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1.
Biomed Pharmacother ; 175: 116659, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692063

RESUMO

Cholangiocarcinoma (CCA), a rare yet notably aggressive cancer, has experienced a surge in incidence in recent years. Presently, surgical resection remains the most effective curative strategy for CCA. Nevertheless, a majority of patients with CCA are ineligible for surgical removal at the time of diagnosis. For advanced stages of CCA, the combination of gemcitabine and cisplatin is established as the standard chemotherapy regimen. Despite this, treatment efficacy is often hindered by the development of resistance. In recent times, immune checkpoint inhibitors, particularly those that block programmed death 1 and its ligand (PD1/PD-L1), have emerged as promising strategies against a variety of cancers and are being increasingly integrated into the therapeutic landscape of CCA. A growing body of research supports that the use of PD1/PD-L1 monoclonal antibodies in conjunction with chemotherapy may significantly improve patient outcomes. This article seeks to meticulously review the latest studies on PD1/PD-L1 involvement in CCA, delving into their expression profiles, prognostic significance, contribution to oncogenic processes, and their potential clinical utility.

2.
J Craniomaxillofac Surg ; 52(3): 347-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38368209

RESUMO

This study evaluated the feasibility of simultaneous temporomandibular joint (TMJ) arthroscopy and orthognathic surgery as a new treatment strategy for anterior disc displacement without reduction (ADDwoR) patients with severe jaw deformities. Twelve ADDwoR patients with facial deformities who underwent arthroscopy and orthognathic surgery between September 2015 and December 2019 were retrospectively evaluated. Pre- and postoperative maximum incisal opening (MIO) and joint pain were recorded. Computed tomography (CT) and three-dimensional cephalometric analysis were performed at 3 (T1) and ≥6 (T2) months postoperatively. Magnetic resonance imaging (MRI) of the TMJ was performed before, ≤7 days after and ≥6 months after surgery. The lateral profile radiological findings, the symmetry of the maxilla and mandible, and the MRI measurements were compared. Anterior disc displacement did not recur, and the maximum incisal opening (MIO) increased from 27.4 mm to 32.7 mm after surgery (p < 0.05). No significant differences were found in the lateral profile, symmetry indices or condylar height via MRI between T1 and T2. Joint morphology and the position of both the maxilla and mandible remained stable during postoperative follow-up, while joint symptoms were markedly relieved and facial appearance was noticeably improved. Combined arthroscopy and orthognathic surgery is effective and recommended for ADDwoR patients with jaw deformities.


Assuntos
Anormalidades Maxilomandibulares , Luxações Articulares , Cirurgia Ortognática , Transtornos da Articulação Temporomandibular , Humanos , Estudos Retrospectivos , Artroscopia , Estudos de Viabilidade , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/cirurgia , Articulação Temporomandibular/cirurgia , Mandíbula/cirurgia , Imageamento por Ressonância Magnética/métodos , Luxações Articulares/cirurgia
3.
Int J Surg ; 110(3): 1463-1474, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38270619

RESUMO

BACKGROUND: Trigeminal neuralgia (TN) is the most common neuropathic disorder in the maxillofacial region. The etiology and pathogenesis of TN have not been clearly determined to date, although there are many hypotheses. OBJECTIVE: The goal of this study was to investigate the interactions between different types of cells in TN, particularly the impact and intrinsic mechanism of demyelination on the trigeminal ganglion, and to identify new important target genes and regulatory pathways in TN. METHODS: TN rat models were prepared by trigeminal root compression, and trigeminal nerve tissues were isolated for spatial transcriptome sequencing. The gene expression matrix was reduced dimensionally by PCA and presented by UMAP. Gene function annotation was analyzed by Metascape. The progression of certain clusters and the developmental pseudotime were analyzed using the Monocle package. Modules of the gene coexpression network between different groups were analyzed based on weighted gene coexpression network analysis and assigned AddModuleScore values. The intercellular communication of genes in these networks via ligand-receptor interactions was analyzed using CellPhoneDB analysis. RESULTS: The results suggested that the trigeminal ganglion could affect Schwann cell demyelination and remyelination responses through many ligand-receptor interactions, while the effect of Schwann cells on the trigeminal ganglion was much weaker. Additionally, ferroptosis may be involved in the demyelination of Schwann cells. CONCLUSIONS: This study provides spatial transcriptomics sequencing data on TN, reveals new markers, and redefines the relationship between the ganglion and myelin sheath, providing a theoretical basis and supporting data for future mechanistic research and drug development.


