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BACKGROUND AND PURPOSE: 3D-printed templates are used in intracavitary/interstitial brachytherapy (3DP-IC/IS) for locally advanced cervical cancer (LACC). We applied failure mode and effects analysis (FMEA) twice in one year to improve 3DP-IC/IS safety. MATERIALS AND METHODS: A risk assessment group was established. We created a process map for 3DP-IC/IS procedures, identifying potential failure modes (FMs) and evaluating occurrence (O), detectability (D), severity (S), and risk priority number (RPN = O*D*S). High RPN values identified high-risk FMs, and quality control (QC) methods were determined by root cause analysis. A second FMEA was performed a year later. RESULTS: The 3DP-IC/IS process included 10 main steps, 48 subprocesses, and 54 FMs. Initial RPN values ranged from 4.50 to 171.00 (median 50.50; average 52.18). Ten high-risk FMs were identified: (1) unreasonable needle track design (171.00/85.50), (2) noncoplanar needle label identification failure (126.00/64.00), (3) template model reconstruction failure (121.50/62.50), (4) improper gauze filling (112.00/60.25), (5) poor needle position (112.00/52.50). QC interventions lowered all high-risk RPN values during the second assessment. CONCLUSIONS: A feasible 3DP-IC/IS process was proposed. Staff training, automatic needle path planning, insertion guidance diagrams, template checking, system commissioning, and template design improvements effectively enhanced process safety.
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Precise modulation of host-guest interactions between programmable Ln-MOFs (lanthanide metal-organic frameworks) and phosphate analytes holds immense promise for enabling novel functionalities in biosensing. However, the intricate relationship between these functionalities and structures remains largely elusive. Understanding this correlation is crucial for advancing the rational design of fluorescent biosensor technology. Presently, there exists a large research gap concerning the utilization of Ln-MOFsto monitor the conversion of ATP to ADP, which poses a limitation for kinase detection. In this work, we delve into the potential of Ln-MOFs to amplify the fluorescence response during the kinase-mediated ATP-to-ADP conversion. Six Eu-MOFs were synthesized and Eu-TPTC ([1,1':4',1â³]-terphenyl-3,3'',5,5''-tetracarboxylic acid) was selected as a ratiometric fluorescent probe, which is most suitable for high-precision detection of creatine kinase activity through the differential response from ATP to ADP. The molecular -level mechanism was confirmed by density functional theory. Furthermore, a simple paper chip-based platform was constructed to realize the fast (20 min) and sensitive (limit of detection is 0.34 U/L) creatine kinase activity detection in biological samples. Ln-MOF-phosphate interactions offer promising avenues for kinase activity assays and hold the potential for precise customization of analytical chemistry.
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Adenosina Difosfato , Adenosina Trifosfato , Estructuras Metalorgánicas , Adenosina Trifosfato/análisis , Adenosina Trifosfato/metabolismo , Estructuras Metalorgánicas/química , Adenosina Difosfato/análisis , Adenosina Difosfato/metabolismo , Adenosina Difosfato/química , Creatina Quinasa/metabolismo , Creatina Quinasa/análisis , Creatina Quinasa/química , Técnicas Biosensibles/métodos , Colorantes Fluorescentes/química , Elementos de la Serie de los Lantanoides/química , AnimalesRESUMEN
Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application.
