KCNAB2 overexpression inhibits human non-small-cell lung cancer cell growth in vitro and in vivo.

Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC patients often have poor prognosis demanding urgent identification of novel biomarkers and potential therapeutic targets. KCNAB2 (regulatory beta subunit2 of voltage-gated potassium channel), encoding aldosterone reductase, plays a pivotal role in regulating potassium channel activity. In this research, we tested the expression of KCNAB2 as well as its potential functions in human NSCLC. Bioinformatics analysis shows that expression of KCNAB2 mRNA is significantly downregulated in human NSCLC, correlating with poor overall survival. In addition, decreased KCNAB2 expression was detected in different NSCLC cell lines and local human NSCLC tissues. Exogenous overexpression of KCNAB2 potently suppressed growth, proliferation and motility of established human NSCLC cells and promoted NSCLC cells apoptosis. In contrast, CRISPR/Cas9-induced KCNAB2 knockout further promoted the malignant biological behaviors of NSCLC cells. Protein chip analysis in the KCNAB2-overexpressed NSCLC cells revealed that KCNAB2 plays a possible role in AKT-mTOR cascade activation. Indeed, AKT-mTOR signaling activation was potently inhibited following KCNAB2 overexpression in NSCLC cells. It was however augmented by KCNAB2 knockout. In vivo, the growth of subcutaneous KCNAB2-overexpressed A549 xenografts was significantly inhibited. Collectively, KCNAB2 could be a novel effective gene for prognosis prediction of NSCLC. Targeting KCNAB2 may lead to the development of advanced therapies.

Strong bacterial stochasticity and fast fungal turnover in Taihu Lake sediments, China.

Understanding the assembly and turnover of microbial communities is crucial for gaining insights into the diversity and functioning of lake ecosystems, a fundamental and central issue in microbial ecology. The ecosystem of Taihu Lake has been significantly jeopardized due to urbanization and industrialization. In this study, we examined the diversity, assembly, and turnover of bacterial and fungal communities in Taihu Lake sediment. The results revealed strong bacterial stochasticity and fast fungal turnover in the sediment. Significant heterogeneity was observed among all sediment samples in terms of environmental factors, especially ORP, TOC, and TN, as well as microbial community composition and alpha diversity. For instance, the fungal richness index exhibited an approximate 3-fold variation. Among the environmental factors, TOC, TN, and pH had a more pronounced influence on the bacterial community composition compared to the fungal community composition. Interestingly, species replacement played a dominant role in microbial beta diversity, with fungi exhibiting a stronger pattern. In contrast, stochastic processes governed the community assembly of both bacteria and fungi, but were more pronounced for bacteria (R2 = 0.7 vs. 0.5). These findings deepen the understanding of microbial assembly and turnover in sediments under environmental stress and provide essential insights for maintaining the multifunctionality of lake ecosystems.

Angiotensin-(1-7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways.

BACKGROUND: There is no available viable treatment for Sepsis-Induced Cardiomyopathy (SIC), a common sepsis complication with a higher fatality risk. The septic patients showed an abnormal activation of the renin angiotensin (Ang) aldosterone system (RAAS). However, it is not known how the Ang II and Ang-(1-7) affect SIC. METHODS: Peripheral plasma was collected from the Healthy Control (HC) and septic patients and Ang II and Ang-(1-7) protein concentrations were measured. The in vitro and in vivo models of SIC were developed using Lipopolysaccharide (LPS) to preliminarily explore the relationship between the SIC state, Ang II, and Ang-(1-7) levels, along with the protective function of exogenous Ang-(1-7) on SIC. RESULTS: Peripheral plasma Ang II and the Ang II/Ang-(1-7) levels in SIC-affected patients were elevated compared to the levels in HC and non-SIC patients, however, the HC showed higher Ang-(1-7) levels. Furthermore, peripheral plasma Ang II, Ang II/Ang-(1-7), and Ang-(1-7) levels in SIC patients were significantly correlated with the degree of myocardial injury. Additionally, exogenous Ang-(1-7) can attenuate inflammatory response, reduce oxidative stress, maintain mitochondrial dynamics homeostasis, and alleviate mitochondrial structural and functional damage by inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thus alleviating SIC. CONCLUSIONS: Plasma Ang-(1-7), Ang II, and Ang II/Ang-(1-7) levels were regarded as significant SIC biomarkers. In SIC, therapeutic targeting of RAAS, for example with Ang-(1-7), may exert protective roles against myocardial damage.

