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RESUMEN Introducción: El cáncer de pulmón está afectando cada vez más a la población de adultos mayores, a medida que la expectativa de vida aumenta. Sin embargo, es difícil establecer la eficacia de la quimioterapia y el pronóstico de estos pacientes es grave. Objetivo: Presentar un caso de paciente adulto mayor con cáncer de pulmón avanzado de células no pequeñas, con una prolongada sobrevida que recibió solamente quimioterapia de primera línea. Caso clínico: Paciente no fumador, de 71 años, diagnosticado con cáncer de pulmón de células no pequeñas avanzado, del subtipo adenocarcinoma, con compromiso pleural. Inició tratamiento con carboplatino 5 AUC y gemcitabina 1,1 g. En el noveno ciclo, se encontró reducción de los nódulos pulmonares, pero también metástasis en el nivel D6-D7. Inició la segunda línea de tratamiento con carboplatino 5,4 AUC, paclitaxel 200 mg y ácido zolendrónico en dosis de 4,0 mg. Debido a eventos adversos, el tratamiento fue cambiado a vinorelbina 2,5 g y ácido zolendrónico 4,0 mg. Tras dos ciclos, el paciente fallece, alcanzando 21 meses de sobrevida global, solo con quimioterapia. Conclusión: El tratamiento del paciente adulto mayor con cáncer de pulmón es complejo. En el presente esquema de quimioterapia, el paciente pudo alcanzar 21 meses de sobrevida global, a pesar de que no fue caracterizado molecularmente.
ABSTRACT Introduction: Lung cancer is taking an increasing toll on the older population as life expectancy increases. However, the efficacy of chemotherapy is difficult to establish and the prognosis of these patients is severe. Objective: Report a case of an older adult patient with advanced non-small cell lung cancer with prolonged survival who received only first-line chemotherapy. Case report: A 71-year-old non-smoker patient diagnosed with advanced non-small cell lung cancer, adenocarcinoma subtype, with pleural involvement. He started treatment with carboplatin 5 AUC and gemcitabine 1,1 g. In the ninth cycle, reduction of pulmonary nodules was found, but he also had metastases at the D6-D7 level. He started the second line of treatment with carboplatin 5,4 AUC, paclitaxel 200 mg and zolendronic acid at a dose of 4,0 mg. Due to adverse events, the treatment was changed to vinorelbine 2,5 g and zolendronic acid 4.0 mg. After two cycles, the patient died, reaching 21 months of overall survival, only with chemotherapy. Conclusion: The treatment of the older adult patient with lung cancer is challenging. In the present chemotherapy treatment, the patient was able to achieve 21 months of overall survival, despite the fact that he was not molecularly characterized.
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@#[Abstract] Objective: To investigate the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC (non-small cell lung cancer) with Meta-analysis. Methods: Literatures regarding the effects of antibiotics on the treatment efficacy of immune checkpoint inhibitors in NSCLC were searched in Pubmed, Cochrane Library, Embase, EBSCO, Chinese Biomedical Literature Database(CBM) and Chinese Journal Full-text Database(CNKI). RevMan 5.3 software was used in this Meta-analysis. Results: Fourteen articles involving 2 505 NSCLC patients were included in this study. Meta-analysis showed that the application of antibiotics could significantly shorten the PFS (HR=1.14, 95%CI =1.04-1.26, P=0.005) and OS (HR=1.30, 95%CI =1.14-1.47, P<0.0001) of NSCLC patients treated with immune checkpoint inhibitors. Conclusion: Application of antibiotics before, concurrently or after immune checkpoint inhibitors in the treatment of NSCLC may significantly shorten PFS and OS, resulting in adverse effect on treatment efficacy.
