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1.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273091

RESUMO

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.


Assuntos
Fator 88 de Diferenciação Mieloide , NF-kappa B , Vírus da Raiva , Transdução de Sinais , Receptor 7 Toll-Like , Receptor 7 Toll-Like/metabolismo , Animais , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Vírus da Raiva/patogenicidade , Vírus da Raiva/imunologia , Camundongos , NF-kappa B/metabolismo , Linhagem Celular , Interleucina-6/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL2/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Raiva/virologia , Raiva/metabolismo , Raiva/imunologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Inflamação/metabolismo
2.
J Cancer Res Ther ; 20(4): 1109-1123, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39206972

RESUMO

ABSTRACT: This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.


Assuntos
Consenso , Neoplasias Pulmonares , Humanos , Diagnóstico Diferencial , Gerenciamento Clínico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/terapia , Estadiamento de Neoplasias/normas , Guias de Prática Clínica como Assunto
3.
Heliyon ; 10(11): e32288, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38912485

RESUMO

Liver cancer is a heterogeneous disease characterized by poor responses to standard therapies and therefore unfavourable clinical outcomes. Understanding the characteristics of liver cancer and developing novel therapeutic strategies are imperative. Ferroptosis, a type of programmed cell death induced by lipid peroxidation, has emerged as a potential target for treatment. Naringenin, a natural compound that modulates lipid metabolism by targeting AMPK, shows promise in enhancing the efficacy of ferroptosis inducers. In this study, we utilized liver cancer cell lines and xenograft mice to explore the synergistic effects of naringenin in combination with ferroptosis inducers, examining both phenotypic outcomes and molecular mechanisms. Our study results indicate that the use of naringenin at non-toxic doses to hepatocytes can significantly enhance the anticancer effects of ferroptosis inducers (erastin, RSL3, and sorafenib). The combination index method confirmed a synergistic effect between naringenin and ferroptosis inducers. In comparison to naringenin or ferroptosis inducers alone, the combined therapy caused more robust lipid peroxidation and hence more severe ferroptotic damage to cancer cells. The inhibition of aerobic glycolysis mediated by the AMPK-PGC1α signalling axis is the key to naringenin's effect on reducing ferroptosis resistance in liver cancer, and the synergistic cytotoxic effect of naringenin and ferroptosis inducers on cancer cells was reversed after pretreatment with an AMPK inhibitor or a PGC1α inhibitor. Taken together, these findings suggest that naringenin could boost cancer cell sensitivity to ferroptosis inducers, which has potential clinical translational value.

4.
Chest ; 165(6): e163-e167, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38852972

RESUMO

This novel report presents the first known case, to our knowledge, of a 16-year-old male patient who experienced intraventricular thrombosis and pulmonary embolism after a Nuss procedure for pectus excavatum, attributed to chronic bar displacement. Two years after the operation, the patient experienced post-exercise cough and hemoptysis, which led to his admission. Imaging revealed pulmonary embolism, thrombosis in the right ventricular outflow tract, and lung infiltrative lesions. We hypothesize that the chronic bar displacement led to its embedment in the right ventricle, resulting in thrombus formation, which subsequently contributed to partial pulmonary embolism. Surgery revealed the bars' intrusion into the right ventricle and lung. This case highlights the risk of severe complications from bar displacement in the Nuss procedure, which necessitates long-term follow-up evaluation, caution against strenuous activities after surgery, and use of thoracoscopic guidance during bar implantation and removal. It underscores the importance of vigilant evaluation for late-stage complications in patients with respiratory distress or thrombosis after a Nuss procedure.


Assuntos
Tórax em Funil , Embolia Pulmonar , Trombose , Humanos , Embolia Pulmonar/etiologia , Embolia Pulmonar/diagnóstico , Masculino , Adolescente , Tórax em Funil/cirurgia , Trombose/etiologia , Trombose/diagnóstico por imagem , Trombose/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Tomografia Computadorizada por Raios X
5.
BMC Cancer ; 24(1): 755, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907210

