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1.
Br J Cancer ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34621044

RESUMO

BACKGROUND: Albumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC. METHODS: Patients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as ≤ -2.60 score and a grade of 2 as a score of > -2.60 to ≤ -1.39. RESULTS: Cabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46-0.86] and 0.42 [0.32-0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66-1.06] and 0.46 [0.37-0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup. DISCUSSION: These results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT01908426.

2.
Cell Death Dis ; 12(10): 935, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642306

RESUMO

Lung adenocarcinoma (LUAD) is most common pathological type of lung cancer. LUAD with brain metastases (BMs) usually have poor prognosis. To identify the potential genetic factors associated with BM, a genomic comparison for BM cerebrospinal fluid (CSF) and primary lung tumor samples obtained from 1082 early- and late-stage LUAD patients was performed. We found that single nucleotide variation (SNV) of EGFR was highly enriched in CSF (87% of samples). Compared with the other primary lung tissues, copy number gain of EGFR (27%), CDK4 (11%), PMS2 (11%), MET (10%), IL7R (8%), RICTOR (7%), FLT4 (5%), and FGFR4 (4%), and copy number loss of CDKN2A (28%) and CDKN2B (18%) were remarkably more frequent in CSF samples. CSF had significantly lower tumor mutation burden (TMB) level but more abundant copy number variant. It was also found that the relationships among co-occurrent and mutually exclusive genes were dynamically changing with LUAD development. Additionally, CSF (97% of samples) harbored more abundant targeted drugs related driver and fusion genes. The signature 15 associated with defective DNA mismatch repair (dMMR) was only identified in the CSF group. Cancer associated pathway analysis further revealed that ErbB (95%) and cell cycle (84%) were unique pathways in CSF samples. The tumor evolution analysis showed that CSF carried significantly fewer clusters, but subclonal proportion of EGFR was remarkably increased with tumor progression. Collectively, CSF sequencing showed unique genomic characteristics and the intense copy number instability associated with cell cycle disorder and dMMR might be the crucial genetic factors in BM of LUAD.

3.
Neurochem Res ; 46(11): 3050-3058, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34347266

RESUMO

Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.

4.
Int J Oral Maxillofac Implants ; 36(4): 715-722, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34411210

RESUMO

PURPOSE: To evaluate the influence of age and trabecular microstructure on peri-implant strain in aging and young mice models under compressive load. MATERIALS AND METHODS: Eighteen 4-week-old female C57BL/6 mice (n = 6) were subjected to a 1.2% calcium content diet (young normal calcium group), and 7-month-old mice (n = 12) were randomly subjected to 0.01% and 1.2% calcium content diets (aging low and normal calcium groups, respectively) for 3 weeks. Histomorphometric and microcomputed tomography (micro-CT) analyses were used to investigate local alveolar bone microstructure. One maxilla segment from each group was reconstructed using micro-CT images to highlight the trabecular microstructure. A finite element analysis based on a computational model of the maxilla segment was performed to investigate peri-implant strain. Implants with three different diameters (0.3, 0.4, and 0.5 mm) were analyzed in these models. RESULTS: The aging low calcium group showed worse cancellous microstructure in hematoxylin and eosin (HE) staining, significantly increased osteoclast numbers (P < .05), and reduced bone volume fraction and trabecular thickness compared with the aging normal calcium group (P < .05). However, the young normal calcium group presented no difference in trabecular microstructure and osteoclast numbers compared with the aging normal calcium group. The aging low calcium group demonstrated increased strain intensity compared with the aging normal calcium group, whereas the young normal calcium and aging normal calcium groups showed comparable strain magnitude. The strain intensity of peri-implant bone increased with worse cancellous microstructure. When the diameter increased from 0.3 mm to 0.4 mm, the percentages of pathologic overload decreased regardless of bone microstructure. CONCLUSION: Deteriorated bone microstructure induced by a low calcium diet determined higher strain intensity, whereas, whenever age had no significant effect on trabecular microstructure, consequently, there was no substantial influence on strain. An increase of implant diameters can improve the strain distribution. Clinical decision-making should take into consideration the patient-specific and site-specific trabecular microstructure in preoperative assessment.


