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1.
Zhongguo Zhong Yao Za Zhi ; 46(4): 837-844, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645088

RESUMO

In this paper, the molecular mechanism of Spatholobi Caulis in the treatment of non-small cell lung cancer(NSCLC) was studied through network pharmacology and molecular docking analysis. With traditional Chinese medicine(TCM) Spatholobi Caulis as the study object, active ingredients of Spatholobi Caulis and corresponding potential drug targets were obtained from Traditio-nal Chinese Medicine Pharmacology Platform(TCMSP) database; GeneCards database was used to collect cancer-related genes; Cytoscape software was used to build Spatholobi Caulis active ingredient-target-pathway relationship network. DAVID database was used for GO and KEGG enrichment analysis of targets, KEGG signaling pathway was visualized, and compounds were screened out for molecular docking. Finally, in vitro experiments on human lung cancer cells, A549 treated with luteolin and licochalcone A were used to preliminarily verify the core targets and pathways, cell proliferation was detected by CCK-8 method, and expressions of caspase-3 and Bax protein were detected by Western blot. A total of 23 active components and 170 potential drug targets were selected from Spatholobi Caulis, involving 127 pathways in total. Molecular docking results showed that licochalcone A,(Z)-3-(4-hydroxy-3-methoxyphenyl)-N-[2-(4-hydroxy-phenyl) ethyl] acrylamide, consumeclose grain successfully docked with the key target EGFR, and binding energy of the three compounds was less than-5 kcal·mol~(-1). CCK-8 results showed that luteolin, licochalcone A, and Spatholobi Caulis extract had the inhibitory effect on human lung cancer A549 cells. Western blot showed that luteolin, licochalcone A and Spatholobi Caulis extract could induce cell apoptosis by increasing the expressions of pro-apoptotic factors caspase-3 and Bax. In this study, the anti-lung cancer effect of Spatholobi Caulis was studied through network pharmacology and molecular docking, in order to provide ideas for the molecular mechanism of Spatholobi Caulis in the treatment of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular
2.
Curr Oncol ; 28(1): 847-852, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567626

RESUMO

The pandemic of SARS-CoV-2 is a serious global challenge affecting millions of people worldwide. Cancer patients are at risk for infection exposure and serious complications. A prompt diagnosis of SARS-CoV-2 infection is crucial for the timely adoption of isolation measures and the appropriate management of cancer treatments. In lung cancer patients the symptoms of infection 19 may resemble those exhibited by the underlying oncologic condition, possibly leading to diagnostic overlap and delays. Moreover, cancer patients might display a prolonged positivity of nasopharyngeal RT-PCR assays for SARS-CoV-2, causing long interruptions or delay of cancer treatments. However, the association between the positivity of RT-PCR assays and the patient's infectivity remains uncertain. We describe the case of a patient with non-small cell lung cancer, and a severe ab extrinseco compression of the trachea, whose palliative radiotherapy was delayed because of the prolonged positivity of nasopharyngeal swabs for SARS-CoV-2. The patient did not show clinical symptoms suggestive of active infection, but the persistent positivity of RT-PCR assays imposed the continuation of isolation measures and the delay of radiotherapy for over two months. Finally, the negative result of SARS-CoV-2 viral culture allowed us to verify the absence of viral activity and to rule out the infectivity of the patient, who could finally continue her cancer treatment.


Assuntos
/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/virologia , Neoplasias Pulmonares/virologia , /isolamento & purificação , Idoso , Portador Sadio/diagnóstico , Feminino , Humanos , Nasofaringe/virologia , RNA Viral/genética , Tempo para o Tratamento
3.
Medicine (Baltimore) ; 100(4): e24472, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530259

