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1.
Front Oncol ; 14: 1424785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39136003

RESUMO

This case report aims to highlight the importance of considering lymphoma as a potential differential diagnosis in patients presenting with laryngeal mass and associated cervical lymphadenopathy, particularly those with a history of chronic tonsillitis. A case of a 63-year-old male patient who underwent bilateral tonsillectomy for tumor in the left tonsil was presented. Two months after the procedure, he developed throat discomfort, dysphagia, neck swelling, and other symptoms. The patient was initially diagnosed with "tongue base mass" and chronic lymphadenitis. Partial excision of the tongue base mass was performed twice in another hospital, revealing chronic inflammation of the epithelial mucosa. Further evaluations, including electron laryngoscopy and imaging studies, were conducted to investigate the condition. A computed tomography (CT) scan showed irregular soft tissue density in the oropharyngeal region, along with multiple lymph nodes in the neck. Subsequent histopathological examination of the lingual base biopsy revealed peripheral T-cell lymphoma with a follicular T-helper cell phenotype. Immunohistochemical staining confirmed specific markers while ruling out other markers. In situ hybridization testing demonstrated positivity for Epstein-Barr virus-encoded RNA, and TCRG clonality was confirmed. The duration from symptom onset to diagnosis was 2 months. This case emphasizes the importance of considering lymphoma in patients with laryngeal mass and associated cervical lymphadenopathy, especially when a history of chronic tonsillitis is present. Accurate diagnosis and early intervention are crucial for effective management and improved patient outcomes.

2.
Front Oncol ; 14: 1384913, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884096

RESUMO

Hyalinizing clear cell carcinomas (HCCCs) are infrequent, malignant tumors characterized by their low-grade nature. They typically originate from minor salivary glands. However, these tumors can potentially emerge in any location with minor salivary glands, including the nasopharynx. This report presents two cases of HCCC in females aged 61 and 72 years, with both tumors approximately 4 cm in size. In the first case, a 72-year-old female presented with recurrent bilateral epistaxis. Imaging studies revealed a nasopharyngeal mass, surgically excised, and histopathological analysis confirmed HCCC. Postoperatively, the patient received combined chemotherapy and radiotherapy, achieving a recurrence-free status 2.5 years later. The second case involves a 61-year-old female with a two-year history of bloody nasal discharge. Imaging studies identified a nasopharyngeal lesion, surgically removed, and histopathological examination confirmed HCCC. This patient underwent radiotherapy followed by combination chemotherapy with paclitaxel and carboplatin, displaying no signs of recurrence upon reevaluation after 10 months. These cases highlight the successful management of HCCC through a comprehensive, multimodal approach, integrating surgical intervention and adjuvant therapy. The favorable outcomes emphasize the significance of a thorough treatment strategy for HCCC in the nasopharynx, providing valuable insights for clinicians. Further studies are essential to enhance our understanding of this rare entity and refine treatment protocols for optimized patient outcomes.

3.
Adv Sci (Weinh) ; 11(4): e2306289, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38044313

RESUMO

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.


Assuntos
Coagulantes , Hemostáticos , Animais , Pós , Aderências Teciduais , Hemorragia , Hemostáticos/farmacologia
4.
Nat Prod Res ; 38(1): 28-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-35867026

RESUMO

Two new phenolic glycosides (1 and 2), one known analogue (3), along with a new diterpene glucoside (4) were obtained from ethanolic extract of the stems of Eurya chinensis R. Br. The structures of these isolated compounds were identified by extensive analysis of HRESIMS and NMR spectroscopic data. The cytotoxicities of these compounds were evaluated on MCF-7, A549, HepG2, CaCo2 and 5-8 F cell lines by MTT method, but no obvious activities were observed.


Assuntos
Diterpenos , Ericales , Humanos , Glicosídeos/farmacologia , Glicosídeos/química , Estrutura Molecular , Células CACO-2 , Glucosídeos , Diterpenos/química
5.
FASEB J ; 38(1): e23354, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085162

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.


Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Neoplasias de Cabeça e Pescoço/genética , Células Epiteliais , Microambiente Tumoral/genética
6.
Sci Rep ; 13(1): 22414, 2023 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-38104177

RESUMO

Endoplasmic reticulum stress (ERS) occurs when misfolded or unfolded proteins accumulate in the endoplasmic reticulum (ER), and it is often observed in tumors, including head and neck squamous cell carcinoma (HNSCC). Relevant studies have demonstrated the prognostic significance of ERS-related long non-coding RNAs (lncRNAs) in various cancers. However, the relationship between ERS and lncRNAs in HNSCC has received limited attention in previous studies. In this study, we aimed to develop an ERS-related lncRNAs prognostic model using correlation analysis, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression analysis based on data from The Cancer Genome Atlas (TCGA) database. The survival and predictive ability of this model were evaluated using Kaplan-Meier analysis and time-dependent receiver operating characteristics (ROC), while nomograms and calibration curves were constructed. Then, functional enrichment analyses, tumor mutation burden (TMB), tumor infiltration of immune cells, single sample Gene Set Enrichment Analysis (ssGSEA), and drug sensitivity analysis were performed. Additionally, we conducted a consensus cluster analysis to compare differences between subtypes of tumors. Finally, we validated the expression of the ERS-related lncRNAs that constructed prognostic risk score model in HNSCC tissues through quantitative real-time PCR (qRT-PCR). We developed a prognostic signature based on seven ERS-related lncRNAs, which showed better predictive performance than other clinicopathological features. The high-risk poor prognosis group had a poorer prognosis in comparison to the low-risk good prognosis. The area under the ROC curve (AUC) predicted by this model for 3-year survival rates of HNSCC patients was 0.805. Enrichment analysis revealed that the differentially expressed genes were primarily enriched in pathways related to immune responses and signal transduction. Low-risk patients had lower TMB, more immune cell infiltrations, and enhanced anti-tumor immunity. Cluster analysis indicated that cluster 3 may have a better prognosis and immunotherapy effect. In addition, the result of qRT-PCR was consistent with our analysis. This prognostic model based on seven ERS-related lncRNAs is a promising tool for risk stratification, survival prediction, and immune cell infiltration status assessment.


Assuntos
Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Humanos , Prognóstico , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Estresse do Retículo Endoplasmático/genética , Neoplasias de Cabeça e Pescoço/genética
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(6): 727-731, 2023 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-37331951

RESUMO

Objective: To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR. Methods: The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed. Results: The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR. Conclusion: Tissue engineering technology can provide a new treatment method for ATR.


Assuntos
Rinite Atrófica , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Alicerces Teciduais , Impressão Tridimensional , Citocinas
8.
Bioact Mater ; 27: 461-473, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37152711

RESUMO

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

9.
BMC Cardiovasc Disord ; 23(1): 173, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997869

RESUMO

BACKGROUND: This study aimed to investigate the correlation between the high-risk characteristics of high-resolution MRI carotid vulnerable plaques and the clinical risk factors and concomitant acute cerebral infarction (ACI). METHODS: Forty-five patients diagnosed with a single vulnerable carotid plaque by MRI were divided into two groups based on whether they had ipsilateral ACI. The clinical risk factors and the observation values or frequency of occurrence of high-risk MRI phenotypes of plaque volume, LRNC, IPH and ulcer were statistically compared between the two groups. RESULTS: A total of 45 vulnerable carotid artery plaques were found in 45 patients, 23 patients with ACI and 22 patients without ACI. There were no significant differences in age, sex, smoking, serum TC, TG and LDL between the two groups (all P > 0.05), but the ACI group had significantly more patients with hypertension (P < 0.05) and the without ACI group coronary heart disease (P < 0.05). The volume of vulnerable carotid plaque in the group with ACI (1004.19 ± 663.57 mm3) was significantly larger than that in the group without ACI (487.21 ± 238.64 mm3) (P < 0.05). The phenotype of vulnerable carotid artery plaque was 13 cases of LRNC, 8 cases of LRNC + IPH, 5 cases of LRNC + Ulcer, and 19 cases of LRNC + IPH + Ulcer. There was no significant difference in this distribution between the two groups (all P > 0.05) with the exception of LRNC + IPH + Ulcer. The 14 cases of LRNC + IPH + LRNC + IPH + Ulcer (60.87%) in the group with ACI and was significantly greater than the 5 (22.73%) in patients without ACI (P < 0.05). CONCLUSION: It is preliminarily thought that hypertension is the main clinical risk factor for vulnerable carotid plaques with ACI and the combination of plaque volume with vulnerable carotid plaque and LRNC + IPH + Ulcer is a high-risk factor for complicated ACI. It has high clinical therapeutic value due to the accurate diagnosis of responsible vessels and plaques with high-resolution MRI.