Losartan attenuates sepsis-induced cardiomyopathy by regulating macrophage polarization via TLR4-mediated NF-κB and MAPK signaling.

Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis with high mortality but no effective treatment. The renin angiotensin (Ang) aldosterone system (RAAS) is activated in patients with sepsis but it is unclear how the Ang II/Ang II type 1 receptor (AT1R) axis contributes to SIC. This study examined the link between the Ang II/AT1R axis and SIC as well as the protective effect of AT1R blockers (ARBs). The Ang II level in peripheral plasma and AT1R expression on monocytes were significantly higher in patients with SIC compared with those in non-SIC patients and healthy controls and were correlated with the degree of myocardial injury. The ARB losartan reduced the infiltration of neutrophils, monocytes, and macrophages into the heart and spleen of SIC mice. Additionally, losartan regulated macrophage polarization from the M1 to the M2 subtype via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby maintaining the mitochondrial dynamics balance in cardiomyocytes and reducing oxidative stress and cardiomyocyte apoptosis. In conclusion, the plasma Ang II level and AT1R expression on plasma monocytes are an important biomarker in SIC. Therapeutic targeting of AT1R, for example with losartan, can potentially protect against myocardial injury in SIC.

[Phosphorus Adsorption Characteristics and Loss Risk in Sediments of Lake Bay During the Overwinter Period of Cyanobacteria].

The overwinter period is the pre-stage of the algal bloom, and the endogenous phosphorus (P) in sediments is one of the main P sources of algal blooms during this period. Based on the investigation of the water quality and sediment pollutants during the overwinter period of cyanobacteria (recruitment period and dormancy period), this study analyzed the P release characteristics of sediments in the horizontal and vertical directions and clarified the P release risk of sediments and the change in microbial community structures. The results showed that the lake bay was moderately eutrophic in the two periods of the study area, and the water quality and sediment nitrogen and P pollution were more serious, and the chlorophyll a content (Chl-a) was still at a high level in the overwinter period. The pseudo-second order model and the modified Langmuir model could respectively describe the P kinetics and sorption isotherm behavior in the sediment. The theoretical maximum P sorption capacities (Qmax) of sediments were bottom layer>middle layer>surface layer, and the highest value was 1.648 mg·g-1 with the highest P sorption rate constant of the pseudo second-order kinetic model of 6.292 g·(mg·min)-1. Additionally, the P adsorption parameters (Qmax, NAP, and EPC0) were mainly affected by the physical and chemical properties of the sediment itself and the nutritional level of the lake bay. The surface sediments from the dormancy period mainly played the role of P sinks, and the part of sediments from the recruitment period played the role of P sources, in which existed the risk of endogenous P release. The analysis of the microbial community structure in sediments indicated that the microbial diversity in the sediments during the dormancy period was higher than that during the recruitment period, and some microbial categories with phosphate-solubilizing function of relative abundance was high.

Landscape and progress of global COVID-19 vaccine development.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected billions of lives globally, and the world hopes to end this epidemic by effective vaccination. In this review, we depict the latest panorama of global COVID-19 vaccine research and development based on different technology platforms, and summarize key characteristics and available evidence on vaccines authorized for emergency use, in order to provide insights into improve coordination in the COVID-19 outbreak response for related stakeholders.

Missed rib fractures on initial chest CT in trauma patients: time patterns, clinical and forensic significance.

OBJECTIVE: To analyze missed rib fractures and proper time for evaluation on CT at different ages and to determine factors that favor missed fractures. METHODS: One hundred patients with rib fractures who underwent CT were classified into three groups according to their age: young, middle-aged, and elderly. CT was performed within 1 to 6 weeks after trauma. The imaging features and temporal changes of rib fractures were analyzed. RESULTS: At the first CT during the initial week, 638 ribs were detected with one or several fractures, overall 838 fractures were confirmed, and 6 were suspected. In the next 2-6 weeks, 47 occult rib fractures were additionally detected. The number of additionally diagnosed fractures was the highest in respectively the 3rd week among younger, 4th week in the middle-aged, and 6th week in the elderly groups. The detection of occult rib fractures was significantly delayed in the middle-aged and elderly groups compared with the young group (p < 0.05). The time to form bony callus was also significantly (p < 0.05) delayed with age, with significantly (p < 0.05) more time needed to form bony callus in the middle-aged (23.8 ± 4.5 days) and elderly (28.48 ± 5.1 days) groups than in the young group (18.0 ± 2.2 days). CONCLUSIONS: Most rib fractures can be detected within the first week after trauma. Detection of occult rib fractures will be delayed with increase of age, and repeated CT scanning should be appropriately postponed in patients at different ages. Trabecula, inner and outer plates, costal angle, and cartilage are the primary locations for occult and subtle fractures which should be carefully evaluated. KEY POINTS: • More rib fractures can be detected on repeated CT scans, especially for subtle and occult rib fractures. • Detection of all rib fractures helps relieve the patient's concerns and determine the degree of personal injury for appropriate evaluation.