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Estadificación de Neoplasias , Neoplasias del Cuello Uterino , Femenino , Humanos , Persona de Mediana Edad , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/secundario , Histerectomía/métodos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology and propose a computational strategy to enhance pathologists' mitosis assessment. The strategy has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum mitotic count in 10 consecutive high-power fields, which can enhance the preciseness, especially in cases with borderline mitotic count. (2) Implementing a collaborative sphere to group a set of pathologists to detect mitoses under each high-power field, which can mitigate subjective random errors in mitosis detection originating from individual detection errors. By depth-first search algorithm (1) , we analyzed 19 meningioma slides and discovered that the proposed algorithm upgraded two borderline cases verified at consensus conferences. This improvement is attributed to the algorithm's ability to quantify the mitotic count more comprehensively compared to other conventional methods of counting mitoses. In implementing a collaborative sphere (2) , we evaluated the correctness of mitosis detection from grouped pathologists and/or pathology residents, where each member of the group annotated a set of 48 high-power field images for mitotic figures independently. We report that groups with sizes of three can achieve an average precision of 0.897 and sensitivity of 0.699 in mitosis detection, which is higher than an average pathologist in this study (precision: 0.750, sensitivity: 0.667). The proposed computational strategy can be integrated with artificial intelligence workflow, which envisions the future of achieving a rapid and robust mitosis assessment by interactive assisting algorithms that can ultimately benefit patient management.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/patología , Índice Mitótico/métodos , Inteligencia Artificial , Mitosis , Neoplasias Meníngeas/patologíaRESUMEN
BACKGROUND: Phenolic endocrine-disrupting chemicals (EDCs) are widespread and easily ingested through the food chain. They pose a serious threat to human health. Magnetic solid-phase extraction (MSPE) is an effective sample pre-treatment technology to determine traces of phenolic EDCs. RESULTS: Magnetic covalent organic framework (COF) (Fe3 O4 @COF) nanospheres were prepared and characterized. The efficient and selective extraction of phenolic EDCs relies on a large specific surface and the inherent porosity of COFs and hydrogen bonding, π-π, and hydrophobic interactions between COF shells and phenolic EDCs. Under optimal conditions, the proposed magnetic solid-phase extraction-high-performance liquid chromatography-ultra violet (MSPE-HPLC-UV) based on the metallic covalent organic framework method for phenolic EDCs shows good linearities (0.002-6 µg mL-1 ), with R2 of 0.995 or higher, and low limits of detection (6-1.200 ng mL-1 ). CONCLUSION: Magnetic covalent organic frameworks (Fe3 O4 @COFs) with good MSPE performance for phenolic EDCs were synthesized by the solvothermal method. The magnetic covalent organic framework-based MSPE-HPLC-UV method was applied successfully to determine phenolic EDCs in beverage and water samples with satisfactory recoveries (90.200%-123%) and relative standard deviations (2.100%-12.100%). © 2023 Society of Chemical Industry.
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Disruptores Endocrinos , Estructuras Metalorgánicas , Humanos , Estructuras Metalorgánicas/química , Cromatografía Líquida de Alta Presión , Bebidas , Extracción en Fase Sólida/métodos , Fenoles , Fenómenos Magnéticos , Agua/química , Límite de DetecciónRESUMEN
The effects of maternal dietary energy and arginine level on embryonic development and serum lipid metabolism were investigated in this study. A 2 × 3 factorial experiment was conducted with six treatments represented by 10 replicates of eight Arbor Acre broiler breeder hens each. Diets fed from 40 to 50 weeks of age were formulated to contain two digestible arginine levels (9.6 g/kg and 14.5 g/kg) and three metabolic energy levels (10.08 MJ ME/kg, 11.88 MJ ME/kg, and 13.68 MJ ME/kg). Artificial insemination was used, and eggs collected from 50 weeks of hens' age were hatched. Embryonic growth, biochemical and endocrine indexes of embryonic serum and allantoic fluid were measured on different embryonic days (E). The results were as follows: Egg weight (E0, E11, E13) and embryonic weight (E12, E15) in the high-energy group (13.68 MJ ME/kg) were significantly decreased (p < 0.01), as were embryonic breast rate (E13, E15, E21), thigh rate (E13-E21) and liver rate (E15-E21). The reciprocal effects of arginine and energy were significant on breast rate (E11, E13, E17), thigh rate (E19, E21) and liver rate (E11, E19) of the embryo (p < 0.05). CHO (E13-E19), high-density lipoprotein (E13, E15, E21), low-density lipoprotein (E15, E19, E21), and blood glucose (E13) levels in embryonic serum decreased with the increase in maternal dietary energy level (p < 0.05), but triglyceride levels (E19, E21) showed the opposite result (p < 0.05). The levels of cholesterol and blood glucose in embryonic serum at E11 and urea nitrogen in allantoic fluid at E11-E15 were significantly decreased in the 14.5 g/kg arginine group (p < 0.01). With the increase in maternal dietary energy and arginine levels, embryonic serum nitric oxide synthases levels (E11, E15, E19) increased significantly (p < 0.01). The reciprocal effect of arginine and energy in maternal diets was significant on the embryonic serum high-density lipoprotein level at E21 (p < 0.05). Embryonic serum insulin levels at E13 were significantly elevated in the high-energy group (13.68 MJ ME/kg). The reciprocal effect of arginine and energy was significant on the embryonic serum growth hormone level (p < 0.01). Embryonic serum growth hormone levels were significantly reduced in the 14.5 g/kg arginine and 13.68 MJ/kg metabolic energy group (p < 0.01). In conclusion, maternal restricted feeding improved embryonic development and regulated lipid metabolism-related indices in embryonic serum. Maternal dietary addition of digestible arginine had a significant effect on lipid metabolism indices in embryos. There was a maternal effect of maternal dietary energy and arginine levels on embryo growth and development. The deposition of maternal nutrients affects the development of embryos.
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OBJECTIVE: To evaluate the impact of bone marrow (BM) irradiation dose on acute haematologic toxicity (HT) in concurrent chemoradiotherapy for cervical cancer. METHODS: Sixty-nine patients with cervical cancer treated with curative or postoperative adjuvant therapy received weekly cisplatin concurrent chemotherapy (CCT) and intensity-modulated radiation therapy (IMRT). The whole pelvic bone marrow (PBM) was delineated and divided into three subsites: ilium (IL), lower pelvis (LP), and lumbosacral spine (LS). Associations between clinical variables, dose volume of BM, including PBM, IL, LP, and LS in the form of x-Vy (volume receiving y Gy for x), and blood cell count nadir were tested using linear regression models. Receiver operating characteristic (ROC) curve analysis was further used to analyse the cutoff values of the variables with p < 0.05 in the multivariate analysis. RESULTS: In 69 patients, the haemoglobin nadir was positive correlated with baseline haemoglobin (p < 0.001), negative correlated with relative LP-V10 (p = 0.005), relative LP-V25 (p = 0.002), relative LP-V50 (p = 0.007), relative LP-mean (p = 0.003), absolute LP-V15 (p = 0.049), absolute LP-V25 (p = 0.004) and absolute LP-V30 (p = 0.009). The platelet nadir was positive correlated with baseline platelets (p = 0.048) and negative correlated with relative LP-V40 (p = 0.028), but there was no significant variable in absolute radiation volume by multivariate analysis. No variables related to the neutrophil nadir were found, and the 69 patients were divided into group A (43 cases) receiving 3-4 cycles of CCT and group B (26 cases) receiving 5-6 cycles of CCT. In group A, the relative IL-V15 (p = 0.014), the relative IL-V50 (p = 0.010) and the absolute LP-V50 (p = 0.011) were negative correlated with the neutrophil nadir. No significant variable was found in group B. No significant variables related to the lymphocyte nadir were found, and the neutrophil-to-lymphocyte ratio (NLR) was analysed. Age (p < 0.05), relative LP-V15 (p = 0.037) and absolute PBM-mean (p < 0.001) were found to be negative related to NLR. CONCLUSION: The dosimetric parameters of relative irradiated volume of BM have more statistically significant datas on acute HT than absolute irradiated volume. The nadir of haemoglobin and platelets and the vertice of NLR were more affected by the irradiation dose to LP, while neutrophils were more affected by the dose to IL. Acute HT was negative related to both low-dose irradiation (V10-30) and high-dose irradiation (V40, V50). For more than 4 cycles of CCT, the effect of BM irradiation on the neutrophils nadir was masked by chemotherapy.