Assuntos
Doenças Desmielinizantes , Neuralgia do Trigêmeo , Ratos , Animais , Neuralgia do Trigêmeo/genética , Ligantes , Transcriptoma , Nervo Trigêmeo , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia
4.
Oral Dis ; 2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37246472

RESUMO

OBJECTIVES: The study aimed to introduce and evaluate a new customized temporomandibular joint-mandible combined prosthesis with 3D printing fabrication. MATERIALS AND METHODS: This was a prospective study including patients with temporomandibular joint-mandible combined lesions. A 3D-printed customized temporomandibular joint-mandible combined prosthesis was implanted to repair the joint and jaw defect. Clinical follow-up and radiographic examinations were taken to assess the clinical efficacy. The assessment indices were compared by the Wilcoxon signed rank test. RESULTS: Eight patients were treated with the combined prosthesis and included in this study. All prostheses were accurately positioned and fixed without wound infection, prosthesis exposure, displacement, loosening, or fracture. All cases had no mass recurrence at the last follow-up point. Pain, diet, mandibular function, lateral mandibular movement to the diseased side, and maximal interincisal opening showed significant improvements at every follow-up point and went to a stable condition at 6 months after the operation. But the lateral movement to the non-operated side was still limited following surgery. CONCLUSION: The 3D-printed combined prosthesis may be an alternative to other well-established reconstructions for temporomandibular joint and mandible defects.

5.
Clin Oral Investig ; 27(6): 2513-2520, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37221432

RESUMO

OBJECTIVE: This study introduces the application of autogenous bone graft for the reconstruction of temporomandibular joint (TMJ) and skull base combined defects. MATERIALS AND METHODS: Patients treated with autogenous bone grafts for reconstruction of the TMJ and skull base were reviewed. All patients underwent virtual surgical design to confirm the osteotomies of the combined lesion and the selections of autogenous bone graft, fabrication of surgical templates to transfer the plan to actual operation, and reconstruction of autogenous bone graft for the TMJ and/or skull base. Surgical outcomes were assessed by clinical examinations and radiological data. RESULTS: Twenty-two patients were involved in this study. Ten patients underwent reconstruction of the skull base by a free iliac or temporal bone graft and preservation of the TMJ. Twelve patients underwent skull base reconstruction by the same methods and total reconstruction of the TMJ by half sternoclavicular joint flap or costochondral bone graft. No severe complications occurred after surgery. The occlusion relationship was stable and similar to that of the preoperative state. The pain and maximal interincisal opening were significantly improved by the 101.2-month follow-up. CONCLUSION: Autogenous bone graft is a good alternative for repairing the TMJ and the skull base structure and function. CLINICAL RELEVANCE: The study introduced the application of autogenous bone graft for the reconstruction of temporomandibular joint and skull base combined defect, which is a good way to repair the defect and restore the function.


Assuntos
Transtornos da Articulação Temporomandibular , Humanos , Transtornos da Articulação Temporomandibular/cirurgia , Articulação Temporomandibular/cirurgia , Retalhos Cirúrgicos , Base do Crânio/cirurgia
6.
World J Clin Cases ; 11(10): 2276-2281, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37122508

RESUMO

BACKGROUND: Paragangliomas are rare neuroendocrine tumors. We hereby report a case of a localized paraganglioma found in the abdominal cavity, and review the relevant literature to improve the understanding of this disease. CASE SUMMARY: A 29-year-old Chinese female patient was referred to our hospital due to an abdominal mass found on physical examination. Imaging revealed a mass in the left upper abdomen, suggestive of either a benign stromal tumor or an ectopic accessory spleen. Laparoscopic radical resection was subsequently performed, and histopathological analysis confirmed the diagnosis of a paraganglioma. The patient was followed up 3 months post-operation, and reported good recovery with no metastasis. CONCLUSION: Radical resection can effectively treat intra-abdominal paragangliomas, with few side effects and low recurrence risk. In addition, early and accurate diagnosis and timely intervention are essential for the prognosis of this disease.

