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1.
JTO Clin Res Rep ; 5(2): 100630, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38361739

RESUMO

MET protooncogene (MET) alterations are known driver oncogenes in NSCLC. Since the identification of MET as a potential therapeutic target, extensive clinical trials have been performed. As a result, MET-targeted therapies, including MET tyrosine kinase inhibitors, monoclonal antibodies, and MET antibody-drug conjugates now play important roles in the standard treatment of MET-altered NSCLC; they have considerably improved the outcomes of patients with tumors that harbor MET oncogenic drivers. Although clinical agents are currently available and numerous other options are in development, particular challenges in the field require attention. For example, the therapeutic efficacy of each drug remains unsatisfactory, and concomitantly, the resistance mechanisms are not fully understood. Thus, there is an urgent need for optimal drug sequencing and combinations, along with a thorough understanding of treatment resistance. In this review, we describe the current landscape of pertinent clinical trials focusing on MET-targeted strategies and discuss future developmental directions in this rapidly expanding field.

2.
Virol J ; 20(1): 288, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049836

RESUMO

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.


Assuntos
Infecções por Vírus Epstein-Barr , Herpes Simples , Infecções por Herpesviridae , Herpesviridae , Herpesvirus Humano 1 , Neoplasias do Colo do Útero , Humanos , Feminino , Herpesvirus Humano 4 , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 2
5.
J Thorac Oncol ; 18(8): 1082-1093, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37085031

RESUMO

INTRODUCTION: To determine the effect of statin use during concurrent chemoradiotherapy (CCRT) on overall survival and esophageal squamous cell carcinoma (ESCC)-specific survival in patients with ESCC receiving standard CCRT. METHODS: In this propensity score-matching cohort study, we used data from the Taiwan Cancer Registry Database and National Health Insurance Research Database to investigate the effects of statin use during the period of CCRT on overall survival and ESCC-specific survival. RESULTS: Statin use during the period of CCRT was found to be a considerable and independent prognostic factor for overall survival and ESCC-specific survival. The adjusted hazard ratio (aHR) for all-cause mortality in the statin group compared with that of the non-statin group was 0.65 (95% confidence interval: 0.51-0.84, p = 0.0009). The aHR for ESCC-specific mortality in the statin group compared with that of the non-statin group was 0.63 (95% confidence interval: 0.47-0.84, p = 0.0016). The use of hydrophilic statins such as rosuvastatin and pravastatin was associated with the greatest survival benefits. A dose-response relationship was also found, with higher cumulative defined daily doses and higher daily intensity of statin use associated with lower mortality. CONCLUSIONS: This study is the first to reveal that statin use during the period of CCRT for ESCC is associated with improvement in overall survival and ESCC-specific survival. In addition, we found that use of rosuvastatin, pravastatin, and simvastatin was associated with better survival outcomes for patients with ESCC receiving CCRT. Furthermore, we found a dose-response relationship of statin use associated with lower ESCC-specific mortality.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Pulmonares , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/terapia , Estudos de Coortes , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pontuação de Propensão , Rosuvastatina Cálcica/uso terapêutico , Pravastatina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quimiorradioterapia/efeitos adversos
6.
Cancer Lett ; 561: 216140, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36948240

RESUMO

Met proto-oncogene exon 14 skipping (METex14) mutations are targetable driver genes in approximately 3% of non-small-cell lung cancers (NSCLCs). Ensartinib, a type Ia MET inhibitor, is a multi-kinase inhibitor that has been approved for ALK-positive NSCLCs. Ensartinib was administered for compassionate use (cohort 1) and in a phase II clinical trial (cohort 2) to patients with METex14 mutant NSCLCs, with ORR as a primary endpoint. Molecular simulation was conducted to evaluate ensartinib c-MET interaction, and cell lines, patient-derived organoids (PDOs), and xenograft models were used to test the effectiveness of ensartinib. Among 29 evaluable patients, the ORR and DCR of ensartinib were 67% and 94% in cohort 1, and 73% and 91% in cohort 2. The median DoR was 6.8 months and median PFS was 6.1 months in the total population. Rash was the most common drug-related adverse event, and peripheral edema of any grade was reported in only 9% patients. Molecular simulations indicated favorable binding of ensartinib to c-MET. The kinase assay demonstrated an IC50 of 7.9 nM of ensartinib against METex14 protein. In vitro, Hs746T (METex14 mutation) and EBC-1 (MET amplification) cells were sensitive to ensartinib, with IC50 values of 31 and 44 nM, respectively. Ensartinib exhibited comparable inhibitory effects on cell migration as crizotinib and tepotinib in both cell types. In vivo, ensartinib suppressed the growth of Hs746T cells. Ensartinib also potently inhibited the viability of PDOs. Overall, Ensartinib exhibited substantial antitumor effects against METex14 mutant NSCLCs in preclinical and clinical trials, with relatively low peripheral edema rates.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Éxons , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , Animais
7.
Biomedicines ; 11(2)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36831114