RESUMO

BACKGROUND: Paired related homeobox 1 (PRRX1) and zinc finger E-box binding homeobox 1 (ZEB1) have been observed to play a vital role in the epithelial-mesenchymal transition (EMT) process in different types of cancer. The microvessel density (MVD) is the most common indicator used to quantify angiogenesis. This study aimed to investigate expression of PRRX1 and ZEB1 in non-small cell lung cancer (NSCLC) and to explore associations between these factors and tumor prognosis, EMT markers and angiogenesis. METHODS: Data for a total of 111 surgically resected NSCLC cases from January 2013 to December 2014 were collected. We used an immunohistochemical method to detect expression levels of PRRX1, ZEB1, and E-cadherin, and to assess MVD (marked by CD34 staining). SPSS 26.0 was employed to evaluate the connection between these factors and clinical and histopathological features, overall survival (OS) and tumor angiogenesis. RESULTS: PRRX1 expression was obviously lower in tumor samples than in control samples. Low expression of PRRX1, which was more common in the high-MVD group than in the low-MVD group (P = .009), correlated positively with E-cadherin expression (P < .001). Additionally, we showed that ZEB1 was expressed at higher levels in tumor samples than in normal samples. High expression of ZEB1 was associated negatively with E-cadherin expression (P < .001) and positively associated with high MVD (P = .001). Based on Kaplan-Meier and multivariate survival analyses, we found that PRRX1, ZEB1, E-cadherin and the MVD had predictive value for OS in NSCLC patients. CONCLUSIONS: These findings suggest that PRRX1 and ZEB1 may serve as novel prognostic biomarkers and potential therapeutic targets.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio/metabolismo , Neoplasias Pulmonares/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Homeobox 1 de Ligação a E-box em Dedo de Zinco
7.
Medicine (Baltimore) ; 100(6): e24688, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578601

RESUMO

RATIONALE: The incidence of nonsmall cell lung cancer (NSCLC) is high. Most nonsmall cell lung cancers have undergone multiple metastases at the time of initial diagnosis, and the 5 year survival rate is low. At present, comprehensive treatments, including systemic chemotherapy, targeted therapy, antiangiogenic therapy, and immunotherapy, prolong the survival of patients with advanced NSCLC. Herein, we report a case of NSCLC with long-term survival. PATIENT CONCERNS: A 61-year-old woman complained of dry cough and shortness of breath and visited our hospital in July 2011. Imaging examination revealed a left upper lung mass with multiple metastases to the liver, adrenal gland, and bone. DIAGNOSES: Stage IVB (cT2aN3M1c) lung adenocarcinoma was diagnosed, with multiple metastases of the lymph nodes, liver, adrenal gland, and bone. INTERVENTIONS AND OUTCOMES: The patient received systemic chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor-targeted therapy, and has survived for more than 9 years. LESSONS: The patient benefited from maintenance chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitor treatment and achieved long-term survival.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/secundário , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Quimioterapia de Manutenção/métodos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Sobreviventes , Tomografia Computadorizada por Raios X/métodos
9.
Medicine (Baltimore) ; 100(7): e24748, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607820

RESUMO

BACKGROUND: E-cadherin, a calcium-dependent cell adhesion molecule, as an important mediator of adhesion and signaling pathway, plays a key role in maintaining tissue integrity. However, the association of E-cadherin expression with clinicopathological features and prognostic value in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the purpose of the study is to explore the clinicopathological features and prognostic value of E-cadherin expression in non-small cell lung cancer by meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched to collect the studies about expression of E-cadherin and clinicopathological features and prognosis of non-small cell lung cancer. The last search time was May 2020. Stata 15.0 software was used for statistical analysis. RESULTS: A total of 35 studies were included, of which the results showed that high expression of E-cadherin compared with its low expression, for overall survival, HR = 0.68 (95% CI:0.64-0.73, P < .05); for disease-free survival or progression-free survival, HR = 0.54 (95% CI: 0.44-0.67); low differentiation of lung cancer compared with moderate and high differentiation, OR = 0.40 (95% CI: 0.27-0.58, P < .05); Advanced lung cancer compared with early stage, OR = 0.54 (95% CI: 0.44-0.66, P < .05); lymph node metastasis compared with non-lymph node metastasis, OR = 0.49 (95% CI: 0.31∼0.77). CONCLUSION: Low expression of E-cadherin is closely related to poor prognosis of patients with NSCLC, promoting tumor staging and lymph node metastasis, inhibiting tumor differentiation as well.