[Temporal and Spatial Distribution Characteristics and Difference Analysis of Nitrogen and Phosphorus in Daihai Lake].

Based on the historical monitoring survey data from 2018 to 2019, the temporal and spatial distribution characteristics and main influencing factors of nitrogen and phosphorus in the overlying water in Daihai Lake were analyzed, and the differences of the temporal and spatial distribution were discussed. The results showed that the content of total nitrogen and total phosphorus in the overlying water was at a high level, especially the total nitrogen content was obviously higher than that in other lakes in China. The content of total nitrogen ranged from 3.29 mg·L-1 to 4.99 mg·L-1, with a mean value of (3.93±0.33) mg·L-1; the content of total phosphorus ranged from 0.063 mg·L-1 to 0.163 mg·L-1, with a mean value of (0.111±0.023) mg·L-1. In spring and summer, the content of total nitrogen and total phosphorus in the overlying deep water from the middle of the lake was significantly higher than that in the surrounding area. In autumn, the contents decreased from east to west, and in winter, the contents in the shallow water of the southern area were higher than that in the northern area. Nitrogen and phosphorus in the overlying water were mainly in the dissolved state, and the proportions of total dissolved nitrogen and phosphorus were 86.62% and 77.84%, respectively. The dissolved nitrogen was dominated by nitrate, whereas dissolved phosphorus was dominated by organic phosphorus. The concentration of lake water and the release of endogenous nutrient salts are the main reasons for the high total nitrogen and phosphorus. To prevent further deterioration of water quality, it is suggested to carry out endogenous treatment and ecological restoration in combination with engineering measures.

Pharmacoeconomic Evaluation of Cancer Biosimilars Worldwide: A Systematic Review.

Background and Purpose: The availability of oncology biosimilars is deemed as a fundamental strategy to achieve sustainable health care. However, there is scarce systematic evidence on economic effectiveness of cancer biosimilars. We aimed to synthesize evidence from pharmacoeconomic evaluation of oncology biosimilars globally, provide essential data and methodological reference for involved stakeholders. Materials and Methods: This systematic review was conducted in PubMed, embase, the Cochrane library, CRD, ISPOR and NICE utill December 31, 2019. Information on basic characteristics, evaluation methodology and results were extracted. Quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards Checklist. Results: For 17 studies identified (13 from Europe and four from United States), the overall quality was generally acceptable. A total of seven biological molecules involved with filgrastim, EPOETIN α, and trastuzumab leading the three. The mostly common evaluation perspective was payer, but the time horizon varied greatly. There were ten studies which adopted cost minimization analysis to evaluate efficiency while seven studies adopted budget impact analysis to address affordability, with cost ratio and cost saving being its corresponding primary endpoint. Although the comparability of included studies was limited and specific results were largely affected by uptake and price discount rates of the oncology biosimilar, the comprehensive results consistently favored its promotion. Conclusion: Globally, the economic evaluation of cancer biosimilars is in its initial phase. However, limited evidence from developed countries consistently supported both cost-effectiveness of efficiency and affordability of oncology biosimilars, while they were largely affected by uptake and price discount rate.

Changes in clinical trials of cancer drugs in mainland China over the decade 2009-18: a systematic review.

As a result of recent, substantial capacity building, a new landscape for cancer drug trials is emerging in China. However, data on the characteristics of cancer drug trials, and how they have changed over time, are scarce. Based on clinical trials published on the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, we aimed to systematically review changes over time in clinical trials of cancer drugs in mainland China from 2009 to 2018, to provide insight on the effectiveness of the pharmaceutical industry and identify unmet clinical needs of stakeholders. A total of 1493 trials of 751 newly tested cancer drugs were initiated. Increases over time were observed for the annual number of initiated trials, newly tested drugs, and newly added leading clinical trial units, with a sharp increase after 2016. Of the 1385 trials in which cancer types were identified, solid tumours (325 [23%] trials), non-small-cell lung cancer (232 [17%]), and lymphoma (126 [9%]) were the most common. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east China (50 [41%]) and the smallest number located in southwest China (4 [3%]). The growth trends we observed illustrate the progress in and increasing capability of cancer drug research and development achieved in mainland China over the decade from 2009. The low number of clinical trials on tumours with epidemiological characteristics unique to the Chinese population and the unbalanced geographical distribution of leading clinical trial units will provide potential targets for policy makers and other stakeholders. Further research efforts should address cancers uniquely relevant to Chinese populations, globally rare cancers, and the balance between equitable drug access, efficiency, and sustainability of cancer drug research and development in mainland China.