Assuntos
Implantes Dentários , Envelhecimento , Animais , Fenômenos Biomecânicos , Implantes Dentários/efeitos adversos , Feminino , Análise de Elementos Finitos , Humanos , Maxila , Camundongos , Camundongos Endogâmicos C57BL , Microtomografia por Raio-X
5.
Cells ; 10(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34359867

RESUMO

BACKGROUND: The kinesin Eg5, a mitosis-associated protein, is overexpressed in many cancers. Here we explored the clinical significance of Eg5 in hepatocellular carcinoma (HCC). METHODS: HCC tissues from surgical resection were collected. Total RNA was prepared from tumorous and nontumorous parts. Eg5 expression levels were correlated with overall survival (OS) and disease-free survival (DFS). In vitro efficacy of LGI-147, a specific Eg5 inhibitor, was tested in HCC cell lines. In vivo efficacy of Eg5 inhibition was investigated in a xenograft model. RESULTS: A total of 108 HCC samples were included. The patients were divided into three tertile groups with high, medium, and low Eg5 expression levels. OS of patients with low Eg5 expression was better than that of patients with medium and high Eg5 expression (median, 155.6 vs. 75.3 vs. 57.7 months, p = 0.002). DFS of patients with low Eg5 expression was also better than that of patients with medium and high Eg5 expression (median, 126.3 vs. 46.2 vs. 39.4 months, p = 0.001). In multivariate analyses, the associations between Eg5 expression and OS (p < 0.001) or DFS remained (p < 0.001). LGI-147 reduced cell growth via cell cycle arrest and apoptosis and induced accumulation of abnormal mitotic cells. In the xenograft model, the tumor growth rate under LGI-147 treatment was significantly slower than under the control. CONCLUSION: High Eg5 expression was associated with poor HCC prognosis. In vitro and in vivo evidence suggests that Eg5 may be a reasonable therapeutic target for HCC.

6.
J Am Dent Assoc ; 152(7): 542-550, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34176568

RESUMO

BACKGROUND: During the COVID-19 pandemic, American Society for Testing and Materials level 3 and level 2 medical face masks (MFMs) have been used for most health care workers and even for the first responders owing to a shortage of N95 respirators. However, the MFMs lack effective peripheral seal, leading to concerns about their adequacy to block aerosol exposure for proper protection. The purpose of this study was to evaluate the peripheral seal of level 3 and level 2 MFMs with a 3-dimensional (3D-) printed custom frame. METHODS: Level 3 and level 2 MFMs were tested on 10 participants with and without a 3D-printed custom frame; the efficiency of mask peripheral seal was determined by means of quantitative fit testing using a PortaCount Fit Tester based on ambient aerosol condensation nuclei counter protocol. RESULTS: The 3D-printed custom frame significantly improved the peripheral seal of both level 3 and level 2 MFMs compared with the masks alone (P < .001). In addition, both level 3 and level 2 MFMs with the 3D-printed custom frame met the quantitative fit testing standard specified for N95 respirators. PRACTICAL IMPLICATIONS: The 3D-printed custom frame over level 3 and level 2 MFMs can offer enhanced peripheral reduction of aerosols when using collapsible masks. With the shortage of N95 respirators, using the 3D-printed custom frame over a level 3 or level 2 MFM is considered a practical alternative to dental professionals.


Assuntos
COVID-19 , Exposição Ocupacional , Humanos , Máscaras , Pandemias , SARS-CoV-2 , Estados Unidos
7.
Mindfulness (N Y) ; : 1-10, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33968270