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@# Objective: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy as comparing with chemotherapy alone for the first-line treatment of advanced NSCLC (non-small lung cancer). Methods: RCTs (randomized controlled trials) on PD-1/PD-L1 inhibitor combined with chemotherapy compared with chemotherapy alone for the first-line treatment of advanced NSCLC were searched in the PubMed, Cochrane Library, EMbase, EBSCO, Chinese Biomedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), and Chinese Scientific Journal Full-text Database (VIP). RevMan 5.2 software was used for the Meta-analysis. Results: Six RCTs with 3 238 advanced NSCLC patients were included in this study. Meta-analysis showed that the combination therapy group was more effective than the chemotherapy alone group in OS (HR=0.86, 95%CI=0.79~ 0.94, P=0.0006) and PFS (HR=0.81, 95%CI=0.78~0.84, P<0.00001). The incidence of adverse reactions, such as thrombocytopenia of grade 1-5, vomiting, diarrhea, hypothyroidism, hyperthyroidism, rash, pneumonitis, colitis, hepatitis, dysgeusia, hepatitis of grade 3-5 and colitis, in combined treatment group were all higher than those in chemotherapy alone group, the differences were statistically significant (P<0.01 or P<0.05). Conclusions: Compared with chemotherapy alone, PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the OS and PFS of patients with advanced NSCLC in the first-line treatment, while the overall incidence of adverse reactions is higher than chemotherapy.
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Objective The purpose of this study was to investigate the mechanism of Bmi-1 regulating the sensitivity of non-small cell lung cancer (NSCLC) to chemotherapy by observing its effects on multidrug-resistance protein 1 (MDR1) and apoptosis-related proteins. Methods Small interfering RNAs (siRNA) targeting Bmi-1 were transfected into A549 and A549/DDP cells of NSCLC and the logarithmic-phase cells were randomly divided into a siRNA-Bmi-1, a siRNA-negative control and a blank control group. The A549 cells were treated with siRNA-Bmi-1, DDP or Bmi-1+DDP, or left untreated (the control). CCK8 assay was employed to measure the 50% inhibitory concentration (IC50) of cisplatin in the A549 and A549/DDP cells before and after treatment. The apoptosis of the cells was detected by flow cytometry, the mRNA expression of Bmi-1 determined by RT-PCR, and the relationship of Bmi-1 with MDR1 and cleaved caspase-3 proteins analyzed by Western blot. Results After transfection, the relative mRNA and protein expressions of Bmi-1 in the A549 and A549/DDP cells were significantly lower in the siRNA-Bmi-1 than in the blank control group (P < 0.05), but higher in the A549/DDP than in the A549 cells. The survival rates of the A549 and A549/DDP cells were decreased with the increased concentration of cisplatin (P < 0.05), even lower in the Bmi-1+DDP than in the DDP subgroup (P < 0.05). The apoptosis rate of the A549 cells was markedly higher in the Bmi-1+DDP than in the DDP, Bmi-1 and control groups ([39.65±3.41]% vs [23.11±1. 62] %, [2.05±1.56]% and [1.98±1.05]%, P < 0.05). After 24 hours of treatment with DDP, both the expressions of Bmi-1 and MDR1 were remarkably elevated, while the down-regulation of Bmi-1 significantly decreased the expression of MDR1 and increased that of cleaved caspase-3. Conclusion The expression of siRNA-Bmi-1 makes non-small lung cancer cells more sensitive to cisplatin, which might be associated with its inhibition of MDR1 expression and activation of apoptosis-related proteins.