7.
J Stomatol Oral Maxillofac Surg ; 124(2): 101336, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36403930

RESUMO

This study aimed to introduce and evaluate the feasibility of a modified transzygomatic approach with preservation of masseter attachment for the management of infratemporal fossa tumors. This retrospective study included 20 patients treated at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, between June 2007 and August 2017. Pre- and postoperative radiological findings (magnetic resonance imaging and computed tomography) were obtained from all patients. During an average 67 months of follow-up, no clinical or radiographic signs were found of recurrence or absorption of zygomatic arch defects. The mean visual analog scale score changed from 5.5 preoperatively to 0.6 postoperatively (P<0.001), while the mean maximum inter-incisal opening improved from 21.5 mm preoperatively to 38.7 mm postoperatively (P<0.001). Thus, managing infratemporal lesions using the modified transzygomatic approach may provide functional and esthetically established outcomes.


Assuntos
Fossa Infratemporal , Neoplasias da Base do Crânio , Humanos , Fossa Infratemporal/patologia , Seguimentos , Neoplasias da Base do Crânio/patologia , Estudos Retrospectivos , China
8.
J Craniofac Surg ; 34(2): e129-e134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35949030

RESUMO

PURPOSE: Open disk repositioning has been long achieving excellent functional and stability outcomes. However, still remains some relapses for whom a second open surgery is often challenging. This study aimed to evaluate the effectiveness of arthroscopic disk reposition as an alternative surgery for unsuccessful cases of anterior disk displacement (ADD) after an initial open disk repositioning. MATERIALS AND METHODS: This retrospective study included all patients who underwent secondary arthroscopy for disk repositioning of the relapsed ADD after an initial open surgery between January 2012 to June 2017. The redo arthroscopic disk repositioning and suturing procedure was the primary predictor input variable in this study. Outcome evaluation was based on both clinical (visual analog scale and maximal interincisal opening) and magnetic resonance imaging data. RESULTS: Twenty-seven joints fulfilling the inclusion criteria were included. A significant improvement was detected at 24-month postoperatively compared with the baseline visual analog scale. The maximal interincisal opening showed a statistical improvement from 25.07 mm preoperatively to 38.44 mm at 24-month postoperatively. Twenty-six joints maintained a stable disk position with only 1 joint relapsed to ADD without reduction. CONCLUSION: Arthroscopic disk reposition and suturing technique is a reliable and effective repeat surgery after failed initial open disk repositioning for management of ADD.


Assuntos
Luxações Articulares , Transtornos da Articulação Temporomandibular , Humanos , Disco da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , Estudos Retrospectivos , Reposicionamento de Medicamentos , Recidiva Local de Neoplasia , Artroscopia/métodos , Imageamento por Ressonância Magnética , Luxações Articulares/cirurgia
9.
Int J Med Sci ; 19(13): 1965-1976, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438920

RESUMO

The injury of Schwann cells is an important pathological feature of peripheral neuropathy. However, the explicit molecular mechanism and blocking method remains to be explored. In this study, we identified an pivotal executor of necroptosis-RIPK1, performed an unique function in response to oxidative stress-induced injury in Rat Schwann cells. We found that after oxidative stress-simulation by H2O2, RIPK1 was activated independent of genetic up-regulation, but through the post-translational modification, including its protein levels, phosphorylation of Serine 166 and Serine 321 sites and its general ubiquitination levels. Under a confocal microscopy, we found that RIPK1 was significantly accumulated into the mitochondria. And the phosphorylation, ubiquitination levels were also elevated in mitochondrial RIPK1, as indicated by immunoprecipitation. Through the administration of N-Acetyl-L-cysteine (NAC), a ROS inhibitor, we found that the phosphorylation, ubiquitination and mitochondrial location of RIPK1 was significantly suppressed. While administration of Necrostatin-1 (Nec-1) failed to influence the levels of ROS and mitochondrial membrane potential, revealing that RIPK1 served as the down-stream regulators of ROS. Lastly, pharmacological inhibition of RIPK1 by Nec-1 attenuated the levels of necroptosis, increased proliferation, as indicated by Annexin V/PI evaluation, CCK-8 detection, TEM scanning and EdU staining. Our results indicate a previous un-recognized post-translational change of RIPK1 in response to oxidative stress in Schwann cells.