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Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Femenino , Humanos , Médula Ósea/efectos de la radiación , Dosificación Radioterapéutica , Neoplasias del Cuello Uterino/radioterapia , Quimioradioterapia/efectos adversos , Radioterapia de Intensidad Modulada/efectos adversos , HemoglobinasRESUMEN
Rare earth fluorides have been widely used in recent years in the field of solid-state lighting. However, the relationship between the structure and luminescence properties is still unclear. Herein, the photoluminescence and structural transition of CeF3:Tb3+ nanoparticles under high pressure were investigated through in situ photoluminescence and X-ray diffraction measurements. Intriguingly, the photoluminescence of CeF3:Tb3+ nanoparticles displays an enhancement from 18.3 to 33.4 GPa, accompanied by the phase transition from the starting hexagonal phase to the orthorhombic phase. It was found that the distance of luminescent centers increased sharply during the high-pressure phase transition, which weakened the quenching effect and improved transmission efficiency. Our work provides more insight into the optical characteristics and structures of rare earth trifluorides.
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Efficient magnetic solid phase extraction using crystalline porous polymers can find important applications in food safety. Herein, the core-shell Fe3O4@COFs nanospheres were synthesized by one-pot method and characterized in detail. The porous COF shell with large surface area had fast and selective adsorption for propylparaben via π-π, hydrogen bonding and hydrophobic interactions. The extraction and desorption parameters were evaluated in detail. Under the optimized conditions, the extraction equilibrium was reached only in 5 min, the maximum adsorption capacity for propylparaben was 500 mg g-1 and the proposed Fe3O4@DhaTab-based-MSPE-HPLC-UV method afforded good linearity (4-20000 µg mL-1) with R2 (0.997), low limits of detection (0.55 µg L-1) and limits of quantification (1.5 µg L-1). Furthermore, the developed method was applied to determine propylparaben in soft drinks with the recoveries (97.0-98.3%) and relative standard deviations (0.61 to 3.75%). These results revealed the potential of Fe3O4@DhaTab as efficient adsorbents for parabens in food samples.
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Estructuras Metalorgánicas , Parabenos , Fenómenos Magnéticos , Extracción en Fase SólidaRESUMEN
OBJECTIVE: The objectives of this study were to evaluate the effects of daily feed intake during the laying period on embryonic myogenic differentiation 1 (MYOD1), myogenic factor 5 (MYF5), and myogenic factor 6 (MYF6) gene expression in genetically fat and lean lines of chickens. METHODS: An experiment in a 2×2 factorial design was conducted with two dietary intake levels (100% and 75% of nutrition recommendation) and two broiler chicken lines (fat and lean). Two lines of hens (n = 384 for each line) at 23th week of age were randomly divided into 4 treatments with 12 replicates of 16 birds. The experiment started at 27th week of age (5% egg rate) and ended at 54th week of age. Hatched eggs from the medium laying period were collected. Real time polymerase chain reaction analysis was used to analyse the MYOD1, MYF5, and MYF6 mRNA levels of E7, E9, E11, E13, and E15 body tissues and E17, E19, and E21 chest and thigh muscle samples. RESULTS: The results indicated that there were significant effects of line, dietary intake, and interactions between them on MYOD1, MYF5, and MYF6 gene mRNA expression levels in embryonic tissues. Low daily feed intake did not change the expression trend of MYOD1 mRNA in either line, but changed the peak values, especially in lean line. Low daily feed intake altered the trend in MYF5 mRNA expression level in both lines and apparently delayed its onset. There was no apparent effect of low daily feed intake on the trends of MYF6 mRNA expression levels in either line, but it significantly changed the values on many embryonic days. CONCLUSION: Maternal nutrient restriction affects myogenesis and is manifested in the expression of embryonic MYOD1, MYF5, and MYF6 genes. Long term selection for fat deposition in broiler chickens changes the pattern and intensity of myogenesis.