RESUMO

BACKGROUND: The role of hemoglobin (HGB) in common malignant tumors remains unclear. METHODS: A retrospective analysis was conducted to identify the correlation between HGB levels and risk of 15 malignant tumors using 50,085 samples from the National Health and Nutrition Examination Survey. Mendelian Randomization analyses (MRAs) were performed based on genome-wide association study data to assess the causal relationship between HGB levels and these malignant tumors using more than 700,000 samples. The robustness of the MRA results was confirmed through various analytical methods. Fifty-six in-house samples were used to investigate the correlation between HGB levels and the prognosis in prostate cancer (PRCA) using the Kaplan-Meier curve. RESULTS: High HGB levels were associated with a higher risk for patients with cervix cancer, melanoma, and non-melanoma skin cancer (OR > 1.000, p < 0.05). It served as a protective factor for colon cancer, esophagus cancer, stomach cancer, bone cancer, lung cancer, renal cancer, and PRCA (OR < 1.000, p < 0.05). Furthermore, MRAs suggested that elevated HGB levels were correlated with a reduced risk of PRCA (OR = 0.869, p < 0.05), with no significant association observed between this marker and the remaining 14 malignant tumors. No pleiotropy or heterogeneity was found in the ultimate results for MRAs (p-values > 0.05), suggesting the robustness of the results. The results derived from the in-house data revealed a relationship between higher HGB values and a more favorable prognosis in PRCA (p < 0.05). CONCLUSION: High circulating HGB levels may play a protective prognostic role for PRCA and serve as a protective factor against the occurrence of PRCA.


Assuntos
Hemoglobinas , Neoplasias , Humanos , Estudos Retrospectivos , Masculino , Feminino , Hemoglobinas/análise , Neoplasias/epidemiologia , Neoplasias/sangue , Neoplasias/genética , Estudo de Associação Genômica Ampla , Prognóstico , Pessoa de Meia-Idade , Análise da Randomização Mendeliana , Fatores de Risco , Inquéritos Nutricionais , Adulto , Idoso , Biomarcadores Tumorais/sangue
6.
Health Aff Sch ; 2(1): qxad083, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38756397

RESUMO

Having health insurance coverage is a strong determinant of cancer care access and survival in the United States. The expansion of Medicaid income eligibility under the Affordable Care Act has increased insurance coverage for working-age adults. Using data from the Cancer Incidence in North America (CiNA) in 2010-2019, we identified 6 432 117 incident cancer cases with known insurance status diagnosed at age 18-64 years from population-based registries of 49 states. Considerable variation in Medicaid coverage and uninsured rate exists across states, especially by Medicaid expansion status. Among expansion states, Medicaid coverage increased from 14.1% in 2010 to 19.9% in 2019, while the Medicaid coverage rate remained lower (range = 11.7% - 12.7%) in non-expansion states. The uninsured rate decreased from 4.9% to 2.1% in expansion states, while in non-expansion states, the uninsured rate decreased slightly from 9.5% to 8.1%. In 2019, 111 393 cancer cases (16.9%) had Medicaid coverage at diagnosis (range = 7.6%-37.9% across states), and 48 357 (4.4%) were uninsured (range = 0.5%-13.2%). These estimates suggest that many patients with cancer may face challenges with care access and continuity, especially following the unwinding of COVID-19 pandemic protections for Medicaid coverage. State cancer prevention and control efforts are needed to mitigate cancer care disparities among vulnerable populations.

7.
J Cancer Res Ther ; 20(2): 651-657, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687936

RESUMO

BACKGROUND: The feasibility and safety of enhanced recovery after surgery (ERAS) for percutaneous computed tomography (CT)-guided microwave ablation (MWA) for treating lung nodules remain unclear. METHODS AND MATERIALS: A total of 409 patients with lung tumors treated at the Department of Thoracic Surgery, First Affiliated Hospital of Guangxi Medical University from August 2020 to May 2023 were enrolled. Perioperative data, including baseline characteristics, operation time, postoperative pain score (visual analog scale [VAS]), hospitalization expenses, postoperative complications, total hospital stay, and patient satisfaction, were observed and recorded. RESULTS: No perioperative mortality occurred in either group and complete ablation was achieved in all patients. Patients in the ERAS group had significantly shorter hospital stays (P < 0.001), reduced operation times (P = 0.047), lower hospitalization expenses (P < 0.001), lower VAS scores (P < 0.001), and fewer complications (P = 0.047) compared with the traditional group. CONCLUSIONS: ERAS for percutaneous CT-guided MWA (ERAA) is safe, effective, and feasible for the treatment of lung nodules.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Neoplasias Pulmonares , Micro-Ondas , Tomografia Computadorizada por Raios X , Humanos , Masculino , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Feminino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Idoso , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Tempo de Internação/estatística & dados numéricos , Cirurgia Assistida por Computador/métodos , Resultado do Tratamento , Ablação por Radiofrequência/métodos , Ablação por Radiofrequência/efeitos adversos , Adulto , Estudos de Viabilidade , Duração da Cirurgia
8.
J Cancer Res Ther ; 20(2): 684-694, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687941

