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1.
J Coll Physicians Surg Pak ; 29(12): S126-S128, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779765

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC) harbouring common EGFR mutations. However, about 10% of EGFR mutations are uncommon mutations and their response to EGFR-TKIs remains unclear. The present case reports a 75-year, female patient with advanced NSCLC, presenting with a new subtype of EGFR exon 19 insertion mutation (IPVAIL insertion), who showed obvious symptom improvement after EGFR-TKIs treatment but a relatively short time of progression-free survival (PFS) and succumbed to tumor 133 days (4.4 months) after diagnosis. In conclusion, patients harbouring new subtype of EGFR exon 19 insertion mutations, IPVAIL insertion may have a poor prognosis. Further experiences are required to characterise these uncommon mutations.

2.
J Cancer Res Clin Oncol ; 145(12): 3021-3036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617075

RESUMO

PURPOSE: In recent years, immune checkpoint blockade (ICB) therapies have shown good clinical responses in various solid cancers. However, a major challenge in the process of ICB treatment is when tumors do not have enough infiltrating T cells. Antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) and its receptors have been approved for the treatment of various malignant solid tumors alone or in combination with other therapies. Our review mainly discusses the preclinical rationale and clinical efficacy of antiangiogenic and ICB combination therapy in urogenital tumors. METHODS: We reviewed relevant literature on preclinical research and clinical trial results regarding antiangiogenic and ICB combination therapy in urogenital tumors from PubMed. In addition, we searched ongoing clinical trials on ClinicalTrials.gov to collect information related to this specific topic. RESULTS: Antiangiogenesis therapy could enhance T cell recruitment and increase T cell infiltration into the tumor microenvironment by blocking VEGF-VEGF receptor 2 binding and downstream signaling pathways to normalize tumor blood vessels. The combination of ICB and antiangiogenesis therapy could improve antitumor activity according to subsequent preclinical experiments and several phase I/II/III clinical trials on urogenital tumors. CONCLUSION: Combined therapy has shown some antitumor efficacy in several urogenital tumors, such as metastatic renal cell carcinoma, metastatic urothelial and genitourinary tumors, endometrial carcinoma, ovarian cancer, and fallopian tube cancer. Combination therapy is a promising strategy that can be used to improve the therapeutic efficacy, and the identification of precise biomarkers of this combined therapy is the direction of future studies.


Assuntos
Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neoplasias Urogenitais/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Humanos , Imunoterapia/métodos , Linfócitos T/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
3.
Integr Cancer Ther ; 18: 1534735419876345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31522574

RESUMO

Hyperthermia is often used in combination with chemotherapy and radiotherapy for cancer treatment. Recently, immunotherapy has become a popular research area, breaking exciting new ground with concurrent immunotherapy and hyperthermia. Much evidence has demonstrated the effectiveness of multidisciplinary synergistic therapy, and the underlying mechanism has been gradually explored. In this review, we focus on the mechanism of various cancer treatments in the current literature and recent advances in hyperthermia. Additionally, we review clinical studies of hyperthermia combined with other therapies in the previous 10 years and propose future prospects for hyperthermia in multidisciplinary synergistic therapy.

5.
Ann Clin Microbiol Antimicrob ; 18(1): 15, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30922382

RESUMO

BACKGROUND: Prosthetic valve endocarditis (PVE) is a rare but severe complication of valve replacement surgery, with an incidence rate of 0.3-1.2% per patient-year. At present, staphylococci are the predominant causative microorganism of PVE. Herein, we report a confirmed case of late PVE in a mechanical aortic valve caused by Mycobacterium tuberculosis. CASE PRESENTATION: A 32-year-old immunocompetent man with recurrent fever and 5-kg weight loss had a history of having undergone the Bentall procedure due to congenital heart disease. Nine years after the operation, he developed a paravalvular abscess in the mechanical aortic valve, presented with evidence of pulmonary tuberculosis on CT scan and was diagnosed with tuberculous endocarditis. This case report highlights a rare and non-negligible example of tuberculous endocarditis involving a mechanical valve. CONCLUSIONS: Tuberculous PVE should be considered in patients with a history of valve replacement, recurrent fever, unexplained weight loss, pulmonary tuberculosis and meaningful valvular findings on echocardiogram.


