The role of cellulases in monophagous leaf-feeding (phyllovorous) insects has been downplayed, however. Phyllovore nutrient economy was mostly studied in Lepidopteran species as models for other leaf-feeding insects. The nutritive value of cellulase for leaf-feeders had been counted as near zero (Bayer et al., 1998, Friend, 1958 and Schroeder, 1986)

because of its indigestibility in most animals, the theory that Lepidoptera are nitrogen limited, lack of cellulase and associated genes in Lepidopteran SB431542 species (http://butterflybase.ice.mpg.de/), and because leaves are one of the least lignified plant structures (Jung and Allen, 1995), especially compared to wood. Today, the role and presence of cellulases in metazoans is being re-evaluated as such enzymes, in particular the glycoside hydrolase family 9 (GH9) endoglucanases, are found in more and more

clades of life (Davison and Blaxter, 2005). Recent findings of GH9 cellulases in facultatively leaf-feeding grasshoppers (Ademolua and Idowu, 2011) and GH45 cellulases and GH 11 xylanases in phyllovorous beetles (Kirsch et al., 2012, Pauchet and Heckel, 2013 and Pauchet et al., 2010) suggest the role of cellulases for other herbivorous insects needs to be re-evaluated. Even Lepidoptera may not be cellulase-free, as their larval Dasatinib in vitro midgut tissues express large amounts of beta-1,3-glucanase: a bacterial lipopolysaccharide recognition protein which, while not a recognized cellulase, may function as a digestion protein (Pauchet et al., 2009). The three main classes of lignocellulolytic enzymes are endo-beta-1,4-glucanases (EGs; Enzyme Commission: 3.2.1.4), beta-glucosidases (BGLs; EC: 3.2.1.21), and exocellobiohydrolases or exocellulases (CBHs; EC: 3.2.1.91) (Watanabe

and Tokuda, 2010). CBHs hydrolyze cellobiose molecules from the terminal ends of cellulose chains and are most common in bacteria and fungi. CBHs of the GH7 family are conspicuous enzymes in the symbiotic protists of certain termites and in asymbiotic marine isopods (King et al., 2010 and Watanabe and Tokuda, 2010). EGs randomly hydrolyze cellulose chains and the BGLs convert the resulting cello-oligomers like cellobiose and cellotriose into glucose, meaning both are needed to fully digest cellulose polymers Rolziracetam into simple sugars. EG activity alone, however, can mediate limited digestion of cellulose on its surface and amorphous regions. Its activity is usually detected on carboxymethylcellulose (CMC) because of the latter’s high sensitivity to EG activity, high solubility in water, and access denial against CBHs (Lo et al., 2000). Beta-glucosidases are ubiquitous endogenous enzymes in insects. They are not solely involved in cellulose digestion in many cases but can catalyze digestion of many other linkages (Watanabe and Tokuda, 2010).

We identified isoform-specific effects on MFS, RFS, and OS, with low levels of CXCL12-α, -β and -γ significantly correlated with worse MFS and RFS. Most notably, we note that low levels of CXCL12-δ associated with worse OS and showed the same trend for RFS and MFS, despite the fact that CXCL12-δ expression does not correlate with expression of the other isoforms. This relationship is robust and persists even after taking into account CXCL12, CXCR4, and CXCR7 expression this website in multi-gene analysis, indicating the independent prognostic significance of CXCL12-δ. These data provide the first evidence that

CXCL12-δ is expressed in human cancer and correlate with a patient outcome. Expression levels of CXCL12 in breast cancer cell lines generally AZD9291 in vitro mirror conclusions from the clinical samples that lower levels of CXCL12 correlate with worse prognosis. We found that breast cancer cell lines without metastatic potential (in mouse models) had higher levels of CXCL12 expression than cell lines that metastasize more widely. Studies of CXCL12 in breast cancer focus on secretion of this chemokine by stromal cells in primary and metastatic sites, frequently overlooking effects of CXCL12 produced by cancer cells.

