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1.
Medicine (Baltimore) ; 100(35): e27121, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477154

RESUMO

BACKGROUND: This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer. METHODS: Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I2 and P-value. RESULTS: Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71-0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71-0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66-2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53-4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21-3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97-1.77, P = .02) were observed between the 2 groups. CONCLUSION: Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Pulmonares/mortalidade
2.
Medicine (Baltimore) ; 100(35): e27138, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477165

RESUMO

RATIONALE: The emergence of immune checkpoint inhibitors has brought new breakthroughs in the treatment of small cell lung cancer (SCLC). Programmed cell death-ligand 1 inhibitors combined with chemotherapy have been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). However, programmed death 1 inhibitors have limited efficacy in the treatment of SCLC. The reason may be related to the abnormal vascular state in the tumor microenvironment. PATIENT CONCERNS: A 55-year-old male patient, presenting cough and sputum for 1 month. DIAGNOSES: The patient was clinically diagnosed with SCLC and staged as ES-SCLC. INTERVENTIONS: Etoposide combined with lobaplatin treatment every 3 weeks for 4 cycles, evaluate as progressive disease. On the basis of the original plan, combined with camrelizumab for 2 cycles, evaluation as progressive disease. Then, the patient was treated with intravenous infusion of camrelizumab plus oral anlotinib. After 4 cycles, evaluation as partial response. Then we continued to use camrelizumab combined with anlotinib treatment for the patient. At the end of 26 cycles, the chest computed tomography examination revealed that the patient had achieved complete remission. OUTCOMES: After treated with carrelizumab combined with anlotinib for 26 cycles, the curative effect was evaluated as complete remission, progression-free survival was 24 months and there was no immune-related adverse reaction during treatment period. Besides, the patient developed complicated hand-foot syndrome, but this symptom was significantly relieved after reducing the dosage of anlotinib. LESSONS: In this case, antiangiogenesis combined with programmed death 1 inhibitors significantly inhibited tumor progression. It also indicated that anlotinib concurrent carrelizumab may be a superior choice for ES-SCLC. Further clinical trials required to confifirm its effificacy and safety.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinolinas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Humanos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Carcinoma de Pequenas Células do Pulmão/induzido quimicamente , Tomografia Computadorizada por Raios X
4.
Nihon Yakurigaku Zasshi ; 156(5): 303-311, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34470936

RESUMO

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, and AXL, among others. This drug is considered to exert excellent antitumor effects by inhibiting these targets simultaneously. Significant improvement in the primary endpoint (overall survival or PFS) were observed in patients on CAB in comparison with controls in a phase-III study in patients with renal cell carcinoma, progressed after treatment with anti-angiogenic agents, and in another phase-III study in patients with previously treated, advanced hepatocellular carcinoma. These results led to the approval of CAB in Japan in 2020 as a therapeutic agent for unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma progressed after cancer chemotherapy, under the trade name of CABOMETYX® (20 mg, and 60 mg tablets). It has been suggested that CAB may modulate the immune system in favor of antitumor immunity and combined use with PD-1 checkpoint inhibitors may exert a synergistic effect. In a phase-III study that examined the efficacy of combination therapy with CAB and nivolumab in treatment-naive patients with advanced renal cell carcinoma, progression-free survival was significantly increased in patients on combination therapy over patients on sunitinib monotherapy. Three global phase-III clinical studies of combination therapy with atezolizumab and CAB in patients with non-small cell lung cancer, castration-resistant prostate cancer, and renal cell carcinoma, are in progress to confirm the efficacy of CAB.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias Pulmonares , Anilidas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Piridinas
5.
Am J Case Rep ; 22: e932252, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491978