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Artocarpus heterophyllus has been used as traditional medicine. This plant is one of the sources of flavonoid. Flavonoid compounds possessed a wide range of biological properties including anticancer. This study was performed to investigate the cytotoxic effect of flavonoids from A. heterophyllus on H460 and MCF-7 cell lines. The interaction of flavonoids and cisplatin against tested cancer cells was also evaluated. MTT assay was used to determine the cytotoxic effect of flavonoid. Isobologram analysis was selected to evaluate the synergistic effect between flavonoid and cisplatin, their interaction was then confirmed using AO/PI staining method. Amongst of flavonoid compounds, artocarpin exhibited strong cytotoxic effect on both MCF-7 and H460 cell lines with IC₅₀ values of 12.53 µg/mL (28.73 µM) and 9.77 µg/mL (22.40 µM), respectively. This compound enhanced anticancer activity of cisplatin against H460 and MCF-7. The combination produced a synergistic effect on H460 and MCF-7 cell lines with a combination index (CI) values of 0.2 and 0.18, respectively. The AO/PI stained demonstrated that the combination of artocarpin and cisplatin caused morphological changes that indicated apoptosis. Moreover, artocarpanone also significantly increased cytotoxic effect of cisplatin compared to its single concentration with CI below than 1. This result suggested the potency of flavonoid named artocarpin to enhance the anticancer activity of cisplatin on H460 and MCF-7 cell lines.
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Apoptosis , Artocarpus , Cell Line , Cisplatin , Flavonoids , MCF-7 Cells , Medicine, Traditional , Methods , PlantsABSTRACT
@#Objective To evaluate the prognosis of different node status on the basis of the eighth TNM classification for lung cancer. Methods We retrospectively reviewed the clinical data of 1 851 non-small cell lung cancer (NSCLC) patients who underwent radical resection between January 2005 and December 2014. There were 1 078 males and 773 females at age of 16–86 (59.7±9.7) years. Survival probability was estimated by the Kaplan-Meier method and significance was assessed by the log-rank test. Results This cohort study was consisted of 1 209 patients with N0, 305 with N1 and 337 with N2. N0 patients were divided into a N0a group and a N0b group according to whether the 13 and 14 level of lymph nodes were examined. The survival rate of the N0a group was significantly higher than that of the N0b group, and the 5-year survival rate was 88.9% and 81.3% (P<0.001), respectively. According to the number of lymph node metastasis stations, N1 was divided into a N1a (single) group and a N1b (multiple) group. And no significant difference was observed between the two groups in survival rate (P=0.562). Based on the presence of lymph nodes of 10–12 level, N1 was divided into a negative group and a positive group. And the negative group was found with significantly higher survival rate than the positive group (5-year survival rate of 78.4% vs. 64.3%, P=0.007). The N2 patients were divided into a single station metastasis group (a N2a1 group), a single station with N1 positive group (a N2a2 group) and a multiple station group (a N2b group), and the percentage was accounted for 22.0% (74/337), 37.7% (127/337) and 40.3% (136/337), respectively. There was a statistical difference in 5-year survival rate (62.2% vs. 56.5% vs. 37.3%) among the three groups (P=0.001). Conclusion Subgroup analysis of N staging in NSCLC patients shows significant survival differences which may be more consistent with multidisciplinary therapy under precise staging patterns.
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Objective To investigate the expression of beclin1 and LC3 in non small cell lung cancer and explore their clinical significance. Methods Immunohistochemistry was applied to confirm expression of Beclin1 and LC3 in 66 samples of NSCC and 52 samples of adjacent tissues. Clinical pathological features were analyzed. Results Beclin1 and LC3 expression were lower in cancer tissues than that in adjacent cancer tissues ,and the dif-ference was statistically significant(46.9%vs 75%,53%vs 80.7%,P<0.05). The expression of Beclin1 and LC3 was down-regulated with TNM staging rising and tissue differentiation decreasing. With tumor enlarging ,Beclin1 down-regulated,and the difference is statistically significant(P<0.05). Expression of Beclin1 was positively cor-related with LC3 expression(r=0.31,P<0.05). Conclusion The down-regulation of autophagy-related protein Beclinl and LC3 might be involved in the genesis and development of non small lung cancer.
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Objective To analyze the mechanism of pigment epithelium?derived factor(PEDF)regulation in lung cancer cell proliferation and migration by vascular endothelial growth factor(VEGF). Methods VEGF expression was observed after overexpression or silencing of PEDF. Proliferation and migration were analyzed by MTT and transwell assays. Real?time PCR and Western blotting were performed to investigate the mechanism underlying PEDF regulation of the VEGF/SRC/FAK pathways. Results PEDF could inhibit the proliferation and migration of A549 cells by VEGF. Conclusion PEDF can be considered as a potential therapeutic target for lung cancer.
