RESUMO
BACKGROUND: MRG002 is a novel HER2-targeted antibody-drug conjugate being investigated in the MRG002-006 trial to evaluate the efficacy and safety in HER2-positive urothelial carcinoma patients. METHODS: This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1. RESULTS: As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CIï¼38.9%-67.5%), with 6.9% CR, and the DCR was 83.7% (95%CIï¼70.0%-91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CIï¼5.4-NE) and 14.9 months (95%CIï¼11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2. CONCLUSION: Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity.
Assuntos
Anticorpos Monoclonais Humanizados , Imunoconjugados , Receptor ErbB-2 , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Idoso , Imunoconjugados/uso terapêutico , Imunoconjugados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/patologia , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/secundárioRESUMO
Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).
RESUMO
OBJECTIVES: This study aimed to assess the feasibility, safety, acceptability, and potential effectiveness of resistance training (RT) with or without ß-Hydroxy ß-Methylbutyrate (HMB) intervention program for ICU patients. DESIGN: Open-label, parallel group, mixed method, randomized controlled trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly allocated to one of four groups. The RT group received supervised multilevel resistance training (RT) using elastic bands, administered by trained ICU nurses. The HMB group received an additional daily dose of 3.0 g HMB. The combination group underwent both interventions concurrently, while the control group received standard care. These interventions were implemented throughout the entire hospitalization period. Primary outcomes included feasibility indicators such as recruitment rate, enrollment rate, retention rate, and compliance rate. Secondary outcomes covered adverse events, acceptability (evaluated through questionnaires and qualitative interviews), and physical function. Quantitative analysis utilized a generalized estimation equation model, while qualitative analysis employed directed content analysis. RESULTS: All feasibility indicators met predetermined criteria. Forty-eight patients were randomly assigned across four arms, achieving a 96% enrollment rate. Most patients adhered to the intervention until discharge, resulting in a 97.9% retention rate. Compliance rates for both RT and HMB interventions approached or exceeded 85%. No adverse events were reported. The intervention achieved 100% acceptability, with a prevailing expression of positive experiences and perception of appropriateness. The RT intervention shows potential improvement in physical function, while HMB does not. CONCLUSIONS: Implementing nurse-led resistance training with elastic bands with or without HMB proved to be feasible and safe for ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: A large-scale, multicenter clinical trials are imperative to definitively assess the impact of this intervention on functional outcomes in this population.
Assuntos
Treinamento Resistido , Humanos , Estado Terminal , Estudos de Viabilidade , ValeratosRESUMO
BACKGROUND: Most sarcomatoid differentiated renal cell carcinoma was differentiated from Chromophobe renal cell carcinoma (KICH) and related to a bad prognosis. Thus, finding biomarkers is important for the therapy of KICH. METHODS: The UCSC was used for determining the expression of mRNA and miRNA and clinical data in KICH and normal samples. KEGG and GO were used for predicting potential function of differently expressed genes (DEGs). Optimal prognostic markers were determined by Lasso regression. Kaplan-Meier survival, ROC, and cox regression were used for assessing prognosis value. GSEA was used for predicting potential function of markers. The relations between markers and immune cell infiltration were determined by Pearson method. The upstream miRNA of markers was predicted in TargetScan and DIANA. RESULTS: The 6162 upregulated and 13,903 downregulated DEGs were identified in KICH. Further CENPE and LDHA were screened out as optimal prognostic risk signatures. CENPE was highly expressed while LDHA was lowly expressed in KICH samples, and the high expressions of 2 genes contributed to bad prognosis. The functions of CENPE and LDHA were mainly enriched in proliferation related pathways such as cell cycle and DNA replication. In addition, the correlation of 2 genes with immune infiltrates in KICH was also observed. Finally, we found that has-miR-577 was the common upstream of 2 genes and the binding sites can be predicted. CONCLUSION: CENPE and LDHA were identified as the important prognostic biomarkers in KICH, and they might be involved in the proliferation of cancer cell.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Humanos , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Ciclo Celular , Neoplasias Renais/genética , MicroRNAs/genética , PrognósticoRESUMO