RESUMO

BACKGROUND Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced non-small cell lung cancer (NSCLC) with positive EGFR mutation. Rashes, nail toxicity, and diarrhea are common adverse events. Hematological adverse effects, including anemia, thrombocytopenia, and lymphocytopenia, have been reported. However, erythrocytosis has not been reported as an adverse event. To the best of our knowledge, we report the first case of acute lower extremity thrombosis presumably caused by osimertinib-induced erythrocytosis. CASE REPORT A 70-year-old man with epidermal EGFR-mutant advanced NSCLC presented with acute left sural pain. The patient's left foot was cold, and peripheral arterial Doppler signals were absent. He had developed erythrocytosis of unknown etiology during osimertinib therapy. Hemoglobin (Hb) and hematocrit were 22.6 g/dL and 62.5%, respectively. Contrast-enhanced computed tomography showed thrombotic occlusion of the popliteal artery. Other than erythrocytosis, there was no possible cause of arterial thrombosis. Osimertinib was discontinued immediately because the NSCLC started to resist treatment and was presumed to be the cause of erythrocytosis. He received endovascular treatment (EVT). Following serial EVT and debridement, his fourth toe was amputated for necrosis. Erythrocytosis persisted 8 months during osimertinib therapy. Hb levels decreased to 15.4 mg/dL due to blood loss complicated with catheter thrombectomy and remained normal for 20 months after osimertinib discontinuation. The patient died of cancer progression. CONCLUSIONS This case suggests the erythrocytosis was possibly caused by osimertinib. We may need to monitor Hb levels during osimertinib therapy and be alert to thrombosis once Hb starts to rise.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Policitemia , Trombose , Acrilamidas , Idoso , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Extremidade Inferior , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Mutação , Policitemia/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos
6.
Nat Commun ; 12(1): 5209, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471106

RESUMO

TGF-ß is secreted in the tumour microenvironment in a latent, inactive form bound to latency associated protein and activated by the integrin αV subunit. The activation of latent TGF-ß by cancer-cell-expressed αV re-shapes the tumour microenvironment, and this could affect patient responses to PD-1-targeting therapy. Here we show, using multiplex immunofluorescence staining in cohorts of anti-PD-1 and anti-PD-L1-treated lung cancer patients, that decreased expression of cancer cell αV is associated with improved immunotherapy-related, progression-free survival, as well as with an increased density of CD8+CD103+ tumour-infiltrating lymphocytes. Mechanistically, tumour αV regulates CD8 T cell recruitment, induces CD103 expression on activated CD8+ T cells and promotes their differentiation to granzyme B-producing CD103+CD69+ resident memory T cells via autocrine TGF-ß signalling. Thus, our work provides the underlying principle of targeting cancer cell αV for more efficient PD-1 checkpoint blockade therapy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Integrina alfaV/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Antígenos CD , Antígeno B7-H1 , Linhagem Celular Tumoral , Feminino , Humanos , Imunoterapia , Cadeias alfa de Integrinas , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos do Interstício Tumoral/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Microambiente Tumoral
7.
Medicine (Baltimore) ; 100(36): e27017, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516491

RESUMO

RATIONALE: Metastatic gastric cancer patients with poor eastern cooperative oncology group performance status (PS) (≥3) were lack of effective anti-tumor strategies. They always lived with poor PS, severe and multiple symptoms, and usually resulted in extremely limited survival time. Herein, we reported a patient diagnosed with gastric cancer metastasized to multiple bones, along with lymphangitis carcinomatosa in lungs, harboring Her-2 and c-MET amplification with poor PS, positively responded to combinational therapy with trastuzumab and crizotinib. PATIENT CONCERNS: The patient complained of persistent cough and fatigue for 2 months, otherwise, she denied smoking, alcohol history, or any other medical or family history. DIAGNOSIS: With the biopsy results from gastroscopy, as well as computer tomography for chest and abdomen, the patient was diagnosed as gastric adenocarcinoma, with metastasis on lungs, left adrenal gland, retroperitoneal lymph nodes, and multiple bones. INTERVENTIONS: Because of the poor PS (PS = 3), as well as Her-2 and c-MET amplification, the patient received combination treatment with trastuzumab and crizotinib as salvage strategy. OUTCOMES: After 2 months' exposure of trastuzumab and crizotinib, symptoms including persistent cough, and chest distress were alleviated significantly. Simultaneously, chest computer tomography showed significant dissipation of lymphangitis carcinomatosa, as well as apparent reduction of pleural effusion. No adverse reactions including nausea, vomiting, diarrhea, or hypertension was observed during the following 2 months. LESSONS: The present case suggested that combinational therapy with trastuzumab and crizotinib might be effective in metastatic gastric cancer patients harboring Her-2 and c-MET amplification, even with a poor PS. It was also implied that gene sequencing might be valuable, especially in patients with limited treatment strategies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica , Crizotinibe/administração & dosagem , Crizotinibe/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-met/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Trastuzumab/administração & dosagem , Trastuzumab/uso terapêutico
8.
Medicine (Baltimore) ; 100(36): e27029, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516493