Assuntos
Peróxido de Hidrogênio , Necroptose , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Células de Schwann , Proliferação de Células , Serina/metabolismo
10.
J Ovarian Res ; 15(1): 117, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36303234

RESUMO

To characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa.


Assuntos
Micobioma , Síndrome do Ovário Policístico , Humanos , Feminino , Sobrepeso/complicações , RNA Ribossômico 16S , Metaboloma , Bactérias/genética
11.
Front Psychol ; 13: 920899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832907

RESUMO

Objective: To investigate the effects of cell phone dependence (CPD) on mental health among undergraduates during the COVID-19 pandemic and further identify the determinants that may affect their mental health in China. Methods: The data were collected from 602 students at a medical school in Shanghai via an online survey conducted from December 2021 to February 2022. The Mobile Phone Addiction Index (MPAI) and Depression Anxiety Stress Scale (DASS) were applied to evaluate CPD and mental health, respectively. Independent sample t-test and one-way analysis of variance (ANOVA) were employed to compare the means of continuous variables among categorical groups. Correlations between continuous variables were detected using Pearson's correlation analysis. Univariable and multivariable logistic regressions were employed to identify the determinants of mental health. Results: Among the 402 eligible students, 73.88% were women with an average age of 20.19 ± 2.36 years. On average, the DASS score was 32.20 ± 11.07, the CPD score was 36.23 ± 11.89, and the cell phone use duration was 7.67 ± 3.61 h/day. CPD was found to have a negative effect on mental health among college students in Shanghai. Additionally, cell phone use duration, age, being senior students, faculty-student relationship, insomnia, tobacco use, obesity, and life satisfaction were clarified as contributing factors to mental health among college students. Conclusion: High degree of CPD could have a negative effect on college students' mental health, which might lead to some psychological problems. Appropriate actions and effective interventions are highly needed to prevent severe psychological injuries among college students in China.

13.
Quant Imaging Med Surg ; 12(2): 1324-1335, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35111627

RESUMO

BACKGROUND: Sjögren syndrome (SjS) is a systemic disease affecting exocrine, including ocular lacrimal, glands. It is uncertain whether ocular microvascular alterations are associated with this disease. In this study, we evaluated retinal and conjunctival microvascular changes in SjS patients using optical coherence tomography angiography (OCTA). METHODS: Twelve SjS patients (24 eyes) and 12 normal controls (24 eyes) were recruited to this study. Three-dimensional conjunctival and retinal OCTA images of each eye were captured and microvascular density was calculated. Each image was analyzed by retinal area based on the early treatment of diabetic retinopathy study method (R, S, L, and I) hemisphere segmentation method (SR, SL, IL, and IR); and central wheel division method (C1-C6). Correlation analyses were used to look for associations between retinal and conjunctival microvascular densities. RESULTS: Superficial and deep retinal layer microvascular density was decreased in SjS patients compared with normal controls (P<0.05). This significant difference was found in both superficial and deep layers in S, L, SL, IL and C1-C3 regions, and additionally in the I and SR regions in the superficial layer. Conversely, in the conjunctiva microvascular density was higher in SjS patients than in controls. In SjS patients, a significant negative correlation was found between conjunctival and both superficial (r=-0.641; P=0.025) and deep (r=-0.958; P<0.0001) microvascular densities. CONCLUSIONS: The changed microvascular densities measured in deep and superficial retinal layers and in the conjunctiva demonstrate that OCTA is a promising method in differentiating the eyes from those with SjS.