Assuntos
Isquemia Encefálica , Estenose das Carótidas , Hipertensão , Placa Aterosclerótica , Acidente Vascular Cerebral , Humanos , Úlcera/complicações , Acidente Vascular Cerebral/etiologia , Artérias Carótidas/diagnóstico por imagem , Imageamento por Ressonância Magnética/efeitos adversos , Isquemia Encefálica/complicações , Placa Aterosclerótica/complicações , Fatores de Risco , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Doença Aguda , Infarto Cerebral/etiologia , Infarto Cerebral/complicações , Hipertensão/complicações , Hipertensão/diagnóstico
10.
J Asian Nat Prod Res ; 25(4): 349-356, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35796599

RESUMO

Two new withaphysalin-type withanolides (18-O-ethylwithaphysalin R and 5-O-ethylphysaminimin C, 1 and 2), along with twelve known withanolides (3-14), were purified and identified from Physalis peruviana L. The chemical structures of these new isolates were elucidated through analyzing spectroscopic and HRESIMS data. All the obtained metabolites were appraised for their potential antiproliferative activity against the human breast cancer cell line MCF-7. Compound 7 was discovered to exhibit potent activity with an IC50 value of 3.51 µM and compounds 2, 6 and 14 showed weak cytotoxic effect.


Assuntos
Antineoplásicos , Physalis , Vitanolídeos , Humanos , Physalis/química , Vitanolídeos/química , Extratos Vegetais/química
11.
Mater Today Bio ; 17: 100468, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36340592

RESUMO

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application.

12.
Front Immunol ; 13: 1013990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189210

RESUMO

Monoclonal immunoglobulin produced by clonal plasma cells is the main cause in multiple myeloma and monoclonal gammopathy of renal significance. Because of the complicated purification method and the low stoichiometry of purified protein and glycans, site-specific N-glycosylation characterization for monoclonal immunoglobulin is still challenging. To profile the site-specific N-glycosylation of monoclonal immunoglobulins is of great interest. Therefore, in this study, we presented an integrated workflow for micro monoclonal IgA and IgG purification from patients with multiple myeloma in the HYDRASYS system, in-agarose-gel digestion, LC-MS/MS analysis without intact N-glycopeptide enrichment, and compared the identification performance of different mass spectrometry dissociation methods (EThcD-sceHCD, sceHCD, EThcD and sceHCD-pd-ETD). The results showed that EThcD-sceHCD was a better choice for site-specific N-glycosylation characterization of micro in-agarose-gel immunoglobulins (~2 µg) because it can cover more unique intact N-glycopeptides (37 and 50 intact N-glycopeptides from IgA1 and IgG2, respectively) and provide more high-quality spectra than sceHCD, EThcD and sceHCD-pd-ETD. We demonstrated the benefits of the alternative strategy in site-specific N-glycosylation characterizing micro monoclonal immunoglobulins obtained from bands separated by electrophoresis. This work could promote the development of clinical N-glycoproteomics and related immunology.


Assuntos
Mieloma Múltiplo , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Glicopeptídeos , Glicosilação , Humanos , Imunoglobulina A , Imunoglobulina G , Polissacarídeos , Sefarose , Espectrometria de Massas em Tandem/métodos
13.
ACS Appl Mater Interfaces ; 14(15): 17093-17108, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35380771