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Background: Few studies have investigated the characteristics of non-BRCA homologous recombination repair (HRR) pathway somatic mutations, and the impact of these mutations on efficacy of treatment in ovarian cancer patients is not clear. Therefore, we conducted this study to analyze the frequency and spectrum of somatic mutations in HRR pathway genes in patients with ovarian cancer and to examine the relationships between somatic mutations in HRR pathway genes and their effects on the efficacy of platinum-based chemotherapy. Methods: We performed targeted sequencing of 688 genes related to the occurrence, development, treatment, and prognosis of solid tumors. Somatic mutations were identified by paired analysis of tumor tissue and germline DNA in blood cells. Results: A total of 38 patients with ovarian cancer were included in the study, and 35 (92.1%) patients were diagnosed with high-grade serous carcinoma. All patients exhibited somatic mutations in the tumor tissue samples. The commonly mutated genes were TP53 (73.7%), BRCA2 (55.3%), NF1 (52.6%), BRCA1 (47.4%), and CDH1 (47.4%). Overall, 71.1% of the patients exhibited mutation in at least one HRR pathway gene. The most frequently altered HRR genes were BRCA2 (55.3%), followed by BRCA1 (47.4%), ATM (44.7%), BARD1 (42.1%), and CHEK1 (36.8%). The median progression-free survival (PFS) in patients with HRR pathway mutation was 36.0 months compared with 13.6 months in patients with no HRR pathway mutation (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.08-0.77; p = 0.016). Patients harboring BRCA1/2 and/or CDK12 mutations displayed a longer PFS (median, 36.0 months) compared with patients with no BRCA1/2 or CDK12 mutation (median, 13.6 months; HR, 0.21; 95% CI, 0.07-0.61; p = 0.004). In multivariate analysis Cox proportional hazards models, after adjustment for tumor stage at diagnosis and histology of initial diagnosis, patients with HRR pathway mutation had a longer PFS than patients with HRR wild-type genes (p = 0.006). Conclusions: HRR pathway somatic mutations are common in Chinese patients with ovarian cancer. HRR pathway somatic mutations were associated with improved sensitivity to platinum-based chemotherapy. Large-scale prospective studies are needed to verify our findings.
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Epithelial ovarian cancer is extremely difficult to treat due to its high recurrence rate and acquired tolerance to chemotherapy. Immune checkpoint inhibitors (ICIs) are expected to be promising solutions for treatment failure. However, the low response rate to a single ICI agent was demonstrated in approximately all published clinical trials. Surprisingly patients with complete response were also noticed as an anecdote. Proper indicators of treatment response were urgently required. Programmed death- ligand 1 expression levels in the tumor tissues provide relatively limited discrimination. Tumor mutation burden (TMB) serves as a more reliable parameter. Here we presented an ovarian cancer case with multiple gene mutations and high TMB, who benefited from a short-term treatment of pembrolizumab and experienced a long-lasting complete response of 2 years till now. The patient was irradiated in the pelvic before pembrolizumab. Our study demonstrated that ICIs might provide survival benefits for ovarian cancer with high TMB and that pelvic radiation might have synergistical effects with immunotherapy.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Carcinoma Epitelial de Ovario/radioterapia , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/radioterapiaRESUMEN
BACKGROUND: Anlotinib is an oral anti-angiogenesis inhibitor targeting vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors, fibroblast growth factor receptors, etc., and its clinical value in cervical cancer is rarely reported. We designed a retrospective study to evaluate the efficacy and safety of anlotinib in patients with persistent, metastatic, or recurrent cervical cancer who have failed first-line therapy, and compare the efficacy of anlotinib with that of apatinib which targets only VEGFR2 and has shown efficacy in recent studies. METHODS: Fifty-two patients with persistent, metastatic, or recurrent cervical cancer who failed first-line therapy and administrated anlotinib or apatinib as monotherapy or combination with chemo-, radio- or immunotherapy were included in this study. Among the 52 patients, 20 patients who received anlotinib from January 2019 to August 2020 were defined as anlotinib group, whereas 32 patients who received apatinib from our previous study were selected as apatinib group. The safety, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were reviewed and recorded. RESULTS: The ORR and DCR in patients receiving anlotinib were 25% and 80%, respectively. The median PFS and OS in anlotinib group were significantly longer than those in apatinib group, respectively (PFS: 5 months vs 3 months, p=0.015; OS: 10 months vs 5 months, p=0.008). Moreover, the patients treated with anlotinib had better survival with a significantly lower cumulative incidence of cancer-related death than those treated with apatinib (HR=0.31, 95% CI: 0.13-0.77, p=0.012). The most common adverse effects in the patients treated with anlotinib were hypertension (20%), fatigue (20%), and nausea (15%). No drug-related death occurred. CONCLUSION: Anlotinib showed beneficial efficacy and safety and can be a treatment option for patients with persistent, metastatic, or recurrent cervical cancer who have failed the first-line therapy.