15.
J Oral Maxillofac Surg ; 80(2): 231-239, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34571046

RESUMO

PURPOSE: Hemimasticatory spasm (HMS) is a masticatory muscle disorder without an effective treatment approach at present. This retrospective analysis aims to investigate the clinical efficacy of temporomandibular arthroscope-assisted masseteric nerve avulsion on HMS and thereby further determine a more effective therapeutic strategy for HMS patients. METHODS: Four patients with HMS receiving temporomandibular arthroscope-assisted masseteric nerve avulsion in the neurology department of oral surgery of our hospital from April 2017 to April 2018 were recruited in this study. Through a clinical follow-up period of 36 months, the comprehensive efficacy of arthroscope-assisted masseteric nerve avulsion was evaluated combined with an electrophysiological electromyogram. Furthermore, the maximum muscle strength and masticatory efficiency of the sound and affected sides were measured to determine whether there were complications. The morphology of the myelin sheath of the masseteric nerve avulsed in the operation was observed under the transmission electron microscope. RESULTS: The 3 years of follow-up showed that complete remission of HMS was seen in 4 patients with the score reduced to grade 0, showing satisfactory clinical efficacy. Electrophysiological electromyogram demonstrated an absence of obvious high-frequency group discharge potential in the 4 patients within 3 years after the operation, and the overall efficacy combined with the clinical efficacy was considered satisfactory. The maximum masseter strength of the sound side had no significant change, but that of the affected side was slightly decreased. The masticatory efficiency of the affected side was slightly decreased immediately after the operation but returned to the preoperative level 1 year after the operation, suggesting that this operation did not affect the masticatory function of the patients. No obvious demyelination was found in the avulsed nervous tissues. CONCLUSIONS: Temporomandibular arthroscope-assisted masseteric nerve avulsion yielded satisfactory and stable overall efficacy on the treatment of HMS. The masticatory efficiency of the affected side was optimally preserved, while the maximum masseter muscle strength of the affected side was partially decreased.


Assuntos
Músculo Masseter , Músculos da Mastigação , Eletromiografia , Humanos , Músculo Masseter/cirurgia , Estudos Retrospectivos , Espasmo/cirurgia
17.
Front Med (Lausanne) ; 8: 808940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957168

RESUMO

Purpose: To elucidate the expression profile and the potential role of long non-coding ribonucleic acids (RNAs) (lncRNAs) in a dry eye disease (DED) model. Methods: A DED model was established in C57BL/6J mice with 0.2% benzalkonium chloride (BAC) twice a day for 14 days. The differentially expressed lncRNAs were detected by RNA-seq technology (Gene Expression Omnibus, GEO GSE186450) and the aberrantly expressed lncRNAs were further verified by RT-qPCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predicate the related candidate genes and potential pathological pathways. Cells from a human corneal epithelial cell line (HCECs) were cultured under hyperosmolarity. The regulation of inflammatory factors by silencing potential targeted lncRNAs was verified in vitro in HCECs. Results: In our study, a significant increase in corneal fluorescence staining and a reduction in tear production were observed in DED mice at all follow-ups compared with the controls, and the differences were increasing over time. In total, 2,649 upregulated and 704 downregulated lncRNAs were identified in DED mice. We selected six aberrantly expressed and most abundant lncRNAs and performed RT-qPCR using the samples for RNA-seq. Chrnb2, Gabarapl2, and Usp31 were thereby confirmed as the most significantly altered lncRNAs. Pathway analysis revealed that the neuroactive ligand-receptor interaction signaling pathway was the most enriched, followed by the calcium signaling pathway and cytokine-cytokine receptor interaction. Following treatment of Gabarapl2 siRNA and Chrnb2 siRNA, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 were significantly downregulated in the HCECs. Conclusion: Our study suggests that Chrnb2 and Gabarapl2 may be involved in the inflammation response by regulating TNF-α, IL-1ß, and IL-6 in DED. These candidate lncRNAs may be both potential biomarkers and therapeutic targets for DED.

18.
BMC Health Serv Res ; 21(1): 1334, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903242

RESUMO

BACKGROUND: Breast cancer imposes a considerable burden on both the health care system and society, and becomes increasingly severe among women in China. To reduce the economic burden of this disease is crucial for patients undergoing the breast cancer surgery, hospital managers, and medical insurance providers. However, few studies have evidenced the prediction of the total hospital expenses (THE) for breast cancer surgery. The aim of the study is to predict THE for breast cancer surgery and identify the main influencing factors. METHODS: Data were retrieved from the first page of medical records of 3699 patients undergoing breast cancer surgery in one tertiary hospital from 2017 to 2018. Multiple liner regression (MLR), artificial neural networks (ANNs), and classification and regression tree (CART) were constructed and compared. RESULTS: The dataset from 3699 patients were randomly divided into training and test sets at a 70:30 ratio (2599 and 1100 records, respectively). The average total hospital expenses were 12520.54 ± 7844.88 ¥ (US$ 1929.20 ± 1208.11). MLR results revealed six factors to be significantly associated with THE: age, LOS, type of disease, having medical insurance, minimally invasive surgery, and receiving general anesthesia. After comparing three models, ANNs was the best model to predict THEs in patients undergoing breast cancer surgery, and its strong predictive performance was also validated. CONCLUSIONS: To reduce the THEs, more attention should be paid to related factors of LOS, major and minimally invasive surgeries, and general anesthesia for these patient groups undergoing breast cancer surgery. This may reduce the information asymmetry between doctors and patients and provide more reliable cost, practical inpatient medical consumption standards and reimbursement standards reference for patients, hospital managers, and medical insurance providers ,respectively.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/cirurgia , China/epidemiologia , Feminino , Hospitais , Humanos , Pacientes Internados , Redes Neurais de Computação
19.
Front Oncol ; 11: 720447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778035

