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1.
Photodiagnosis Photodyn Ther ; : 104093, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641030

RESUMO

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

2.
Medicine (Baltimore) ; 103(16): e37831, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640322

RESUMO

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.


Assuntos
Proteína Quinase CDC2 , Carcinoma de Células Escamosas , Ciclina A2 , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Biologia Computacional , Ciclina A2/genética , Ciclina A2/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
3.
J Med Chem ; 67(4): 3190-3202, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38320123

RESUMO

Fibroblast activation protein (FAP), which is expressed on the cell membranes of fibroblasts in most solid tumors, has become an important target for tumor diagnosis and treatment. However, previously reported 99mTc-labeled FAPI-04 complexes have high blood uptake, limiting their use in the clinic. In this work, six 99mTc-labeled FAPI-46 derivatives with different linkers (different amino acids, peptides, or polyethylene glycol) were prepared and evaluated. They had good in vitro stability, hydrophilicity, and good specificity for FAP. The biodistribution and MicroSPECT images revealed that they all had high specific tumor uptake for FAP, and their blood uptake was significantly decreased. Among them, [99mTc]Tc-6-1 exhibited the highest target-to-nontarget ratios (tumor/blood: 6.06 ± 1.19; tumor/muscle: 10.26 ± 0.44) and good tumor uptake (16.15 ± 0.83%ID/g), which also had significantly high affinity for FAP, good in vivo stability, and safety. Therefore, [99mTc]Tc-6-1 holds great potential as a promising molecular tracer for FAP tumor imaging.


Assuntos
Quinolinas , Transporte Biológico , Linhagem Celular Tumoral , Compostos Radiofarmacêuticos/química , Distribuição Tecidual , Tecnécio/química
4.
Laryngoscope ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37987235

RESUMO

OBJECTIVE: We developed a novel method for thyroidectomy using a single-incision oral vestibular approach. To assess its advantages and disadvantages, we compared the perioperative parameters of this approach with those of transoral three-incision thyroidectomy and trans-areolar thyroidectomy. METHODS: In a study of 136 papillary thyroid carcinoma patients (2016-2018), precise thyroidectomy and neck dissection were conducted. Among them, 52 chose single-incision oral vestibular approach, 33 chose three-incision variant, and 51 underwent trans-areolar thyroidectomy. Perioperative aspects of the transoral single-incision group were compared with those of transoral three-incision group, and transthoracic group. RESULTS: In the cohort, meticulous tumor level VI lymph node dissection was performed, achieving intended resection extent with one case requiring a switch from transoral to transthoracic approach. No nerve palsy occurred in the transoral group. Thyroidectomy duration varied significantly across groups. Transoral single-incision had a shorter duration than transoral three-incision and longer than transthoracic. Minor differences were observed in blood loss and drainage. Perioperative factors like hematoma, infection, hypocalcemia, et al., remained consistent. Notably, no tumor recurrence was observed in this study. CONCLUSIONS: This new transoral video-assisted neck surgery (TOVANS) method for thyroidectomy without gas insufflation approach did not increase the surgical complexity compared with the transoral vestibular three-incision thyroidectomy and the trans-areolar thyroidectomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 2023.