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Antineoplásicos/farmacología , Indoles/farmacología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Quinolinas/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Administración Oral , Antineoplásicos/administración & dosificación , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Indoles/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , Piridinas/farmacología , Quinolinas/administración & dosificación , Estudios Retrospectivos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: Radiotherapy (RT) is recommended as an extensive therapeutic regimen for cancer patients; however, cancer radio-resistance results from reduced oxygen levels (hypoxia) in the tumor microenvironment. Herein, we report a therapeutic strategy that greatly enhances the treatment effects of RT. METHODS: Specifically, papaverine (ppv), an FDA-approved smooth muscle relaxant, was applied in the strategy. Ppv improved blood flow via vasodilation to deliver sufficient oxygen to the hypoxic solid tumor and further resulted in increased tumor penetration of the radiosensitizer, significantly enhancing the radiosensitization compared with no ppv treatment. Additionally, tantalum oxide nanospheres were cloaked in red blood cell membranes (TaOx@M) to achieve greater biocompatibility, non-immunogenicity, and a longer circulation time. RESULTS: As a high-Z element, tantalum provides localized dose enhancement and thereby boosts the efficacy of RT. Vasodilation, the oxygenation of cancer cells, and the improved accumulation and retention of TaOx@M in the tumor region were verified in vivo. Furthermore, compared with RT alone, the combined vasodilation and nanosphere camouflaging strategy more efficiently suppressed the growth of K7M2 tumors in mice. CONCLUSION: The results of this study suggest that the integration of TaOx@M and ppv has excellent potential for improving RT efficacy.
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Neoplasias , Fármacos Sensibilizantes a Radiaciones , Animales , Línea Celular Tumoral , Eritrocitos , Humanos , Ratones , Papaverina , Microambiente TumoralRESUMEN
BACKGROUND: The role of additional chemotherapy in pulmonary sarcomatoid carcinoma (PSC) is controversial. This study aimed to investigate the function of chemotherapy in PSC patients with surgical resection. METHODS: PSC patient information between 2004 to 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. X-tile software was used to calculate the optimal cut-off value to divide groups. The disease stages were recalculated according to the American Joint Commission on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging system. Propensity score matching (PSM) analysis was conducted to balance the baseline of patients. Kaplan-Meier analysis and Cox proportional hazards analysis were used to evaluate survival outcome. RESULTS: A total of 865 PSC patients were included in our study. Among them, 611 patients were only operated with surgery, and the 254 others were treated with additional chemotherapy. The median age was 69.0 years (interquartile range, 61.6 to 76.3 years). Kaplan-Meier analysis showed that patients with additional chemotherapy had longer overall survival (OS) and cancer-specific survival (CSS, P<0.05). The median OS and the 1-, 3-, 5-year OS rates were 36.0 months (95% CI: 20.5-51.5 months), 72.7%, 49.6% and 38.5% in the chemotherapy group and 29.0 months (95% CI: 23.6-34.4 months), 63.2%, 44.5% and 37.6% in the non-chemotherapy group, respectively. The OS advantage of chemotherapy was not statistically significant after PSM analysis. Moreover, Cox proportional hazards model showed that chemotherapy was an independent prognosis factor for better OS and CSS. In subgroup of stages II and III, the chemotherapy group had a survival advantage (P<0.05). Patients with young age, female gender, low histology grade, large tumor size and lobectomy surgical resection benefited more from chemotherapy. CONCLUSIONS: Chemotherapy is recommended for stages II and III PSC patients undergoing surgery, especially for those with young age, female gender, low histology grade, large tumor size and lobectomy surgical resection.