RESUMO

Esophageal cancer is a common and aggressive cancer, with a five-year survival rate of approximately 20%. Therefore, identifying safe and effective medications that can reduce the risk of esophageal cancer is of great importance. OBJECTIVE: To examine the association between H1-antihistamines (AHs) use and the incidence of esophageal squamous cell carcinoma (ESCC) in a head-to-head propensity score matching (PSM) comparative study. DESIGN: Retrospective cohort study. SETTING: Nationwide population-based study in Taiwan. PARTICIPANTS: 1289,526 adults from the National Health Insurance Research Database from 2008 to 2018. EXPOSURES: AH use. MAIN OUTCOMES AND MEASURES: Incidence rates (IRs), incidence rate ratios (IRRs), and adjusted hazard ratios (aHRs) of ESCC in AH users compared with nonusers. RESULTS: AH users had a significantly higher IR of ESCC than nonusers (1.47 vs. 1.36 per 100,000 person-years). The IRR (95% CI) for ESCC was 1.18 (1.08-1.28) in AH users compared with nonusers. After adjustment for age, sex, income levels, urbanization, cigarettes smoking, alcoholic related diseases, comorbidities, medication use, and Charlson Comorbidity Index scores, the aHR (95% CI) for ESCC was 1.22 (1.12-1.33) in AH users compared with nonusers. A dose-response relationship was also observed, with aHRs for AH use at 28-182, 183-488, 489-1043, and >1043 cumulative defined daily doses (cDDDs) of 1.12, 1.20, 1.25, and 1.37, respectively, compared with <28 cDDDs. CONCLUSIONS AND RELEVANCE: Our study found a significant association between AH use and the increased risk of ESCC, with a dose-response relationship. This study suggests that AH use may increase the risk of ESCC, especially at high doses, and highlights the importance of caution when prescribing AHs.

8.
Nanoscale Adv ; 4(4): 1213-1219, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36131761

RESUMO

Manipulation of artificial molecular rotors/motors is a key issue in the field of molecular nanomachines. Here we assemble non-planar SnPc molecules on an FeO film to form two kinds of rotors with different apparent morphologies, rotational speeds and stabilities. Both kinds of rotors can switch to each other via external field stimulation and the switch depends on the polarity of the applied bias voltage. Furthermore, we reveal that the molecular fragment has a great influence on the motions of molecules. Combining scanning tunneling microscopy and DFT calculations, two braking mechanisms are addressed for molecular rotors. One is the transformation of adsorption configurations under the external electric field stimulus that enables the molecular rotor to stop/restart its rotation. The other is the introduction of embedded molecular fragments that act as a brake pad and can stop the molecular rotation. We find that the rotation can be recovered by separating the molecule from the fragments. Our study suggests a good system for manipulating molecular rotors' properties in nanophysics and has important value for the design of controllable molecular machines.

9.
PLoS Pathog ; 17(12): e1010098, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860863

RESUMO

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.


Assuntos
Vírus da Influenza A Subtipo H9N2/genética , Influenza Aviária/virologia , Influenza Humana/virologia , Vírus Reordenados/genética , Proteínas da Matriz Viral/metabolismo , Zoonoses Virais/virologia , Animais , Galinhas/virologia , Humanos , Vírus da Influenza A/genética , Liberação de Vírus
10.
J Pers Med ; 11(11)2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34834561

