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1.
Eur Arch Otorhinolaryngol ; 281(7): 3707-3715, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38671169

RESUMO

PURPOSE: To evaluate the clinical implication of magnetic resonance imaging (MRI)-derived skeletal muscle index (SMI) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients undergoing induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) and further to develop a nomogram for predicting survival prognosis. METHODS: SMI was determined through baseline MRI at the third cervical level. The nomogram was based on a training cohort involving 409 LANPC patients. We validated the prognostic accuracy of this prognostic model in an internal validation cohort (n = 204) and an external independent cohort (n = 272). RESULTS: SMI was an independent risk factor for OS. A prognostic model comprising age, TNM stage and SMI for individual survival prediction was developed and graphically represented as a nomogram. The model showed favorable discrimination (C-index: 0.686), predictive accuracy [time dependent area under the curve (tAUC) at 5 years: 0.70], and calibration, and was further validated in the internal and external validation datasets. A risk stratification derived from the model stratified these patients into three prognostic subgroups with significantly different survival. CONCLUSIONS: Low SMI accessed by MRI was significantly associated with poor overall survival in LANPC patients undergoing IC + CCRT. Moreover, we established and validated a novel nomogram involving age, TNM stage and SMI that could provide accurate prognostic stratification among this population.


Assuntos
Imageamento por Ressonância Magnética , Músculo Esquelético , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Nomogramas , Humanos , Masculino , Imageamento por Ressonância Magnética/métodos , Feminino , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Adulto , Prognóstico , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem , Quimiorradioterapia , Idoso , Quimioterapia de Indução , Estudos Retrospectivos , Fatores de Risco
2.
Virulence ; 15(1): 2327096, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38466143

RESUMO

Legionella pneumophila (L. pneumophila) is a prevalent pathogenic bacterium responsible for significant global health concerns. Nonetheless, the precise pathogenic mechanisms of L. pneumophila have still remained elusive. Autophagy, a direct cellular response to L. pneumophila infection and other pathogens, involves the recognition and degradation of these invaders in lysosomes. Histone deacetylase 6 (HDAC6), a distinctive member of the histone deacetylase family, plays a multifaceted role in autophagy regulation. This study aimed to investigate the role of HDAC6 in macrophage autophagy via the autophagolysosomal pathway, leading to alleviate L. pneumophila-induced pneumonia. The results revealed a substantial upregulation of HDAC6 expression level in murine lung tissues infected by L. pneumophila. Notably, mice lacking HDAC6 exhibited a protective response against L. pneumophila-induced pulmonary tissue inflammation, which was characterized by the reduced bacterial load and diminished release of pro-inflammatory cytokines. Transcriptomic analysis has shed light on the regulatory role of HDAC6 in L. pneumophila infection in mice, particularly through the autophagy pathway of macrophages. Validation using L. pneumophila-induced macrophages from mice with HDAC6 gene knockout demonstrated a decrease in cellular bacterial load, activation of the autophagolysosomal pathway, and enhancement of cellular autophagic flux. In summary, the findings indicated that HDAC6 knockout could lead to the upregulation of p-ULK1 expression level, promoting the autophagy-lysosomal pathway, increasing autophagic flux, and ultimately strengthening the bactericidal capacity of macrophages. This contributes to the alleviation of L. pneumophila-induced pneumonia.


Assuntos
Legionella pneumophila , Legionella , Doença dos Legionários , Pneumonia , Animais , Camundongos , Autofagia , Desacetilase 6 de Histona/genética , Legionella pneumophila/genética , Doença dos Legionários/genética , Macrófagos
3.
Clin Exp Immunol ; 213(2): 221-234, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37249005