Assuntos
Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Medicina Baseada em Evidências/métodos , Humanos , Metástase Linfática/patologia , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias/métodos , Prognóstico , Intervalo Livre de Progressão
10.
Kyobu Geka ; 74(1): 40-47, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33550318

RESUMO

OBJECTIVES: To explore the clinicopathological and surgical characteristics and to determine the prognostic outcome of patients who underwent second pulmonary resection for secondary primary lung cancer(SPLC). PATIENTS: We retrospectively examined 35 patients who underwent second pulmonary resection for secondary primary non-small cell lung cancer from 2009 to 2016. RESULTS: The median age was 67 years and 54% of patients were male. Twenty-one patients were resected for synchronous disease and 14 were resected for metachronous disease. The median interval between first and second surgery was 9.8 months. Six patients underwent lobectomy twice for both lung cancers. Sublober resection was significantly performed at second surgery, and tumor size of SPLC was significantly smaller than that of first cancer. There was no significant difference for pathological stage between first and second cancer:27 patients were diagnosed as stageⅠat first surgery, and 33 were diagnosed as stageⅠat second surgery. The five-year recurrence free survival (RFS) rate was 74.1%, and five-year overall survival (OS) rate was 85.7%. There were no significant survival differences between synchronous and metachronous secondary cancer groups for RFS and OS. Surgical pro cedures and secondary cancer profile (synchronous or metachronous) were not associated with postoperative survival by univariate and multivariate analyses. CONCLUSIONS: Surgical resection for SPLC may be tolerable if lobectomy is required for curative resection.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Idoso , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
Medicine (Baltimore) ; 100(4): e24159, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530206

RESUMO

BACKGROUND: The incidence of non-small cell lung cancer (NSCLC) in Uygur population is gradually increasing recently. In view of the great diagnostic and prognostic values of cell-free DNAs (cfDNA) detection, this study focus on a liquid biopsy to explore the value of cfDNA mutation in healthy and NSCLC patients in 2 ethnicities. METHODS: The concentration and sequencing of cfDNA in NSCLC and healthy subjects was assessed with a standard information analysis procedure, including detection, annotation, and statistical analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to analyze the function of mutant genes and related pathways. Totally, 133 subjects, including 35 Uygur NSCLC patients, 10 Uygur healthy subjects, 63 cases of Han NSCLC patients and 25 Han health control, were admitted to the hospital. RESULTS: There were a lower proportion of adenocarcinoma and higher percentage of smoking rate for Uygur patients. For cfDNA level between NSCLC and healthy subjects, Han patients exhibited sharp increase while there was no statistical difference in Uygur population. In addition, the mutation frequency of cfDNA in Han patients (72.6%) was significantly higher than Uygur patients (45.7%). There were 5 gene mutations only found in Han patients and ABCC11 showed a higher mutation frequency in Uygur population as a common one. Finally, Go and Kyoto Encyclopedia of Genes and Genomes analysis showed apprent functional enrichments and pathway changes between 2 ethnicities. CONCLUSION: There existed distinct distributions of cancer subtypes, smoking proportion, cfDNA level, and mutation patterns between Han and Uygur patients. The results may be a useful tool in NSCLC patients' diagnosis as well as individualized therapy between ethnicities in future.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/etnologia , DNA Tumoral Circulante/sangue , Neoplasias Pulmonares/etnologia , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , China/epidemiologia , Bases de Dados Genéticas , Grupos Étnicos , Feminino , Ontologia Genética , Genótipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fumar/etnologia
12.
Medicine (Baltimore) ; 100(3): e24393, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546082

RESUMO

RATIONALE: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have elicited favorable anti-tumor activity in non-small cell lung cancer especially the lung adenocarcinoma. Interstitial lung disease (ILD) is 1 of the fatal side effects of EGFR-TKIs. However, such type of side effect has not been observed in the follow-up during the treatment of the third-generation EGFR-TKI Almonertinib (also called HS-10296). Here, we first report an Almonertinib-induced ILD in an elderly female patient. PATIENT CONCERNS: A 70-year-old female diagnosed with " lung adenocarcinoma with intracranial metastasis" harboring a mutation of EGFR 19DEL was administrated with Almonertinib 110 mg orally as the first-line treatment. However, she presented with chest tightness, and shortness of breath, accompanying with paroxysmal dry cough 3 months after the initiation of Almonertinib. DIAGNOSES: Extensive relevant examinations did not provide conclusive results and the chest computed tomography showed a diffuse ILD in bilateral pulmonary. INTERVENTIONS: The patient was diagnosed with Almonertinib-induced ILD in the absence of no other potential causes. She discontinued Almonertinib and was treated with oxygen uptaken and methylprednisolone. OUTCOMES: The whole symptoms were eliminated and the chest computed tomography showed ILD got remission after the prescription of methylprednisolone. LESSONS: Almonertinib has potential to cause the rare but severe interstitial lung disease. Clinicians should keep cautious of this when prescribing Almonertinib.