The assessment of population genetic structure is the basis for understanding the genetic information of indigenous breeds and is important for the protection and management of indigenous breeds. However, the population genetic differentiation of many local breeds still remains unclear. Here, we performed a genome-wide comparative analysis of Jinding, Liancheng white, Putian black, and Shanma ducks based on the genomic sequences using RAD sequencing to understand their population structure and genetic diversity. The population parameters showed that there were obvious genetic differences among the four indigenous breeds, which were separated groups. Among them, Liancheng white and Shanma ducks may come from the same ancestor because the phylogenetic tree forms three tree trunks. In addition, during the runs of homozygosity (ROH), we found that the average inbreeding coefficient of Liancheng white and Putian black ducks was the lowest and the highest, respectively. Five genomic regions were considered to be the hotspots of autozygosity among these indigenous duck breeds, and the candidate genes involved a variety of potential variations, such as muscle growth, pigmentation, and neuroregulation. These findings provide insights into the further improvement and conservation of Fujian duck breeds.
RESUMO
BACKGROUND: Based on the theory of postural control and the role of cognitive capacity, this study analyses how physical ability and somatosensory impairment influence affective symptoms in patients with stroke. METHODS: The cross-sectional study with a consecutive sampling approach was conducted in 10 different rehabilitation departments in Yunnan Province, China between August 2019 and February 2021. A total of 1,058 patients with stroke were included according to the inclusion criteria and exclusive criteria. Their important functions were evaluated including somatosensory measurement, Brunnstrom recovery stage, manual muscle testing (MMT), Barthel index (BI), mini-balance evaluation systems test (Mini-BEST), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAM-A), and Hamilton Depression Scale (HAM-D). Exploratory Factor Analysis was used to construct the measure models. A path analysis was performed to estimate the role of balance impairment and cognitive capacity as mediators in the relationships between somatosensory impairment, physical ability and affective symptoms. RESULTS: By comparing two models, the final model indicated a good global model fit to the data [χ2=243.5, χ2/df=5.181, goodness-of-fit index (GFI) =0.977, comparative five index (CFI) =0.944, Tucker-Lewis index (TLI) =0.922, standardized root mean square residual (SRMR) =0.063, and root mean square error of approximation (RMSEA) =0.063, Akaike information criterion (AIC) =303.51, Bayesian information criterion (BIC) =304.26], although Chi-square test was not significant due to the large sample size. In the path analysis, somatosensory impairment significantly negative influenced balance impairment (P<0.05, ß=-0.061), and physical ability significantly positively affected balance impairment (P<0.001, ß=0.893). A mediation analysis was conducted to show that balance impairment mainly mediated the relationship between physical ability and affective symptoms (R2=0.996), while the relationship between physical ability and affective symptoms was mediated slightly by cognitive capability (R2=0.108). CONCLUSIONS: These results suggest that balance impairment mainly mediates the relationship between physical ability and affective symptoms, while cognitive capacity slightly medicates this relationship. Rehabilitation professionals and family caregivers should pay more attention to balance function, which will help to strengthen the physical ability and improve post-stroke mood disorders.