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Objective To investigate the genetic polymorphisms of the glutathione S-transferase M1 and T1 genes(GSTM1 and GSTT1),and eval-uate the oxidative damage in patients with non-small lung cancer(N-SCLC). Methods A total of 110 patients with N-SCLC and 100 healthy indi-viduals were recruited in this case-control study. Multiplex polymerase chain reaction(PCR)analysis was used to identify the genotypes. The activi-ty of malondialdehyde(MDA),nitric oxide(NO),and the total antioxidant capacity(T-AOC)were detected by spectroscopic analysis using assay kits. Results The frequencies of the GSTM1,T1,and GSTM1/T1 null genotypes in the patient group were significantly higher than those in control group(OR1=2.071,P1=0.009;OR2=1.900,P2=0.024;OR3=3.258,P3=0.003). The activity of MDA and NO were obviously higher in the pa-tient group compared with the control group(P<0.001),and T-AOC was obviously lower in patient group than those in control group(P<0.001). The activity of MDA,and NO were higher but the T-AOC were lower in patients with GSTM1,T1 and GSTM1/T1 null genotypes than those in pa-tients with GSTM1,T1 and GSTM1/T1 present genotypes(P<0.001). Conclusion Our results suggest that oxidative damage may play a impor-tant role in patients with N-SCLC,and the N-SCLC patients with GSTM1and GSTT1deletion genotypes are more susceptible to oxidative damage.
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Objective To investigate the relationship of epidermal growth factor receptor (EGFR) mutation with clinical features of baselines as well as serum CEA level in patients with recurrent non-small cell lung cancer (NSCLC). Methods A total of 54 patients with first recurrence of advanced lung cancer who had received chemotherapy were included in this study. ADx-ARMS was performed to detect EGFR gene mutations in surgical specimens taken from the primary tumor. Serum CEA level was measured by the electrochemical luminescence method. Results The mutation rate of EGFR was significantly higher in females than in males (χ2= 11.868, P =0.006), with a total mutation rate of 60.8%in 106 patients. The rate was higher in adenocarcinoma than in other histological types(χ2=6.002,P=0.014), and significantly higher in non-smokers than in smokers (χ2= 8.502,P=0.004) and in the patients with serum CEA level over or equal to 5.0 ng/mL than those with CEA level less than 5.0 ng/mL (χ2=22.543,P=0.000). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence was associated with EGFR gene mutations (P = 0.002). Conculsions Serum CEA level is closely associated with the presence of EGFR gene mutations in patients with first recurrence of advanced NSCLC. A higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations. CEA level can be used as a potential indicator to determine EGFR mutation.
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Objective To compare the serum anti-survivin antibody levels between benign and malignant lung tumor,thus to provide evidence for using anti-survivin antibody as an indicator in non-small cell lung cancer.Methods ELISA was used to measure the level of anti-survivin antibody in healthy population(control group,n=60),benign lung tumor patients(benign lung tumor group,n=60) and non-small cell lung cancer patients(non-small cell lung cancer group,n=60). Results The anti-surviving antibody did not express 11.7%(7/60) in the control group and almost no expression 20.0%(12/60) in the benign lung tumor group,with no significant difference between the two groups(P＞0.05).In the non-small cell lung cancer group,the anti-survivin antibody expressed in 41 patients,which was significantly higher than those in the benign lung tumor group(x2=38.352,P＜0.01).Conclusion Anti-survivin antibody does not express in the healthy population and the benign lung tumor patients,whereas shows high expression in non-small cell lung cancer.This finding indicates that anti-survivin antibody can provide important evidence for non-small cell lung cancer diagnosis,and can be used as an indicator for non-small lung cancer screening.