RESUMO

OBJECTIVES: Gypenoside (Gyp) is easily degraded in the gastrointestinal tract, resulting in its low bioavailability. We aimed to develop a tumor-targeted Gyp nanodrug delivery system and to investigate its antitumor effect in vitro. MATERIALS AND METHODS: We used Gyp as the therapeutic drug molecule, mesoporous silica (MSN) and liposome (Lipo) as the drug carrier and protective layers, and aptamer SYL3C as the targeting element to establish a tumor-targeted nanodrug delivery system (i.e., SYL3C-Lipo@Gyp-MSN). The characteristics of SYL3C-Lipo@Gyp-MSN were investigated, and its drug release performance, cell uptake, and antitumor activity in vitro were evaluated. RESULTS: A tumor-targeted Gyp nanodrug delivery system was successfully prepared. The SYL3C-Lipo@Gyp-MSN was spherical or ellipsoidal; had good dispersion, which enabled it to specifically target and kill the liver tumor cell HepG2; and effectively protected the early leakage of Gyp. CONCLUSIONS: We have established a tumor-targeted nanodrug delivery system that can target and kill liver cancer cells and may provide a strategy for preparing new nanodrug-loaded preparations of traditional Chinese medicine.


Assuntos
Gynostemma , Lipossomos , Humanos , Gynostemma/química , Lipossomos/química , Células Hep G2 , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Dióxido de Silício/química , Liberação Controlada de Fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Nanopartículas/química , Nanopartículas/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem
9.
J Natl Cancer Inst ; 116(7): 1169-1172, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38400782

RESUMO

The experiences of cancer survivors with the COVID-19 pandemic in the United States during 2021 and 2022, when vaccinations became widely available, are largely undocumented. Using nationally representative survey data in 2021 and 2022, we found that compared with adults without a cancer history, cancer survivors were more likely to have at least 2 COVID-19 vaccines (2021: 66.6% vs 62.3%, P = .003; 2022: 77.0% vs 72.4%, P < .001) and as likely to have a COVID-19 infection history (2021: 14.1% vs 14.2%, P = .93; 2022: 39.9% vs 39.3%, P = .55) but, once infected, were more likely to develop moderate to severe symptoms (2021: 62.5% vs 54.2%, P = .02; 54.5% vs 61.3%; P = .13). Among cancer survivors, younger age, lower educational attainment, lack of health insurance, and more comorbidities were statistically significantly associated with lower vaccination rates (P < .001). Among infected cancer survivors, being female and younger were associated with higher likelihood of developing moderate to severe symptoms (P < .001). Our findings suggest tailored efforts to prevent and control COVID-19 infections for cancer survivors.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Sobreviventes de Câncer , SARS-CoV-2 , Vacinação , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Sobreviventes de Câncer/estatística & dados numéricos , Estados Unidos/epidemiologia , Feminino , Masculino , Vacinas contra COVID-19/administração & dosagem , Pessoa de Meia-Idade , Idoso , Adulto , SARS-CoV-2/imunologia , Vacinação/estatística & dados numéricos , Neoplasias/epidemiologia , Adulto Jovem , Comorbidade
10.
Clin Lung Cancer ; 25(1): e1-e4, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37880076

RESUMO

BACKGROUND: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy. PATIENTS AND METHODS: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled. CONCLUSIONS: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT05457049 (CTONG 2201).