Assuntos
Análise de Mediação , Acidente Vascular Cerebral , Sintomas Afetivos , Teorema de Bayes , China , Estudos Transversais , Humanos , Acidente Vascular Cerebral/complicaçõesRESUMO
Animal evolution is characterized by frequent turnover of sexually dimorphic traits-new sex-specific characters are gained, and some ancestral sex-specific characters are lost, in many lineages. In insects, sexual differentiation is predominantly cell autonomous and depends on the expression of the doublesex (dsx) transcription factor. In most cases, cells that transcribe dsx have the potential to undergo sex-specific differentiation, while those that lack dsx expression do not. Consistent with this mode of development, comparative research has shown that the origin of new sex-specific traits can be associated with the origin of new spatial domains of dsx expression. In this report, we examine the opposite situation-a secondary loss of the sex comb, a male-specific grasping structure that develops on the front legs of some drosophilid species. We show that while the origin of the sex comb is linked to an evolutionary gain of dsx expression in the leg, sex comb loss in a newly identified species of Lordiphosa (Drosophilidae) is associated with a secondary loss of dsx expression. We discuss how the developmental control of sexual dimorphism affects the mechanisms by which sex-specific traits can evolve.
Assuntos
Proteínas de Drosophila , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Caracteres Sexuais , Diferenciação SexualRESUMO
This study aimed to explore the role and mechanism of circ_0014359 in the OSCC. We firstly investigated the expression levels of circ_0014359 in OSCC tissues and cell lines. Then, the effects of knocking down circ_0014359 on cellular viability, apoptosis, migration, and invasion of OSCC cell lines were observed by cell counting kit-8 assay, flow cytometry, and transwell assay. Xenografts mouse model was established to explore the in vivo effect of circ_0014359 on the tumor volume and size of OSCC. We found that circ_0014359 was highly expressed in the OSCC tissues and cell lines compared to the normal controls (P<0.05). The expression of circ_0014359 was associated with the survival of patients (P<0.05). For the OSCC cell lines, circ_0014359 knock down induced apoptosis and inhibited migration, invasion, and epithelial-mesenchymal transition of OSCC cells (P<0.001). In vivo, silencing the circ_0014359 blocked the growth of OSCC tumors. The circ_0014359 can directly interact with the micro-RNA-149 (miR-149). Inhibition of miR-149 can rescue the inhibitory effects of circ_0014359 knock down on OSCC cells. The circ_0014359-miR-149 pathway may be a novel target for developing strategies for the diagnosis and treatment of OSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Animais , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Contrast-induced nephropathy (CIN) is a common complication with adverse outcome after iodinated-contrast injection, yet still lacking effective medication. Heme oxygenase-1 (HO-1) has been reported to play an important role against renal injuries. Hemin, a HO-1 inducer and anti-porphyria medicine, may have a promising effect against CIN. In this study, we aim to investigate the effect of hemin on CIN model and the underlying molecular mechanisms in human proximal tubule epithelial cells (HK-2). To mimic a common condition in percutaneous coronary intervention (PCI) patients, CIN was induced by intravenous iopromide in high-fat fed diabetic rats. We found hemin, given right before iopromide, mitigated CIN with enhanced antioxidative capacity and reduced oxidative stress. HK-2 cells insulted by iopromide demonstrated decreased cell vitality and rising reactive oxygen species (ROS), which could also be inhibited by hemin. The effects of hemin involved a key molecule in ferroptosis, glutathione peroxidase (GPX4), whose down-expression by small interfering RNA (siRNA) reversed the effect of hemin on HK-2 cells. Furthermore, hemin's induction of GPX4 involved HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2). Either HO-1 or Nrf2 inhibitor prevented hemin's effect on GPX4 to a comparable extent, and over-expression of Nrf2 increased GPX4 expression. Moreover, intervention of ferroptosis inhibitor liproxstatin-1 also alleviated CIN in vivo. Therefore, we showed hemin mitigated CIN, inhibiting oxidative stress and ferroptosis, by upregulation of GPX4 via activation of HO-1/Nrf2. Hemin, as a clinical medicine, has a translational significance in treating CIN, and anti-ferroptosis is a potential therapeutic strategy for CIN.