RESUMO

ABSTRACT: There has been no effective biomarker for small cell lung cancer (SCLC) patients with first-line immune checkpoint inhibitors (ICIs) treatment. The predictive value of neuron-specific enolase (NSE) in this cohort remains unclear.The medical records of 254 consecutive SCLC patients receiving programmed cell death receptor-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors were compiled from January 2015 to October 2020 in Chinese PLA General Hospital. Survival analysis was performed to explore the prognostic role of NSE at baseline and 3 weeks post treatment.One hundred two advanced SCLC patients treated with first-line PD-1/PD-L1 inhibitors were enrolled in this study. Normal baseline NSE levels were correlated with significantly prolonged progression-free survival (PFS, median: 8.7 vs 4.7 months, P = .006) and overall survival (OS, median: 23.8 vs 15.2 months, P = .014) compared with elevated baseline NSE levels, so as for normal NSE levels at 3 weeks with prolonged PFS (median PFS: 8.4 vs 4.5 months, P = .0002) and OS (median OS: 23.3 vs 7.4 months, P < .0001). Intriguingly, elevated NSE levels at 3 weeks were associated with shorter PFS (median PFS: 4.5 vs 5.8 months, P = .04) and OS (median OS: 5.5 vs 14.7 months, P < .0001) compared with normal NSE levels in the elevated baseline NSE subgroup. Most subgroup analyses stratified by clinical characteristics confirmed the prognostic value of baseline NSE level.Elevated NSE levels at baseline and 3 weeks were associated with worse prognosis in advanced SCLC patients receiving first-line ICIs treatment. NSE level might be applied as a useful prognostic tool for SCLC patients with immunotherapy.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fosfopiruvato Hidratase/sangue , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , China , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Registros Médicos , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Análise de Sobrevida
9.
Medicine (Baltimore) ; 100(36): e27161, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34516509

RESUMO

BACKGROUND: Huachansu injection (HCS) is a widely used traditional Chinese medicine for advanced non-small cell lung cancer (NSCLC) to alleviate the adverse drug reactions (ADRs) and enhance the clinical efficacy of chemotherapy. OBJECTIVE: To evaluate the efficacy and safety of HCS as an adjunctive treatment to platinum-based chemotherapy (PBC) for advanced NSCLC. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. A total of nine databases were searched to select randomized controlled trials (RCTs) of HCS plus PBC to treat NSCLC from inception to October 10, 2020. RCTs on HCS plus PBC vs PBC alone for advanced NSCLC were included. Dichotomous data were pooled as risk ratio (RR) with 95% confidence intervals. RCTs compared to HCS plus PBC vs PBC alone were included. Primary outcomes were objective response rate (ORR) and disease control rate (DCR), and secondary outcomes were survival rate, quality of life (QOL), and adverse drug reactions (ADRs). GRADE software was used to access the quality of evidence. RESULTS: A total of 32 RCTs, including 2753 patients, were included. Compared to PBC alone, HCS plus PBC improved the ORR, DCR, 1- and 2-year survival rates, and QOL and alleviated neutropenia, thrombocytopenia, nausea, vomiting, anemia, liver injury, renal injury, and alopecia. CONCLUSIONS: Compared to PBC alone, HCS plus PBC improved the clinical efficacy and alleviated the ADRs in advanced NSCLC patients. Considering the limitations of the included RCTs, high-quality trials with longer follow-ups are needed to further confirm the results.