RESUMO

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Hyperthermia is widely used in combination with chemotherapy and radiotherapy to enhance therapeutic efficacy in NPC treatment, but the underlying anti-tumor mechanisms of hyperthermia remain unclear. Complement C3 has been reported to participate in the activation of immune system in the tumor microenvironment, leading to tumor growth inhibition. In this study, we aimed to explore the effect and mechanisms of hyperthermia and investigate the functional role of complement C3 in NPC hyperthermia therapy (HT). The serum levels of complement C3 before and after hyperthermia therapy in patients with NPC were analyzed. NPC cell lines SUNE1 and HONE1 were used for in vitro experiment to evaluate the function of complement C3 and HT on cell proliferation and apoptosis. SUNE1 xenograft mouse model was established and tumor-bearing mice were treated in water bath at a constant temperature of 43°C. Tumor samples were collected at different time points to verify the expression of complement C3 by immunohistochemical staining and western blot. The differential expressed genes after hyperthermia were analyzed by using RNA sequencing. We found that complement could enhance hyperthermia effect on suppressing proliferation and promoting apoptosis of tumor cells in NPC. Hyperthermia decreased the mRNA expression of complement C3 in tumor cells, but promoted the aggregation and activation circulating C3 in NPC tumor tissue. By using in vitro hyperthermia-treated NPC cell lines and SUNE1 xenograft tumor-bearing mice, we found that the expression of heat shock protein 5 (HSPA5) was significantly upregulated. Knockdown of HSPA5 abrogated the anti-tumor effect of hyperthermia. Moreover, we demonstrated that hyperthermia downregulated CD55 expression via HSPA5/NFκB (P65) signaling and activated complement cascade. Our findings suggest that therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development via HSPA5/NFκB/CD55 pathway in NPC.


Assuntos
Hipertermia Induzida , Neoplasias Nasofaríngeas , Humanos , Animais , Camundongos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Chaperona BiP do Retículo Endoplasmático , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/metabolismo , Complemento C3/genética , Complemento C3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Antígenos CD55 , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral
4.
Cancer Imaging ; 23(1): 26, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36915156

RESUMO

PURPOSE: Carotid artery invasion (CAI) has been demonstrated to be an important prognosticator in some head and neck cancers. This study aimed to examine the prognostic value of radiologic CAI (rCAI) by cervical lymphadenopathy in nasopharyngeal carcinoma (NPC). METHODS: NPC patients treated between January 2013 and December 2016 were included. Pre-treatment MRIs were reviewed for cervical rCAI according to the radiologic criteria. Univariate and multivariate models were constructed to assess the association between cervical rCAI and clinical outcomes. A new N classification system was proposed and compared to the 8th AJCC system. RESULTS: The percentage of patients with MRI-positive lymph nodes was 84.7% (494/583), of whom cervical rCAI cases accounted for 42.3% (209/494). Cervical rCAI was associated with significantly poorer OS, DFS, DFFS and RFFS compared to non-rCAI (P < 0.05). Multivariate analyses confirmed that cervical rCAI was an independent prognosticator for DFS and DFFS, surpassing other nodal features, such as laterality, size, cervical node necrosis (CNN) and radiologic extranodal extension (rENE), while location of positive LNs remained independently associated with OS, DFS and DFFS. We propose a refined N classification: New_N1: upper neck LNs only without cervical rCAI; New_N2: upper neck LNs only with cervical rCAI; New_N3: upper and lower LNs. The proposed classification broadened the differences in OS, DFS and DFFS between N1 and N2 disease, and achieved a higher c-index for DFS and DFFS. CONCLUSIONS: Cervical rCAI was an independent unfavorable indicator of NPC. Compared to the AJCC system, the proposed N category showed satisfactory stratification between N1 and N2 disease, and better prediction of distant metastasis and disease failure.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Prognóstico , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Estadiamento de Neoplasias , Metástase Linfática/patologia , Estudos Retrospectivos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Imageamento por Ressonância Magnética/métodos , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia
5.
Am J Otolaryngol ; 44(2): 103717, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36516528