Assuntos
Valva Aórtica/cirurgia , Endocardite Bacteriana/microbiologia , Cardiopatias/cirurgia , Próteses Valvulares Cardíacas/microbiologia , Mycobacterium tuberculosis/fisiologia , Complicações Pós-Operatórias/microbiologia , Adulto , Valva Aórtica/diagnóstico por imagem , Endocardite Bacteriana/diagnóstico por imagem , Cardiopatias/congênito , Cardiopatias/diagnóstico por imagem , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Masculino , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
6.
Cancer Biol Ther ; 20(4): 391-396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30307354

RESUMO

BACKGROUND: Substantial progress has been made in metastatic colorectal cancer (mCRC) treatment, but there is still a fraction of patients cannot find any effective therapeutic strategy after guideline-recommended standard chemotherapy and molecular targeted therapy. CASE PRESENTATION: Here we present a KRAS/NRAS/BRAF wild-type mCRC patient who has been previously treated with FOLFIRI (fluorouracil, leucovorin, and irinotecan), XELOX (capecitabine and oxaliplatin), cetuximab and bevacizumab, and then received the next generation sequencing (NGS) and whose metastatic subcutaneous nodule was resected to generate patient-derived xenograft (PDX) models. The NGS revealed HER-2 amplification as well as an activating mutation S310F and PDX models tested several drugs finding that afatinib was the optimal agent with notable efficacy and well tolerance among 6 regimens. Therefore, this patient started to take afatinib orally and achieved 3 months progression-free survival (PFS) and relief of clinical symptoms without severe adverse effects. CONCLUSIONS: NGS and PDX models have great significance for precision and individualized medicine in the mCRC treatment, especially for patients whose diseases have been progressed after multiline standard therapies.

7.
Cell Cycle ; 17(24): 2666-2683, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30382763

RESUMO

Multiple myeloma (MM) is a cancer that occurs in plasma cells, which fall under the category of white blood cells that are in charge of antibody production. According to previous studies, microRNA-497 (miR-497) functions as a tumor suppressor in several types of cancer, including gastric cancer and colorectal cancer. Therefore, the present study aims to investigate the effects of miR-497 on cellular function of human MM cells through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway by targeting Raf-1. The differentially expressed genes and miRs in MM, and the relationship between the miR and gene were verified. It was found that Raf-1 was a target gene of miR-497. The data obtained from MM tissues showed increased Raf-1 level and decreased miR-497 level. MM cells were treated with mimic, inhibitor and siRNA in order to evaluate the role of miR-497, Raf-1 and MAPK/ERK in MM. The expression pattern of miR-497, Raf-1, ERK1/2, survivin, B-cell lymphoma-2 (Bcl-2) and BCL2-Associated X (Bax) as well as the extent of ERK1/2 phosphorylation were determined. Retored miR-497 and si-Raf-1 resulted in increases in the Bax expression and cell apoptosis and decreases in the expressions of Raf-1, MEK-2, survivin, Bcl-2, along with the extent of ERK1/2 phosphorylation. In addition, the biological function evaluations of MM cells revealed that miR-497 mimic or si-Raf-1 led to suppression in cell proliferation, invasion and migration. In conclusion, our results have demonstrated that miR-497 targets Raf-1 in order to inhibit the progression of MM by blocking the MAPK/ERK signaling pathway.


Assuntos
MicroRNAs/metabolismo , Mieloma Múltiplo/patologia , Proteínas Proto-Oncogênicas c-raf/metabolismo , Animais , Antagomirs/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-raf/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo
8.
J Infect ; 77(3): 249-257, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29898409

RESUMO

Multiple reassortant strains of novel, highly pathogenic avian influenza A have recently emerged and spread over the world. Here we report on a 68-year-old woman in Jiangsu, China, with influenza A(H7N4) infection and associated illness, which strongly demonstrating the ability of the virus to spread from animals to humans and thus emphasizing the importance of continuous surveillance of the emerging viruses.


Assuntos
Vírus da Influenza A/classificação , Vírus da Influenza A/isolamento & purificação , Influenza Humana/diagnóstico , Influenza Humana/virologia , Idoso , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Antivirais/administração & dosagem , China , Feminino , Genoma Viral , Humanos , Vírus da Influenza A/genética , Influenza Humana/patologia , Metilprednisolona/administração & dosagem , Moxifloxacina/administração & dosagem , Oseltamivir/administração & dosagem , Radiografia Torácica , Análise de Sequência de DNA , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Emerg Infect Dis ; 24(6): 1087-1090, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29774834

RESUMO

We report human endophthalmitis caused by pseudorabies virus infection after exposure to sewage on a hog farm in China. High-throughput sequencing and real-time PCR of vitreous humor showed pseudorabies virus sequences. This case showed that pseudorabies virus might infect humans after direct contact with contaminants.


Assuntos
Endoftalmite/epidemiologia , Endoftalmite/virologia , Herpesvirus Suídeo 1 , Pseudorraiva/epidemiologia , Pseudorraiva/virologia , Animais , China/epidemiologia , Endoftalmite/diagnóstico , Endoftalmite/história , Evolução Molecular , Feminino , Genes Virais , História do Século XXI , Humanos , Pessoa de Meia-Idade , Filogenia , Pseudorraiva/diagnóstico , Pseudorraiva/história
10.
Oncotarget ; 8(15): 25323-25333, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28445978