5.
Int Immunopharmacol ; 125(Pt A): 111136, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37935090

RESUMO

The impact of liver fibrosis on the deterioration of hepatocellular carcinoma (HCC) remains controversial. We hope to explore this issue through establishing a fibrosis-hypoxia-glycolysis-immune related prognostic model. Liver fibrosis-related genes from Molecular Signatures Database were used to evaluate the degree of fibrosis in HCC patients from the TCGA database. The patients were divided into two groups using the fibrosis-related expression matrix based on the algorithm uniform manifold approximation and projection (UMAP) and evaluated for fibrosis by UMAP cluster and gene enrichment analysis. Prognostic model was constructed by differential analysis, LASSO, and multivariate regression analysis. Immune-infiltration analysis was performed by CIBERSORT. Quantitative PCR and immunohistochemistry were performed to measure the gene expression levels in HCC patients from our hospital. In 365 HCC patients from the TCGA database, 111 HCC patients with high fibrosis score have a worse prognosis than those with low fibrosis based on 129 genes related to liver fibrosis, which may be caused by the interaction between fibrosis, angiogenesis, hypoxia, glycolysis, inflammatory response, and high immune infiltration. We constructed a Fibrosis-Hypoxia-Glycolysis-Immune Prognostic Model (FHGISig), which could significantly predict disease progression in HCC patients. Furthermore, we revealed a close correlation between FHGISig and immune cell infiltration level as well as immune checkpoints. Finally, PCR results found TFF3 mRNA was significantly lower in cirrhotic HCC patients compared with non-cirrhotic ones. Liver fibrosis is a poor-prognostic factor for HCC, and our FHGISig could significantly predict disease progression, which could also be a potential predictive marker for immunotherapy in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Prognóstico , Neoplasias Hepáticas/genética , Cirrose Hepática , Hipóxia , Progressão da Doença
6.
ACS Pharmacol Transl Sci ; 6(11): 1681-1691, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37974617

RESUMO

As the "molecule of the century", 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) is a radioactive 18F-labeled glucose derivative with a wide range of applications for positron emission tomography (PET) imaging. Single photon emission computed tomography (SPECT) imaging is widely used, but there is no clinical probe comparable to [18F]FDG. In our previous work, [99mTc]Tc-CN5DG and [99mTc]Tc-CN7DG were successfully developed and achieved high-quality SPECT images. However, they still have the disadvantage of low tumor uptake and/or high uptake by nontarget organs. To develop novel tumor imaging agents with high tumor uptake and excellent tumor/nontarget ratios, in this study, starting from d-glucosamine hydrochloride, four phenyl group-containing isonitrile ligands were designed, synthesized, and radiolabeled with 99mTc. All the complexes had high radiochemical purity and good hydrophilicity and stability. Biodistribution experiments showed that [99mTc]Tc-L4 (i.e., [99mTc]Tc-CNMBDG) had the highest tumor uptake and tumor/background ratios among the four probes. In SPECT imaging studies, the tumor detected by [99mTc]Tc-L4 was more clearly visible than that of [99mTc]Tc-CN7DG because of the inappreciable interference from abdominal uptake. Preliminary clinical studies of [99mTc]Tc-L4 have been conducted and successfully showed the lesion location in a patient with non-small-cell lung cancer. In summary, [99mTc]Tc-L4 is expected to be a promising tumor SPECT imaging agent.

7.
Mol Pharm ; 20(9): 4528-4536, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37661815

RESUMO

Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel 18F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator. The corresponding [18F]AlF-NOTA-PBB complex was prepared with high radiochemical purity (98.4 ± 0.15%) and yield (58.7 ± 4.5%) within 35 min without requiring HPLC purification through a simple one-step 18F-labeling strategy of NOTA-AlF chelation chemistry. The radiotracer was lipophilic (log P = 0.095 ± 0.003) and had good stability in vitro and in vivo. The cellular uptake studies performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) showed that radioactive uptake was blocked by preincubating with a molar dose of palbociclib and it had a nanomolar binding affinity to CDK4/6 (IC50 = 16.23 ± 1.84 nM), demonstrating a CDK4/6-mediated uptake mechanism. Its ex vivo biodistribution in nude mice-bearing MCF-7 tumors showed obvious tumor uptake and a high tumor/muscle ratio of [18F]AlF-NOTA-PBB, and tumor uptake was inhibited with 100 µg of palbociclib, demonstrating specific binding to CDK4/6. Radioactivity accumulation in MCF-7 tumors was observed in PET imaging with [18F]AlF-NOTA-PBB. Based on the results of this work, [18F]AlF-NOTA-PBB has the promising capability as a CDK4/6-targeted tumor imaging agent.


