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1.
J Cell Physiol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039488

RESUMO

Lung cancer remains the leading cause of cancer-related death all over the world. In spite of the great advances made in surgery and chemotherapy, the prognosis of lung cancer patients is poor. A substantial fraction of long noncoding RNAs (lncRNAs) can regulate various cancers. A recent study has reported that lncRNA HOXB-AS3 plays a critical role in cancers. However, its biological function remains unclear in lung cancer progression. In the current research, we found HOXB-AS3 was obviously elevated in NSCLC tissues and cells. Functional assays showed that inhibition of HOXB-AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and meanwhile, triggered cell apoptosis. Furthermore, the lung cancer cell cycle was mostly blocked in the G1 phase whereas the cell ratio in the S phase was reduced. Also, A549 and H1975 cell migration and invasion capacity were significantly repressed by the loss of HOXB-AS3. The PI3K/AKT pathway has been implicated in the carcinogenesis of multiple cancers. Here, we displayed that inhibition of HOXB-AS3 suppressed lung cancer cell progression via inactivating the PI3K/AKT pathway. Subsequently, in vivo experiments were utilized in our study and it was demonstrated that HOXB-AS3 contributed to lung cancer tumor growth via modulating the PI3K/AKT pathway. Overall, we implied that HOXB-AS3 might provide a new perspective for lung cancer treatment via targeting PI3K/AKT.

2.
Int Microbiol ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872322

RESUMO

Antibiotic resistance is a growing global challenge to public health. Polymyxin is considered to be the last-resort antibiotic against most gram-negative bacteria. Recently, discoveries of a plasmid-mediated, transferable mobilized polymyxin resistance gene (mcr-1) in many countries have heralded the increased threat of the imminent emergence of pan-drug-resistant super bacteria. MCR-1 is an inner membrane protein that enables bacteria to develop resistance to polymyxin by transferring phosphoethanolamine to lipid A. However, the mechanism associated with polymyxin resistance has yet to be elucidated, and few drugs exist to address this issue. Here, we review our current understanding regarding MCR-1 and small molecule inhibitors to provide a detailed enzymatic mechanism of MCR-1 and the associated implications for drug design.

3.
Onco Targets Ther ; 12: 5793-5803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410024

RESUMO

Background: ASAP3 was first identified as a protein that promotes cell proliferation in hepatocellular carcinoma and later reported to be an Arf6-specific Arf GTPase-activating protein that regulates cell migration associated with cancer cell invasion. Materials and methods: Patients and tissue samples were from Hubei Cancer Hospital, human lung adenocarcinoma cell lines were obtained from the cell bank of the Chinese Academy of Science, nude mice (BALB/c nu/nu) were obtained from Shanghai SLAC Laboratory Animal Co. Ltd. Our methods contained immunohistochemistry, Western blotting, reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence staining, stable transfection of lung adenocarcinoma cells, chromatin immunoprecipitation (CHIP) and luciferase assay, wound healing and cell migration assay. Results: In this study, we show that ASAP3 overexpression promotes migration and invasiveness in human lung adenocarcinoma cells and accelerates tumor progression in a xenograft mouse model. In patient tumor samples, ASAP3 overexpression was significantly associated with lymph node metastasis and reduced overall survival. We also show that ASAP3 expression is induced under hypoxic conditions through hypoxia-inducible factor 1α (HIF-1α), which binds directly to HER1 or/and HER2 (hypoxia response element) in the ASAP3 promoter. ASAP3 overexpression counteracts the inhibition of lung adenocarcinoma progression caused by HIF-1α knockdown both in vitro and in vivo. Conclusion: Our results identify ASAP3 as a downstream target of HIF-1α that is critical for metastatic progression in lung adenocarcinoma.

4.
J Thorac Dis ; 10(7): 3983-3991, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30174840

RESUMO

Background: Aberrant activation of eIF4E is critically involved in the progression and chemoresistance of various cancers. Elevated expression of eIF4E has also been documented in human cancerous esophageal tissues. However, the role of eIF4E in esophageal cancer is unclear. Methods: We analysed the levels of eIF4E expression and eIF4E function in a number of normal and cancerous esophageal cancer cell lines, and studied its underlying mechanism. Results: We observed that eIF4E expression varies in different esophageal cancer cell lines but was significantly elevated in all tested esophageal cell lines as compared to the control cell lines. We demonstrated that eIF4E inhibition via genetic and pharmacological approaches inhibits cancer cell growth and survival. This inhibition also augments 5-flurouracil's (5-FU's) efficacy as demonstrated with both the in vitro esophageal cancer culture system and our in vivo xenograft mouse model. Of note, the sensitivity of esophageal cancer cells to ribavirin or eIF4E knockdown correlates well with the expression levels of eIF4E, demonstrating that esophageal cells with higher eIF4E expression are more sensitive to eIF4E inhibition. We further confirmed that the mechanism of action of ribavirin on esophageal cancer cells was through suppressing the Akt/mTOR/eIF4E and eIF4E-regulated pathways. Conclusions: To our knowledge, our work is the first to demonstrate the multiple roles of eIF4E in esophageal cancer. eIF4E was shown to promote cancer cell growth and survival, and protected the cells from chemotherapy. Our work also demonstrated that ribavirin is an attractive candidate for the treatment of esophageal cancer.