[Fluorescence Spectral Characteristics of Fluorescent Dissolved Organic Matter (FDOM) in the Surface Sediments from Lihu Lake].

This study investigated the spectral characteristics of fluorescent dissolved organic matter (FDOM) in sediments of Lihu Lake using three-dimensional excitation-emission matrix fluorescence spectroscopy (EEMS),and discussed the correlation between source of FDOM and organic or inorganic nitrogen.The results indicated that the surface sediments in Lihu Lake consisted of three fluorescence fractions (Ⅱ),humic-like C1(240,310/420 nm),C2(260,360/460 nm),and tryptophan-like C3(225,275/340 nm).The total fluorescence intensity ranged from 49.97 to 159.19 R.U.·g-1,and decreased from east to west with higher values in coast district than in lake center.The relative proportions of C1,C2,and C3 were 33.63%,26.87% and 39.49%,respectively.The fluorescence index (FI),biological origin index (BIX),and humification index (HIX) ranged from 1.96 to 2.22,0.69 to 0.94,and 2.62 to 4.39.It indicated that the main source of FDOM in Lihu Lake was from endogenesis,and mainly derived from microbes,algae and other newly autochthonous sources.The results illustrated,the fluorescence intensity had significant correlation with organic and inorganic nitrogen (P<0.01),and had higher correlation with inorganic nitrogen.

Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R mutations exhibit different responsiveness to EGFR-TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes. METHODS: Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR-TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high-performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next-generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations. RESULTS: Of the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR-TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression-free survival (PFS) after first-line EGFR-TKI treatment (14.4 vs. 11.4 months, P = 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment, and there was no significant difference in the co-existence of T790M mutation with EGFR 19 del and L858R mutations before EGFR-TKI treatment (5.6% vs. 8.8%, P = 0.554) or after treatment (24.4% vs. 35.4%, P = 0.176). In addition, 24 patients with EGFR 19 del and 19 with L858R mutations were analyzed by NGS, and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes. CONCLUSIONS: Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858R mutations. Whether the heterogeneity of tumors with EGFR 19 del and L858R mutations contribute to a therapeutic response difference needs further investigation.

[Determination of Background Value and Potential Ecological Risk Assessment of Heavy Metals in Sediments of the Danjiangkou Reservoir].

The aim of this study was to explore the pollution level and potential ecological risk of heavy metals in sediments of the Danjiangkou Reservoir, and the study obtained the background value of heavy metals of the surface sediments using reference element and statistical methods. The results indicated that the background values of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb were 41.18, 34, 32.13, 76.84, 10.46, 0.70, 0.07 and 27.11 mg·kg-1, respectively. In addition, the potential ecological risks of the eight heavy metals in sediments were assessed using the Hakanson ecological risk index method. The values of RI for these eight metals in surface sediments ranged from 29.49 to 214.11, with the mean value of 118.91, and the pollution level was low. Furthermore, the Cfi value was in the order of Cd> Hg> Zn> Cr> Pb> Ni> As=Cu with the mean value of 1.05-1.31, and the pollution level varied from low to intermediate. The Cfi values of Cd and Hg were higher than those of other heavy metals with the mean values of 1.31 and 1.24, respectively, which should be paid more attentions.

[Variation of Nitrogen Forms in Sediments of Lihu Lake During Mineralization].