RESUMO

Wound dressings that promote quick hemostasis and are highly efficient in healing wounds are urgently needed to meet the increase in clinical demands worldwide. Herein, a dihydrazide-modified waterborne biodegradable polyurethane emulsion (PU-ADH) and oxidized hyaluronic acid (OHA) were autonomously cross-linked to form a hybrid hyaluronic acid-polyurethane (HA-PU) cryogel by hydrazone bonding at -20 °C. Through its specific macroporous structure (which is approximately 220 µm) constructed by aggregated PU-ADH particles and long-chain OHA, a dried cryogel can have a dramatically compressed volume (1/7 of its original volume) with stable fixation, and it can swell rapidly by absorbing water or blood to approximately 22 and 16 times its dried weight, respectively, in a few minutes. This instantaneous shape-recovering ability favors fast hemostasis in minimally invasive surgery. Moreover, this cryogel is superior to gauze, has excellent biocompatibility, and quickly coagulates blood (in approximately 2 min) by activating the endogenous coagulation system. Comparably, an injectable HA-PU hydrogel with the same components as the HA-PU cryogel was prepared at room temperature, and it exhibited good self-healing properties. An in vivo evaluation of a rat liver hemostasis model and rat skin defect model revealed that the cryogel in fast hemostasis has great potential and superior wound-healing abilities, decreases immune inflammation, and promotes the regeneration of angiogenesis and hair follicles. Consequently, this work proposes a versatile method for constructing biodegradable hybrid cryogels via autonomous cross-linking between synthesized polymer emulsions and natural polymers. The hybrid cryogels demonstrated great potential for applications as high-performance wound dressings.


Assuntos
Criogéis , Ácido Hialurônico , Animais , Criogéis/química , Criogéis/farmacologia , Hemostasia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Polímeros/química , Poliuretanos/farmacologia , Ratos , Cicatrização
14.
Nat Prod Res ; 36(8): 2021-2027, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33131334

RESUMO

Two new compounds (1 and 2), belonging to C-20 oxygenated ent-kauranes-type diterpenoids, were identified from the aerial parts of Isodon serra. Their structures were elucidated by extensive analysis of HRESI-MS and NMR spectroscopic data. Both these two compounds possess a common 7,20-epoxy-ent-kauranes skeleton with a hydroxyl group rarely occurring at C-13. Compounds 1 and 2 were evaluated for their cytotoxic activity against Hela-60 and HepG2 as well as the antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli.


Assuntos
Antineoplásicos Fitogênicos , Diterpenos do Tipo Caurano , Diterpenos , Isodon , Antineoplásicos Fitogênicos/química , Diterpenos/análise , Diterpenos/farmacologia , Diterpenos do Tipo Caurano/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isodon/química , Estrutura Molecular , Componentes Aéreos da Planta/química
15.
BMC Surg ; 21(1): 340, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496808

RESUMO

BACKGROUND: Subglottic paragangliomas (PGs) are exceptionally rare and unpredictable, occasionally presenting at an atypical location. There are three different clinical forms of subglottic PGs: intraluminal (tracheal PGs), extraluminal (thyroid PGs) and the mixed type (both intraluminal and extraluminal, mixed-subglottic PGs). These tumors are usually misdiagnosed as other relatively common primary thyroid or laryngotracheal tumors, and the treatment is troublesome. CASE PRESENTATION: A 22-year-old male patient with subglottic PGs has been successively misdiagnosed as thyroid tumors and subglottic hemangiomas, and lastly underwent local extended lumpectomy and laryngotracheal reconstruction with a pedicled thoracoacromial artery perforator flap (PTAPF). The patient was decannulated successfully after the second-stage tracheal reconstruction with a local flap, and no evidence of local recurrence and distant metastasis of the tumor until now. CONCLUSION: Subglottic PGs can be easily misdiagnosed as laryngotracheal or thyroid tumors when presented at an atypical location. It is essential for otolaryngologists and head and neck surgeons to remain vigilant against these tumors. If the tumor is not diagnosed or removed completely, patients may encounter a risk of lethal paroxysm, which is incredibly troublesome.


Assuntos
Neoplasias Laríngeas , Paraganglioma , Procedimentos de Cirurgia Plástica , Neoplasias da Glândula Tireoide , Adulto , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/cirurgia , Masculino , Recidiva Local de Neoplasia , Paraganglioma/diagnóstico , Paraganglioma/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Adulto Jovem
16.
Eur J Med Chem ; 223: 113730, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34388483

