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BACKGROUND@#Anlotinib is a newly developed small molecule multiple receptor tyrosine kinase (RTK) inhibitor that was approved for the treatment of patients with lung cancer in China. We aim to report 3 cases of rare complication of anlotinib-bronchial fistula (BF) during the treatment of lung cancer patients and summarize the possible causes.@*METHODS@#We collected three patients who developed BF due to anlotinib treatment, and conducted a search of Medline and PubMed for medical literature published between 2018 and 2020 using the following search terms: "anlotinib," "lung cancer," and "fistula."@*RESULTS@#Our literature search produced two case reports (three patients) which, in addition to our three patients. We collated the patients' clinical characteristics including demographic information, cancer type, imaging features, treatment received, risk factors for anlotinib related BF, and treatment-related outcomes. The six patients shared some common characteristics: advanced age, male, concurrent infection symptoms, diabetes mellitus (DM), advanced squamous cell and small cell lung cancers, centrally located tumors, tumor measuring ≥5 cm in longest diameter, and newly formed tumor cavitation after multi-line treatment especially after receiving radiotherapy. Fistula types included broncho-pericardial fistula, broncho-pleural fistula, and esophago-tracheobronchial fistula. Six patients all died within 6 months.@*CONCLUSIONS@#Although anlotinib is relatively safe, it is still necessary to pay attention to the occurrence of BF, a rare treatment side effect that threatens the quality of life and overall survival of patients. Anlotinib, therefore, requires selective use and close observation of high-risk patients.
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<p><b>BACKGROUND</b>Tumor cells can reduce the number of dendritic cells (DCs) in the tumor environment and cause DC dysfunction through autocrine or paracrine pathways. We sought to measure cyclooxygenase-2 (COX-2) expression in bombesin-inhibited DCs treated with theanine in vitro and to explore the protection and activation effects of theanine on DCs.</p><p><b>METHODS</b>Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were used to analyze the effects of theanine on COX-2 expression and interleukin (IL)-12/IL-10 secretion of bombesin-treated DCs.</p><p><b>RESULTS</b>DCs acquired an impaired phenotype as a result of bombesin treatment. Theanine increased the expression of mature DC surface molecules. The number of cell apoptosis with the treatment of bombesin and theanine significantly decreased, accounting for 15.9%, compared with 26.1% of cell apoptosis with bombesin. COX-2 expression in bombesin-treated DCs was inhibited by theanine in a dose-dependent manner. Theanine promoted DC secretion of IL-12. IL-12 levels reached (137.4 ± 4.9) pg/ml with theanine at 200 µmol/L. However, theanine inhibited the secretion of IL-10 in a dose-dependent manner. IL-10 levels were only (58.4 ± 6.9) pg/ml with theanine at 200 µmol/L.</p><p><b>CONCLUSION</b>Theanine inhibits the transcription and translation of COX-2 and regulates the balance of IL-10/IL-12 secretion in bombesin-inhibited DCs, leading to the recovery of a state of activation in DCs.</p>
Subject(s)
Humans , Bombesin , Pharmacology , Cells, Cultured , Cyclooxygenase 2 , Metabolism , Dendritic Cells , Metabolism , Enzyme-Linked Immunosorbent Assay , Glutamates , Pharmacology , Interleukin-10 , Metabolism , Interleukin-12 , MetabolismABSTRACT
ObjectiveTo investigate the prognostic factors of non-small cell lung cancer (NSCLC) after resection.MethodsClinical data of 131 NSCLC patients who underwent resection were reviewed and divided into chemotherapy group(86 cases) and non-chemotherapy group(45 cases) according to the treatment method.Survival rate was calculated by Kaplan-Meier method.The prognosis was analyzed by Cox proportional hazards model.ResultsThe median survival time (MST) of squamous cell carcinoma (76 cases),bronchial alveolar cell carcinoma( 8 cases),adenocarcinoma( 35 cases ),adenosquamous carcinoma (12 cases) was 60,54,34,24 months respectively (P＜0.05).For the patients of stage Ⅰ B,the MST of chemotherapy group and non-chemotherapy group was 75 and 76 months respectively(P ＞ 0.05 ).Multivariate analysis showed that tumor size,T stage,N stage,chemotherapy were independent prognostic factors (P =0.080,0.002,0.000,0.029).Conclusions Squamous cell carcinoma and bronchial alveolar cell carcinoma have better prognosis than adenocarcinoma,adenosquamous carcinoma.For the patients of stage Ⅰ B,the survival time can't be prolonged through platinum-based chemotherapy.Tumor size,T stage,N stage,chemotherapy are independent prognostic factors.