Assuntos
Neoplasias , Animais , Camundongos , Quinase 4 Dependente de Ciclina , Camundongos Nus , Distribuição Tecidual , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Quelantes
8.
Pharmaceuticals (Basel) ; 16(9)2023 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-37765084

RESUMO

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel 99mTc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable 99mTc-complexes ([99mTc]Tc-L1, [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5). Corresponding rhenium analogues of [99mTc]Tc-L1 were synthesised and suggested the structures of these 99mTc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands. [99mTc]Tc-L1 is hydrophilic, while the lipophilicities of [99mTc]Tc-L2, [99mTc]Tc-L3, [99mTc]Tc-L4 and [99mTc]Tc-L5 are close. In vitro cell experiments showed that all five novel 99mTc-complexes had higher uptake in hypoxic cells compared with aerobic cells, which indicates the complexes have good hypoxia selectivity. The biodistribution of the five 99mTc-complexes in S180 tumour-bearing mice showed that they all had certain uptake in the tumours. Among them, [99mTc]Tc-L1 had the highest tumour-to-muscle (4.68 ± 0.44) and tumour-to-blood (3.81 ± 0.46) ratios. The introduction of polyethylene glycol (PEG) chains effectively reduced the lipophilicity and decreased uptake by the liver, intestine and blood but also increased clearance from the tumours. In vivo metabolic studies showed [99mTc]Tc-L1 kept intact and remained stable in tumour, blood and urine at 2 h post-injection. The results of SPECT imaging showed that [99mTc]Tc-L1 had significant tumour uptake at 2 h post-injection, but there was still high uptake in abdominal organs such as the liver and kidney, suggesting that this complex needs to be further optimised before being used for tumour hypoxia imaging.

9.
Regen Ther ; 24: 245-255, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37534237

RESUMO

Objective: The physiological process of wound healing is dynamic, continuous, and intricate. Nowadays, full-thickness burn wounds are treated by autologous skin transplantation. Unfortunately, when substantial burns develop, there are fewer donor sites accessible, making it difficult to satisfy the requirement for large-scale skin transplants and increasing the risk of patient mortality. This study investigated the possibility of using a newly created hypoimmunogenic epidermal cell sheet to heal skin wounds. Methods: Transfection with lentivirus was used to generate Keratinocytes (KCs) that overexpress Indoleamine 2,3-Dioxygenase (IDO). Western blotting and quantitative polymerase chain reaction were used to measure IDO levels. To evaluate the function of IDO+ keratinocytes, CCK-8 and Transwell assays were performed. In cell sheet induction media, KCs and Fibroblasts (FBs) were cultured to yield epidermal cell sheets. The full-thickness skin excisions of BALB/c mice were transplanted with epidermal cell sheets. To assess the tumorigenicity of IDO+ keratinocytes, BALB/c nude mouse xenograft models were also used. CD3 and CD31 immunofluorescence labeling of wound tissue on day 12 to identify T lymphocyte infiltration and capillary development. ELISA measurement of IL-1 and TNF-α concentrations. Results: IDO + keratinocytes dramatically enhanced the expression levels of IDO mRNA and protein, as well as the amount of kynurenine in the conditioned media of IDO+ keratinocytes, compared to the Control and NC groups. CD8+ T cell apoptosis was considerably greater in the IDO group than in the Control and NC groups. Nevertheless, the proliferation and migratory capabilities of IDO+ keratinocytes were not substantially different from those of the Control and NC groups. In vitro cultivation of the hypoimmunogenic epidermal cell sheet was effective. In vivo transplantation experiments demonstrated that IDO+ epidermal cell sheets can effectively promote wound healing without tumorigenicity, and IDO+ epidermal cell sheets may promote wound healing by decreasing the expression levels of inflammatory factors (TNF and IL-1) in wound tissue, decreasing CD3+ T lymphocytes, and increasing infiltration and new capillaries in wound tissue. Conclusion: In this study, we successfully constructed the hypoimmunogenic epidermal cell sheet and demonstrated that the hypoimmunogenic epidermal cell sheet could accelerate wound healing.