However, epigenetic silencing of the CXCL12 promoter has been reported in breast cancer cells with greater metastatic potential, and re-expressing CXCL12 limits metastatic disease in mouse xenograft models [25]. Our analysis of cell lines may inform likely sources of various CXCL12 isoforms in tumor microenvironments. Breast cancer cells express CXCL12-α, -β, and -γ with very minimal expression of δ, which could indicate that stromal cells are the predominant source of the δ isoform in primary breast cancers. We also note that CXCL12-γ is higher than α and β in our panel of breast cancer cell lines, which is opposite the pattern in primary tumors. Differences between data C-X-C chemokine receptor type 7 (CXCR-7) from cell lines versus tumors may reflect dynamic regulation of CXCL12 isoforms in vivo, greater contributions of stromal cells to overall expression of CXCL12-α and -β in breast tumors, or simply genomic changes as the original

cancer samples were transformed into immortalized cell lines. In addition, CXCL12 levels within the tumor microenvironment may be affected by posttranslational modification, such as cleavage by CD26 or matrix-metalloproteinase-2 [50] and [51]. Isoform-specific differences in expression and breast cancer outcomes suggest distinct functions of individual splice variants of CXCL12 on disease progression. Recent studies have begun to identify unique biochemical properties of CXCL12 isoforms, particularly α, β, and γ. While all isoforms share the same core structure, CXCL12-β, -γ, -δ, -ε, and -φ differ by inclusion of exons that add 4, 40, 51, 1, or 11 additional amino acids, respectively, to the carboxy terminus of the molecule [24].

3 (20%) lesions could be snared without dissection, 3 lesions had to be dissected completely, and the remaining 9 had partial dissection followed by snaring. All lesions were nonpolypoid (IIa=60%, IIb=33%, and IIc=7%). They were precisely isolated in the patients with long-segment (33% of patients), short-segment (20%) and islands (47%) of Barretts. Pathology showed HGD in 4, T1a in 5, T1b in 4 and LGD in 2 patients. There was no residual in any patient; one follow-up is pending. Standardized ESD-U of early neoplasia of Barretts is feasible, safe and able to achieve R0 resection rates. The border of the neoplasia can

be identified using currently Selleck BTK inhibitor available IEE techniques. “
“Possibility of submucosal endoscopic myotomy for esophageal achalasia was reported by Pasricha

J et al. using porcine model, and then present authors developed clinical application of peroral endoscopic myotomy (P.O.E.M) for esophageal stenotic motility disorders including achalasia. A single institute registered prospectively study (UMIN 000001901) was carried out in Showa University Northern Yokohama Hospital. From September 2008 and November 2012, 300 consecutive cases (except one) of esophageal achalasia received POEM. Only one case received laparoscopic Heller Dor surgery because of patient’s GSK2118436 cell line wish. Male was 127 cases and female was 173 cases. Average age was 45 y.o. (from 3 to 87 y.o.). Suffering period from dysphagia was 10.1 years on average (0.4-62.4). 41 cases of sigmoid achalasia were involved. Ten consecutive surgical failures also received POEM. Initial success rate of POEM was 98.2% (Eckerdt score<3)

and final success rate was 100%. In 5 cases second POEM procedure was successfully carried out. The reasons for second POEM procedure were either incomplete myotomy at primary POEM (2 cases) or advanced sigmoid achalasia (3 cases). Second POEM improved Eckerd score below 3 in all cases. Operating time was 110.2 (50-245 min). Length of myotomy was 14.1 cm on average (esophagus 11.2 cm, stomach 2.9 cm). Major complication was nothing. buy Decitabine 9 minor complications were experienced; one pneumothorax due to air insufflation, one intramucosal hematoma, one local peritonitis at lessor omentum and 6 mucosal injuries during the procedure. All of them are conservatively treated. Eckerdt score was 6.13 before POEM and dramatically decreased 1.37 in 2 months later, and 1.33 in one year later (statistically significant, Wilcoxon, Signed-ranks test, P<0.01). LES resting pressure was 27.3 mmHg before POEM and reduced to 13.4 mmHg after POEM (statistically significant, Paired T test, P<0.01). 4.9% in 300 cases received regular dose PPI to control post-POEM GERD. In all cases GERD symptom were easily controlled. There is no severe GERD which needs laparoscopic fundoplication. Final success rate (Eckerdt score<3) of POEM in 300 cases was 100% and middle-term outcome of POEM was excellent with no recurrence of dysphagia.