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasia Residual/tratamento farmacológico , Estudos Prospectivos
11.
J Cancer Res Ther ; 19(6): 1533-1543, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38156919

RESUMO

BACKGROUND: Lymph node metastasis (LNM) is an essential factor affecting the prognosis of patients with lung squamous cell carcinoma (LUSC), as well as a critical consideration for the choice of treatment strategy. Exploring effective methods for predicting LNM in LUSC may benefit clinical decision making. MATERIALS AND METHODS: We used data collected from the Surveillance, Epidemiology, and End Results (SEER) database to develop machine learning algorithm classifiers, including boosted trees (BTs), based on the primary clinical parameters of patients to predict LNM in LUSC. Training on a large-sample training cohort (n = 8,063) allowed for the construction of several concise classifiers for LNM prediction in LUSC, which were then validated using test and in-house cohorts (n = 2,017 and 57, respectively). RESULTS: The six classifiers established in this research enabled distinction between patients with and without LNM. Among these classifiers, the BT classifier was the top performer, with accuracy, F1 scores, precision, recall, sensitivity, and specificity values of 0.654, 0.621, 0.654, 0.592, 0.592, and 0.711, respectively. The precision recall (PR) and receiver operating characteristic (ROC) (with area under the curve = 0.714) curves also supported this result, which was validated by the in-house cohort. Notably, the tumor stage was a critical factor in determining LNM in patients with LUSC. CONCLUSIONS: The use of classifiers, especially the BT classifier, may serve as a useful tool for improving clinical precision and individualized treatment of patients with LUSC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Metástase Linfática/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Aprendizado de Máquina , Algoritmos , Pulmão/patologia , Linfonodos/patologia
12.
Lancet Oncol ; 24(8): 855-867, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37541271

RESUMO

BACKGROUND: The emergence of COVID-19 disrupted health care, with consequences for cancer diagnoses and outcomes, especially for early stage diagnoses, which generally have favourable prognoses. We aimed to examine nationwide changes in adult cancer diagnoses and stage distribution during the first year of the COVID-19 pandemic by cancer type and key sociodemographic factors in the USA. METHODS: In this cross-sectional study, adults (aged ≥18 years) newly diagnosed with a first primary malignant cancer between Jan 1, 2018, and Dec 31, 2020, were identified from the US National Cancer Database. We included individuals across 50 US states and the District of Columbia who were treated in hospitals that were Commission on Cancer-accredited during the study period. Individuals whose cancer stage was 0 (except for bladder cancer), occult, or without an applicable American Joint Committee on Cancer staging scheme were excluded. Our primary outcomes were the change in the number and the change in the stage distribution of new cancer diagnoses between 2019 (Jan 1 to Dec 31) and 2020 (Jan 1 to Dec 31). Monthly counts and stage distributions were calculated for all cancers combined and for major cancer types. We also calculated annual change in stage distribution from 2019 to 2020 and adjusted odds ratios (aORs) using multivariable logistic regression, adjusted for age group, sex, race and ethnicity, health insurance status, comorbidity score, US state, zip code-level social deprivation index, and county-level age-adjusted COVID-19 mortality in 2020. Separate models were stratified by sociodemographic and clinical factors. FINDINGS: We identified 2 404 050 adults who were newly diagnosed with cancer during the study period (830 528 in 2018, 849 290 in 2019, and 724 232 in 2020). Mean age was 63·5 years (SD 13·5) and 1 287 049 (53·5%) individuals were women, 1 117 001 (46·5%) were men, and 1 814 082 (75·5%) were non-Hispanic White. The monthly number of new cancer diagnoses (all stages) decreased substantially after the start of the COVID-19 pandemic in March, 2020, although monthly counts returned to near pre-pandemic levels by the end of 2020. The decrease in diagnoses was largest for stage I disease, leading to lower odds of being diagnosed with stage I disease in 2020 than in 2019 (aOR 0·946 [95% CI 0·939-0·952] for stage I vs stage II-IV); whereas, the odds of being diagnosed with stage IV disease were higher in 2020 than in 2019 (1·074 [1·066-1·083] for stage IV vs stage I-III). This pattern was observed in most cancer types and sociodemographic groups, although was most prominent among Hispanic individuals (0·922 [0·899-0·946] for stage I; 1·110 [1·077-1·144] for stage IV), Asian American and Pacific Islander individuals (0·924 [0·892-0·956] for stage I; 1·096 [1·052-1·142] for stage IV), uninsured individuals (0·917 [0·875-0·961] for stage I; 1·102 [1·055-1·152] for stage IV), Medicare-insured adults younger than 65 years (0·909 [0·882-0·937] for stage I; 1·105 [1·068-1·144] for stage IV), and individuals living in the most socioeconomically deprived areas (0·931 [0·917-0·946] for stage I; 1·106 [1·087-1·125] for stage IV). INTERPRETATION: Substantial cancer underdiagnosis and decreases in the proportion of early stage diagnoses occurred during 2020 in the USA, particularly among medically underserved individuals. Monitoring the long-term effects of the pandemic on morbidity, survival, and mortality is warranted. FUNDING: None.