RESUMO

PURPOSE: The goal of this study was to establish a nomogram that included pre-treatment tumor size and lymph node (LN) size to assess personalized overall survival (OS) of patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results dataset was used to extract statistics for 1083 individuals with NPC (training cohort). In the validation cohort, 266 patients were included from the Affiliated Cancer Hospital & Institute of Guangzhou Medical University. Age, tumor-node-metastasis (TNM) stage, pre-treatment tumor size, and LN size were chosen in both the training and validation sets to build a nomogram to forecast the 3-year and 5-year OS probability using the multivariate Cox regression model. Using the C-index, calibration plot, and receiver operating characteristic (ROC) curve, the predictive model's predictive value and discriminative capacity were determined. RESULTS: Pre-treatment tumor size, LN size, age, and TNM stage were all independent prognostic factors in the multivariate analysis. After combining these characteristics, a nomogram with a C-index of 0.7367 in the training cohort and 0.795 in the validation cohort was created, suggesting strong predictive capacity. Analysis of the ROC curve revealed that the constructed nomogram was clinically applicable. CONCLUSIONS: In patients with NPC, the developed nomogram, which includes pre-treatment tumor size, LN size, age, and TNM stage, is a reliable predictive predictor of OS.


Assuntos
Neoplasias Nasofaríngeas , Nomogramas , Humanos , Prognóstico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Linfonodos/patologia , Estadiamento de Neoplasias
6.
Gene ; 853: 147095, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36464173

RESUMO

BACKGROUND: Epigenetic mechanismshave been reported to involve in shaping tumor immune microenvironment (TME). However, the role of RNA N6-methyladenosine (m6A) modification in breast cancerhas not been fully explored. METHODS: Based on m6A modification and TME infiltration characteristics of 2249 breast cancer patients, we comprehensively correlated m6A modification with immune landscapeby screeningcandidate genes, function analysis and constructing m6Asignatures. Principal component analysis was used to establish the m6Ascore. Both LASSO and Cox regression analyses were used to evaluate its prognostic value.Functional assays and immunohistochemistry were used to evaluate the expression of m6A regulators and immune cell infiltration. RESULTS: Based on the dysregulated expression of m6A, three distinct clusters were identified that displayed diverse types of tumour-associated TME cell infiltration in breast cancer.Gene signatures, stromal activity, and clinical prognosis were assessed by the m6Ascore. m6Ascore could function as a biomarker for predicting the therapeutic response to targeted therapy and immunotherapy.The dysregulated expression of m6Aregulators mediated the immune cell infiltration in the TME. CONCLUSION: Basedonthestudy,weidentified the signature and potential mechanism of m6AmodificationsthatmodifyTME cell infiltration. Thus, targeting m6A regulators may provide a promisingmethodoftreatingBRCA.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/genética , Mama , Adenosina/genética , Epigenômica , Microambiente Tumoral/genética
7.
Int J Biol Markers ; 37(1): 21-30, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35099330

RESUMO

PURPOSE: To evaluate the prognostic effect of pretreatment serum superoxide dismutase (SOD) activity in locoregionally advanced nasopharyngeal carcinoma. METHODS: A total of 498 patients diagnosed with stage III-IVA nasopharyngeal carcinoma between January 2013 and December 2016 were involved in this study. The X-tile program was used to determine the cut-off value of pretreatment serum SOD activity based on disease-free survival. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the impact of serum SOD levels on survival outcomes. The receiver operating characteristic (ROC) curve analysis was used to compare the prognostic value of clinical stage, pretreatment serum SOD level, and the combination of them regarding disease-free survival. RESULTS: Based on the X-tile plot, the optimal cutoff value of pretreatment serum SOD activity for disease-free survival was 146.0U/mL. As a dichotomous variable, SOD was significantly higher in non-keratinizing differentiated disease (P = 0.027) and early T stage (P = 0.011). Compared with the lower subset, higher SOD activity predicted an inferior 3-year rates of overall survival (84.6 vs. 94.7%, P < 0.001), distant metastasis-free survival (78.3 vs. 92.8%, P < 0.001) and disease-free survival (78.2 vs. 92.8%, P < 0.001). Multivariate analysis verified that the SOD activity was an independent prognostic indicator to predict distant metastasis, disease progression, and death. The area under the ROC curve (AUC) of the combination was superior to that of clinical stage or SOD alone for disease-free survival (both P < 0.01). CONCLUSION: Serological SOD activity before treatment is an important prognostic indicator for patients with stage III-IV non-metastatic nasopharyngeal carcinoma undergoing chemoradiation therapy.