Assuntos
Acrilamidas/efeitos adversos , Compostos de Anilina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptores ErbB/genética , Doenças Pulmonares Intersticiais/etiologia , Acrilamidas/uso terapêutico , Idoso , Compostos de Anilina/uso terapêutico , Feminino , Humanos
13.
Medicine (Baltimore) ; 100(4): e24272, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530215

RESUMO

ABSTRACT: Chemotherapy/chemoradiotherapy are still the fundamental treatment for advanced lung cancers. To reduce side effects and improve life quality, lienal polypeptide (LP) could be used in combine with chemotherapy/chemoradiotherapy. Moreover, LP could regulate immune system and possibly reduce the side effects of chemotherapy drugs.In our study, 1658 lung cancer patients from 10 hospitals were retrospectively analyzed and divided into LP group and non-LP group by whether using LP during their treatment. Kaplan-Meier curves and Log-rank test was used to detect the difference of progression-free survival and overall-survival between the 2 groups. Two-sided P-values of less than .05 indicated statistical significance. All analyses were performed with SAS software (version 9.4 SAS Institute, Cary, NC).Results showed that the number of patients who had progressed diseases in LP group and control group were 532 (64.2%) and 507 (61.2%). Log Rank test showed that median progression-free survival for LP group was 12.1 months and 11.4 months for control group (P = .3478). Statistical analyses revealed significantly difference in overall-survival between LP group and control group (23.6 months vs 18.9 months, P = .0177). The overall adverse effect rates were non-significantly different with 9.9% in the LP group and 9.3% in the non-LP group (P = .6767).In conclusion, our research results indicated that LP used in combination with chemotherapy/chemoradiotherapy was a safe and effective treatment for patients of advanced lung cancer. LP could also reduce the adverse effects of chemotherapy/chemoradiotherapy, thereby improving patients' life qualities, and potentially improving prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/mortalidade , Neoplasias Pulmonares/terapia , Peptídeos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
Medicine (Baltimore) ; 100(4): e24300, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530219

RESUMO

RATIONALE: Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. PATIENT CONCERNS: A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). DIAGNOSES: MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. INTERVENTIONS: Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. OUTCOMES: Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. LESSONS: As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Anilidas/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/genética , Piridinas/administração & dosagem , Adenocarcinoma de Pulmão/genética , Idoso , Quimioterapia Combinada , Transição Epitelial-Mesenquimal/genética , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Mutação , Resultado do Tratamento
15.
Drugs Today (Barc) ; 57(1): 17-25, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33594387

RESUMO

Molecular profiling of non-small cell lung cancer (NSCLC) in the past decade has revealed numerous oncogenic driver events in NSCLC leading to several highly effective therapies. While a promising target, small-molecule inhibition of MET signaling has proven difficult. Capmatinib is a specific inhibitor of MET with Food and Drug Administration (FDA) accelerated approval in 2020 for the treatment of NSCLC harboring MET exon 14 skipping mutations. As a first-line therapy, 68% of patients in phase II clinical trials responded to capmatinib with a median duration of 12.6 months and a manageable safety profile. Although FDA approval is currently limited to MET exon 14 skipping mutations, capmatinib has shown potential in other subsets of MET-dysregulated NSCLC for which ongoing studies are underway. This review covers the preclinical and early clinical data leading to capmatinib's approval, discusses the management of treatment-related toxicities, and offers potential avenues of further research.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Imidazóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas c-met/genética , Triazinas
16.
Medicine (Baltimore) ; 100(5): e24194, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592864