RESUMO

Scarce evidence is available in Asia for estimating the long-term risk and prognostic factors of major complications such as re-rupture, vasospasm, or re-stroke for patients with aneurysmal subarachnoid hemorrhage (SAH) undergoing endovascular coil embolization or surgical clipping. This is the first head-to-head propensity score-matched study in an Asian population to demonstrate that endovascular coil embolization for aneurysmal SAH treatment is riskier than surgical clipping in terms of re-rupture, vasospasm, or re-stroke. In addition, the independent poor prognostic factors of vasospasm or re-stroke were endovascular coil embolization, male sex, older age (≥65 years; the risk of vasospasm increases with age), hypertension, congestive heart failure, diabetes, previous transient ischemic attack, or stroke in aneurysmal SAH treatment. BACKGROUND: To estimate the long-term complications and prognostic factors of endovascular coil embolization or surgical clipping for patients with ruptured aneurysmal subarachnoid hemorrhage (SAH). METHODS: We selected patients diagnosed with aneurysmal SAH between 1 January 2011 and 31 December 2017. Propensity score matching was performed, and Cox proportional hazards model curves were used to analyze the risk of re-rupture, vasospasm, and re-stroke in patients undergoing the different treatments. FINDINGS: Multivariate Cox regression analysis revealed that the adjusted hazard ratio (aHR) of re-rupture for endovascular coil embolization compared with surgical clipping was 1.36 (95% confidence interval [CI]: 1.17-1.57; p < 0.0001). The aHRs of the secondary endpoints of vasospasm and re-stroke (delayed cerebral ischemia) for endovascular coil embolization compared with surgical clipping were 1.14 (1.02-1.27; p = 0.0214) and 2.04 (1.83-2.29; p < 0.0001), respectively. The independent poor prognostic factors for vasospasm and re-stroke were endovascular coil embolization, male sex, older age (≥65 years; risk increases with age), hypertension, congestive heart failure, diabetes, and previous transient ischemic attack or stroke. INTERPRETATION: Endovascular coil embolization for aneurysmal SAH carries a higher risk than surgical clipping of both short- and long-term complications including re-rupture, vasospasm, and re-stroke.

11.
Cancers (Basel) ; 13(18)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34572955

RESUMO

PURPOSE: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. METHODS: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I-III colon adenocarcinoma who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into COPD and non-COPD (Group 1 and 2) groups through propensity score matching. RESULTS: In total, 1512 patients were eligible for further comparative analysis between non-COPD (1008 patients) and COPD (504 patients) cohorts. In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality for Group 1 compared with Group 2 was 1.17 (1.03, 1.29). In patients with colon adenocarcinoma undergoing curative resection, the aHRs (95% CIs) for all-cause mortality in patients with hospitalization frequencies of ≥1 and ≥2 times for AECOPD within 1 year before adenocarcinoma diagnosis were 1.08 (1.03, 1.51) and 1.55 (1.15, 2.09), respectively, compared with those without AECOPD. CONCLUSION: In patients with colon adenocarcinoma undergoing curative resection, COPD was associated with worse survival outcomes. Being hospitalized at least once for AECOPD within 1 year before colon adenocarcinoma diagnosis was an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for AECOPD within 1 year before diagnosis was associated with poorer survival. Our study highlights the importance of COPD management, particularly the identification of frequent exacerbators and the prevention of AECOPD before standard colon adenocarcinoma treatments are applied.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34199671

RESUMO

PURPOSE: To estimate long-term medical resource consumption in patients with subarachnoid aneurysmal hemorrhage (SAH) receiving surgical clipping or endovascular coiling. PATIENTS AND METHODS: From Taiwan's National Health Insurance Research Database, we enrolled patients with aneurysmal SAH who received clipping or coiling. After propensity score matching and adjustment for confounders, a generalized linear mixed model was used to determine significant differences in the accumulative hospital stay (days), intensive care unit (ICU) stay, and total medical cost for aneurysmal SAH, as well as possible subsequent surgical complications and recurrence. RESULTS: The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping, respectively) who were eligible for further analysis. The mean accumulative hospital stay significantly differed between coiling (31.2 days) and clipping (46.8 days; p < 0.0001). After the generalized linear model adjustment of gamma distribution with a log link, compared with the surgical clipping procedure, the adjusted odds ratios (aOR; 95% confidence interval [CI]) of the medical cost of accumulative hospital stay for the endovascular coil embolization procedure was 0.63 (0.60, 0.66; p < 0·0001). The mean accumulative ICU stay significantly differed between the coiling and clipping groups (9.4 vs. 14.9 days; p < 0.0001). The aORs (95% CI) of the medical cost of accumulative ICU stay in the endovascular coil embolization group was 0.61 (0.58, 0.64; p < 0.0001). The aOR (95% CI) of the total medical cost of index hospitalization in the endovascular coil embolization group was 0·85 (0.82, 0.87; p < 0.0001). CONCLUSIONS: Medical resource consumption in the coiling group was lower than that in the clipping group.