Assuntos
Meios de Contraste , Células Epiteliais , Ferroptose , Fármacos Hematológicos , Hemina , Nefropatias , Animais , Células Cultivadas , Meios de Contraste/efeitos adversos , Diabetes Mellitus Experimental/etiologia , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Ferroptose/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Fármacos Hematológicos/farmacologia , Heme Oxigenase-1/metabolismo , Hemina/farmacologia , Humanos , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Nefropatias/prevenção & controle , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/fisiopatologia , Fator 2 Relacionado a NF-E2/metabolismo , Intervenção Coronária Percutânea , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , RNA Interferente Pequeno/genética , Ratos , Transdução de SinaisRESUMO
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that can develop in numerous organs, most commonly in the lungs and rarely in the brain. Here, we reported a 55-year-old patient with nasopharyngeal IMT and the recurrence in the skull base, slope and pterygoid sinus who underwent cranial base and slope tumor resection. Postoperative magnetic resonance imaging (MRI) and multiplex immunohistochemistry (mIHC) showed tumor recurrence and metastasis to the intracalvarium. While genetic testing revealed no significant related gene mutations, tertiary mutations in NSD1 and SOX9 genes were identified in the tumor tissues. The patient achieved partial remission after receiving 7 cycles of immunotherapy (toripalimab 240 mg for 1 cycle followed by 6 cycles of sintilimab 200 mg), and MRI examination indicated an almost complete remission of intracranial IMT after 16 cycles of immunotherapy. In summary, the novel class of immune-targeted agents may be effective in clinical management of rare intracranial IMT.
RESUMO
Osteoporosis (OP) is a systemic bone metabolic disease with complicated pathogenesis and is difficult to cure clinically. The regulatory mechanisms of OP are needed to be further investigated. In the present study, we focused on the role of myocardial infarction-associated transcript (MIAT) in OP development and examined the underlying mechanism. The serum expression levels of MIAT in samples from patients with OP and healthy controls were compared using quantitative reverse transcription-PCR (qRT-PCR). The dual-luciferase reporter assay was used to confirm the relationship between MIAT and its potential target microRNA, i.e., miR-150-5p. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and transfected with MIAT shRNA, with or without miR-150-5p inhibitor. EdU staining and colony formation analysis were performed to determine the proliferation ability of these cells. Furthermore, the TUNEL assay and flow cytometry were used to assess BMSC apoptosis. Finally, RT-PCR and Western blot assays were employed to assess the expression of osteogenic differentiation biomarkers. Compared with controls, the expression of MIAT was significantly increased, whereas that of miR-150-5p was markedly decreased in patients with OP. MIAT and miR-150-5p expression levels exhibited a strong negative correlation. Furthermore, osteogenic differentiation indicators were suppressed in serum of OP patients. MIAT was downregulated, and miR-150-5p was upregulated in induced to osteogenic differentiation BMSCs. Furthermore, downregulation of MIAT dramatically promoted osteogenic differentiation, increased proliferation, and inhibited apoptosis in BMSCs; miR-150-5p inhibitor abrogated the effects of MIAT. In conclusion, lncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of BMSCs.
Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Infarto do Miocárdio , Osteoporose , RNA Longo não Codificante/genética , Apoptose/genética , Medula Óssea/metabolismo , Medula Óssea/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Osteogênese/genética , Osteoporose/metabolismo , RNA Longo não Codificante/metabolismoRESUMO
An implant template with great precision is significantly critical for clinical application. Currently, the application of an immediate implant remains limited by the deviations between the planned and actual achieved positions and long periods required for preparation of implant templates. Material Extrusion (MEX), as one kind of 3D printing method, is well known for its low cost and easy operation. However, the accuracy of the implant template printed by MEX has not been fully researched. To investigate the accuracy and feasibility of in vitro computer-guided surgery assisted with a MEX printed template, unidentified plaster samples missing a maxillary molar are digitalized. Mimics software (Materialise, Leuven, Belgium) is used for preoperative design. Surgical templates are fabricated by a MEX 3D printer (Lingtong III, Beijing SHINO, Beijing, China). Postoperative CBCT data are obtained after surgical template placement. The differences in positions of X, Y, Z, and dXYZ as well as angulations between the placed and the designed template are measured on labiolingual and mesiodistal planes. The deviations of the planned and the actual outcome in each dimension are observed and analyzed. Data from different samples indicate that the mean deviation of the angle measures approximately 3.640°. For position deviation, the maximum deviation is found in the z-direction and the mean deviation is about 0.365 ± 0.136 mm. The mean deviation of space Euclidean distance dXYZ is approximately 0.537 ± 0.123 mm. Implant templates fabricated by MEX present a relatively high accuracy for tooth-supported guide implantation.