RESUMO

BACKGROUND: The relationship between p53 expression and chemosensitivity of non-small cell lung cancer (NSCLC) is unclear. This study aims to explore the correlation between p53 expression and sensitivity to platinum-based chemotherapy in patients with NSCLC. METHODS: Pubmed, Web of Science, EMBASE, CNKI, China Wanfang databases were searched for studies on the relationship between the p53 expression and the chemosensitivity to platinum drugs in patients with NSCLC. The last search time was May 2020. Stata 15.0 software was used for statistical analysis. RESULTS: A total of 21 studies were included, covering 1387 patients in total. The results showed that the pooled OR = 1.55 (95%CI: 1.05∼2.29, P < .05), for Asian population, the pooled OR = 1.67 (95%CI: 0.95∼3.09, P > .05), for Caucasian population, the pooled OR = 1.34 (95%CI: 0.74∼2.43), there was no significant difference between Asian and Caucasian. The results of subgroup analysis of publication year showed that, the pooled OR = 2.07 (95%CI: 1.39∼3.07, P < .01), the heterogeneity among the studies decreased remarkably after 2005. The subgroup analysis of advanced patients showed that the pooled OR = 1.93 (95%CI: 1.27∼2.93), the difference was statistically significant. CONCLUSION: Patients with p53 negative expression is more sensitive to platinum-based chemotherapy than those with p53 positive expression in NSCLC, especially in advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Compostos de Platina/farmacologia , Proteína Supressora de Tumor p53/genética , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Testes Farmacogenômicos , Resultado do Tratamento
17.
Medicine (Baltimore) ; 100(5): e24292, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592873

RESUMO

RATIONALE: Gefitinib is a first-line palliative chemotherapy drug used to treat advanced non-small-cell lung cancer (NSCLC) in patients who have an epidermal growth factor receptor (EGFR) mutation. However, approximately two-thirds of NSCLC patients with EGFR-tyrosine kinase inhibitor experience dermatological toxicity. Cutaneous toxicity is usually not life threatening but can necessitate modification or discontinuation of medication in severe cases. In this case, despite a reduction in the dose of gefitinib due to side effects, combined treatment with modified Bojungikki-tang (BJKIT) increased progression-free survival (PFS) in an advanced NSCLC patient. PATIENT CONCERNS: An 83-year-old Asian woman presented with chief complaints of chronic cough, dyspnea, weight loss, and anorexia. DIAGNOSES: The patient was diagnosed with stage IV NSCLC (T2aN3M1), adenocarcinoma with metastasis to the lymph node, brain, and bone based on image scan and biopsy. An EGFR deletion was detected in exon 19. INTERVENTIONS: The patient was treated with gefitinib (250 mg/d) and traditional herbal medicine, modified Bojungikki-tang (BJIKT). However, after 1 year of combination therapy, gefitinib was tapered down to once per week while modified BJIKT was maintained. OUTCOMES: A partial response was achieved, but after 3 months severe papulopustular skin rashes developed and became aggravated with time. Thus, the gefitinib dose was reduced. However, the PFS has been maintained for approximately 78 months. LESSONS: Despite the reduction in gefitinib dose due to side effects, the combined treatment of gefitinib and the modified BJIKT has maintained a PFS of over 78 months, indicating that modified BJIKT enhanced the anti-cancer effect of gefitinib in a patient with advanced NSCLC harboring the EFGR mutation, and may have delayed acquired resistance, the main limitation on the efficacy of gefitinib. Further investigations including clinical trials are needed to confirm these effects.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB/genética , Gefitinibe , Neoplasias Pulmonares , Fitoterapia/métodos , Dermatopatias , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Feminino , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Dermatopatias/induzido quimicamente , Dermatopatias/diagnóstico , Dermatopatias/prevenção & controle
18.
Nat Commun ; 12(1): 295, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436560

RESUMO

Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N6-methyladenosine (m6A) modification of circNDUFB2. Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , RNA Circular/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Proteína DEAD-box 58/metabolismo , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Estabilidade Proteica , Proteólise , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
19.
Gan To Kagaku Ryoho ; 48(1): 57-61, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468724

RESUMO

OBJECTIVE: Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs. METHODS: The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group). RESULTS: The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer. CONCLUSION: At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Renais , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Estudos Retrospectivos , Fatores de Risco
20.
JAMA Netw Open ; 4(1): e2034065, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33502482

RESUMO

Importance: The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. Objectives: To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. Design, Setting, and Participants: This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non-small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. Main Outcomes and Measures: Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. Results: For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. Conclusions and Relevance: This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.


Assuntos
Técnicas de Apoio para a Decisão , Modelos Teóricos , Metástase Neoplásica/diagnóstico , Neoplasias/diagnóstico , Tempo para o Tratamento/estatística & dados numéricos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias/terapia , Medição de Risco
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