RESUMO

Objectives: Using a prospective longitudinal design, this paper examines a serial mediation model of the associations between self-compassion, trait mindfulness, caregiver stress, and depressive symptoms among the family caregivers of patients with lung cancer. Methods: A four-wave design was used, with initial assessment (T1) and three follow-ups, at the 2nd month (T2), the 5th month (T3), and the 8th month (T4). A total of 123 family caregivers completed the baseline measurements, including caregiver stress, self-compassion, trait mindfulness, and depressive symptoms. Data were analyzed by serial mediation models to determine the causal ordering of these variables. Results: Nearly one-quarter of the family caregivers suffered from clinically significant depressive symptoms and the severity of their depression remained unchanged throughout the 8-month follow-up period. Both cross-sectional and longitudinal path analyses revealed that the relationship between self-compassion and depressive symptoms was mediated sequentially by trait mindfulness and caregiver stress. The subscale analysis indicated that the association of higher compassionate action with fewer depressive symptoms was through chain-mediating effects of higher mindful awareness and lower caregiver stress. Conclusions: Family caregivers who have higher levels of self-compassion tend to have more mindfulness; greater mindfulness leads to lower levels of perceived caregiving stress which, in turn, links to fewer symptoms of depression. Both self-compassion and mindfulness could be regarded as protective factors for caregivers to reduce caregiving stress and depression.

8.
J Transl Med ; 19(1): 213, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001135

RESUMO

Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.


Assuntos
Glioma , MicroRNAs , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , MicroRNAs/genética , Prognóstico , Receptores de GABA-A , Transcriptoma
9.
J Am Dent Assoc ; 152(6): 455-462, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34044977

RESUMO

BACKGROUND: The route of transmission of severe acute respiratory syndrome coronavirus 2 has challenged dentistry to improve the safety for patients and the dental team during various treatment procedures. The purpose of this study was to evaluate and compare the effectiveness of dental evacuation systems in reducing aerosols during oral prophylactic procedures in a large clinical setting. METHODS: This was a single-center, controlled clinical trial using a split-mouth design. A total of 93 student participants were recruited according to the inclusion and exclusion criteria. Aerosol samples were collected on blood agar plates that were placed around the clinic at 4 treatment periods: baseline, high-volume evacuation (HVE), combination (HVE and intraoral suction device), and posttreatment. Student operators were randomized to perform oral prophylaxis using ultrasonic scalers on 1 side of the mouth, using only HVE suction for the HVE treatment period and then with the addition of an intraoral suction device for the combination treatment period. Agar plates were collected after each period and incubated at 37 °C for 48 hours. Colony-forming unit (CFU) counts were determined using an automatic colony counter. RESULTS: The use of a combination of devices resulted in significant reductions in CFUs compared with the use of the intraoral suction device alone (P < .001). The highest amounts of CFUs were found in the operating zone and on patients during both HVE and combination treatment periods. CONCLUSIONS: Within limitations of this study, the authors found significant reductions in the amount of microbial aerosols when both HVE and an intraoral suction device were used. PRACTICAL IMPLICATIONS: The combination of HVE and intraoral suction devices significantly decreases microbial aerosols during oral prophylaxis procedures.


Assuntos
Microbiologia do Ar , COVID-19 , Controle de Infecções Dentárias , Aerossóis , Humanos , SARS-CoV-2
10.
Clin Cancer Res ; 27(5): 1570-1579, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33446563

RESUMO

PURPOSE: Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. EXPERIMENTAL DESIGN: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. RESULTS: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition-high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. CONCLUSIONS: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.

11.
Psychol Health ; : 1-13, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998574

RESUMO

OBJECTIVE: The present study examined the potential mediating influences of meaning in life and quality of life in the relationship of trait mindfulness and depressive symptoms in lung cancer patients. Design: We adopted a cross-sectional design studying a sample of patients with non-small cell lung cancer, aged 20-65 years, and receiving cancer treatments or follow-up care. Main Outcome Measures: The outcome measures included Beck Depression Inventory-II, European Organisation for Research and Treatment of Cancer Core Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and lung cancer specific complementary measure (EORTC QLQ-LC13), Five Facet Mindfulness Questionnaire, and the meaning in life questionnaire. Results: Among 116 lung cancer patients, 26.72% of them had clinically significant depressive symptoms. The presence of meaning, quality of life (QOL) functioning and symptom distress mediated the relationship of trait mindfulness and depressive symptoms. Multiple mediation analyses found that the presence of meaning in life was the main mediator. Conclusion: The reductions of depressive symptoms might be related to trait mindfulness enhancing lung cancer patients' perceptions of meaning in life. A mindfulness program has the potential to improve depressive symptoms in people with lung cancer.