RESUMO
The fabrication of high-precision scaffolds with excellent biocompatibility for tissue engineering has become a research hotspot. Two-photon polymerization (TPP) can break the optical diffraction limit and is used to fabricate high-resolution three-dimensional (3D) microstructures. In this study, the biological properties, and machinability of photosensitive gelatin methacrylate (GelMA) hydrogel solutions are investigated, and the biocompatibility of 3D scaffolds using a photosensitive GelMA hydrogel solution fabricated by TPP is also evaluated. The biological properties of photosensitive GelMA hydrogel solutions are evaluated by analyzing their cytotoxicity, swelling ratio, and degradation ratio. The experimental results indicate that: (1) photosensitive GelMA hydrogel solutions with remarkable biological properties and processability are suitable for cell attachment. (2) a micro/nano 3D printed scaffold with good biocompatibility is fabricated using a laser scanning speed of 150 µm/s, laser power of 7.8 mW, layer distance of 150 nm and a photosensitive GelMA hydrogel solution with a concentration of 12% (w/v). Micro/nano additive manufacturing will have broad application prospects in the tissue engineering field.
RESUMO
Excellent biocompatibility and corrosion resistance of implants are essential for Ti6Al4V parts fabricated by selective laser melting (SLM) for biomedical applications. To achieve better corrosion resistance and biocompatibility of Ti6Al4V parts, the effects of SLM processing parameters on the corrosion resistance and the biocompatibility of Ti6Al4V parts are investigated by changing the scanning speeds and laser powers. The detailed influence mechanism of processing parameters on the properties of Ti6Al4V parts is studied from two aspects, including microstructure and defects. It is found that the corrosion resistance and biocompatibility of Ti6Al4V parts can be adjusted by changing the scanning speed and the laser power due to the constituent phase and the number and size of defect holes of Ti6Al4V parts. Compared with the laser power, the scanning speed has a stronger influence on the performance of the part, which can be used as "coarse tuning" based on the performance requirements. At the scanning speed of 1100 mm/s and the laser power of 280 W, Ti6Al4V parts with better corrosion resistance can be obtained. Ti6Al4V parts with better biocompatibility are fabricated at the scanning speed of 1200 mm/s and the laser power of 200 W.
RESUMO
To explore the effects of lncRNA GACAT1/miR-149 molecular axis on the proliferation, apoptosis, migration and autophagy of oral squamous cell carcinoma (OSCC) cells, and to explore its molecular mechanism. The expressions of lncRNA GACAT1 and miR-149 in tissues and cell lines of patients with OSCC were detected by qRT-PCR. Si-control, GACAT1-siRNA, inhibitor NC and miR-149 inhibitors were transfected into OSCC cells separately or in combination with Lipofectamine 2000. The binding sites between lncRNA GACAT1 and miR-149 were predicted using the miRanda website, and the targeting relationship was verified by dual-luciferase assay. The expression of lncRNA XIST and miR-149 was detected by qRT-PCR. CCK-8 assay was used to detect cell activity. Cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration ability was detected by Transwell assay. The expression of migration and autophagy-related proteins was detected by western blot. LncRNA GACAT1 was highly expressed in cancer tissues and cell lines of OSCC patients (P < 0.01), while miR-149 was low expressed (P < 0.01). LncRNA GACAT1 binds to miR-149 targeting. The down-regulation of lncRNA GACAT1 inhibited the proliferation and migration of OSCC cells and promoted apoptosis and autophagy (P < 0.01). The transfection of miR-149 inhibitor had the opposite effect. Knockdown of lncRNA GACAT1 and transfection with miR-149 inhibitor reversed the effect of GACAT1 silencing on OSCC cells. Inhibition of lncRNA GACAT1 can inhibit the proliferation and migration of OSCC cells, promote apoptosis and autophagy, and the mechanism may be related to the targeting of miR-149.
Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Bucais/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Apoptose , Autofagia , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca/metabolismo , Boca/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , TransfecçãoRESUMO
We describe a case of recurrent glioblastoma treated with anlotinib in this report. The patient was administered anlotinib 12 mg p.o. once every day (days 1-14, with a 21-day cycle) (anlotinib clinical study NCT04004975) and oral temozolomide chemotherapy 100 mg/m2 (days 1-7, days 15-21, 28-day cycle; 12 cycles). After 2 months of therapy, the patient achieved a partial response that has been maintained for >17 months of follow-up. Molecular characterization confirmed the presence of a TERT promoter mutation, wild-type IDH1/2, an FGFR3-TACC3 fusion, and FGFR3 amplification in the patient. Anlotinib is a multitarget tyrosine kinase inhibitor that was originally designed to inhibit VEGFR2/3, FGFR1-4, PDGFRα/ß, and c-Kit. Patients with TERT promoter mutations and high-grade IDH-wild-type glioma have shorter overall survival than patients with IDH-wild-type glioma without TERT promoter mutations. However, this patient had a favorable clinic outcome, and FGFR3-TACC3 fusion may be a new marker for treatment of glioma with anlotinib. KEY POINTS: This case study is believed to be the first report that FGFR3-TACC3 fusion could be a novel indication to treat recurrent glioblastoma with the drug anlotinib. This case exhibited an exceptional response (maintained partial response >17 months) after 2-month combined therapy of anlotinib and oral temozolomide chemotherapy. This case also underscores the importance of molecular diagnosis for clinically complex cases. Tumor tissue-based assessment of molecular biomarkers in brain tumors has been successfully translated into clinical application.
Assuntos
Glioblastoma , Quinolinas , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Humanos , Indóis , Proteínas Associadas aos Microtúbulos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Receptor Tipo 3 de Fator de Crescimento de FibroblastosRESUMO
No genomic sequence of Mycobacterium isolated from orchids has been reported yet; therefore, this study intends to analyze the complete genomic sequence of a growth-promoting Mycobacterium from orchid Doritaenopsis. Mycobacterium strain Mya-zh01 was isolated from the flower stalk of Doritaenopsis Jiuhbao Red Rose. Our results show that Mya-zh01 can effectively produce and secrete the plant growth hormone indole-3-acetic acid (IAA). Inoculation of Mya-zh01 increased root number and length, plant height, leaf number, and leaf length in Doritaenopsis. Furthermore, inoculation of Mya-zh01 promotes seed germination in Doritaenopsis. We sequenced and assembled chromosome for Mya-zh01 (5,027,704 bp with 68.48% GC content), which was predicted to encode 4968 proteins with functions in oxidation reduction, growth, plasma membrane, ATP and DNA binding, carbon metabolism and biosynthesis of amino acids pathways. Mya-zh01 may trap iron from nature or host cells to facilitate the growth of the orchids by producing two siderophores (Mycobactin and Nocobactin NA). Four pathways (tryptamine, indole-3-acetamide, indole-3-pyruvate, and flavin monooxygenase) and seven enzymes [tryptophan synthase alpha chain, tryptophan synthase beta chain, amidase, monoamine oxidase, indole-3-pyruvate monooxygenase, indole-3-pyruvate decarboxylase and aldehyde dehydrogenase (NAD +)] involved in IAA biosynthesis were predicted in Mya-zh01 genome. In conclusion, this study demonstrated the significance of Mya-zh01 in facilitating plant growth and seed germination in Doritaenopsis by IAA biosynthesis, which provides a new insight into the mechanism of plant-bacteria interaction in Doritaenopsis.