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Objective: To observe the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in non-small cell lung cancer(NSCLC), and to discuss its clinical significance. Methods: The expression of EGFR and VEGF was detected in 82 NSCLC and 20 non-malignant pulmonary samples by immunohistochemical method. The expression of EGFR and VEGF in NSCLC patients with various pathological characteristics was observed and the correlation between them was analyzed. Results: The positive rates of EGFR and VEGF in 82 NSCLC samples were obviously higher than those in the 20 non-malignant samples(53.66% vs 0 for EGFR, 62.20% vs 25% for VEGF, both P<0.05). The expression of EGFR in NSCLC samples was significantly correlated with the sex of patients, pathological types of cancer (squamous-cell carcinoma vs adenocarcinoma), presence of lymph node metastasis, and TNM stages(P<0.05). The expression of VEGF in NSCLC was correlated with lymph node metastasis and TNM stages (P<0.05). It was also noticed that higher expression of EGFR or VEGF was associated with poor prognosis of patients (P<0.05). The expression of EGFR was correlated with VEGF expression in pulmonary tissues of NSCLC patients(rs = 0.314, P<0.05). Conclusion: EGFR and VEGF are over-expressed in NSCLC tissues and the 2 are correlated with each other, which may serve as predicator for prognosis and a therapeutic target of NSCLC patients.
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Objective To investigate the expression of survivin and bcl-xl in non-small cell lung cancer(NSCLC)and their relationship.Methods The NSCLC tissuechips including 32 cores were constructed and expression of survivin and bcl-xl was examined by immunohistochemical technique in 30 normal bronchial epithelium and 32 primary NSCLC.Results The positive rate of survivin and bcl-xl protein in NSCLC was 71.9% and 81.3% respectively,significantly higher than that in the normal ones(P0.05).The expression of bcl-xl protein was closely related to cell differentiation(P0.05).The over-expression of survivin and bcl-xl was positively correlated(P
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Background and purpose:Both very important therapeutic targets of NSCLC,vascular endothelial growth factor (VEGF) and epidermal growth factor receptors (EGFR),are over expressed in non-small cell lung cancer (NSCLC).The aim of this study was to discuss the expression of VEGF and EGFR in NSCLC as well as its clinical significance.Methods:The expression of VEGF and EGFR was detected in 186 NSCLC samples using the immunohistochemical method.The expression of VEGF and VEGR in NSCLC patients with various pathological characteristics was observed and the correlation between them was analyzed.Results:The expression of VEGF in NSCLC was correlated with lymph node metastasis (P
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Background and purpose:Twist has been identifi ed as tumor metastasis promoter transcription factor and KiSS-1 has been identified as tumor metastasis suppressor gene,and both of them have been identified to be associated with the metastatic potential of non-small cell lung cancer(NSCLC) .Our aim was to identify the expression of both Twist and KiSS-1 in NSCLC and analyze their correlation with patients’ survival.Methods:Immunohistochemical staining using monoclonal Twist and KiSS-1 antibody were performed on paraffi n embedded specimens from 61 patients diagnosed with NSCLC,and 15 specimens of tumor surrounding lung tissue were used as control.The association with clinicopathologic data and prognosis of NSCLC were analyzed.Results:The expression of Twist was significantly higher in NSCLC than in tumor surrounding lung tissue(P
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Background and purpose:Pemetrexed is a multitargeted anti-metabolite. Pemetrexed has been approved as the second-line treatment in non-small cell lung cancer. Our aim was to evaluate the clinical effi ciency and toxicity of pemetrexed in treatment of advanced retreated non-small cell lung cancer. Methods:17 advanced retreated NSCLC patients received pemetrexed at a dose of 500 mg/m2, the chemotherapy was repeated every 21 days on two cycles until progressive disease or untolerant adverse effects. Results:Among 17 patients, the overall response rate was 11.8%, the clinical benefi t rate was 76.5%, and the main toxicity was hematological toxicties. Conclusions: Pemetrexed is effective in treatment of advanced retreated non-small lung cancer and the toxicity can be well tolerated.