12.
Adv Mater ; 32(43): e2001628, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945035

RESUMO

Hydrogels with adhesive properties have potential for numerous biomedical applications. Here, the design of a novel, intrinsically adhesive hydrogel and its use in developing internal therapeutic bandages is reported. The design involves incorporation of "triple hydrogen bonding clusters" (THBCs) as side groups into the hydrogel matrix. The THBC through a unique "load sharing" effect and an increase in bond density results in strong adhesions of the hydrogel to a range of surfaces, including glass, plastic, wood, poly(tetrafluoroethylene) (PTFE), stainless steel, and biological tissues, even without any chemical reaction. Using the adhesive hydrogel, tissue-adhesive bandages are developed for either targeted and sustained release of chemotherapeutic nanodrug for liver cancer treatment, or anchored delivery of pancreatic islets for a potential type 1 diabetes (T1D) cell replacement therapy. Stable adhesion of the bandage inside the body enables almost complete tumor suppression in an orthotopic liver cancer mouse model and ≈1 month diabetes correction in chemically induced diabetic mice.

13.
World J Clin Cases ; 8(12): 2554-2565, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32607332

RESUMO

BACKGROUND: In December 2019, an ongoing outbreak of coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China. The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan. Therefore, it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province. To date, a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders, clinical classification, and with or without basic diseases. AIM: To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang (China) and provide a reliable reference for the prevention and control of COVID-19. METHODS: From January 16 to March 2, 2020, a total of 48 confirmed cases of COVID-19 were reported in Hengyang, and those cases were included in this study. The diagnostic criteria, clinical classification, and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) released by National Health Commission and National Administration of Traditional Chinese Medicine. The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction. All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software. RESULTS: A total of 48 cases of COVID-19 were collected, of which 1 was mild, 38 were moderate, and 9 were severe. It was unveiled that there were 31 (64.6%) male patients and 17 (35.4%) female patients, with a female-to-male ratio of 1.82:1. The range of age of patients with COVID-19 was dominantly 30-49 years old [25 (52.1%) of 48], followed by those aged over 60 years old [11 (22.9%)]. Besides, 29.2% (14 of 48) of patients had basic diseases, and 57.2% (8 of 14) of patients with basic diseases were aged over 60 years old. The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production [15 (31.5%) of 48], rural migrant workers from Hengyang to Wuhan [15 (31.5%)], and service workers operating in the service sector [8 (16.7%)]. The mean latent period was 6.86 ± 3.57 d, and the median was 7 [interquartile range (IQR): 4-9] d. The mean time from onset of symptoms to the first physician visit was 3.38 ± 2.98 (95%CI: 2.58-9.18) d, with a median of 2 (IQR: 1-5) d, and the mean time from hospital admission to confirmed diagnosis was 2.29 ± 2.11 (95%CI: 1.18-6.42) d, with a median of 2 (IQR: 1-3) d. The main symptoms were fever [43 (89.6%) of 48], cough and expectoration [41 (85.4%)], fatigue [22 (45.8%)], and chills [22 (45.8%)]. Other symptoms included poor appetite [13 (27.1%)], sore throat [9 (18.8%)], dyspnea [9 (18.8%)], diarrhea [7 (14.6%)], dizziness [5 (10.4%)], headache [5 (10.4%)], muscle pain [5 (10.4%)], nausea and vomiting [4 (8.3%)], hemoptysis [4 (8.3%)], and runny nose [1 (2.1%)]. The numbers of peripheral blood leukocytes, lymphocytes, and eosinophils were significantly reduced in the majority of the patients. The levels of C-reactive protein, fibrinogen, blood glucose, lactate dehydrogenase, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (γ-GT), myoglobin (MB), and creatine kinase (CK) were increased in 64.6%, 44.7%, 43.2%, 37.0%, 29.5%, 22.9%,20.8%, 21.6%, 13.6%, and 12.8% of patients, respectively. The incidence of ALT elevation in male patients was remarkably higher than that in females (P < 0.01), while the incidences of AST, CK, and blood glucose elevations in severe patients were remarkably higher than those in moderate patients (P < 0.05, respectively). Except for the mild patients, chest computed tomography showed characteristic pulmonary lesions. All the patients received antiviral drugs, 38 (79.2%) accepted traditional Chinese medicine, and 2 (4.2%) received treatment of human umbilical-cord mesenchymal stem cells. On March 2, 2020, 48 patients with COVID-19 were all cured and discharged. CONCLUSION: Based on our results, patients with COVID-19 often have multiple organ dysfunction or damage. The incidences of ALT elevation in males, and AST, CK, and blood glucose elevations in severe patients are remarkably higher.