Assuntos
Aneurisma Intracraniano , Hemorragia Subaracnóidea , Estudos de Coortes , Humanos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos , Pontuação de Propensão , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento
13.
Virology ; 561: 28-35, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34139638

RESUMO

Reassortant Eurasian avian-like (EA) H1N1 virus, possessing 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes, namely G4 genotype, has replaced the G1 genotype EA H1N1 virus (all the genes were of EA origin) and become predominant in swine populations in China. Understanding the pathogenicity of G4 viruses in pigs is of great importance for disease control. Here, we conducted comprehensive analyses of replication and pathogenicity of G4 and G1 EA H1N1 viruses in pigs. G4 virus exhibited enhanced replication, increased duration of virus shedding, and caused more severe respiratory lesions in pigs compared with G1 virus. G4 virus, with viral ribonucleoprotein (vRNP) complex genes of pdm/09 origin, exhibited higher levels of nuclear accumulation and higher polymerase activity, which is essential for improved replication of G4 virus. These findings indicate that G4 virus poses a great threat to both swine industry and public health, and control measures should be urgently implemented.


Assuntos
Vírus da Influenza A Subtipo H1N1/patogenicidade , Infecções por Orthomyxoviridae/veterinária , Vírus Reordenados/patogenicidade , Doenças dos Suínos/virologia , Animais , Núcleo Celular/metabolismo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Pulmão/patologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , RNA Polimerase Dependente de RNA/metabolismo , Vírus Reordenados/genética , Vírus Reordenados/fisiologia , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Suínos , Doenças dos Suínos/patologia , Traqueia/patologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Virulência , Replicação Viral , Eliminação de Partículas Virais
14.
Eur J Neurol ; 28(9): 3012-3021, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34192398

RESUMO

BACKGROUND AND PURPOSE: To determine the long-term survival outcomes of and prognostic factors for survival in patients with a ruptured intracranial aneurysm (RIA) who underwent endovascular coil embolization or surgical clipping. METHODS: We selected patients who had received a diagnosis of RIA between January 1, 2011 and December 31, 2017. Propensity score matching was performed, and Cox proportional hazards model curves were plotted to analyze all-cause mortality in patients undergoing different treatments. RESULTS: The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping groups, respectively) who were eligible for inclusion. In multivariate Cox regression analyses, the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for endovascular coil embolization compared with surgical clipping were 0.87 (95% CI, 0.79-0.97). The aHRs for the ages of 65 to 74, 75 to 84, and ≥85 years compared with the ages of 20 to 64 years were 1.82 (95% CI, 1.60-2.07), 3.35 (95% CI, 2.93-3.84), and 6.99 (95% CI, 5.51-8.86), respectively. Surgical clipping; old age; male sex; treatment during 2011 to 2013; presence of diabetes, congestive heart failure, hypertension, chronic kidney disease, or end-stage renal disease; history of stroke or transient ischemic attack; Charlson Comorbidity Index ≥2; attendance of nonacademic hospitals; and low income were significant independent prognostic factors for poor survival. CONCLUSIONS: Compared with surgical clipping, endovascular coil embolization led to more favorable survival outcomes in patients with RIAs.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Adulto , Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Estudos de Coortes , Humanos , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Resultado do Tratamento , Adulto Jovem
15.
J Biomol Struct Dyn ; 39(10): 3435-3448, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32367770

RESUMO

Two naphthalene-containing compounds, 4-hydroxy-6,7-dimethoxy-1-(4-(trifluoromethyl)phenyl)-2-naphthoic acid (A) and 4-hydroxy-6,7-dimethoxy-1-phenyl-2-naphthoic acid (B), were prepared by several steps. Their bindings to human serum albumin (HSA) were studied by ultraviolet-visible (UV-vis) absorption, fluorescence, synchronous fluorescence, three-dimensional fluorescence, circular dichroism (CD) spectroscopies and molecular docking. The crystal data of these compounds show the structure of the compounds. The results show that the mechanism of the interaction between compound A and HSA is mixed-quenching (both dynamic and static quenching), while that of compound B and HSA is static quenching. The number of binding sites, binding constants and binding distance (r) were obtained. The interaction processes are spontaneous. A mainly interacts with HSA through typical hydrophobic interaction, and B binds to HSA mainly by the hydrogen bonds and van der Waals forces. The conformation of HSA changes slightly after the addition of the compounds. Besides, molecular docking method was used to study the interaction details between the compounds and HSA. This is helpful to understand the absorption and metabolism of these two compounds in the body, and provides a basis for designing naphthalene-containing drugs. Communicated by Ramaswamy H. Sarma.