10.
Eur J Pharmacol ; 952: 175805, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37247812

RESUMO

Pathological angiogenesis plays a major role in many disease processes, including cancer and diabetic retinopathy. Antiangiogenic therapy is a potential management for pathologic angiogenesis. The novel synthetic compound 221S-1a, derived from captopril, tanshinol and borneol, may have antiangiogenic properties. On the basis of MS, NMR and HPLC analysis, the structure of 221S-1a was identified. The cellular uptake and metabolism of this compound was also observed. Next, the antiangiogenic properties of 221S-1a were evaluated in tumor-xenograft and OIR models in vivo. The inhibitory properties of 221S-1a on endothelial cell proliferation, migration, tube formation and sprouting were detected in vitro. Furthermore, 221S-1a induced G1/S phase arrest was detected by PI staining flow cytometry analysis and Cyclin D, Cyclin E expression. 221S-1a inhibited ERK1/2 activation and nuclear translocation, in addition to downregulation of c-Myc, a transcription factor that regulates cell cycle progression. Molecular docking indicated the interaction of 221S-1a with the ATP-binding site of ERK2, leading to the inhibition of ERK2 phosphorylation and a concomitant inhibition of ERK1 phosphorylation. In conclusion, 221S-1a inhibited the G1/S phase transition by blocking the ERK1/2/c-Myc pathway to reduce tumor and OIR retinal angiogenesis. These novel findings suggest that 221S-1a is a potential pharmacologic candidate for treating pathological angiogenesis.


Assuntos
Proteínas Proto-Oncogênicas c-myc , Transdução de Sinais , Humanos , Simulação de Acoplamento Molecular , Neovascularização Patológica/tratamento farmacológico , Proliferação de Células
11.
Photodiagnosis Photodyn Ther ; 42: 103612, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37220842

RESUMO

Keloids display many cancerous properties, including uncontrolled and invasive growth, high rates of recurrence as well as similar bioenergetics. 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is an effective treatment that performs cytotoxic effects by producing reactive oxygen species (ROS), which is linked to lipid peroxidation and ferroptosis. Herein, we explored underlying mechanisms of 5-ALA-PDT against keloids. We identified that 5-ALA-PDT led to elevated levels of ROS and lipid peroxidation in keloid fibroblasts, accompanied by downregulation of xCT and GPX4, which are associated with anti-oxidation effects and ferroptosis inhibition. These results may indicate that 5-ALA-PDT treatment increases ROS while inhibiting xCT and GPX4, thus promoting lipid peroxidation to induce ferroptosis in keloid fibroblasts.


Assuntos
Ferroptose , Queloide , Fotoquimioterapia , Humanos , Ácido Aminolevulínico/farmacologia , Ácido Aminolevulínico/uso terapêutico , Queloide/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Regulação para Baixo , Fibroblastos
12.
Mol Pharm ; 20(6): 2942-2950, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37083360

RESUMO

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a 99mTc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic 99mTc-labeled complex ([99mTc]Tc-DP-FAPI) was obtained by kit formulation. In vitro cellular uptake and saturation binding assays were performed in FAP-transfected HT-1080 cells (FAP-HT-1080). The biodistribution was characterized, and micro-single-photon emission computed tomography (SPECT) imaging was performed in BALB/c nude mice bearing U87 MG tumors. Furthermore, a first-in-man application was performed in four healthy volunteers and three patients with gastrointestinal tumors. In vitro, the nanomolar Kd values of [99mTc]Tc-DP-FAPI indicated that it had significantly high target affinity for FAP. Biodistribution and micro-SPECT imaging studies showed that [99mTc]Tc-DP-FAPI exhibited high uptake and high tumor-to-nontargeted ratios. The calculated effective dose for [99mTc]Tc-DP-FAPI was approximately <5 mSv in four healthy volunteers. In three patients with gastrointestinal tumors, [99mTc]Tc-DP-FAPI quantitative SPECT/CT revealed high and reliable uptake. [99mTc]Tc-DP-FAPI exhibited high selectivity and affinity for FAP in vitro. The safety and effectiveness of [99mTc]Tc-DP-FAPI in primary tumor imaging have been confirmed by animal and clinical studies, revealing the potential clinical application value of this tracer.