14.
Clin Transl Radiat Oncol ; 22: 76-82, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32280792

RESUMO

Background and purpose: Thoracic re-irradiation may be an alternative treatment for lung cancer patients who develop intrathoracic locoregional recurrence without systemic progression. This study aimed to retrospectively assess locoregional control, clinical outcomes, and toxicities in lung cancer patients who received thoracic re-irradiation. Materials and methods: We retrospectively reviewed 50 lung cancer patients who received thoracic re-irradiation using conventional photon radiotherapy (RT) and stereotactic body radiotherapy (SBRT) between 2009 and 2017. The correlations of clinicopathologic factors, treatment factors, and dosimetric factors of RT with time to local progression (TTLP), progression-free survival (PFS), and overall survival (OS) after starting thoracic re-irradiation were calculated using log-rank tests and Cox regression models. Results: The median re-irradiation dose in equivalent dose in 2-Gy fractions was 51.1 Gy, and the mean re-irradiation planning target volume was 201.58 ml. The median mean lung dose (MLD) was 4.18 Gy, and the total lung volumes receiving a dose of 5 Gy (lung V5) and of 20 Gy (V20) were 19.8% and 5.85%, respectively. The TTLP, PFS, and OS were 18.0, 5.9, and 25.1 months, respectively. Lung V5 (p < 0.001), V20 (p = 0.011), and MLD (p = 0.002) were significantly associated with grade ≥2 lung toxicity. Seven (14%) patients developed lethal lung events. Subsequent chemotherapy following thoracic re-irradiation was significantly correlated with lethal lung events (p = 0.009). Conclusion: Promising local control can be achieved with thoracic re-irradiation in lung cancer patients with locoregional recurrence. However, unexpected lethal lung events may occur, especially in patients receiving systemic therapy following thoracic re-irradiation.

15.
Oncologist ; 25(9): e1280-e1285, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32271494

RESUMO

LESSONS LEARNED: For patients with advanced hepatocellular carcinoma after failure of first-line sorafenib monotherapy, second-line axitinib provides modest efficacy with tolerable toxicity. The discrepant tumor responses and survival outcomes in trials using axitinib as salvage therapy highlight the importance of optimal patient selection with the aid of clinical biomarkers. BACKGROUND: Multikinase inhibitors have been effective treatment for hepatocellular carcinoma (HCC). This multicenter phase II study explored the efficacy and safety of second-line axitinib for advanced HCC. METHODS: Patients with advanced HCC and Child-Pugh A liver function, experiencing progression on first-line sorafenib monotherapy, were eligible. Axitinib 5 mg twice daily was given continuously with allowed dose escalation. Tumor assessment was performed according to RECIST version 1.1. The primary endpoint was rate of disease control. RESULTS: From April 2011 to March 2016, 45 patients were enrolled. Thirty-seven patients (82%) tested positive for hepatitis B surface antigen. The disease control rate was 62.2%, and the response rate was 6.7%, according to RECIST criteria. Median progression-free survival (PFS) and overall survival (OS) were 2.2 months and 10.1 months, respectively. Treatment-related adverse events were compatible with previous reports of axitinib. CONCLUSION: Second-line axitinib has moderate activity and acceptable toxicity for patients with advanced HCC after failing the first-line sorafenib monotherapy.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Sorafenibe/uso terapêutico , Resultado do Tratamento
16.
Cancer Cell ; 37(2): 226-242.e7, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049047

RESUMO

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC. Surveying the transcriptomes of ∼6,000 FTE cells, predominantly from non-ovarian cancer patients, identified 6 FTE subtypes. We used subtype signatures to deconvolute SOC expression data and found substantial intra-tumor NGH. Importantly, NGH-based stratification of ∼1,700 tumors robustly correlated with survival. Our findings lay the foundation for accurate prognostic and therapeutic stratification of SOC.