5.
Medicine (Baltimore) ; 97(21): e10681, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29794744

RESUMO

RATIONALE: This combination of fluticasone propionate (FP) and the long-acting ß2-agonist salmeterol (Salm) can control the symptoms of asthma and COPD better than FP or Salm on their own and better than the combination of inhaled corticosteroids plus montelukast. FP/Salm has been shown to control symptoms of asthma and COPD better than a double dose of inhaled steroids. The patient in our report had a history of COPD, and suffered relapse of RP when given only steroids. It is possible that COPD history helps explain this patient's more difficult treatment course. Therefore, this combination may be more effective than inhaled steroids for patients with a history of COPD. PATIENT CONCERS: This patient suffered adverse reactions triggered by methylprednisolone: weight gain, hyperglycaemia and sleep disturbance after more than two months of intravenous and oral prednisolone. These reactions disappeared when we switched the patients to FP/Salm maintenance therapy. DIAGNOSES: The patient underwent upper right lobectomy in September 2011. Immunohistochemistry indicated low squamous cell differentiation, and he was diagnosed with stage IIB disease (T2N1M0) according to the Union for International Cancer Control (UICC) (7th edition).One month after repeat radiotherapy, the patient experienced fever (37.6°C), cough, chest distress and shortness of breath. We performed serologic tests, laboratory tests for procalcitonin and C-reactive protein, as well as sputum and blood cultures to rule out bacterial infection. Chest CT showed consolidation with air bronchogram in the hilum of the right lung and ground-glass densities in the right lower lobe and left upper lobe. These radiographic signs are typical of RP. Since the patient required oxygen, he was diagnosed with grade III RP. INTERVENTIONS: After the patinet was diagnosed with grade III RP. The patient was immediately prescribed oxygen, anti-infectives for prophylaxis, treatments to facilitate expectoration and prevent asthma, and most importantly, intravenous methylprednisone at an initial dose of 60  per day. And we cut the steroid dose in half every one week when the patient's symptoms improved obviously, and the patchy shadow on the chest radiograph sharply reduced. Then we give him FP (500 mg)/Salm (50 mg) twice daily for two months. Then the dose was halved for an additional two months. OUTCOMES: The patient showed no signs of tumor or RP relapse by the last follow-up in March 2018. LESSONS: This maintenance therapy of FP/Salm for patient with grade III RP may help avoid relapse when steroid therapy is tapered, particularly for patients with a history of COPD. It may also reduce risk of steroid-associated adverse effects. Based on the results observed with our patient, we intend to design a prospective trial to assess the efficacy of FP/Salm when used as preventive treatment for patients at high risk of RP, and when used as maintenance treatment for patients with grade III RP.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Combinação Fluticasona-Salmeterol/uso terapêutico , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/tratamento farmacológico , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Pulmão/patologia , Pulmão/efeitos da radiação , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pneumonite por Radiação/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
J Thorac Dis ; 6(12): 1831-3, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25589983

RESUMO

A 50-year-old active male with a smoking history of 30 years (20 cigarettes per day) was admitted to hospital because of more than one month's cough without sputum. No comorbidity was present. The preoperative examination showed: blood test normal, ECG normal, cardio-pulmonary function normal, chest computed tomography (CT) display right upper lobe (RUL) mass of 5 cm diameter. Bronchoscopy examination and biopsy indicated large cell neuroendocrine carcinoma (LCNEC) in the take-off of RUL bronchus. No metastatic focus was found after emission computed tomography (ECT) scan of whole body bone, abdominal US scanning and brain MR. After initial evaluation, the clinical stage before operation was cT2bN0M0 (IIA stage). A selective video-assisted thoracic surgery (VATS) operation was arranged after 9 days of smoking cessation. Lateral position, one 10 mm trocar for camera in the 7th intercostals space in the mid-auxiliary line, 4 cm trocar for operation in the 4th intercostal space in the anterior axillary line, 15 mm trocar for auxiliary operation in the 8th intercostal space in the scapula line, the patient received VATS RUL lobectomy, plus systemic mediastinal lymph nodes dissection. The procedure of 200 minutes operation was smooth with blood loss of about 150 mL. Chest tube was removed 6 days after operation, and the patient discharged 11 days after the operation; The post-operation pathological examination showed RUL LCNEC, and the pathological stage was pT2bN0M0R0 (IIA stage). The patient has received four cycles of EP adjuvant chemotherapy per 21 days and is still alive without disease recurrence and metastasis after re-examination.

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