The development of the algorithm was based on an assumption of small excitation angles, and it was shown that without the described split-and-reflect configuration, the pulses’ selectivity severely degrades when they are scaled to excite large tip-angles. This degradation was attributed to an increasing nonlinear phase variation in the αα profile that

grows with flip angle. Unfortunately, the degradation cannot be mitigated by explicit design of an αα filter with a zero phase response combined with use of the full inverse SLR transform rather than the small-excitation version used in the described algorithm, since see more as noted earlier it is impossible to design an FIR filter with the required αα magnitude response and zero phase response. Nor can the degradation be mitigated by adjusting the areas of the pre- and rewinding A(t)A(t) lobes: this approach could eliminate first-order phase variation AZD9291 cell line in the αα profile in the slice, but would leave a phase roll across the αα and ββ profiles, and consequently nonzero αIαI and βIβI that would degrade the MxyMxy profile further. While the described split-and-reflect modification

to the pulses enables pulses designed by the algorithm to excite selective large-tip-angle profiles up to 180°, there will still be some loss in selectivity due to the bandwidth narrowing effect [26]. Attaining the most accurate large-tip excitations will require the development of a novel approach to inverting the ββ profile along a bipolar trajectory, subject pentoxifylline to a zero-phase αα. Recent advances in multidimensional SLR pulse design may lead to the development of such a method in the future [27] and [28]. The design of |B1+|-selective refocusing pulses remains an open problem and will require a different problem formulation than that developed here. Previous reports of |B1+|-selective pulse design approaches [9] and [10] did not address the design of pulses

with tip angles greater than 90°. In addition to the pulse construction described here, Ref. [9] describes a ‘transposed sinc pulse’ configuration (Fig. 6 in Ref. [9]), which is equivalent to playing the first half the waveforms presented here with twice the ΔωRF(t)ΔωRF(t) amplitude. While the shorter duration of these pulses is attractive, compared to the full pulses their excitation profiles are degraded since the |B1+|-frequency trajectory visits only positive frequencies, leading to increased ββ amplitude in the stopband and corresponding undesired excitation. Inversion pulses constructed this way also exhibit substantially degraded and narrowed profiles. It is possible that future work will reveal an approach to design these pulses that can accurately account for or mitigate these effects. There remain multiple questions to be answered regarding the use and performance of |B1+|-selective pulses, which have not been previously addressed and are beyond the scope of the present work.

2E). The MMP loss was increased from 6% to 63% in untreated and DQQ treated MOLT-4 cells, respectively (Fig. 2E). We investigate the pathway of apoptosis induced by DQQ in MOLT-4 cells by monitoring the level of different mitochondrial proteins and caspases. Upregulation of Bax and down regulation of Bcl-2 have long been associated with the activation of apoptosis. DQQ inhibit the mitochondrial

anti-apoptotic protein Bcl-2 and induce the translocation of Bax from cytosol to mitochondria and simultaneously released cytochrome c from mitochondria to cytosol, which was associated with mitochondrial membrane potential loss (Fig. 3A, 2E). DQQ drastically reduce the Bcl-2/Bax ratio in MOLT-4 cells from 10 to 0.2 levels (Fig. 3 C). The Bcl-2/Bax ratio has also been found Metformin nmr to play key role in the activation of caspase-3 [25]. Caspase activation is one of the basic events in the process of apoptosis. DQQ significantly induce caspase-3 and -8 levels (4 times) in MOLT-4 cells in a dose dependant manner (Fig. 3B). The caspase activation was further confirmed by western blotting against procaspase-3 and procaspase-8 (Fig. 3A). DQQ significantly alter mitochondrial apoptotic proteins and caspase-8 level that interlinks both the apoptotic pathway and Selleckchem E7080 finally lead to caspase-3 activation and PARP-1 cleavage (Fig. 3A-C). The above data suggest that DQQ

induced apoptosis in MOLT-4 cells via both extrinsic and intrinsic pathways. The role of AKT/mTOR has long been contemplated in the regulation of autophagy and apoptosis. This pathway has been reported as a negative regulator of HSP90 both apoptosis and autophagy [26]. Therefore, it was evident to see the effect of DQQ on the proteins of AKT/mTOR pathway. Western blot analysis