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Purpose:The phase I study was conducted to evaluate the maximum tolerated dose (MTD) and toxicity of weekly administered docetaxel combined with cisplatin in patients with non-small cell lung cancer ( NSCLC ). The other objective was to measure the pharmacokinetic/dynamics (PK/PD).Methods:In the dose escalation study, 15 patients with unresectable and metastatic untreated NSCLC with performance status(0-1) were enrolled. Escalating doses of D 25 mg/m 2 (30 mg/m 2, 35 mg/m 2, 40 mg/m 2) on day 1, 8, 15 were given as a 30 min iv infusions and C 75 mg/m 2 30 min iv infusion after D on day 1 and the cycle was repeated every 4 weeks. Blood samples were drawn on day 1 and 15 in the first cycle to measure the PK. Dose limiting toxicity(DLT) was based on Cycle 1 and defined as any Grade 3 non-hematologic toxicity not declining to Grade 2 or less within 4 days or any Grade 4 toxicity. Results:Chemotherapy was repeated for at least two cyc1es every 28 days. All patients were assessable for toxicities. Although grade 3/4 neutropenia occurred, there were no significant modifications of chemotherapy schedule. One patient developed an infection (DLT). Non-hematological toxicities, including nausea/vomiting, a1opecia, fluid intension and asthenia were tolerable. Based on these data, the MTD has not yet reached up to dose level of docetaxel of 40mg/m 2 weekly given in combination with cisplatin 75mg/m 2 every 4 weeks at the fixed dose. The exposure to docetaxel after Ⅳ administration on day 1 in combination with cisplatin and on day 15 without cisplatin , increased proportional to the dose for the range 25 to 40 mg/m 2, as measured by Cmax and AUC. No statistically significant difference between clearance values was shown for the 4 dose levels. The pharmacokinetics of docetaxel was not influenced by the coadministration of cisplatin on day 1 as compared to day 15, as the CmaxN, AUCN and CL were not statistically significantly different on both days. Fourteen patients were eva1uab1e for response, five cases achieved partial response, and thus the overall response was 35.7%. 1, 2, and 3 year survivals were 73%, 27%, and 20%, respectively. Weekly administration of docetaxel at 35mg/m 2 (days 1, 8, l5) combined with cisplatin 75mg/m 2 (day 1) is recommended for phase Ⅱ studies. Conclusions:Using the weekly schedule, toxicity was mainly manifested by non-hematologic profile and was well tolerated. A phase Ⅱ study is currently ongoing with docetaxel 35mg/m 2 as the suggested dosage.
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Purpose:To evaluate the clinical effects and indications of surgical treatment of non small lung cancer invading the left atrium and great vessels and trachea carina. Methods:From August 1998 to Auguest 2003, we performed operations on patients with non-small lung cancer invading the left atrium in 3 cases, invading the descending aorta in 1 case, invading trachea carina in 3 cases; all the patients have been examined to exclude distant metastasis, including nuclear bone scan to exclude bone metastasis; there were 2 cases of left pneumonectomy and one of right pneumonectomy invading the left atrium, there were 3 cases of right sleeve pneumonectomy invading the trachea carina. For the cases invading the descending aorta, we performed the operation with atrium-aorta bypass, Pathology examination: all of the cases were squamous lung cancer, staging of T 4N 0M 0 for 6 cases,T 4N 2M o for 1 case. Results:No complication, follow up: 6 cases survived more than 1 year,1 case survived more than 9 months;4 cases were alive for more than 3 years, 1 case invading the atrium died in 30 months because of brain metastasis,1 case invading the carina died in 15 months because of pulmonary infection. Conclusions:For localized advanced non-small lung cancer invading the aorta and invading the carina and the atrium, if we selected the patient correctly and with a good surgical technique with complete radical resection of the tumor ,we can acquire good results.