RESUMO

Alterations in lipid metabolism, commonly disregarded in the past, have been accepted as a hallmark for cancer. Exploring cancer therapeutics that interrupt the lipid metabolic pathways by monotherapy or combination with conventional chemotherapy or immunotherapy is of great importance. Here we modified cisplatin with an FDA-approved hypolipidemic drug, bezafibrate (BEZ), via the well-established Pt(IV) strategy, affording two multi-functional Pt(IV) anticancer agents cis,cis,trans-[Pt(NH3)2Cl2(BEZ)(OH)] (CB) and cis,cis,trans-[Pt(NH3)2Cl2(BEZ)2] (CP) (BEZ = bezafibrate). The Pt(IV) prodrug CB exhibited an enhanced anticancer activity up to 187-fold greater than the clinical anticancer drug cisplatin. Both CB and CP had less toxicity to normal cells, showing higher efficacies and superior therapeutic indexes than cisplatin. Mechanism studies revealed that the bezafibrate-conjugated Pt(IV) complex CB, as a representative, could massively accumulate in A549 cells and genomic DNA, induce DNA damage, elevate intracellular ROS levels, perturb mitochondrial transmembrane potentials, activate the cellular metabolic sensor AMPK, and result in profound proliferation inhibition and apoptosis. Further cellular data also provided evidence that phosphorylation of AMPK, as a metabolic sensor, could suppress the downstream HMGB1, NF-κB, and VEGFA, which may contribute to the inhibition of angiogenesis and metastasis. Our study suggests that the antitumor action of CB and CP mechanistically distinct from the conventional platinum drugs and that functionalizing platinum-based agents with lipid-modulating agents may represent a novel practical strategy for cancer treatment.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Bezafibrato/química , Hipolipemiantes/química , Platina/química , Pró-Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pró-Fármacos/farmacologia , Transdução de Sinais/efeitos dos fármacos
17.
Head Neck ; 43(9): 2634-2643, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33942931

RESUMO

BACKGROUND: We assessed the safety and efficacy of supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL-CHEP) in patients with laryngeal cicatricial stenosis. METHODS: Sixteen patients receiving SCL-CHEP for severe laryngeal cicatricial stenosis between 2017 and 2018 were reviewed. Decannulation rate and tracheostomy closure time were used to evaluate efficacy. The Voice Handicap Index-10 (VHI-10), Voice-related Quality of Life (V-RQOL) scale and Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale were used to assess vocal function. Fiberoptic endoscopic evaluation of swallowing (FEES) was performed and the Penetration-Aspiration Scale (PAS), Eating Assessment Tool-10 (EAT-10), and Swallow Quality of Life Questionnaire (SWAL-QOL) were used to assess swallowing function. RESULTS: Thirteen patients (81.25%) were decannulated successfully. The average tracheostomy closure time was 45.15 days. There was no observed postoperative complications or recurrence of stenosis. VHI-10 and V-RQOL scores showed significantly improved V-RQOL (p < 0.05). FEES-PAS, EAT-10, and SWAL-QOL showed no swallowing function damage. CONCLUSIONS: SCL-CHEP is effective and safe for patients with severe laryngeal cicatricial stenosis. Accurate pre-procedure evaluation is especially important for patient selection and surgical success.


Assuntos
Neoplasias Laríngeas , Qualidade de Vida , Constrição Patológica , Cartilagem Cricoide/cirurgia , Humanos , Neoplasias Laríngeas/cirurgia , Laringectomia , Recidiva Local de Neoplasia
18.
Biochem Pharmacol ; 188: 114523, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33741331

RESUMO

Triple-negative breast cancer (TNBC) shares the molecular features facilitating epithelial-to-mesenchymal transition (EMT), which contributed to tumor invasion and metastasis. A platinum(IV) conjugate ketoplatin deriving from FDA-approved drugs cisplatin and ketoprofen was designed and prepared to enhance antitumor activity and suppress EMT in TNBC via positive impact on inflammatory microenvironment by modulating COX-2 signal. As a prodrug, ketoplatin afforded 50.26-fold higher cytotoxicity than cisplatin against TNBC mesenchymal-stem cell-like MDA-MB-231 cells, partly attributing to its dramatic increase of cellular uptake and DNA damage. More importantly, EMT progress in MDA-MB-231 was markedly restrained by ketoplatin, resulting from the suppression of vimentin and N-cadherin mediated by down-regulated COX-2. Further in vivo investigation exhibited that ketoplatin effectively inhibited tumor growth and reduced systemic toxicity compared to cisplatin. Overall, ketoplatin possessed high antitumor activity and low toxicity against TNBC MDA-MB-231 in vitro and in vivo.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/análogos & derivados , Cetoprofeno/administração & dosagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Células A549 , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/química , Cisplatino/administração & dosagem , Cisplatino/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Células HeLa , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Cetoprofeno/análogos & derivados , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
19.
BMC Surg ; 21(1): 108, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658017