Assuntos
Neoplasias , Animais , Humanos , Camundongos , Fibroblastos/metabolismo , Camundongos Nus , Neoplasias/genética , Neoplasias/metabolismo , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos
13.
Pharmaceuticals (Basel) ; 16(4)2023 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-37111368

RESUMO

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [99mTc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without purification, [99mTc]Tc-CNMCHDG had a high radiochemical purity of over 95% and great in vitro stability and hydrophilicity (log P = -3.65 ± 0.10). In vitro cellular uptake studies showed that the uptake of [99mTc]Tc-CNMCHDG was significantly inhibited by pre-treatment with D-glucose and increased by pre-treatment with insulin. Preliminary cellular studies have demonstrated that the mechanism by which the complex enters into cells may be related to GLUTs. The results of biodistribution and SPECT imaging studies displayed high tumor uptake and good retention of [99mTc]Tc-CNMCHDG in A549 tumor-bearing mice (4.42 ± 0.36%ID/g at 120 min post-injection). Moreover, [99mTc]Tc-CNMCHDG exhibited excellent tumor-to-non-target ratios and a clean imaging background and is a potential candidate for clinical transformation.

14.
J Med Chem ; 66(7): 4952-4960, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-36972467

RESUMO

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment due to its selective expression on cancer-associated fibroblasts (CAFs) in most solid tumor stroma. Two FAP inhibitor (FAPI) derived ligands (L1 and L2) containing different lengths of DPro-Gly (PG) repeat units as linkers were designed and synthesized with high affinity for FAP. Two stable hydrophilic 99mTc-labeled complexes ([99mTc]Tc-L1 and [99mTc]Tc-L2) were obtained. In vitro cellular studies show that the uptake mechanism is correlated with FAP uptake, and [99mTc]Tc-L1 shows a higher cell uptake and specific binding to FAP. A nanomolar Kd value for [99mTc]Tc-L1 indicates its significantly high target affinity for FAP. The biodistribution and microSPECT/CT images obtained for U87MG tumor mice show that [99mTc]Tc-L1 has high tumor uptake with specificity to FAP and high tumor-to-nontarget ratios. As an inexpensive, easily made, and widely available tracer, [99mTc]Tc-L1 holds great promise for clinical applications.


Assuntos
Diagnóstico por Imagem , Fibroblastos , Camundongos , Animais , Linhagem Celular Tumoral , Distribuição Tecidual , Transporte Biológico
15.
J Oncol ; 2023: 7487306, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816366

RESUMO

Objective: Radiofrequency coblation (RFC) is a relatively new method that has opened up new perspectives in treating oropharyngeal squamous cell carcinoma (OPSCC). Our study was designed to explore the feasibility and effectiveness of RFC-assisted transoral surgery (RFC-TOS) for primary OPSCC. Methods: Sixty-nine cases of OPSCC from February 2005 to November 2020 were retrospectively analyzed, including 31 in the RFC-TOS group and 38 in the open surgery group. No difference was observed in demographic and oncological characteristics. Results: The significance between the RFC-TOS group and the open surgery group was proved in intraoperative bleeding volume (34.10 ± 10.10 ml vs. 193.68 ± 21.00 ml, P < 0.001), durations of surgery (79.58 ± 8.45 min vs. 217.87 ± 17.65 min, P < 0.001), time to resume oral feeding (1.64 ± 0.41 d vs. 11.58 ± 1.41 d, P < 0.001), duration of hospitalization (7.84 ± 0.66 d vs. 15.66 ± 1.62 d, P < 0.001), and the total costs (22846.22 ± 1821.55¥ vs. 41792.24 ± 4150.86¥, P < 0.001). The rates of 5-year overall survival (OS), 5-yeardisease-specific survival (DSS), and 5-year local control rate (LC) were 69.1%, 71.7%, and 75.7%, respectively, in the RFC-TOS group and 71.0%, 73.4%, and 73.7% in the open surgery group (P > 0.05). Conclusions: RFC-TOS is a feasible alternative transoral approach for OPSCC. The reported perioperative and oncologic outcomes are satisfactory.