of different proteins of this pathway revealed that DQQ significantly hampered the expression of pAKT, pmTOR and its substrate pP70S6 K in MOLT-4 cells (Fig. 3A). The most significant inhibitory effect was on pmTOR followed by its substrate p70S6 K (Fig. 3A). The mTOR kinase IC50 value of DQQ was found to be 6 nM in a cell free Elisa assay (Fig. 3D). DQQ was found to be a strong mTOR inhibitor and its expression almost negligible, even at low concentration (2 μM). The autophagy induction in cells treated with DQQ was analyzed by acridine orange staining. The results of acridine orange staining revealed that it induced formation of acidic vacuolar organelles (AVO) in MOLT-4 cells, while the number of AVO was negligible in control cells. The number of AVO increased with increasing doses of DQQ (Fig. 4A). Furthermore, western blot analysis of key proteins of autophagy such as beclin1, ATG7, ATG5 and LC3-II revealed that DQQ significantly increased their expression in a dose dependent manner (Fig. 4A). The autophagy induction was further confirmed by LC3 immunofluorescence. The results indicated that DQQ treatment induced dose dependent increase in LC3 fluorescence in MOLT-4 cells (Fig.

, 2009). The iceberg output used as forcing is derived from a modified version of Bigg et al., 1996 and Bigg et al., 1997 iceberg model, developed by Martin and Adcroft (2010) and coupled to ORCA025, an eddy-permitting global implementation of the NEMO ocean model (Madec, 2008), to simulate the trajectories and melting of calved icebergs from Antarctica and Greenland in the presence http://www.selleckchem.com/products/MDV3100.html of mesoscale variability and fine-scale dynamical structure. Icebergs are treated as Lagrangian particles, with the distribution of icebergs by size derived from observations (see Bigg et al.,

1997 and Table 1). The momentum balance for icebergs comprises the Coriolis force, air and water form drags, the horizontal pressure gradient force, a wave radiation force, and interaction GSI-IX cell line with sea ice. The mass balance for an individual iceberg is governed by bottom melting, buoyant convection at the side-walls and wave erosion (see Bigg et al., 1997). This configuration has been run for 14 years, and the associated freshwater fluxes used here are averages over years 10–14. Southern Hemisphere calving and melting rates are in near balance after 10 years, but further decades of simulation would be needed for global balance, due to slower equilibration of calving and melting in the Northern Hemisphere. An average pattern

of icebergs is our primary interest, which is why we settled for a relatively short integration time. For our purposes a detailed treatment of various mass loss processes is not necessary, because only the amount of freshwater release applied to the ocean is of interest. Nevertheless, the many different processes that affect the SMB

indicate that uncertainties are to be expected and distinction between mass loss processes and geographical locations needs to be made (Shepherd et al., 2012). The most obvious response aminophylline to increased atmospheric temperatures is the melting of ice. This mass loss can be associated with adding freshwater directly offshore of the coast of the region where the melt takes place. We designate this freshwater source as run-off, or R for short. Run-off is contrasted with another form of mass loss that produces icebergs. The calving of icebergs from glaciers we call ice discharge, or D. The important difference is that icebergs are free floating chunks of ice and can drift to other locations and melt. This last observation prompts us to introduce the distinction between near (N) and far (F) freshwater forcing. A near forcing is always adjacent to the coast of origin and a far forcing is not restricted like this. The output of the iceberg drift and melt simulation gives us the location and relative magnitude of the far source of freshwater forcing. We assume spatial patterns on an annual cycle for these contributions, with magnitudes varying in time. The scaling factors are provided by the mass loss projections in the two polar regions.

New members are elected by current active members through a highly selective process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care, and public health. Kathleen Zelman, MPH, RD, has been honored with the American Society for Nutrition’s

2011 Science Media Award. The check details award is given for consistent, accurate nutrition science reporting for a general audience over the last year. The award honors Zelman for her achievements in the nutrition science media and also recognizes her efforts in fostering the public’s understanding and appreciation of current nutrition issues based on science. At the 2010 Food & Nutrition Conference & Expo (FNCE) in Boston, MA, Tanya M. Horacek, PhD, RD, was named this year’s winner of ADA’s Margaret Dullea Simko Memorial Award for Excellence at a Clinical Poster Session. This award is given to recognize quality poster sessions at FNCE and encourage high-quality poster session admissions in the future. Funded by friends and colleagues of Margaret D. Simko. Ashlee H. VX-809 cost Schoch was named