RESUMO

Tumor-infiltrating immune cells, associated with tumor progression, are promising prognostic biomarkers. However, the relationship between levels of gene expression and that of immune cell infiltration in cervical cancer prognosis is unknown. In this study, three cervical cancer gene expression microarrays (GSE6791, GSE63678 and GSE55940) were obtained from the GEO database. The IDO1 gene was identified by differentially expressed gene screening. The gene expression profiles of TCGA and GTEx databases along with comprehensive bioinformatics analysis identified that the IDO1 gene was upregulated in cervical cancer with significant difference in expression at different N stages. In addition, it was also upregulated in HPV16 positive sample. The pan-cancer analysis identified that IDO1 was highly expressed in most cancers. TIMER analysis revealed that the expression of IDO1 in CESC shows positive correlation with CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells. IDO1 expression showed remarkable positive correlation with all immune cell markers except M1 macrophages. CD8+ T cell infiltration GSEA results showed that IDO1 was mainly associated with tumor immune-related signaling pathways.

20.
PLoS One ; 16(11): e0258951, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34762666

RESUMO

Radiation therapy plays a major role in the treatment of lung cancer patients. However, cancer cells develop resistance to radiation. Tumor radioresistance is a complex multifactorial mechanism which may be dependent on DNA damage and repair, hypoxic conditions inside tumor microenvironment, and the clonal selection of radioresistant cells from the heterogeneous tumor site, and it is a major cause of treatment failure in non-small cell lung cancer (NSCLC). In the present investigation caveolin-1 (CAV-1) has been observed to be highly expressed in radiation resistant A549 lung cancer cells. CRISPR-Cas9 knockout of CAV-1 reverted the cells to a radio sensitive phenotype. In addition, CAV-1 overexpression in parental A549 cells, led to radiation resistance. Further, gene expression analysis of A549 parental, radiation resistant, and caveolin-1 overexpressed cells, exhibited overexpression of DNA repair genes RAD51B, RAD18, SOX2 cancer stem cell marker, MMPs, mucins and cytoskeleton proteins in resistant and caveolin-1 over expressed A549 cells, as compared to parental A549 cells. Bioinformatic analysis shows upregulation of BRCA1, Nuclear Excision DNA repair, TGFB and JAK/STAT signaling pathways in radioresistant and caveolin-1 overexpressed cells, which may functionally mediate radiation resistance. Immunohistochemistry data demonstrated heterogeneous expression of CAV-1 gene in human lung cancer tissues, which was analogous to its enhanced expression in human lung cancer cell line model and mouse orthotopic xenograft lung cancer model. Also, TCGA PanCancer clinical studies have demonstrated amplification, deletions and missense mutation in CAV-1 gene in lung cancer patients, and that CAV-1 alteration has been linked to poor prognosis, and poor survival in lung cancer patients. Interestingly, we have also optimized ELISA assay to measure caveolin-1 protein in the blood of A549 radiation resistant human xenograft preclinical mouse model and discovered higher level of caveolin-1 (950 pg/ml) in tumor bearing animals treated with radiation, as compared to xenograft with radiosensitive lung cancer cells (450 pg/ml). Thus, we conclude that caveolin-1 is involved in radio-resistance and contributes to tumor aggression, and it has potential to be used as prognostic biomarker for radiation treatment response, and tumor progression for precision medicine in lung cancer patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Caveolina 1/metabolismo , Neoplasias Pulmonares/patologia , Tolerância a Radiação , Células A549 , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Caveolina 1/genética , Reparo do DNA/genética , Dosagem de Genes , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Análise em Microsséries , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Mapas de Interação de Proteínas/genética , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto
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