16.
Front Surg ; 10: 1083961, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36793309

RESUMO

Objective: This study aims to evaluate the effect of bilateral nasal packing on sleep oxygen saturation and its influencing factors on the first night after general anesthesia. Method: A total of 36 adult patients who underwent bilateral nasal packing with a nonabsorbable expanding sponge after general anesthesia surgery were prospectively studied. All these patients underwent overnight oximetry tests before and the first night after surgery. The following oximetry variables were collected for analysis: the lowest oxygen saturation (LSAT), the average oxygen saturation (ASAT), the oxygen desaturation index of ≥4% (ODI4), and the percentage of time with oxygen saturation below 90% (CT90). Results: Among the 36 patients, the incidences of both sleep hypoxemia and moderate-to-severe sleep hypoxemia increased with bilateral nasal packing after general anesthesia surgery. All the pulse oximetry variables we studied deteriorated significantly after surgery: both LSAT and ASAT decreased significantly (P < 0.05), while both ODI4 and CT90 increased significantly (P < 0.05). In a multiple logistic regression analysis, body mass index (BMI), LSAT, and modified Mallampati grade were found to be independently predictive for a larger decrease in LSAT (≥5%) after surgery (all P's < 0.05). Conclusion: Bilateral nasal packing after general anesthesia could induce or aggravate sleep hypoxemia, especially in patients with obesity, relatively normal sleep oxygen saturation, and high modified Mallampati grades.

17.
J Clin Sleep Med ; 19(2): 303-308, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36263860

RESUMO

STUDY OBJECTIVES: To investigate the feasibility and effectiveness of nasopharyngeal tube (NPT) insertion in alleviating sleep hypoxemia during the first night after velopharyngeal surgery in patients with obstructive sleep apnea syndrome (OSAS). METHODS: In this prospective nonblinded, randomized, controlled study, 46 patients with obstructive sleep apnea syndrome (OSAS) who underwent velopharyngeal surgery were enrolled and randomly allocated to the control group (with no NPT insertion) and the NPT insertion group. Both groups underwent overnight pulse oximetry tests during the first postoperative night. RESULTS: One patient in the NPT insertion group was excluded because of involuntary self-removal of NPT during sleep. A total of 45 patients with OSAS were included for analysis, with 23 in the control group and 22 in the NPT insertion group. No significant differences in preoperative baseline information were found between the two groups. Compared with the patients in the control group, those patients in the NPT insertion group showed a significantly higher value of the lowest oxygen saturation of oximetry during the first postoperative night (85.0 ± 4.0% vs 79.3 ± 8.0%) (P = .005). The percentage of patients with lowest oxygen saturation of oximetry < 80% in the NPT insertion group was only 9.1% (2 of 22), which was significantly lower than 39.1% (9 of 23) in the control group (P = .035). No patient reported unbearable discomfort related to NPT insertion. The most common mild discomfort was occasional pharyngeal foreign body sensation (6 of 22, 27.3%). CONCLUSIONS: NPT insertion could lessen the severity of sleep hypoxemia during the first night after velopharyngeal surgery in patients with OSAS and showed excellent compliance. This method could be a potential alternative option for decreasing the risks of complications related to severe sleep hypoxemia during the early postoperative days. CITATION: Zhang J, Guan S, Zhang C, Du X, Li T, Xiao S. Nasopharyngeal tube effects on alleviating sleep hypoxemia during the first night following velopharyngeal surgery in patients with obstructive sleep apnea syndrome. J Clin Sleep Med. 2023;19(2):303-308.