Assuntos
Venenos de Anfíbios/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Platina/uso terapêutico , Venenos de Anfíbios/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/patologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Neoplasias Pulmonares/patologia , Masculino , Fitoterapia , Compostos de Platina/administração & dosagem , Resultado do Tratamento
10.
World J Surg Oncol ; 19(1): 278, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530849

RESUMO

BACKGROUND: We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment. PATIENTS AND METHODS: We investigated 60 cases of patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to screen for ALK rearrangement. Fluorescence in situ hybridization (FISH) was used to detect the percentage of ALK-positive cells. The primary objectives of the study were the progression-free survival (PFS), the 3-year overall survival, and the 3-year overall survival (OS) rates. The secondary objectives of the study were the disease control rate (DCR) and the overall response rate (ORR). RESULTS: We compared the pathological cytomorphologic features of 60 cases of ALK-positive pulmonary adenocarcinoma, of which 21 cases were ALK-positive with signet ring cell cytomorphologic characteristics. There were statistical differences in the ORR (p = 0.019), DCR (p = 0.032), and PFS (p = 0.047) between the signet ring cell group and group without signet ring cells. Of these, 37 cases were ALK-positive with EML4 (echinoderm microtubule associated protein like 4)-ALK high percentage of positivity group. These cases benefited more from crizotinib treatment in the ORR (p = 0.046) and achieved a longer PFS (p = 0.036) compared to those with EML4-ALK low percentage of positivity group. CONCLUSIONS: Signet ring cell cytomorphologic characteristics of pulmonary adenocarcinoma are associated with the percentage of ALK-positive cells. Signet ring cell cytomorphologic characteristics and the percentage of ALK-positive cells might predict the prognosis of pulmonary adenocarcinoma with crizotinib treatment. TRIAL REGISTRATION: The study was approved by the Institutional Review Board (Medical Ethics Committee of Yantai Yuhuangding Hospital). The registration number is NO.2016[193].


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Prognóstico , Estudos Prospectivos , Inibidores de Proteínas Quinases
11.
Cancer Genomics Proteomics ; 18(5): 661-673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34479918

RESUMO

BACKGROUND/AIM: Coronavirus disease 2019 (COVID-19) poses a great challenge for the treatment of cancer patients. It presents as a severe respiratory infection in aged individuals, including some lung cancer patients. COVID-19 may be linked to the progression of aggressive lung cancer. In addition, the side effects of chemotherapy, such as chemotherapy resistance and the acceleration of cellular senescence, can worsen COVID-19. Given this situation, we investigated the role of paclitaxel (a chemotherapy drug) in the cell proliferation, apoptosis, and cellular senescence of gefitinib-resistant non-small-cell lung cancer (NSCLC) cells (PC9-MET) to clarify the underlying mechanisms. MATERIALS AND METHODS: PC9-MET cells were treated with paclitaxel for 72 h and then evaluated by a cell viability assay, DAPI staining, Giemsa staining, apoptosis assay, a reactive oxygen species (ROS) assay, SA-ß-Gal staining, a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and Western blotting. RESULTS: Paclitaxel significantly reduced the viability of PC9-MET cells and induced morphological signs of apoptosis. The apoptotic effects of paclitaxel were observed by increased levels of cleaved caspase-3 (Asp 175), cleaved caspase-9 (Asp 330) and cleaved PARP (Asp 214). In addition, paclitaxel increased ROS production, leading to DNA damage. Inhibition of ROS production by N-acetylcysteine attenuates paclitaxel-induced DNA damage. Importantly, paclitaxel eliminated cellular senescence, as observed by SA-ß-Gal staining. Cellular senescence elimination was associated with p53/p21 and p16/pRb signaling inactivation. CONCLUSION: Paclitaxel may be a promising anticancer drug and offer a new therapeutic strategy for managing gefitinib-resistant NSCLC during the COVID-19 pandemic.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Gefitinibe/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502019