Assuntos
Neoplasias Nasofaríngeas , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Estadiamento de Neoplasias , Prognóstico , Superóxido Dismutase
8.
Asia Pac J Clin Oncol ; 18(2): e111-e118, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33945215

RESUMO

PURPOSE: To investigate whether the addition of fluorouracil to docetaxel and cisplatin induction chemotherapy (IC) can truly improve the prognosis of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: A total of 801 patients newly diagnosed with non-metastatic locoregionally advanced NPC were included as the subjects. In this study, propensity score matching (PSM) was used for analysis of overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS), and the chi-squared test or Fisher's exact test was used to investigate toxic reactions. RESULTS: Patients received treatment with docetaxel and cisplatin (TP) or docetaxel, cisplatin and fluorouracil (TPF). With a median follow-up time of 60 months (range: 5-124 months), the TPF group had better 5-year OS (84.7% vs 79.0%; P = 0.037), PFS (84.6% vs 76.8%; P = 0.008) and DMFS (89.5% vs 82.3%; P = 0.004) than the TP group. After PSM, 258 patients were matched in each cohort. The Kaplan-Meier analysis showed that the 5-year OS, PFS and DMFS were 85.5%, 84.2% and 89.2%, respectively, in the TPF group, higher than the 80.8%, 75.0% and 81.4%, respectively, in the TP group (P = 0.048, 0.009 and 0.006, respectively). Moreover, the multivariate analysis revealed that different IC regimens were independent prognostic factors for PFS and DMFS (P = 0.014 and 0.010, respectively). CONCLUSION: This study found that compared with the TP regimen, TPF induction chemotherapy is associated with improved survival in patients with locoregionally advanced NPC. TPF can produce more mucosal and nausea/vomiting adverse reactions than TP.


Assuntos
Quimioterapia de Indução , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Cisplatino , Docetaxel , Fluoruracila/efeitos adversos , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Pontuação de Propensão , Estudos Retrospectivos
9.
J Cancer Res Clin Oncol ; 148(11): 2959-2969, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34822015

RESUMO

OBJECTIVE: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC). METHODS: We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups. RESULTS: A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0-1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia. CONCLUSION: Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT.


Assuntos
Leucopenia , Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Cisplatino/efeitos adversos , Humanos , Quimioterapia de Indução/métodos , Leucopenia/induzido quimicamente , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos
10.
Oncol Res Treat ; 44(11): 602-612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34601467