Assuntos
Células Epiteliais/patologia , Neoplasias das Tubas Uterinas/metabolismo , Tubas Uterinas/patologia , Neoplasias Ovarianas/patologia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Epitélio/metabolismo , Epitélio/patologia , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Heterogeneidade Genética , Humanos , Neoplasias Ovarianas/metabolismo
17.
Chin Med J (Engl) ; (6): 657-663, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32097205

RESUMO

BACKGROUND: Mallet fracture is avulsion of the terminal extensor tendon from the base of the distal phalangeal bone with a bony fragment. This study was performed to evaluate the anatomical characteristics of mallet fractures, investigate a new mallet fracture classification system using anatomical and imaging methods, and discuss the treatment schemes for different types of mallet fracture. METHODS: Sixty-four fresh cadaveric fingers were divided into four groups, and models of different types of mallet fracture with distal interphalangeal joint instability were established by dissecting 25%, 50%, 75%, and 100% of the bilateral collateral ligaments. The effect of mallet fractures on the stability of the distal interphalangeal joint was then observed. The lateral radiographs of mallet fractures in 168 patients were analyzed and classified according to the involvement of the joint surface in the fracture, the thickness of fracture, the untreated time after injury, and the complication of distal interphalangeal joint palmar subluxation. Forty-seven patients were surgically treated by reconstruction of extensor tendon insertion, the Ishiguro method, or single Kirschner wire fixation. RESULTS: The established mallet fracture model showed that the distal interphalangeal joint was stable when the bilateral collateral ligaments were cut off by 25% (t = -0.415, P = 0.684) and significantly unstable when this range was ≥50% (50% transection: t = -6.363, P < 0.001; 75% transection: t = -17.036, P < 0.001; 100% transection: t = -30.977, P < 0.001, respectively). The mallet fractures were divided into Types I, II, and III (fracture involving <20%, 20%-50%, and >50% of the joint surface, respectively). Type II was further divided into Types IIa and IIb according to whether the course of injury was < or ≥2 weeks, respectively. The mean post-operative flexion of the distal interphalangeal joint was 63.4°â€Š±â€Š7.9°, and the mean extension lag was 6.7°â€Š±â€Š4.6°. CONCLUSIONS: The lateral collateral ligament is the main factor that maintains the stability of the distal interphalangeal joint. Classification that combines the involvement of the joint surface in the fracture, the thickness of the fracture, and the untreated time after injury is reasonable and will help to choose an appropriate operational method.


Assuntos
Traumatismos dos Dedos/classificação , Fraturas Ósseas/classificação , Adolescente , Adulto , Cartilagem Articular/lesões , Feminino , Falanges dos Dedos da Mão/lesões , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Adulto Jovem
18.
Ying Yong Sheng Tai Xue Bao ; 31(1): 25-34, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957377