runner-up for the award. Tell Us Your Issue We care about the concerns of ADA members and want to hear from you. There are four easy ways to submit your issues: • E-mail [email protected]. You will receive immediate confirmation that your message has been received and action will be taken within 2 months. For more information, visit ADA’s member home page and click on Member Issues or visit www.eatright.org/issues. Deadline for submitting material for the People and Events section is the first of the month, 3 months before the date of the issue (eg, May 1 for the August issue). Cobimetinib price Publication of an educational event is not an endorsement by the Association of the event or sponsor. Send material to: Ryan Lipscomb, Editor, Journal of the American Dietetic Association, 120 S. Riverside Plaza, Suite 2000, Chicago, IL 60606; [email protected]; 312/899-4829; or fax, 312/899-4812. Frances Selzer Talbert, RD, October 2010, was one of the founding members of the Mississippi Dietetic

Association. She began her career as a dietitian after graduating from St Catherine’s College in St Paul, MN. During World War II, Talbert was commissioned as a lieutenant in the Army Air Corps, and for her service she was the first female inducted into the Oxford, MS, American Legion post. She later became the founding dietitian at the North Mississippi Regional Center, where she worked until her retirement. “
“In the article “Development of the 2010 US Dietary Guidelines Advisory Committee Report: Perspectives from a Registered Dietitian” in the November 2010 issue of the Journal of the American Dietetic Association, reference 10 on page 1645 was mistakenly listed as: “US Department of Health and Human Services, and US Department of Agriculture (HHS, USDA). Dietary Guidelines for Americans, 7th edition. Washington, DC: US Government Printing Office; 2010.

A major constituent in focal adhesions, mediating downstream intracellular signaling is focal adhesion kinase (FAK). Focal adhesions are known to be involved in mechanosensation and downstream signaling in various cell types, and external mechanical forces have a direct role in their formation [65]. Paxillin proteins are predominantly “localized” to upper and lower “poles” of fibular osteocyte cell bodies, whereas they are evenly distributed across the osteocyte cell bodies in calvaria suggesting that focal adhesions are formed in osteocytes along the direction of principle strains within the bone [64]. FAK is essential for mechanotransduction in osteoblasts [68], and FAK has a similar role

in osteocyte mechanotransduction [69]. It was found that mechanical stimulation by means of a pulsatile fluid flow induced stabilization

of β-catenin in osteocytes GSK2118436 cost in a FAK-dependent mechanism [69]. Interestingly, knockdown of membrane-type matrix metalloproteinase-1 (MT1-MMP) increased the number and size of focal adhesions in cultured MLO-Y4 osteocytes concomitantly with an enhanced NO production and c-jun and c-fos mRNA expression in response to mechanical stimulation [70]. This indicates that MT1-MMP knockdown osteocytes have an increased sensitivity to mechanical loading and demonstrates a novel and unexpected potential role for MT1-MMP in mechanosensing. Primary cilia are single cytoplasmic organelles found in virtually all eukaryotic cells. They protrude into the extracellular space selleck chemicals from the cell surface and function as mechanosensors in tissues such as kidney. Osteocytes also possess a single primary cilium [71]. PKD1/PC1, a mechanosensory protein in the kidney that localizes to primary cilia, is known to

play a role in normal bone structure. It is not yet established if PKD1 functions via the primary cilia or it has a function in another location in the cell. Interestingly, PLEKHB2 MC3T3-E1 osteoblasts and MLO-Y4 osteocytes possess primary cilia that project from the cell surface and deflect during fluid flow [72]. These primary cilia are required for the osteocyte response to dynamic fluid flow in vitro. However, the location of the primary cilium, i.e. on the osteocyte cell body, makes it difficult to envision a role for the primary cilium as a flow sensor for osteocytes in vivo, because physical laws dictate that loading-induced fluid flow will primarily occur around the osteocyte cell processes and it is difficult to envision how a primary cilia could fit into the lacuno-canalicular space without being already severely bent [58] and [36]. An alternative hypothesis, postulated by Bell, suggests that cells sense hydraulic pressure by using the primary cilium as a sensor of hydrostatic pressure, but no experimental evidence to support this hypothesis currently exists [73].