Assuntos
Nasofaringe , Apneia Obstrutiva do Sono , Humanos , Estudos Prospectivos , Nasofaringe/cirurgia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Hipóxia/terapia , Hipóxia/complicações , Oximetria , Sono
18.
Laryngoscope ; 133(1): 133-138, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35460273

RESUMO

OBJECTIVES: To investigate the feasibility, safety, and effectiveness of endoscopic-assisted resection of benign parotid tumors via concealed post-auricular sulcus incision. METHODS: Between October 2019 and March 2021, eligible patients with diagnosed benign parotid tumors were prospectively included and randomly assigned to two groups: the endoscope-assisted post-auricular sulcus incision group (endoscope group) and the conventional Blair "S" incision group (conventional group). RESULTS: A total of 45 patients were finally included, including 24 subjects in the endoscope group and 21 subjects in the conventional group. No obvious differences were observed in basic information between these two groups of patients. The surgical incision length in endoscope group patients was 4.0 ± 0.4 cm, which was significantly shorter than that in conventional group patients, 10.3 ± 1.6 cm (p < 0.001). The total intraoperative blood loss, the first post-operative day drainage volume, the total post-operative drainage volume, and the total drainage days were all significantly lower in endoscope group patients than in conventional group patients (all p < 0.05). Among 3 months follow-ups, no local recurrence or residual tumor were found in both groups of patients, and there were none of them had permanent facial paralysis or parotid fistula. The self-evaluated appearance satisfaction VAS scores of endoscope group patients were all 0, which was significantly lower than that of conventional group patients, 4.7 ± 1.6 (p < 0.001). CONCLUSION: Compared with the conventional Blair "S" incision surgery, the endoscope-assisted resection of the benign parotid tumors via concealed post-auricular sulcus incision was safe and effective and showed advantages of faster recovery and better self-assessments of appearance satisfaction. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:133-138, 2023.


Assuntos
Paralisia Facial , Neoplasias Parotídeas , Ferida Cirúrgica , Humanos , Endoscópios , Endoscopia , Glândula Parótida/cirurgia , Glândula Parótida/patologia , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Complicações Pós-Operatórias/patologia , Ferida Cirúrgica/patologia
19.
Pharmaceuticals (Basel) ; 17(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38256883

RESUMO

Molecular imaging is partly defined as in vivo imaging of biological or biochemical processes using various markers [...].

20.
Front Neurol ; 13: 1024743, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408490

RESUMO

Objective: To explore the association between laryngopharyngeal reflux disease (LPRD)-related symptoms and the Eustachian tube (ET) function in adult patients with otitis media with effusion (OME). Materials and methods: A total of 105 adult patients with OME were retrospectively studied. All these patients had undergone tubomanometry (TMM) test for the affected ears before treatments. The LPRD-related symptoms were all assessed by the Reflux Symptom Index (RSI) scale. Results: Among the 105 included patients, the numbers of subjects with only one and both two ears affected were 65 (57.1%) and 40 (42.9%), respectively. Therefore, a total of 145 affected ears were studied. For these affected ears, a linear regression analysis that included sex, age, BMI, smoking history, drinking history, RSI value, and the condition of the contralateral ear suggested that only RSI value was significantly associated with TMM value (P < 0.001), with the correlation coefficient of -0.112. Among the 9 symptoms in RSI scale, affected ears with the following symptoms (vs. affected ears without) showed significantly lower TMM values: excess throat mucus or postnasal drip, difficulty swallowing food, liquids, or pills, and sensations of something stuck in your throat or a lump in your throat (all P < 0.05). Conclusion: LPRD may disrupt ET function in adult OME patients. A higher RSI score is independently predictive for a bad ET patency in such patients and is indicative for an additional anti-reflux therapy.

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