Assuntos
Mycobacterium/genética , Orchidaceae/microbiologia , Desenvolvimento Vegetal , Sementes/microbiologia , Flores/microbiologia , Germinação , Mycobacterium/isolamento & purificação , Mycobacterium/metabolismoRESUMO
BACKGROUND: To compare the diagnostic value of prostate cancer (PCa) between holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed the clinical data of 2909 patients who underwent surgery for benign prostatic hyperplasia (BPH) from January 2008 to June 2018. A total of 1362 patients received HoLEP, and 1547 patients received TURP. The baseline patient characteristics were collected. We then compared the perioperative outcomes of these patients who diagnosed with incidentally diagnosed prostatic carcinoma (IDPC) or PCa after BPH surgeries. RESULTS: The total detection rate of PCa in HoLEP group was higher than that in TURP group (85/6.24% vs. 61/3.94%, p = 0.005). Specifically, 55(4.6%) patients were diagnosed with IDPC in HoLEP group with prostate-specific antigen (PSA) less than 4 ng/ml, and 37(2.7%) patients in TURP group (p = 0.014). For the patients with PSA between 4 and 10 ng/ml, 15(13.9%) patients were diagnosed with PCa after HoLEP, and 6(5.0%) patients after TURP (p = 0.023). But the detection rate of PCa was not significantly different between the two groups when PSA was over 10 ng/ml. On the other hand, 57 in 1215 patients with no prostate biopsy preoperatively were diagnosed with PCa after HoLEP, while 42 in 1370 patients after TURP (4.7% vs. 3.1%, p = 0.040), respectively. Twenty-six patients received once biopsy and diagnosed with PCa in HoLEP group, while 15 patients in TURP group (18.4% vs. 8.9%, p = 0.018), respectively. However, no significant difference was observed for patients who received twice prostate biopsy in the two groups. CONCLUSIONS: The present study showed that HoLEP can provide a higher total detection rate of PCa when compared with TURP. Besides, this superiority was especially embodied in patients with PSA less than 10 ng/ml.
Assuntos
Terapia a Laser/métodos , Lasers de Estado Sólido/uso terapêutico , Próstata/patologia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/diagnóstico , Ressecção Transuretral da Próstata/métodos , Idoso , Idoso de 80 Anos ou mais , Hólmio , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: The goal of this study is to compare the feasibility, safety, and efficacy of the preemptive indwelling of double-J stents (PI-DJS) versus the conventional preemptive indwelling of ureteral catheters (PI-UC) in percutaneous nephrolithotomy (PCNL) via a randomized, controlled clinical study. MATERIALS AND METHODS: A total of 75 patients with complex renal calculi underwent PCNL surgery and were randomized, using random number table, to receive either a PI-DJS (37 cases) or a PI-UC (38 cases). All operations were performed by the same experienced surgeon. Several outcomes were measured, including duration of operation, time to establish passage, level of hemoglobin decline, rate of stone clearance and incidence of complications. RESULTS: Guided by B-ultrasound, percutaneous passages were successfully established in all patients who then underwent one-stage PCNL. The time required to establish a passage using a PI-DJS was 7.5min, whereas that of the group who received a PI-UC was 11.5min (P < 0.01). There was no significant difference between the two groups in terms of operation duration, postoperative Hb decline rate, stone clearance rate, and perioperative complication incidences (all P > 0.05). CONCLUSION: PI-DJS during PCNL allowed for a reliable and stable reflux from the bladder into the renal pelvis to produce an artificial hydronephrosis without the formation of microbubbles, unlike conventional ureteral catheters.