RESUMO

INTRODUCTION: Nasopharyngeal carcinoma (NPC) originates from the mucous epithelium of the nasopharynx. Although induction chemotherapy plus concurrent chemoradiotherapy is the major therapeutic protocol used for locally advanced NPC without metastasis, more research studies are needed to evaluate the curative effects. We aim to identify the therapeutic effects and prognosis after induction chemotherapy plus concurrent chemoradiotherapy in the treatment of locally advanced NPC under the intensity-modulated radiotherapy mode. METHODS: The patients (N = 544) with locally advanced NPC (III and Iva, UICC 8th) after intensity-modulated radiotherapy with induction chemotherapy and concurrent chemoradiotherapy were included in this study. We analyzed the characteristics of patients including gender, age, smoking status, tumor node staging system, clinical stage, pathological type, the therapy protocol of induction chemotherapy and concurrent chemoradiotherapy, and chemotherapy prescription. RESULTS: We have found the 5-year survival rates of overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 85.21%, 78.51%, 90.71%, and 85.21% in follow-up, and these data indicated that our therapeutic procedure provided beneficial effects on survival rates. Subsequently, the chemotherapy drug based on docetaxel (DOC) provided a more beneficial effect on survival rate compared with taxol (TXT) (all estimated HR >1; p = 0.005, 0.004, and <0.001 of OS, PFS, and DMFS), but there was no significant difference between chemotherapy drugs based on cisplatin (DDP) and nedaplatin (NDP) in treating NPC patients (p = 0.390, 0.549, 0.364, and 0.645 of OS, PFS, LRRFS, and DMFS). The therapeutic effects of induction chemotherapy revealed no difference between TPF and TP (T: DOC or TXT, P: DDP or NDP, and F: 5-fluorouracil) (p = 0.541, 0.897, 0.498, and 0.765 of OS, PFS, LRRFS, and DMFS). In addition, there was also no significant change between concurrent chemotherapy with TP dual drugs or a single platinum drug (being excluded in the multivariate model using forward [Wald] procedure). Moreover, the survival rate showed no difference between platinum accumulation dose of more or less than 150 mg/m2 for concurrent chemotherapy (being excluded in the multivariate model using forward [Wald] procedure). CONCLUSION: Our results indicate that induction chemotherapy plus concurrent chemoradiotherapy under intensity-modulated radiotherapy which is the standard therapeutic method for locally advanced NPC provides beneficial therapeutic effects, and it is worthy of further study.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/uso terapêutico , Humanos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Retrospectivos
11.
Front Immunol ; 12: 719650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413862

RESUMO

Background: The optimal second-line systemic treatment model for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains controversial. A Bayesian network meta-analysis (NMA) was performed to address this issue with regard to efficacy and toxicity. Methods: By searching MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials and Web of Science, we extracted eligible studies. Efficacy, represented as overall survival (OS) and progression-free survival (PFS), and overall toxicity, represented as ≥ grade 3 severe acute events (sAE), were assessed to compare the following 7 treatment models through an NMA: standard-of-care therapy (SoC), single targeted therapy different from SoC (ST), double targeted therapy (DT), targeted therapy combined with chemotherapy (T+C), single immune checkpoint inhibitor therapy (SI), double immune checkpoint inhibitor therapy (DI) and single chemotherapy different from SoC (SC). Rank probabilities according to the values of the surface under the cumulative ranking curve (SUCRA) were separately determined for efficacy and toxicity. Results: In total, 5285 patients from 24 eligible studies were ultimately screened, with 5184, 4532 and 4026 involved in the NMA of OS, PFS and sAE, respectively. All qualifying studies were absent from first-line immune checkpoint inhibitor therapy. In terms of OS, SI was superior to the other treatments, followed by DI, ST, T+C, SoC, DT and SC. Other than SI and SC, all treatments tended to be consistent, with hazard ratios (HRs) close to 1 between groups. For PFS, ST ranked first, while DT ranked last. For the toxicity profiles, compared with the other models, SI resulted in the lowest incidences of sAE, with statistical significance over SoC (odds ratio [OR] 0.31, 95% credible interval [CrI] 0.11 to 0.90), ST (OR 0.23, 95% CrI 0.06 to 0.86) and DT (OR 0.11, 95% CrI 0.02 to 0.53), while DT was the worst. When the SUCRA values of OS and sAE were combined, a cluster plot illustrated the superiority of SI, which demonstrated the best OS and tolerability toward sAE. Conclusion: For R/M HNSCC patients without immune checkpoint inhibitors in the first-line setting, SI may serve as the optimal second-line systemic treatment model, demonstrating the best OS and least sAE.


Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Teorema de Bayes , Tomada de Decisão Clínica , Terapia Combinada , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Humanos , Metástase Neoplásica , Estadiamento de Neoplasias , Metanálise em Rede , Prognóstico , Recidiva , Retratamento , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Resultado do Tratamento
12.
Front Oncol ; 11: 655856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816312

RESUMO

The treatment of anaplastic lymphoma kinase (ALK)-positive locally advanced non-small-cell lung cancer (NSCLC) is challenging because there is no randomized controlled trial has been reported. The value of neoadjuvant and adjuvant targeted therapy remains unclear. Herein, we show that systemic treatment with ALK inhibitor crizotinib before surgery can provide the potential to cure the initially inoperable tumor. A 27-year-old man was diagnosed with a stage IIIAcT3N2M0 (7thUICC/AJCC) upper left lung adenocarcinoma harboring EML4-ALK fusion gene. Clinically, the patient had a large primary lesion adjacent to the pericardium and regional lymph node metastasis at the ipsilateral mediastinum. Poor tumor response was observed after 3 cycles of chemotherapy (gemcitabine plus cisplatin), and upon multidisciplinary discussion, the patient was started with 250 mg crizotinib twice daily. Successive clinical examinations showed a progressive reduction of the lesions. After 2 months of therapy, the patient was downstaged to cT2aN2M0, then video-assisted thoracic surgery was performed and the final histopathological stage was ypT2aN2M0. The treatment with crizotinib (250 mg, qd) was continued more than 30 months post surgery and stopped until intracranial oligometastasis. The patient's overall survival (OS) time is 68 months at last follow-up. This case presented here supports the use of neoadjuvant and adjuvant treatment with ALK inhibitors in ALK positive locally advanced NSCLC.

13.
Int J Radiat Oncol Biol Phys ; 110(4): 1234-1247, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33621661

RESUMO

PURPOSE: Polo-like kinase 1 (PLK1) is a protein kinase that is overexpressed in breast cancer and may represent an attractive target for breast cancer treatment. However, few studies have investigated the relationship between PLK1 and radiosensitivity in breast cancer. Here, we attempted to explore whether PLK1 inhibition could sensitize breast cancer cells to radiation. METHODS AND MATERIALS: Breast cancer cells were treated with PLK1 small interference RNA or the PLK1-inhibitor, GSK461364. Cell proliferation was assessed using a colony formation assay. Cell cycle analyses were performed by flow cytometry. DNA damage, autophagy, and reactive oxygen species induced by ionizing radiation were detected by immunofluorescence, Western blot, and flow cytometry, respectively. Microtubule-associated protein 1 light chain 3 alpha (LC3) puncta were detected using an immunofluorescence assay. A clonogenic survival assay was used to determine the effect of PLK1 inhibition on cell radiosensitivity. A xenograft mouse model of breast cancer cells was used to investigate the potential synergistic effects of PLK1 inhibition and irradiation in vivo. Finally, the expression of PLK1 and LC3 in the breast cancer tissues was evaluated by immunohistochemistry. RESULTS: PLK1 inhibition significantly suppressed the proliferation and increased the radiosensitivity of breast cancer cells. Pharmacologic inhibition of PLK1 by the selective inhibitor, GSK461364, enhanced the radiosensitivity of breast cancer cells in vivo (n = 4, P = .002). Mechanistically, PLK1 inhibition led to the downregulation of radiation-induced reactive oxygen species and autophagy, thereby increasing the radiosensitivity of breast cancer cells. Additionally, we detected a positive correlation between the expression of PLK1 and LC3 in human breast cancer samples (n = 102, R = 0.486, P = .005). CONCLUSIONS: Our findings indicate that PLK1 inhibition enhances the radiosensitivity of breast cancer cells in a manner associated with the suppression of radiation-induced autophagy. The inhibition of PLK1 represents a promising strategy for radiosensitizing breast cancer.


Assuntos
Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Camundongos , Quinase 1 Polo-Like
14.
J Cancer ; 12(1): 18-27, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391399