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BACKGROUND: To quantify the dosimetric parameters of different bone marrow sparing strategies and to determine the optimal strategy for cervical cancer patients undergoing postoperative intensity-modulated radiotherapy (IMRT). METHODS: Fifteen patients with cervical cancer were selected for analysis. The planning target volume (PTV) and the organs at risks (OAR) including small bowel, bladder, rectum, femoral heads, os coxae (OC), lumbosacral spine (LS) and bone marrow (BM) were contoured. For each patient, four IMRT plans with different strategies were generated, including one plan without BM as the dose-volume constraint, namely IMRT (N) plan, and three bone marrow sparing (BMS-IMRT) plans. The three BMS-IMRT plans used the BM, OC, OC and LS respectively, as the BM OAR, namely as IMRT (BM), IMRT (OC) and IMRT (OC + LS) plans. Dose volumes for the target and the OARs were compared using analysis of variance (ANOVA). RESULTS: Compared with IMRT (N) plans, the dose to the small bowel, bladder, rectum and femoral heads showed no increase in the three BMS-IMRT plans. However, the irradiated dose to BM, OC and LS significantly decreased. In particular, the mean dose of BM, OC and LS decreased by about 5Gy (p < 0.05) in IMRT (BM) plans while the average volume receiving ≥20, ≥30, ≥40Gy decreased by 7.1-24.2%. The LS volume receiving 40Gy showed the highest decrease (about 31.2%, p < 0.05) in IMRT (OC + LS) plans. On the other hand, in comparison with IMRT (BM), IMRT (OC) reduced the dose volume of to the OC, but increased the dose to LS while IMRT (OC + LS) plans reduced both the OC and the LS volume at all dose levels. Specifically, the V20 of OC and LS in the IMRT (OC + LS) plan decreased by 11.5 and 11.2%, respectively. CONCLUSION: By introducing the os coxae and lumbosacral spine as the dose-volume constraints, the IMRT plans exhibited the best sparing of the bone marrow without compromising the dose to surrounding normal structures. Therefore, we recommend adding the os coxae and lumbosacral spine as the BM OAR in such plans.
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Médula Ósea/efectos de la radiación , Tratamientos Conservadores del Órgano/métodos , Órganos en Riesgo/efectos de la radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/normas , Neoplasias del Cuello Uterino/radioterapia , Adulto , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND Intensity-modulated radiotherapy (IMRT) is the standard treatment for patients with nasopharyngeal cancer (NPC). However, the dose-volume criteria for adjacent anatomically normal organs at risk (OARs) remain controversial. The aim of this study was to evaluate the effects of higher than conventional doses of static and dynamic IMRT on the locoregional control of NPC, patient survival, and brainstem radiation toxicity. MATERIAL AND METHODS Patients (n=186) with stage III and stage IVa NPC underwent high-dose static and dynamic IMRT treatment (68-76.96 Gy) with or without chemotherapy for 34-57 days. Overall survival (OS), the presence of distant metastases, and brainstem toxicity were assessed. One-year, three-year, and five-year follow-up was performed. RESULTS High-dose IMRT alone or in combination with chemotherapy resulted in a 100% objective response rate and significantly improved OS rates, with one-year, three-year, and five-year OS rates of 94.1%, 89.8%, and 88.2%, respectively. The local recurrence rate (17.6%), and distant metastasis to the lung, liver, and bone (17.2%), and mortality (n=22) were reduced. Chemotherapy was the only factor that was significantly correlated with patient survival. Brainstem toxicity was reduced in patients treated with static IMRT (0.07%) and dynamic IMRT (0.08%). There were 26 additional factors that were not found to significantly affect brainstem toxicity. CONCLUSIONS High-dose static or dynamic IMRT combined with chemotherapy improved survival and reduces distal metastasis with a very low occurrence of brainstem toxicity in patients with locally advanced NPC. These findings might provide therapeutic guidance for clinicians when planning optimal dose-volume IMRT parameters.