After 10 years of controlling point source sewage in Lihu Lake, the total nitrogen in water is still at a higher level. To explore the effects of sediment nitrogen release on overlying water, the method of submerged water cultivation was used to study changing characteristics of different nitrogen species in the process of sediment mineralization and the exchange between organic nitrogen and inorganic nitrogen of the mineralization process transformation process was discussed. The results showed that, the mean value of free nitrogen(FN) increased from 94.26 mg·kg-1 to 230.71 mg·kg-1 after nitrogen mineralization in the sediment, when ammonium and solved organic nitrogen (SON) were dominant; the mean value of exchangeable nitrogen (EN) increased from 82.50 mg·kg-1 to 165.32 mg·kg-1 with ammonium being the main species; the mean value of acid solution nitrogen (HN), which gave priority to amino acid nitrogen (AAN), decreased from 1044.70 mg·kg-1 to 815.93 mg·kg-1, and residual nitrogen (RN) basically remained unchanged. In the submerged cultivation process, acid solution state of total nitrogen fell from 67.18% to 52.50%, the reduction was mainly caused by mineralization and decomposition of AAN and ammonium nitrogen (AN), moreover, AAN was one of the most effective sources of inorganic nitrogen after sediment mineralization. Comparison of the results of estuaries and lakes showed that, the larger the amount of sediment was, the more the mineralized inorganic nitrogen was.

Rechallenge with pemetrexed-based chemotherapy improves the survival of patients with advanced non-squamous non-small-cell lung cancer.

Rechallenge chemotherapy with pemetrexed was shown to be efficient in malignant pleural mesothelioma; however, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, we retrospectively enrolled 31 patients with non-squamous NSCLC who had achieved disease control with initial pemetrexed treatment, followed by rechallenge with pemetrexed-based chemotherapy (PBC) upon disease progression. After the rechallenge, 5 patients (16.1%) achieved partial remission (PR), 17 (54.8%) achieved stable disease (SD) and 9 (29.1%) experienced progressive disease. The treatment was generally well tolerated, with a low rate of toxicity. The median progression-free survival (PFS) was 3.8 months with the rechallenge. Patients with a PFS of ≥10 months with initial PBC exhibited longer PFS and overall survival (OS) with the rechallenge compared to those with a PFS of <10 months with initial PBC (PFS: 6.2±0.33 vs. 3.1±0.26 months, respectively; P=0.011; and OS, 19.8±3.2 vs. 9.2±1.1 months, respectively; P=0.005). The time from the termination of initial PBC to disease progression was also associated with survival after the rechallenge. However, the response to initial PBC (PR vs. SD) did not affect PFS after the rechallenge. No significant differences were observed in thymidylate synthase expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene fusion, or epithelial growth factor receptor mutation status between pemetrexed-sensitive and pemetrexed-resistant patients. Our results demonstrated that rechallenge with PBC was well tolerated and survival after the rechallenge was associated with survival during initial PBC. Therefore, patients with a PFS of ≥10 months or time-to-disease progression ≥3 months may be considered as candidates for pemetrexed rechallenge.

[Heavy metal speciation and stability in the sediment of Lihu Lake].

The spatial occurrence characteristics of the speciation of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in sediments of the lake body and river mouths of Lihu Lake were studied. Meanwhile, combined with the spatial distribution of metals in interstitial water, the stability and bio-availability of various forms of studied metals were discussed. The results showed that metals in interstitial water and extractable metals in surface sediments both had obvious spatial heterogeneity, and the metal contents in retreated fishery district were lower. High value areas of Cr, Cu and Zn distributed in belt along Baojie Bridge and Lihu Lake Bridge, and the high value areas of Ni, As, Cd, Hg distributed in sector extending from river mouths to the lake body. Most metals mainly existed in residue state except for Cd, Cu and Ni, the extractable content of which respectively accounted for 71.02%, 54.79% and 50.62% of the total content. The stability of eight studied metals was in the order of Cr > Pb > Hg > As > Cu > Ni > Zn > Cd. Cd and Zn were unstable in most studied sites, so there was higher risk of quick desorption and release. Toxicity assessment of interstitial water showed that the tested metals would not pose acute toxicity for aquatic ecosystem, but Hg and Pb in some districts, especially in the river mouths, might pose chronic toxicity for the benthonic organisms.

[Prognosis related clinical and molecular factors in malignant pleural mesothelioma].