Assuntos
COVID-19 , Neoplasias , Adulto , Masculino , Humanos , Idoso , Feminino , Estados Unidos/epidemiologia , Adolescente , Pessoa de Meia-Idade , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Medicare , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/patologia
13.
NPJ Vaccines ; 8(1): 76, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231060

RESUMO

Pseudomonas aeruginosa (PA) is a leading cause of hospital-acquired and ventilator-associated pneumonia. The multidrug-resistance (MDR) rate of PA is increasing making the management of PA a global challenge. Messenger RNA (mRNA) vaccines represent the most promising alternative to conventional vaccines and are widely studied for viral infection and cancer immunotherapy while rarely studied for bacterial infections. In this study, two mRNA vaccines encoding PcrV- the key component of the type III secretion system in Pseudomonas and the fusion protein OprF-I comprising outer membrane proteins OprF and OprI were constructed. The mice were immunized with either one of these mRNA vaccines or with the combination of both. Additionally, mice were vaccinated with PcrV, OprF, or the combination of these two proteins. Immunization with either mRNA-PcrV or mRNA-OprF-I elicited a Th1/Th2 mixed or slighted Th1-biased immune response, conferred broad protection, and reduced bacterial burden and inflammation in burn and systemic infection models. mRNA-PcrV induced significantly stronger antigen-specific humoral and cellular immune responses and higher survival rate compared with the OprF-I after challenging with all the PA strains tested. The combined mRNA vaccine demonstrated the best survival rate. Moreover, the mRNA vaccines showed the superiority over protein vaccines. These results suggest that mRNA-PcrV as well as the mixture of mRNA-PcrV and mRNA-OprF-I are promising vaccine candidates for the prevention of PA infection.

14.
Signal Transduct Target Ther ; 6(1): 411, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34857736

RESUMO

Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.


Assuntos
Sistemas CRISPR-Cas , Mutação INDEL , Neoplasias Hepáticas , PTEN Fosfo-Hidrolase , Proteína Supressora de Tumor p53 , Animais , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Macaca fascicularis , Masculino , Metástase Neoplásica , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
J Cancer Res Ther ; 17(5): 1141-1156, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34850761

RESUMO

The Expert Consensus reviews current literatures and provides clinical practice guidelines for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The main contents include the following: (1) clinical evaluation of GGN; (2) procedures, indications, contraindications, outcomes evaluation, and related complications of thermal ablation for GGN; and (3) future development directions.


Assuntos
Hipertermia Induzida/métodos , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/cirurgia , Lesões Pré-Cancerosas/cirurgia , Nódulo Pulmonar Solitário/cirurgia , Consenso , Prova Pericial , Humanos
16.
Zhongguo Fei Ai Za Zhi ; 24(5): 305-322, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-33896152

RESUMO

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
.


Assuntos
Neoplasias Pulmonares/cirurgia , Nódulo Pulmonar Solitário/cirurgia , Técnicas de Ablação , Tomografia Computadorizada Quadridimensional , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem
17.
Front Cell Dev Biol ; 9: 783527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35127707

RESUMO

mRNA vaccines have become a promising alternative to conventional cancer immunotherapy approaches. However, its application on colorectal cancer (CRC) remains poorly understood. We herein identified potential antigens for designing an effective mRNA vaccine, further to build an immune landscape for the accurate selection of patients for mRNA vaccine therapy. Raw transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were retrieved. Consensus clustering algorithm was applied to divide the CRC samples into four immune subtypes. Immunogenomics analysis was further integrated to characterize the immune microenvironment of each immune subtype. Six tumor antigens were found to be associated with poor prognosis and infiltration of antigen-presenting cells (APCs) in CRC patients. Furthermore, each of the immune subtypes showed differential cellular and molecular features. The IS2 and IS4 exhibited significantly improved survival and higher immune cell infiltration compared with IS1 and IS3. Immune checkpoint molecules and human leukocyte antigen also showed significant differential expression in four immune subtypes. Moreover, we performed graph structure learning-based dimensionality reduction to visualize the immune landscape of CRC. Our results revealed a complex immune landscape that may provide directions for mRNA vaccine treatment of CRC and define appropriate vaccination patients.