RESUMO

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. Among NSCLC, giant cell carcinoma of the lung (GCCL) is a rare pathological subtype with poor prognosis, with no confirmed evidence about its epidemiological features or therapeutic efficiency of EGFR-TKIs. We present two advanced GCCLs with sensitive EGFR mutations, also collected the cases of GCCL from our hospital and the Surveillance, Epidemiology, and End Results (SEER) program. Kaplan-Meier methods and Cox proportional hazards modeling were used to perform the survival analyses. Both two cases of advanced GCCL with sensitive EGFR mutations benefited from EGFR-TKIs. Twelve GCCLs were recorded in our hospital from May 2006 to July 2015. GCCL is associated with males (83.3%) and smoking status (63.6%). The EGFR mutation rate was 40.0%. In SEER database, the total number of GCCLs was 184, 0.11% for all NSCLCs. In Kaplan-Meier analysis, the 5-year overall survival of GCCL patients was significantly lower than that of non-GCC NSCLC (16% and 19%; P<0.001), and it was confirmed in multivariate analysis. Further survival analyses indicated that male were more susceptible to GCCL and GCCL was prone to metastasize. Only age and M stage were independent prognostic factors for GCCL in the multivariate analysis. In conclusion, GCCL was an unfavorable prognostic factor and associated with males and metastasis. GCCL patients with sensitive EGFR mutations may also benefit from EGFR-TKI, we therefore recommend the evaluation of EGFR in the treatment of advanced GCCL.


Assuntos
Carcinoma de Células Gigantes/epidemiologia , Receptores ErbB/genética , Neoplasias Pulmonares/epidemiologia , Carcinoma de Células Gigantes/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Programa de SEER
11.
Oncotarget ; 8(3): 4342-4351, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28008147

RESUMO

BACKGROUND: The role of surgical therapy in gastric cancer patients with distant metastases remains controversial. This retrospective analysis was performed to identify whether gastric cancer patients with distant metastases might benefit from surgery. PATIENTS AND METHODS: A total of 5185 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer with distant metastases from 2004 to 2009 were included. Patients were divided into the following three groups: patients who underwent resection of both the primary tumor and distant metastatic tumors ('PMTR' group), patients who only underwent resection of the primary tumor ('PTR' group) and patients who did not undergo any surgery ('No surgery' group). We employed the Kaplan-Meier analysis, the log-rank test and multivariate Cox proportional hazards regression models to estimate the survival time of the different groups. RESULTS: A total of 5185 patients had a median survival time (MST) of 9.0 months. The improvement in survival of the 'PMTR' and 'PTR' groups was significantly different compared with that of the 'No surgery' group (MST, 12.0 vs 12.0 vs 9.0 months, respectively, P<0.001; 1-year survival rate, 49.6% vs 49.1% vs 30.1%, respectively, P<0.001; 3-year survival rate, 12.5% vs 15.1% vs 5.8%, respectively, P<0.001), whereas no significant difference was found between the 'PMTR' group and 'PTR' group (P=0.642). Multivariate Cox proportional analysis showed that surgery was an independent prognostic factor ('PMTR', hazard ratio (HR) =0.648, 95% confidence interval (CI) 0.574-0.733, P<0.001; 'PTR', HR=0.631, 95% CI 0.583-0.684, P<0.001). CONCLUSIONS: This retrospective analysis demonstrated that combined PTR and metastasectomy or PTR alone were independent prognostic factors for survival improvement in gastric cancer patients with distant metastases. Because no statistically significant difference in survival was observed between the 'PMTR' group and 'PTR' group, PTR, which is a more minor surgery, might be more appropriate than PMTR in clinical practice for gastric cancer patients with distant metastases.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Metastasectomia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Programa de SEER , Resultado do Tratamento
12.
Contemp Oncol (Pozn) ; 20(4): 320-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27688730

RESUMO

AIM OF THE STUDY: Many studies have shown that interferon-α (IFN-α) enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-α with gefitinib in human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different EGFR and K-Ras gene statuses. MATERIAL AND METHODS: An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR) and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3). RESULTS: There was an additive interaction when gefitinib was combined with IFN-α in all cell lines; however, there was antagonism when gefitinib followed IFN-α pretreatment in three cell lines. Notably, IFN-α pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells. Surprisingly, while IFN-α inhibited STAT3 phosphorylation in cell lines, gefitinib could do so. CONCLUSIONS: The results might confirm the hypothesis that IFN-α induces gefitinib sensitivity of NSCLC, and IFN-α inhibits phosphorylation of STAT3, which may be dependent on EGFR signal activation playing a role in the reduction of gefitinib sensitivity after IFN-α treatment in NSCLC cell lines.

13.
Medicine (Baltimore) ; 94(36): e1484, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26356712

RESUMO

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.


Assuntos
Adenocarcinoma , Carboplatina/administração & dosagem , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib/administração & dosagem , Neoplasias Pulmonares , Pemetrexede/administração & dosagem , Neoplasias Gástricas , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/fisiopatologia , Adenocarcinoma de Pulmão , Antineoplásicos/administração & dosagem , Biópsia , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/fisiopatologia , Humanos , Achados Incidentais , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
14.
Onco Targets Ther ; 7: 841-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24920926

RESUMO

Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

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