OBJECTIVE: To identify potential prognosis related clinical and molecular factors in malignant pleural mesothelioma (MPM). METHODS: Seventy-nine patients with MPM treated in Beijing Cancer Hospital from June 1996 to May 2012 were enrolled in this study. Clinical and pathological data were collected, including age, gender, smoking status, treatment, response, and molecular biomarkers such as thymidylate synthetase (TS) expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangement. The primary endpoint was overall survival (OS). SPSS 16.0 statistical analysis software was used for univariate analysis. The expression of TS was detected by immunohistochemistry (IHC). Fluorescence in situ hybridization (FISH) was performed to detect EML4-ALK gene rearrangement. Efficacy of the chemotherapy regimen including pemetrexed was analyzed with these molecular biomarkers. RESULTS: The median survival time (MST) of all patients was 15.5 months (95% CI: 10.6 - 20.4). Univariate survival analysis revealed that treatment factors including receiving operation, systemic chemotherapy, pemetrexed-based chemotherapy and capability of receiving second (or above) line chemotherapy were significantly related with OS. The MST of patients receiving operation was 5.4 months (95% CI: 3.6 - 7.3), significantly shorter than the 17.7months (95% CI: 11.8 - 23.5) in those who didn't receive operation (P = 0.030). Patients receiving systemic chemotherapy had a longer MST of 18.0 months (95% CI: 12.3 - 23.8) as compared to the 7.9 months (95% CI: 1.1 - 14.7) in those who didn't (P = 0.001). The MST of pemetrexed-based chemotherapy was 21.9 months (95% CI: 14.1-29.7) compared with 8.8 months (95% CI: 4.2 - 13.4) of regimens without pemetrexed (P = 0.000). For patients capable of receiving second (or above) line chemotherapy the MST was longer (21.0 months, 95% CI: 12.7 - 29.3) than those who could not (12.1 month, 95% CI: 6.4 - 17.8 month), P = 0.022. For the 42 patients treated with pemetrexed-based chemotherapy, the objective response rate (ORR) was 33.3% (14/42), the disease control rate (DCR) was 78.6% (33/42), the median progression-free survival (PFS) was 4.8 months (95% CI: 3.6 - 6.0) and MST was 21.9 months (95% CI: 14.1 - 29.7). Twenty-nine patients provided adequate specimens for detection of TS expression and 6 cases (20.7%) were positive. EML4-ALK gene rearrangement was studied in 32 patients and 6 (18.8%) were positive. TS expression was found to be inversely related to PFS of pemetrexed-based chemotherapy (P = 0.041). The MST was 19.6 months (95% CI: 6.0 - 7.9) in EML4-ALK-positive patients and 9.57 months (95% CI: 2.7 - 4.3) in negative ones (P = 0.159). CONCLUSIONS: Systemic chemotherapy especially pemetrexed-based regimen was proved to be a superior option for MPM with a significantly prolonged OS. Correlation between TS expression or EML4-ALK rearrangement and outcome of pemetrexed-based chemotherapy for MPM may contribute to future individualized treatment, which needs further validation from large-scale prospective studies.

[Correlation between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors and EGFR mutations in advanced squamous cell lung cancer].

OBJECTIVE: To investigate the frequency of epidermal growth factor receptor (EGFR) mutations and their correlation with the efficacy of tyrosine kinase inhibitors (EGFR-TKI) in advanced squamous cell lung cancer. METHODS: This retrospective study enrolled 79 patients with advanced squamous cell lung cancer who received EGFR-TKI at Department of Thoracic Medical Oncology in Peking University Cancer Hospital from June 2004 to June 2011. Among them, 67 patients had tissue and/or plasma EGFR exon 19 and 21 mutation detection in order to make an analysis on the relationship between EGFR mutation and the TKI's effect. RESULTS: The disease control rate (DCR) was 56% in all the patients. The median progression free survival (mPFS) and median overall survival (mOS) was 3.7 months (95%CI: 2.0 - 5.0) and 11.5 months (95%CI: 6.6 - 14.2), respectively. Of the 67 patients who received EGFR mutation detection, there were 31 patients harboring EGFR-mutation, for whom the DCR was 71% (22/31), and mPFS and mOS was 6.3 months (95%CI: 2.2 - 10.0) and 13.5 months (95%CI: 7.3 - 18.6) respectively. 36 patients' EGFR status were wild type, for whom the DCR was 44% (16/36), mPFS and mOS was 2.2 months (95%CI: 1.1 - 4.0) and 6.4 months (95%CI: 4.0 - 12.0). There were 17 patients who received erlotinib and 7 patients who received gefitinib as second or more line treatment. mPFS and mOS were 7.9 months and 15.8 months in the erlotinib group, respectively; and the mPFS and mOS were both 6.3 months in gefitinib group; the difference between the 2 groups did not reach statistical significance. Cox-regression analysis showed that EGFR mutation was significantly correlated with PFS and OS (P < 0.05, respectively). EGFR mutation was significantly correlated with DCR by Chi-square test, P < 0.05. CONCLUSIONS: EGFR mutation was a predictor for advanced squamous cell lung cancer to EGFR-TKI. However, the effect was inferior in advanced squamous cell lung cancer as compared to lung adenocarcinoma. Erlotinib tended to be superior to gefitinib.