RESUMO

The lungs play a very important role in the human respiratory system. However, many factors can destroy the structure of the lung, causing several lung diseases and, often, serious damage to people's health. Nerve growth factor (NGF) is a polypeptide which is widely expressed in lung tissues. Under different microenvironments, NGF participates in the occurrence and development of lung diseases by changing protein expression levels and mediating cell function. In this review, we summarize the functions of NGF as well as some potential underlying mechanisms in pulmonary fibrosis (PF), coronavirus disease 2019 (COVID-19), pulmonary hypertension (PH), asthma, chronic obstructive pulmonary disease (COPD), and lung cancer. Furthermore, we highlight that anti-NGF may be used in future therapeutic strategies.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Pulmão/patologia , Fator de Crescimento Neural/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/patologia , COVID-19/tratamento farmacológico , COVID-19/patologia , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/patologia , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular/métodos , Fator de Crescimento Neural/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia
13.
Anticancer Res ; 41(9): 4215-4228, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475041

RESUMO

BACKGROUND/AIM: Tyrosine kinase inhibitors (TKIs) are used for the treatment of both wild type and mutant non-small cell lung cancer (NSCLC); however, acquired resistance is a major clinical challenge. Herein, we aimed to investigate the effects of telmisartan (Tel), CFM 4.16 and sorafenib combination in rociletinib resistant NSCLC tumors. MATERIALS AND METHODS: 3D spheroid cultures and western blotting were used for evaluating cytotoxic effects and protein expression. An in vivo rociletinib resistant H1975 xenograft model of NSCLC was developed by subcutaneous injection of rociletinib resistant H1975 cells into nude mice. RESULTS: Tel, CFM 4.16 and sorafenib combination displayed superior anti-cancer effects in 3D spheroid cultures and a rociletinib resistant H1975 xenograft model of NSCLC by decreasing the protein expression of oncogenic and cancer stem cell markers (Nanog, Sox2 and Oct4). CONCLUSION: Tel facilitates effective penetration of CFM 4.16 and sorafenib in rociletinib resistant H1975 models of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Esferoides Celulares/citologia , Compostos de Espiro/administração & dosagem , Telmisartan/administração & dosagem , Tiadiazóis/administração & dosagem , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Nus , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Esferoides Celulares/efeitos dos fármacos , Compostos de Espiro/farmacologia , Telmisartan/farmacologia , Tiadiazóis/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Anticancer Res ; 41(9): 4321-4331, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475052

RESUMO

BACKGROUND/AIM: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are key drugs in cancer treatment due to their minor adverse effects and outstanding anticancer effects. However, drugs for overcoming EGFR-TKI resistance are not in clinical use so far. Therefore, to overcome resistance, we focused on lurasidone, a new antipsychotic drug, due to its mild adverse effect profile from the viewpoint of drug repositioning. MATERIALS AND METHODS: We explored the effects of lurasidone alone or in combination with EGFR-TKI on the growth of osimertinib-resistant cancer cells the anti-apoptotic marker expression such as survivin, and autophagy levels by LC-3B expression. RESULTS: Within a non-toxic concentration range in normal cells, lurasidone and osimertinib combination therapy showed a growth-inhibitory effect in osimertinib-resistant cancer cells in vitro and in vivo. Furthermore, lurasidone decreased survivin expression and mildly induced autophagy. CONCLUSION: Lurasidone may increase the sensitivity to osimertinib in osimertinib-resistant cancer cells in drug repurposing.