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Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidad Modulada/métodos , Adulto , Anciano , Tronco Encefálico/patología , Tronco Encefálico/efectos de la radiación , Quimioradioterapia/métodos , Quimioradioterapia/mortalidad , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/mortalidad , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Radiationinduced lung injury (RILI) is a major complication of thoracic radiotherapy that starts as exudative inï¬ammation and proceeds to lung ï¬brosis, and additional studies are required to develop methods to ameliorate RILI. The aim of this study was to explore whether the nicotinic acetylcholine receptor subtype7 (α7nAChR) agonist GTS21 has a protective effect against RILI. C57BL6 mice were irradiated with 12 Gy to induce a mouse model of RILI. Some of the mice received an i.p. injection of 4 mg/kg GTS21 for three days with or without radiation treatment. Mice were sacrificed at 1, 3, 7, 14 and 21 days and at 3 and 6 months after irradiation. The results showed that GTS21 treatment significantly relieved RILI by decreasing TNFα, IL1ß and IL6 production in serum via inhibition of NFκB activation and downregulation of TLR4 and HMGB1 expression in the lungs. In addition, we found that GTS21 may regulate the MMP/TIMP balance in RILI. Finally, we found that GTS21 inhibited NOX1 and NOX2 expression, which subsequently reduced ROS levels and Hif1α expression in RILI. However, GTS21 showed little effect on lung tissue without radiation exposure. The results above were also validated in RAW264.7 macrophages. Our results showed that activation of the cholinergic antiinflammatory pathway via the α7nAChR agonist GTS21 reduced RILI. The protective effect of GTS21 against RILI is partly attributed to inhibition of the HMGB1/TLR4/NFκB pathway and ROS production. Thus, activation of the α7nAChR pathway may lead to new possibilities in the therapeutic management of RILI.
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Compuestos de Bencilideno/farmacología , Fibrosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Lesión Pulmonar/tratamiento farmacológico , Agonistas Nicotínicos/farmacología , Piridinas/farmacología , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Fibrosis/metabolismo , Fibrosis/patología , Inflamación/metabolismo , Inflamación/patología , Lesión Pulmonar/metabolismo , Lesión Pulmonar/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/patologíaRESUMEN
Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients. Knockdown of Ulk1 or the inhibition of Ulk1 by the selective inhibitor SBI0206965, inhibited cell proliferation, induced cell apoptosis and enhanced the sensitivity of cisplatin against NSCLC cells. Moreover, we demonstrated that Ulk1 exerted oncogenic activity in NSCLC by modulating both autophagy and apoptosis pathways. Inhibition of autophagy by SBI0206965 sensitized NSCLC cells to cisplatin by inhibiting cisplatin induced cell-protective autophagy to promote apoptosis. Furthermore, SBI0206965 promoted apoptosis in NSCLC cells independent of autophagy, which was partly mediated by destabilization of Bcl2/Bclxl. In summary, our results show that inhibition of Ulk1 suppresses NSCLC cell growth and sensitizes NSCLC cells to cisplatin by modulating both autophagy and apoptosis pathways, and that Ulk1 might be a promising target for NSCLC treatment.