RESUMO

BACKGROUND: Tracheobronchial foreign body aspiration (TFBA) is a critical disease in children and is extremely dangerous, even life-threatening. The factors affecting the occurrence and prognosis of TFBA are complex. The purpose of this study is to examine the external and intrinsic factors affecting clinical features of TFBA in West China and propose potential effective intervention measures. METHODS: We retrospectively analyzed the clinical data of pediatric patients diagnosed with TFBA with foreign bodies (FBs) removed by rigid bronchoscopy under general anesthesia at the otolaryngology department from December 2017 to November 2018. The data included age, sex, clinical symptoms, type and location of FB, guardians, prehospital duration and residence of these pediatric patients. RESULTS: The ratio of males (72) to females (53) was 1.4:1. Children aged from 1 to 3 years accounted for 76% (95/125) of patients. Cough, continuous fever and dyspnea were the primary symptoms. The right primary bronchus was the most common location of FB detection by rigid bronchoscopy (67 cases, 53.6%). Organic FBs were most common in our study. Guardians of patients significantly differed in the rural (parents 16, grandparents 31) and urban (parents 52, grandparents 26) groups (χ2 = 12.583, p = 0.000). More children in the rural group than in the urban group had a treatment delay longer than 72 h. More children in the group with no history of FB aspiration (12, 25%) than in the group with prior FB aspiration had a treatment delay longer than 72 h. CONCLUSION: Pediatric TFBA is a common emergency in otolaryngology. Age, sex, tracheobronchial anatomy and other physiological elements were defined as intrinsic factors, while guardians, residence, FB species and prehospital time were defined as external factors of TFBA. External and intrinsic factors both influence the occurrence and progression of TFBA. It is extremely important to take effective measures to control external factors, which can decrease morbidity and mortality.


Assuntos
Brônquios , Corpos Estranhos , Traqueia , Broncoscopia , Pré-Escolar , China , Feminino , Corpos Estranhos/diagnóstico , Corpos Estranhos/cirurgia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
20.
Am J Otolaryngol ; 42(2): 102787, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33316724

RESUMO

OBJECTIVES: Transoral laser microsurgery (TLM) has gradually gained approval in the treatment of early glottic cancer. However, the oncological outcomes of TLM for glottic cancer with anterior commissure (AC) involvement are still a controversial topic. We aimed to systematically review the literature on glottic cancer (Tis-T2) with patients who received TLM as first choice therapy and to evaluate several prognostic outcomes in patients with or without AC involvement. METHODS: A systematic literature retrieval was conducted in PubMed, Medline (Ovid) and Web of Science. Risk ratio (RR) between AC involvement (AC+) or without AC involvement (AC-) was assessed and 95% confidence interval(95%CI) was calculated, which was performed on RevMan 5.3. RESULTS: A total of 20 literatures were included when comparing the local recurrence (LR) rate of patients with or without AC involvement, and the results suggested LR matters in group AC+ over group AC- (RR = 2.39, 95%CI = 1.99-2.86, p < 0.00001). The 5-year overall survival(5yOS) rate included 10 studies, and there was no significant difference between AC+ and AC- (RR = 0.98, 95%CI = 0.93-1.02, p = 0.35). The laryngeal preservation rate (LPR) of AC+ was lower than that of AC- (RR = 0.97, 95%CI = 0.94-1.00, p = 0.04). CONCLUSION: The results indicate that the prognosis of early glottic cancer with AC involvement is more likely to have higher local recurrence and lower LPR but no statistical difference in 5yOS rate.


Assuntos
Glote/cirurgia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringe/patologia , Terapia a Laser/métodos , Microcirurgia/métodos , Procedimentos Cirúrgicos Bucais/métodos , Feminino , Humanos , Neoplasias Laríngeas/mortalidade , Masculino , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
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