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Objective To reveal the impact of anti-lung cancer A549 by theanine, which may regulate T lymphocytes through dendritic cells (DCs), and to observe the immune protection of theanine on SCID mice transplanted tumors. Methods SCID mice were reconstructed after immunization, then A549 cells were inoculated. The immune protection and immune treatment of theanine stimulated DCs were observed. Results In the theanine-stimulated DC group, as well as DC group, the time needed to form tumor were significantly prolonged (F = 29. 5, P ＜ 0. 01). And the transplanted tumors were smallest (F =69. 51, P ＜0. 01) and lightest (F = 190. 9, P ＜0. 01) in the theanine-stimulated DC group. 50 days after tumor-bearing, the transplanted tumors in the theanine-stimulated DC group were smaller than in the control group, and the surface were smoother with no adhesions. Under light microscope, a large thin slice necrosis was showed in the theanine-stimulated DC group, and the VEGF expression was also reduced (F = 31.4, P ＜ 0. 01). Conclusions The anti-tumor immune protection and treatment mechanism of theanine-stimulated DCs were possibly through regulation of T cells, as well as the VEGF expression reducing,thereby inhibited tumor blood vessel formation.
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Objective To investigate the effects and distribution of 4 efflux pumps and correlated mutation of regulatory gene in multi-drug resistance Pseudomonas aeruginosa (Pa) in Hunan province. Methods Forty non-duplicated clinical strains of multiple-drug-resistant Pseudomonas aeruginosa were collected in Hunan in 2008, then the phenotype was screened with efflux pumps inhibitor phenylalanine-L-β-naphthylamide and 4 antimicrobial susceptibility test discs. Genes of the efflux pump membrane fusion protein were amplified by PCR, and correlated efflux pump regulatory genes were amplified and sequenced to analyze the role of efflux pump gene expression in multi-drug resistance compared to that of 18 strains with non-multi-drug resistance. Re-suits The positivity rates of MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY-OprM were 45.0% (18/40), 30.0% (12/40), 42.5% (17/40) and 12.5% (5/40) respectively with phenotype screening in multi-drug resistance group. The positivity rates of mexA, mexC, mexE and mexX were 100% (58/58), 22.5% (9/40), 45.0% (18/40) and 22.5% (9/40) with RT-PCR. The overexpressed positivity rates of mexA and mexX were 55.0% (22/40) and 22.5% (9/40) respectively by semi-quantitative analysis with real-time PCR. However, no over-expression of mexA and mexX in non-multi-drug resistance group with real-time PCR. The positive expression rates of mexC and mexE with RT-PCR were 11.1% (2/18), 38.9% (7/18) in non-multi-drug resistance group. The difference of overexpression of mexA and mexX was significant(P<0.001, P=0.045) between two groups. The strain Pa20 with mexA overexpressian displayed gene mutations in mexR(164GTC→GAG) and amino acid substitution(126Val→Glu), the strain Pa34 with overexpression of mexX had 164GCG→GAG,55Ala→GIu. Conclusion Most of Pa with multi-drug resistance contained the resistant mechanism of efflux pumps and most-ly due to the overexpression of MexAB-OprM and MexXY-OprM in Hunan. There are mostly regulatory genes mutation in the strains with overexpression of MexAB-OprM and MexXY-OprM.