Assuntos
Acrilamidas/administração & dosagem , Compostos de Anilina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Cloridrato de Lurasidona/administração & dosagem , Survivina/metabolismo , Células A549 , Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Cloridrato de Lurasidona/farmacologia , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Gan To Kagaku Ryoho ; 48(9): 1096-1099, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521783

RESUMO

Immune checkpoint inhibitors(ICIs)are playing an increasingly important role in the treatment of cancer. In the field of lung cancer, ICIs are widely administered from primary therapy to maintenance therapy after chemoradiation for non-small cell lung cancer. However, excluding tumor proportion score(TPS)for PD-L1, no other biomarker has been reported to be clinically useful. While many biomarkers are being searched for, analysis of intestinal microbiota is attracting attention as a parameter that may reflect immune status. Research on the relationship between ICIs and gut microbiota has expanded worldwide after 2 reports in Science in 2015. In a study in which the gut microbiota of ICI-treated patients was transplanted into germ-free mice, enhanced antitumor effects were observed in the group that received gut microbiota from the response group, suggesting the possibility of stool transplantation. At the same time, when Akkermansia muciniphila, which is one of the mucin-degrading bacteria, was ingested by mice transplanted with non-responsive gut microbiota, a portion of tumor-infiltrating T cells increased on tumor localization, indicating the effect of changes in gut microbiota. In addition, there is a possibility that the anti-tumor effect may be enhanced by the effect of metabolites on immune cells in the blood rather than the gut microbiota itself, and the analysis of metabolites produced by bacteria is attracting attention. In our department, we have analyzed the intestinal microbiota of 25 non-small cell lung cancer patients treated with anti- PD-1 antibody. Although we have achieved diversity and identification of specific bacterial species, analysis of bacterial metabolites will be important in the future when considering the impact of the intestinal microbiota on immune cells. The gut microbiota is not only a biomarker for the treatment of ICIs, but also has the potential to create an immune state that facilitates the effects of ICI by changing the gut environment and metabolites.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Camundongos
16.
BMJ Open ; 11(9): e049123, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475167

RESUMO

OBJECTIVES: Derived neutrophil-to-lymphocytes ratio (dNLR) has recently been reported as a novel potential biomarker associated with prognosis of non-small cell lung cancer (NSCLC). However, evidence for the prognostic utility of dNLR in patients with NSCLC treated with immune checkpoint inhibitors (ICIs) remains inconsistent. The objective of this work was to evaluate the association between pretreatment dNLR and prognosis of patients with NSCLC treated with ICIs. DESIGN: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for eligible studies up to 16 October 2020. ELIGIBILITY CRITERIA: (1) Human subjects receiving ICIs therapy and who had been diagnosed with NSCLC; (2) the baseline values of dNLR were obtained; (3) the objective of the study was to investigate the relationships between dNLR and overall survival (OS) or progression-free survival (PFS) in NSCLC and (4) HR and 95% CI were displayed in the original article or could be extracted from Kaplan-Meier curves. DATA EXTRACTION AND SYNTHESIS: Two investigators extracted data independently. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with Cochran's Q test and I2 statistics. Publication bias of studies was assessed by Begg's test and Egger's test. We used V.12.0 of the Stata statistical software. RESULTS: This analysis included eight studies (2456 cases) on the prognostic utility of dNLR in ICI therapy for NSCLC. The results indicate that higher dNLR significantly predicted poor OS (HR=1.65, 95% CI 1.46 to 1.88; p<0.001) and PFS (HR=1.38, 95% CI 1.23 to 1.55; p<0.001). Subgroup analyses of OS-related studies indicated that there were similar results in stratifications by ethnicity, sample size, type of HR and dNLR cut-off value. As for PFS-related studies, subgroup analyses showed no significant difference in Asian populations. Publication biases were not detected using Begg's test and Egger's linear regression test. CONCLUSIONS: This meta-analysis indicated that elevated pretreatment dNLR may be a negative prognostic predictor for patients with NSCLC treated with ICIs. More large-sample and higher-quality studies are warranted to support our findings. PROSPERO REGISTRATION NUMBER: CRD42021214034.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos , Neutrófilos , Prognóstico
17.
J Int Med Res ; 49(9): 3000605211016998, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34521243

