinder its clinical translation. Further robust investigations are required to validate these findings, elucidate the underlying mechanisms of propofol, and facilitate its potential translation into clinical practice.