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<p><b>BACKGROUND AND OBJECTIVE</b>Epidemiology of lung cancer will be changed along with time and region. The aim of this study is to acknowledge the tendency of primary lung cancer in hunan province in recent years by comparing and analyzing the distribution of gender, age, area, smoking and pathology of patients who were initial diagnosed lung cancer and ancestral or permanent residence of hunan province in 1997 and 2007.</p><p><b>METHODS</b>Clinical data of 908 patients with primary lung cancer hospitalized in Xiangya hospital were collected and evaluated.</p><p><b>RESULTS</b>Compared patients in 2007 with those in 1997, ratio between male and female dropped from 3.8:1 to 2.98:1, while the proportion of young patients who were under 40 years old raised from 4.4% to 8.6% (chi2 = 4.465, P = 0.035), patients living in the county raised from 19.9% to 40.1% (chi2 = 30.670, P < 0.001), smoking rate of patients from county raised from 16.9% to 39.9% (chi2 = 24.939, P < 0.01). In addition, the proportion of rare histological types of lung cancer were also increased from 1.3% to 4.5% (chi2 = 5.142, P = 0.023).</p><p><b>CONCLUSION</b>Female patients, young patients, rural patients and rare histological types of lung cancer may have a tendency of increase in hunan province in recent years, whereas smoking cessation education should be strengthened.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Age Factors , China , Lung Neoplasms , Epidemiology , Risk Factors , Sex Factors , Smoking , EpidemiologyABSTRACT
Objective To observe the effect of theanine in vitro and in vivo, including suppression of lung tumor growth, tumor an-giogenesis and promotion of apoptosis. Methods The inhibitory effects of theanie on lung cancer A549 cells were analyzed by MTT assays. The cell cycle and the apeptotic percentage of A549 cells were detected by FCM. The angiogenesis effect of theanine was observed with CAM model. The inhibitory effects of theanine were observed with lung carcinoma nude mice model, and the immunohistochemic technique was used to investigate the expression of CD34 and VEGF (vascular endothelial growth factor). Results Treatment of A549 cells with VEGF re-sulted in significant dose-dependent and time-dependent inhibition. FCM detection indicated that administration of EGCG resulted in an in-crease in cells in the S phase of the cell cycle and a typical apoptosis peak before the GI phase with an apoptosis rate of 15.9%. There was a significant difference in tumor volume and weight in theanine group compared with control group after two-week treatment, and the tumor in-hibition rate was 43.6%. There was no significant difference in expression of VEGF in tumor tissue according to tumor MVD marked by CD34 between the theanie group and control group. Thus, theanine could obviously inhibit tumor angiogenesis. Conclusion VEGF can ar-rest lung tumor growth via the promotion of tumor cell apoptosis and the inhibition of tumor angiogenesis.
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<p><b>BACKGROUND</b>There is still disadvantage in animal model for lung cancer study, no matter what is xenograft nude mice or rats/mice lung neoplasm induced by carcinogenesis.The purpose of the current investigation is to explore a simple and convenient and reliable method for lung neoplasm animal model.</p><p><b>METHODS</b>The prepared 36 female Sprague Dawley (SD) rats, with the range from 180 to 220g of body weight, were randomly divided into two groups, each group included 18 rats. In the study group, the rats were given 2mg of 3, 4-benzopyrene soluting in 0.2mL corn oil every two-weekly pulmonary injection for 4 times through right middle-chest percutaneous puncture under control of anaesthesia by pentobarbital sodium i.p. The controls were only given 0.2mL corn oil injection simultaneously. The rats were sacrificed after suffering from dyspnea, and the survived rats were sacrificed at narcotism in 1 year after the first 3, 4-benzopyrene toxicosis. Lung, brain, liver, esophagus and stomach of all rates were anatomized in search of tumor.</p><p><b>RESULTS</b>No lung neoplasm was found in the control group within 1-year observation. The earliest dyspnea caused by lung malignant neoplasm was observed in 16 week after the first injection in a rat treated with 3, 4-benzopyrene oil, then 10 rats were sacrificed and found with malignant neoplasm in theirs right lung when the rats suffered from dyspnea, and 1 rat was found a huge tumour in its right lower limb in 26 weeks after treatment. The other 6 rats were sacrificed in 1 year after the first 3, 4-benzopyrene oil treatment, in which 1 rat was found with a malignant neoplasm in its right lung and 5 rats were normal. No tumor was found in brain, liver, esophagus and stomach. Out of these 18 rats, 12 (66.67%) lung malignant neoplasms and 1 limb malignant neoplasm were found within 1 year in the experimental group which yielded a total cancerogenic rate of 72.22% (13/18). The lung neoplasms included: 2 poor-differentitaed squamous cell carcinomas, 3 adenocarcinomas and 7 undifferentiated carcinomas.</p><p><b>CONCLUSIONS</b>The results suggest that 3,4-benzopyrene pulmonary injection by percutaneous puncture may provide an efficiency method for lung neoplasm model established in rats.</p>
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Objective To investigate superoxide dismutase(SOD) activity in peripheric blood of type 2 diabetic patients(NIDDM) complicated with diabetic nephropathy(DN) and SOD alteration after insulin treatment.Methods Three groups of individuals were selected.Group A included 46 cases of NIDDM patients with DN.Group B included 43 cases of NIDDM patients with stable blood sugar.Group C included 40 cases of normal individual.Xanthine enzyme method was used to test SOD.Results The total SOD(T-SOD),CuZn-SOD,Mn-SOD in group A,B and C were 94 7?10 7,58 3?6 2 and 36 4?4 3;101 6?9 3,61 5?5 6 and 39 6?3 7;104 4?8 9,63 7?5 3 and 40 7?4 1;respectively.The SODs level in group A were significant lower than those in group B and group C(P