18.
Pak J Pharm Sci ; 33(1(Special)): 499-504, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32173649

RESUMO

The purpose was to investigate the efficacy and safety of Osimertinib in the treatment of advanced non-small cell lung cancer and to analyze its effects on the expression of serum matrix metalloproteinase-7 (MMP-7) and matrix metallo-proteinase-9 (MMP-9). Eighty patients were equally divided into observation and control group. The observation group was given Osimertinib combined with conventional chemotherapy and the other was treated with conventional chemotherapy alone. The short-term efficacy, the levels of serum MMP-7, MMP-9 and adverse reactions were compared. The effectiveness and clinical benefit rate of the observation group were 62.50% and 92.50% respectively, significantly higher than the control group. There was no significant difference in MMP-7 and MMP-9 before treatment however there was a significant difference after treatment, and the serum MMP-7 & MMP-9 levels showed a trend of increasing with decreasing efficacy. After treatment, comparing with control group, serum MMP-7 and MMP-9 levels were significantly lower, the Karnofsky score was significantly higher, and the improvement effect of the quality of life was statistically significant. Besides, the incidence of leukopenia, thrombocytopenia, anemia and gastrointestinal symptoms were significantly lower. In the treatment of patients with advanced non-small cell lung cancer, Osimertinib significantly reduced the expression of serum MMP-7, MMP-9, improved the clinical benefit and quality of life of patients. The clinical efficacy was significant with a high safety.


Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Metaloproteinase 7 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Acrilamidas/efeitos adversos , Idoso , Compostos de Anilina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/psicologia , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/psicologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
19.
Nanoscale Res Lett ; 14(1): 390, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872318

RESUMO

How to deliver chemotherapeutic drugs efficiently and selectively to tumor cells to improve therapeutic efficacy remains a difficult problem. We herein construct an efficient cell-targeting drug delivery system (Sgc8-MSN/Dox) based on aptamer-modified mesoporous silica nanoparticles that relies on the tumor-targeting ability of the aptamer Sgc8 to deliver doxorubicin (Dox) to leukemia cells in a targeted way, thereby improving therapeutic efficacy and reducing toxicity. In this work, Sgc8-MSN/Dox showed sustained Dox release, and they targeted and efficiently killed CCRF-CEM human acute T lymphocyte leukemia cells, suggesting potential as a cancer therapy.

20.
World J Gastroenterol ; 25(26): 3359-3369, 2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31341361

RESUMO

Aptamers are a class of single oligonucleotide molecules (DNA or RNA) that are screened from random DNA or RNA oligonucleotide chain libraries by the systemic evolution of ligands by exponential enrichment technology. The selected aptamers are capable of specifically binding to different targeting molecules, which is achieved by the three-dimensional structure of aptamers. Aptamers are similar in function to monoclonal antibodies, and therefore, they are also referred to as "chemical antibodies". Due to their high affinity and specificity and low immunogenicity, aptamers are topics of intense interest in today's biological targeting research especially in tumor research. They not only have high potential for clinical advances in tumor targeting detection but also are highly promising as targeted tumor drug carriers for use in tumor therapy. Various experimental studies have shown that aptamer-based diagnostic and therapeutic methods for liver cancer have great potential for application. This paper summarizes the structure, characteristics, and screening methods of aptamers and reviews the recent research progress on nucleic acid aptamers in the targeted diagnosis and treatment of liver cancer.


Assuntos
Aptâmeros de Nucleotídeos/química , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Animais , Antineoplásicos/administração & dosagem , Aptâmeros de Nucleotídeos/administração & dosagem , Modelos Animais de Doenças , Portadores de Fármacos/química , Humanos , Microscopia Intravital/métodos , Ligantes , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Microscopia de Fluorescência/métodos , Sondas Moleculares/administração & dosagem , Sondas Moleculares/química , Estrutura Molecular , Sensibilidade e Especificidade
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