RESUMO

Patients with idiopathic pulmonary fibrosis (IPF) occasionally experience acute exacerbations after surgery for lung cancer. Several recent studies have revealed a prophylactic effect of perioperative pirfenidone treatment on postoperative acute exacerbations of IPF in patients with lung cancer. A 75-year-old woman consulted with her pulmonologist because of an IPF shadow detected by follow-up chest computed tomography 2 months after surgical treatment of biliary cancer. Another 7 months later, chest computed tomography showed a 23- × 14-mm nodule located in the right lower lobe with high accumulation of fluorodeoxyglucose detected by positron emission tomography, resulting in a radiological diagnosis of primary lung cancer with IPF. We administered perioperative pirfenidone treatment followed by right lower lobectomy using uniportal video-assisted thoracoscopic surgery after attaining a pathological diagnosis of adenocarcinoma. The patient developed no acute exacerbations of IPF during the postoperative period, and she had no recurrence of lung cancer for 15 months after surgery. We successfully used a combination of perioperative antifibrotic medication and minimally invasive surgery after lung cancer surgery in a patient with IPF.


Assuntos
Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Idoso , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia , Piridonas , Cirurgia Torácica Vídeoassistida
18.
Ann Palliat Med ; 10(8): 9267-9275, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488412

RESUMO

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.


Assuntos
Apendicite , Colestase , Neoplasias Pulmonares , Pneumonia , Idoso , Anticorpos Monoclonais Humanizados , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico
19.
Clin Drug Investig ; 41(9): 825-828, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347284

RESUMO

FKB238 is a biosimilar of bevacizumab (a monoclonal antibody against vascular endothelial growth factor) approved for use in the same types of cancer as reference bevacizumab. FKB238 has similar physicochemical and pharmacodynamic properties to those of reference bevacizumab and pharmacokinetic similarity was shown in healthy volunteers and in patients with non-small cell lung cancer (NSCLC). FKB238 demonstrated equivalent clinical efficacy to reference bevacizumab in patients with advanced or recurrent nonsquamous NSCLC, with similar tolerability, safety and immunogenicity profiles.


Assuntos
Medicamentos Biossimilares , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico
20.
FASEB J ; 35(9): e21798, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339064

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID-19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR-ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium-binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID-19, pathological similarities of the affected lungs between COVID-19 and S100A8-induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll-like receptor 4/Myeloid differentiation protein-2 (TLR4/MD-2) and mediates hyper-inflammation even after elimination of endotoxin-producing extrinsic pathogens, analogous findings between COVID-19-associated ARDS and pre-metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID-19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID-19-associated ARDS.


Assuntos
COVID-19/complicações , Calgranulina A/fisiologia , Síndrome da Liberação de Citocina/etiologia , Inflamação/etiologia , Pandemias , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/genética , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/fisiologia , Animais , Antivirais/farmacologia , COVID-19/genética , COVID-19/patologia , Calgranulina A/sangue , Calgranulina A/genética , Quimiocina CXCL11/sangue , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/patologia , Dissacarídeos/farmacologia , Dissacarídeos/uso terapêutico , Modelos Animais de Doenças , Descoberta de Drogas , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Humanos , Inflamação/genética , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Antígeno 96 de Linfócito/fisiologia , Macaca mulatta , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Mutação , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/metabolismo , Especificidade da Espécie , Fosfatos Açúcares/farmacologia , Fosfatos Açúcares/uso terapêutico , Receptor 4 Toll-Like/fisiologia , Regulação para Cima , Internalização do Vírus
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