Assuntos
Naftalenos , Albumina Sérica Humana , Sítios de Ligação , Dicroísmo Circular , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Termodinâmica
16.
Front Oncol ; 11: 760703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004282

RESUMO

BACKGROUND: High PD-L1 expression in non-small cell lung cancer (NSCLC) is evident to predict elevated immunotherapy efficacy, to which NSCLC with onco-driver gene mutations is probed with poor responsiveness. Thus, it is of great interest to investigate how effective immune monotherapy is in the presence of concurrent high PD-L1 expression and driving gene mutation. PATIENTS AND METHODS: We present a case of squamous lung cancer with high PD-L1 expression and HER2 exon 20 insertion (20Ins) who presented hyperprogressive disease (HPD) after being treated with PD-1 inhibitor. RESULTS: A 71-year-old female was diagnosed with advanced squamous lung cancer with 98% tumor proportion score of PD-1 and 20ins. She benefited from first-line docetaxel cisplatin followed by 2 months second-line afatinib. Third-line pembrolizumab monotherapy was then given. Unfortunately, she rapidly progressed with dramatically enlarged primary site as well as mediastinal lymph nodes and pleural effusion only 2 weeks later, presenting severe dyspnea and dysphagia. Re-biopsy was conducted, and we found that compared with the baseline, CD8+ T cells were largely recruited only in tumor stroma but not in tumor parenchyma. Tumor-associated macrophages were notably increased in both tumor stroma and parenchyma. Concomitantly, CD56dim NK cells in tumor parenchyma were decreased. CONCLUSIONS: Application of immune monotherapy in patients with positive driver genes demands extreme caution, even harboring high PD-L1 expression. Abnormality of tumor microenvironment might be critically involved in immune checkpoint inhibitor-induced HPD. Further study in greater depth is required.

17.
Rev. esp. enferm. dig ; 112(10): 797-804, oct. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-201206

RESUMO

BACKGROUND: long noncoding RNAs (lncRNAs) have attracted attention recently. However, many inconsistencies frequently appeared for the early diagnosis of digestive tract cancers (DTCs). We performed this meta-analysis to describe the diagnostic performance of lncRNAs in the discrimination of DTCs. METHODS: data were extracted from PubMed, Web of Science, Embase, and Cochrane Library. Their quality was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Such parameters as sensitivity and specificity were included for pooled analyses. The STATA 12.0 and Meta-Disc 1.4 software packages were used to perform the statistical analysis. RESULTS: sixty-nine papers were included in this meta-analysis. The pooled analysis of DTCs showed that lncRNAs had a sensitivity of 0.78 and a specificity of 0.80. The area under the summary ROC curve (AUC) was 0.86. For gastric cancer (GC), the pooled sensitivity and specificity were 0.77 (95 % CI: 0.72-0.81) and 0.75 (95 % CI: 0.71-0.79), respectively, and the AUC was 0.83. For colorectal cancer (CRC), these three parameters were 0.82 (95 % CI: 0.76-0.86), 0.84 (95 % CI: 0.79-0.88), and 0.90, respectively. For esophageal cancer (EC), sensitivity was 0.74 (95 % CI: 0.67-0.80) and specificity reached 0.86 (95 % CI: 0.72-0.93), with an AUC of 0.82. CONCLUSIONS: LncRNAs show potential diagnostic value for discrimination between DTCs


No disponible


Assuntos
Humanos , RNA Longo não Codificante , Biomarcadores Tumorais , Neoplasias Gastrointestinais/diagnóstico , RNA Longo não Codificante/genética , Diagnóstico Precoce , Trato Gastrointestinal/patologia , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Sensibilidade e Especificidade
18.
J Sci Food Agric ; 100(12): 4612-4617, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32418235

RESUMO

BACKGROUND: Irradiation can cause lipid oxidation of fish. This study aimed to examine the effect of radiation (method, dose and dose rate) on the acid value (AV), peroxide value (PV), thiobarbituric acid reactive substances (TBARS) content and fatty acid profile of fresh and freeze-dried largemouth bass flesh. RESULTS: AV, PV and TBARS presented a dose-dependent increase in fish meat for both cobalt-60 (60 Co) and electron beam (EB) irradiation. With a 6 kGy dose of radiation, all measured indices in the 60 Co group were significantly higher than those in the EB group (P < 0.05 or P < 0.01). With a 3 kGy dose of radiation, AV, PV and TBARS in the 200 Gy min-1 dose rate group were significantly lower than those in the 2 and 80 Gy min-1 groups (P < 0.05). After 60 Co irradiation, AV, PV and TBARS in most fresh samples were significantly higher than those in freeze-dried samples (P < 0.01). And 60 Co irradiation decreased the unsaturated fatty acid (UFA) content in fresh samples and increased the UFA content in freeze-dried samples. Our study indicated that 60 Co irradiation, particularly at a low dose rate, accelerated lipid oxidation in fish meat. A large amount of muscle moisture enhances the amount of UFA loss in fish meat during 60 Co irradiation. CONCLUSIONS: A low dose (3 kGy) of EB irradiation, a high dose rate (200 Gy min-1 ) of 60 Co irradiation or freeze-drying treatment can alleviate the lipid oxidation of largemouth bass meat. © 2020 Society of Chemical Industry.