RESUMO

To examine the effects of management measures on carbon and nitrogen contents, as well as their distribution and structural characteristics of different soil fractions in Moso bamboo plantations, we compared three types of the bamboo forests (undisturbed, extensively managed, and intensively managed) and the control secondary broadleaved evergreen forest using the methods of physical fractionation, chemical and biological analysis and Fourier-transform infrared spectroscopy (FTIR). The results showed that soil total organic carbon (TOC) and total nitrogen (TN) content, as well as free particulate organic carbon and nitrogen, soluble organic carbon and nitrogen (DOC, DON), and mineral-associated organic carbon and nitrogen in the undisturbed and extensively managed Moso bamboo plantations were significantly increased compared with that in the control. The distribution ratio of free particulate organic carbon and nitrogen in the undisturbed Moso bamboo plantation significantly increased, with mineral-associated organic carbon being the largest reservoir of soil organic carbon (67.6%). Intensive management resulted in the decrease of soil organic carbon, total nitrogen storage, and the contents of each component, but significantly increased DOC/TOC, the ratio of microbial biomass nitrogen to TN as well as the ratio of microbial biomass carbon to TOC (microbial quotient). Management measures significantly affected the chemical structure of SOC. Compared with the control, the relative intensities of phenolic and alcoholic-OH, aliphatic methyl and methylene, aromatic C=C, and carbonyl C=O absorption were higher in the SOC of undisturbed and extensively managed Moso bamboo plantations, and soil hydrophobicity was significantly increased. Results from correlation analysis showed that soil hydrophobicity and the content of aliphatic and aromatic groups were negatively correlated with microbial quotient and positively correlated with TOC and TN content. In conclusion, the increased inputs of organic matter residues (such as litter and roots) could contribute to the relative accumulation of chemical resistance compounds with reduced human disturbance, which significantly enhanced chemical stability of soil organic carbon. Soil clay minerals played a key role in protecting soil organic carbon through the formation of mineral-organic compounds, which facilitate the stability of soil carbon storage and the long-term preservation of soil carbon.


Assuntos
Carbono , Nitrogênio , China , Florestas , Humanos , Poaceae , Solo
19.
FEBS Open Bio ; 10(3): 362-370, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31930721

RESUMO

Chronic fluoride exposure from drinking water may result in endemic fluorosis. To better understand the mechanisms by which some people are resistant to fluorosis, here we investigated the effect of treatment with NaF (sodium fluoride) on production of reactive oxygen species (ROS), morphological changes in mitochondria, the mRNA expression of Fas ligand (Fas-L), and the protein expression of cleaved caspase-3 in regular L-929 cells and fluoride-resistant (FR) L-929 cells. While morphological changes indicative of apoptosis and a network of fragmented mitochondria were observed in regular L-929 cells after NaF treatment, there were no morphological changes in FR L-929 cells after NaF treatment. Treatment with 10 mm NaF induced a significant difference in the production of ROS, triggered the expression of cleaved caspase-3, and upregulated the mRNA expression of Fas-L in regular L-929 cells. However, there was no significant production of ROS in FR L-929 cells. Additionally, cleaved caspase-3 and upregulated Fas-L were not detected in FR L-929 cells. These results suggest that FR fibroblasts are resistant to oxidative stress and apoptosis induced by fluoride.

20.
Chemosphere ; 238: 124619, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31450114

RESUMO

Perfluorooctane sulfonamide (FOSA) is known as a key intermediate of perfluorooctane sulfonic acid (PFOS) precursors, which can be frequently detected in the environment and biota. FOSA could be bioaccumulated in earthworms from soil, but the contributions of enzymes and gut microbes involved in the biotransformation of FOSA in earthworms have not been identified. Therefore, the effects of enzyme inhibitors and intestinal microflora on biotransformation of FOSA in earthworms were investigated in the present study. FOSA was biotransformed to form PFOS by earthworms obtained from in vivo and in vitro tests. The addition of FOSA had significantly positive effects on cytolchrome P450 (CYP450) and glutathione-s-transferase (GST) activities, suggesting CYP450 and GST are likely involved in the enzymatic transformation. In addition, both 1-Aminobenzotriazole (ABT) and ezatiostat hydrochloride (TLK199), which were selected to inhibit the CYP and GST enzymes, respectively, demonstrated inhibition effects on biotransformation of FOSA in earthworms with a dose-dependent relationship. However, the concentrations of FOSA weren't changed by the bacteria isolated from worm gut, suggesting that gut bacteria did not contribute to FOSA biotransformation in earthworms. The results of this study confirm that the transformation of FOSA in earthworms is mediated mainly by enzymes rather than by gut microbes.


Assuntos
Ácidos Alcanossulfônicos/metabolismo , Biodegradação Ambiental , Biotransformação , Sistema Enzimático do Citocromo P-450/metabolismo , Fluorcarbonetos/metabolismo , Microbioma Gastrointestinal , Glutationa Transferase/metabolismo , Oligoquetos/metabolismo , Animais , Oligoquetos/microbiologia
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