RESUMO

Objective: To investigate the clinical value of induction chemotherapy (IC) with docetaxel plus cisplatin (TP) followed by concurrent chemoradiotherapy (CCRT) with TP in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 544 patients with locoregionally advanced NPC that was newly diagnosed from January 2009 to December 2015 were included in this study. Among these patients, 251 were treated with TP induction chemotherapy followed by CCRT with cisplatin (DDP) alone (TP + DDP group), 167 were treated with TP followed by CCRT with TP (TP + TP group), and 126 were treated with docetaxel, DDP and fluorouracil (TPF) followed by CCRT with DDP alone (TPF + DDP group). Overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS) were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Results: Survival analysis showed that the 5-year OS, PFS and DMFS rates in the TP + DDP group were significantly lower than those in the TP + TP group after propensity score matching (PSM). Multivariate analysis revealed that CCRT with TP was an independent prognostic factor for OS, PFS and DMFS. During CCRT, the incidence rates of grade 3/4 nausea/vomiting, oral mucositis, leukocytopenia and neutropenia were significantly increased in the TP + TP group compared with the TP + DDP group (all P < 0.05). To further explore the value of TP + TP, we performed PSM again with the TPF + DDP group. After PSM, there were 100 patients in each group. Survival analysis showed no significant differences in the 5-year OS, PFS, DMFS and LRRFS rates between the two groups. During IC and CCRT, the rate of grade 3/4 nausea/vomiting in the TPF + DDP group was higher than that in the TP+TP group (9.0% vs. 2.0%, P = 0.030; 18.0% vs. 8.0%, P = 0.036, respectively). No significant difference in the incidence of grade 3/4 hematologic toxicity was found between the two groups (all P > 0.05). Conclusion: TP + TP can reduce the distant metastasis of locoregionally advanced NPC and improve OS compared with TP + DDP; TP + TP has the same effect as TPF + DDP and is clinically feasible.

15.
Front Oncol ; 11: 788497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35117992

RESUMO

PURPOSE: To explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal carcinoma (LA-NPC). PATIENTS AND METHODS: TILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs-LYM% score = 0), middle-risk group (MRG) (TILs-LYM% score = 1), and low-risk group (LRG) (TILs-LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs-LYM% status with clinicopathological factors and survival, were evaluated. RESULTS: As a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan-Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs-LYM% score of 0, 1, and 2 (all P <0.05). Further multivariate analyses showed that TILs-LYM% score was an independent factor affecting survival of the patients, and HRG (TILs-LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89, P <0.001), death (HR = 8.08, P = 0.008), distant metastasis (HR = 7.66, P = 0.001), and local relapse (HR = 5.18, P = 0.013) compared with LRG (TILs-LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs-LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone. CONCLUSIONS: A positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs-LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.

16.
Cancer Cell Int ; 20: 498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061850

RESUMO

BACKGROUND: Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC. METHODS: Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro. RESULTS: By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9. CONCLUSION: IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.

17.
J Cancer ; 11(23): 6782-6789, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123269

RESUMO

Aims: This study aimed to investigate the clinical value of induction chemotherapy (IC) with docetaxel, 5-fluorouracil plus nedaplatin followed by concurrent chemoradiotherapy (CCRT) with nedaplatin for locoregional advanced nasopharyngeal carcinoma (NPC). Materials and Methods: In total, 269 patients diagnosed with locoregional advanced NPC between June 2012 and June 2017 were retrospectively included and divided into two groups: IC (docetaxel plus nedaplatin and 5-fluorouracil) followed by nedaplatin-based CCRT (TNF + N group, n = 146) and IC (docetaxel plus cisplatin and 5-fluorouracil) followed by cisplatin-based CCRT (TPF + P group, n = 123). The Kaplan-Meier method and Cox proportional hazards model were applied to analyse survival and prognosis. After propensity score-matched (PSM), 113 patients remained in each group. Toxicities were compared between the two groups using the Chi-square test or Fisher's exact test. Results: The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) rates of the TNF + N and TPF + P groups were 90.7% vs. 92.3% (P = 0.315), 78.9% vs. 79.4% (P = 0.715), 82.4% vs. 85.1% (P = 0.441) and 96.1% vs. 93.3% (P = 0.414), respectively, with no significant difference in 3-year survival outcome between the two groups, and this outcome was confirmed after using PSM analyses. In the PSM cohort, a significant higher frequency of grade 3/4 vomiting was observed in the TPF + P group compared to the TNF + N group (22.1% vs. 0%, P = 0.000). However, 15.9% of patients in the TNF + N group had grade 3/4 thrombocytopenia in comparison with 6.2% in the TPF + P group (P = 0.020). Conclusions: The TNF regimen followed by CCRT with nedaplatin is an alternative treatment strategy to the standard TPF regimen followed by CCRT with cisplatin for patients with locoregional advanced NPC.