2011). This site provides inadequate data for easterly winds. Waves were observed from the coast or a small pier at a distance of 200–300 m from the coast in an area, which was about 3–5 m deep. Pakri in the western part of the Gulf of Finland (59°23′37″N, 24°02′40″E) is the only wave observation site that is largely open to waves generated in the northern Baltic Proper (Zaitseva-Pärnaste et al. 2009). The observation conditions were particularly good: the observer was located on

the top of a 20 m high cliff and the water depth of the area over which the waves were observed was 8–11 m. Data from the Narva-Jõesuu meteorological station in Narva Bay (59°28′06″N, 28°02′42″E) characterize check details wave properties PF-562271 in the eastern part of the Gulf of Finland (Räämet & Soomere 2010a, Räämet et al. 2010, Soomere et al. 2011). The site is open to waves approaching from west to north. Waves are observed from a 12.8 m high platform in an area 3–4 m deep and located about 200–250 m from the coast. All the listed coastal sites only conditionally represent open sea conditions. The sheltering effect of the shoreline and the relatively small water depth may at times significantly alter the local wave properties compared to those in the open sea due to

the shoaling, breaking and refraction of the waves. The potential distortions obviously affect the results of single observations (for example, they generally lead to a certain underestimation of wave heights) but apparently do not significantly alter the qualitative features of the overall wave statistics

and evidently do not impact on the nature of long-term variations and trends in wave Thymidylate synthase properties. The routine and technology for the observations were identical at all visual observation sites. They are presented in several of the above-cited sources and we just describe the key features of the routine here. The entire procedure relies on the classical zero-crossing method. The observer noted the five highest waves during a 5-min time interval. Both the mean height H of these five waves and the highest single wave Hmax were filed until about 1990. The mean wave height is normally used in the analysis; when it was missing, it was substituted by the maximum wave height. As the latter was, on average, only 6% higher than the mean wave height at Vilsandi ( Soomere & Zaitseva 2007), the potential difference is much smaller than the accuracy of the determination of the wave height. The wave period was determined as a mean period of 30 waves from three consecutive observations of sections of 10 waves (not necessarily the highest ones).

Brain scans were required for those patients who revealed brain metastases at baseline. When confirming complete or partial tumor response, bone scans were required for patients with bone metastases at baseline. Primary endpoints were PFS, as assessed by an IRC, and safety profile. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), and OS. Exploratory analyses examined concordance between different selleck screening library EGFR mutation testing methodologies, and concordance between serum and tumor tissue at screening. EGFR mutation status alterations in serum before and after treatment were observed. The statistical plan assumed a median PFS of 7 months in the

historical control group and 11 months in the erlotinib treatment group. The primary analysis was planned for 11 months after the last patient was enrolled to confirm superiority of erlotinib over the historical control. Given an expected median PFS of 11 months, 93 patients were necessary to provide statistical power of 80% to confirm the superiority

of the lower confidence boundary of the observed median PFS compared with the threshold median PFS of 7 months. The target sample size was 100 patients, taking into consideration patients GSK-3 cancer who would prove to be ineligible for the study. For PFS (the primary efficacy endpoint), OS, and duration of response, median and 95% CIs were estimated using Kaplan–Meier survival methodology. CI limits were calculated according to the Greenwood method. Response rate and DCR were summarized by presenting the rate and 95% CIs according to Pearson–Clopper. The analysis of safety parameters (co-primary endpoint) was descriptive: all AEs were converted to MedDRA preferred terms and summary tables were produced. For laboratory parameters,

descriptive summary tables or graphs of change over time were produced. According to the statistical analysis plan, all patients who received at least 1 dose of study treatment would be included in the safety population. The modified intention-to-treat (ITT) population for the efficacy analysis excluded all patients with major protocol violations. Between 8 April 2010 and 6 October 2010, 103 patients with confirmed EGFR mutations were enrolled and received erlotinib, comprising the safety population. The majority of patients (95/103; 92%) had their samples screened Fossariinae in local practice, while the remaining 8 (8%) had their samples screened at a central laboratory. One patient was excluded from the modified ITT population as they had a major protocol violation after enrollment. The baseline characteristics for the safety population are shown in Table 1. At the time of data cut-off for the primary analysis (1 September 2011), 44 patients remained in the study, either on treatment or in follow-up. At the primary analysis (data cut-off 1 September 2011), median PFS with first-line erlotinib was 11.8 months (95% CI: 9.7 to not reached).