Assuntos
Radioisótopos de Cobalto/química , Irradiação de Alimentos/métodos , Lipídeos/química , Carne/efeitos da radiação , Animais , Bass , Ácidos Graxos Insaturados/química , Carne/análise , Oxirredução
19.
Rev Esp Enferm Dig ; 112(10): 797-804, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32338027

RESUMO

BACKGROUND: long noncoding RNAs (lncRNAs) have attracted attention recently. However, many inconsistencies frequently appeared for the early diagnosis of digestive tract cancers (DTCs). We performed this meta-analysis to describe the diagnostic performance of lncRNAs in the discrimination of DTCs. METHODS: data were extracted from PubMed, Web of Science, Embase, and Cochrane Library. Their quality was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Such parameters as sensitivity and specificity were included for pooled analyses. The STATA 12.0 and Meta-Disc 1.4 software packages were used to perform the statistical analysis. RESULTS: sixty-nine papers were included in this meta-analysis. The pooled analysis of DTCs showed that lncRNAs had a sensitivity of 0.78 and a specificity of 0.80. The area under the summary ROC curve (AUC) was 0.86. For gastric cancer (GC), the pooled sensitivity and specificity were 0.77 (95 % CI: 0.72-0.81) and 0.75 (95 % CI: 0.71-0.79), respectively, and the AUC was 0.83. For colorectal cancer (CRC), these three parameters were 0.82 (95 % CI: 0.76-0.86), 0.84 (95 % CI: 0.79-0.88), and 0.90, respectively. For esophageal cancer (EC) sensitivity was 0.74 (95 % CI: 0.67-0.80) and specificity reached 0.86 (95 % CI: 0.72-0.93), with an AUC of 0.82. CONCLUSIONS: LncRNAs show potential diagnostic value for discrimination between DTCs.


Assuntos
Neoplasias Gastrointestinais , RNA Longo não Codificante , Biomarcadores Tumorais , Detecção Precoce de Câncer , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/genética , Humanos , RNA Longo não Codificante/genética
20.
RSC Adv ; 10(16): 9476-9485, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35497211

RESUMO

Three couples of coordination polymers (CPs), namely, [Co((R/S)-Hcna)2] n (1-D/L), [Cd6((1R,2R/1S,2S)-cpba)4(phen)6(H2O)3] n (2-D/L) and [Cd2((1R,2R/1S,2S)-Hcpba)2(phen)2] n (3-D/L) {(R/S)-H2cna = (R/S)-6-(1-carboxyethoxy)-2-naphthoic acid, (1R,2R/1S,2S)-H3cpba = (1R,2R/1S,2S)-2,2'-((5-carboxy-1,3-phenylene)bis(oxy))dipropionic acid, phen = 1,10-phenanthroline} are successfully synthesized under hydrothermal conditions. Structural analysis shows that CP 1 has a 3D 3,6-c net structure with a point symbol of (4·62)2(42·610·83). CPs 2 and 3 are obtained under very similar reaction conditions except using different solvent ratios. The presence of the planar chelating ligand phen in CPs 2 and 3 limited the spatial growth of the structure, resulting in the formation of different 1D structures. All CPs crystallized in the chiral space group P21, CPs 1-3 are all SHG active. Their luminescence sensing activities for organics such as antibiotics, pesticides and nitro aromatics are also investigated. The results showed that CP 1 can effectively identify trace amounts of nitrofurans (NFs) and CP 3 has obvious recognition ability toward nitrofurans (NFs) and nitroimidazoles (NMs). Both CPs 1 and 3 could selectively detect 2,6-dichloro-4-nitroaniline (DCN). The luminescence of CPs 1 and 3 can also be quenched by (D/L)-4-nitrophenylalanine ((D/L)-NPA) and (1R,2R/1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol ((1R,2R/1S,2S)-ANPO).

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