18.
Biomater Sci ; 8(23): 6695-6702, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33108416

RESUMO

As the barrier between the human body and the outside world, the skin is vulnerable to pathogenic microorganisms, especially when suffering from skin injuries such as burns. Staphylococcus aureus remains the most common type of bacteria that infects humans, and the surging drug resistance poses a major threat to the treatment of these infections. Here we report the development of antibacterial photodynamic peptides (APPs) that are constructed based on the covalent conjugation of an antibacterial peptide and the photosensitizer chlorin e6 (Ce6). Peptide conjugation significantly increases the photo-stability of Ce6, while retaining its ROS generation capability under photo-irradiation. The APPs combine the antibacterial activity of the peptide and the photodynamic therapy of Ce6, and under the assistance of mild laser irradiation, can eradicate bacterial infection and inhibit the formation of bacterial biofilms ex vivo. One of the APPs, (GKRWWKWWRR)2KGGK(Ce6)G, AMP2-Ce6, with Ce6 conjugated with the dimeric peptide, showed exceptional antibacterial activity with an MIC90 value around 3.2 µM without photo-irradiation and <0.1 µM with short light treatment. Supported by a hydrogel matrix composed of gelatin and recombinant human collagen III protein (rhCol III) mimicking the extracellular matrix of skin cells, AMP2-Ce6 efficiently accelerated the healing rate of wounds and improved the quality of wound healing in mice infected with Staphylococcus aureus. Altogether, here we report the development of antibacterial photodynamic peptides, which together with a regenerative matrix material exhibit an added effect against staphylococcal skin infection. This composite material holds promise as a new type of wound dressing material for skin infection and wound healing.


Assuntos
Fotoquimioterapia , Porfirinas , Infecções Cutâneas Estafilocócicas , Animais , Antibacterianos/farmacologia , Camundongos , Peptídeos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico
19.
Cell Death Dis ; 11(9): 758, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934196

RESUMO

Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.


Assuntos
Glioma/metabolismo , Glioma/radioterapia , RNA Longo não Codificante/metabolismo , Ubiquitina Tiolesterase/metabolismo , Autofagia/fisiologia , Neoplasias Encefálicas , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Glioma/genética , Glioma/patologia , Humanos , RNA Longo não Codificante/genética , Tolerância a Radiação , Transfecção , Ubiquitina Tiolesterase/genética
20.
Front Oncol ; 10: 781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733787

RESUMO

Randomized controlled trials have failed to report any survival advantage for WBRT combined with SRS in the management of brain metastases, despite the enhanced local and distant control in comparison to each treatment alone. Literature review have revealed important role of primary histology of the tumor when dealing with brain metastases. NSCLC responds better to combined approach even when there was only single brain metastasis present while breast cancer has registered better survival with SRS alone probably due to better response of primary tumor to advancement in surgical and chemotherapeutic agents. Furthermore, mutation status (EGFR/ALK) in lung cancer and receptor status (ER/PR/HER2) in breast cancer also exhibit diversity in their response to radiotherapy. Radioresistant tumors like renal cell carcinoma and melanoma brain metastases have achieved better results when treated with SRS alone. Secondly, single brain metastasis may benefit from local and distant brain control achieved with combined treatment. These diverse outcomes suggest a primary histology-based analysis of the radiotherapy regimens (WBRT, SRS, or their combination) would more ideally establish the role of radiotherapy in the management of brain metastases. Molecularly targeted therapeutic and immunotherapeutic agents have revealed synergism with radiation therapy particularly SRS in treating cancer patients with brain metastases. Clinical updates in this regard have also been reviewed.

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