Unfortunately, both of these studies were mainly discovery effort

Unfortunately, both of these studies were mainly discovery efforts to establish a reliable and reproducible workflow for the analysis of carrier protein-bound peptides and have yet to validate their putative OvCa markers in independent cohorts. The identification of autoantibody signatures in serum has also been investigated for OvCa biomarker discovery. OvCa is often characterized by the complex network of inflammatory cytokines present in find more the microenvironment and the involvement of immune-related cells such as tumour-associated macrophages. As such, populations of anti-tumour antibodies may be present and

detection of said immunological responses to tumorigenesis may help to detect early stage disease. In a laying hen model of human

OvCa, Barua et al. identified 11 proteins as immunoreactive ovarian antigens through LC MS [52]. Although this was the first study to identify immunoreactive ovarian antigens by serum anti-tumour antibodies, the authors recognized the fact that the ovarian antigens could MK0683 ic50 not discriminate laying hens with non-malignant ovarian conditions from those with OvCa. Philip et al. investigated the immunoproteome of OvCa and healthy control sera, as well as that of the conditioned media of the OVCAR3 and SKOV3-A2 cell lines [53]. Overall, 8 autoantibody-reactive autoantigens were identified that were present in all five cancer serum composites and in both cell lines: A-kinase anchor protein 9, eukaryotic translation initiation factor 4, midasin, RAD50, talin 1, vinculin, vimentin, and centrosome-associated protein 350. Furthermore, the authors identified a subset of the MS-generated autoantigens that were implicated in both

humoral (B-cell) and cell-mediated (T-cell) immunity. However, the suggested novel autoantibody biomarkers for OvCa diagnosis were not validated in an independent cohort. Future studies will thus need to address how well such putative autoantibody-based markers perform in independent, blinded validation. A final approach that has been gaining popularity is MALDI MS imaging of cancer tissues to identify markers that may be shed into the extracellular space. In this technique, tissues are directly subjected to ionization and mass analysis to generate an array of mass spectra for all positions across the tissue specimen. Resminostat As a result, the protein content of specific regions of interest can be determined, as well as the spatial distribution of specific proteins across the tissue [54]. El Ayed et al. was able to identify the reg-alpha fragment of the 11S proteasome activator complex as a putative biomarker through correlative analyses between MALDI MS imaging and immunohistochemical analysis with an anti-reg-alpha C-terminal antibody [55]. Expression of this protein was validated using Western blot and PCR on the SKOV-3 OvCa cell line. However, the authors did not validate overexpression of the marker in clinical samples. Liu et al.

The main outcomes of the study was success and complication rates

The main outcomes of the study was success and complication rates. Table 1 EUS-guided intra-arterial chemotherapy appears to be safe feasible in a subset of patients with metastatic liver disease. Further studies are necessary before a formal recommendation is made. Table 1.

EUS-FNI Conventional P N (%) 12 (100%) 13(100%) — Age 65,2 ± 18,7 59,7 ± 21,3 NS Sex (M/F) 6/5 8/4 NS Lesions size median (mm) 3,9 (11-46mm) 3,5 (9-44mm) 0,14 Liver Segments  II 5 6 NS  III 4 5 NS  V 3 1 NS Decreased selleck inhibitor size after 10 sessions  70-100% 4 (33.3%) 5 (38.4%) NS  50-70% 5 (41.7%) 6 (46.3%) NS  < 50% 3 (25.0%) 2 (15.3%) NS Response rate (reduction of lesional) contrast enhancement 85% 90% 0.097 Median duration of hospitalization (days; range) 3 (1-10) 5 (2-13) 0.016 Complications Hematoma: 1 Abdominal pain: 3 Port infection: 2 Abdominal pain: 6 Embolia: 1 Artery thrombosis: 1 0.032 Total 4 Total: 10 Median survival (months) 9-19 12-17 0.068 Median complication free survival (months) 7.2 8.1 0.071 SF 36  Pre selleck compound 67 64 NS  Post 73 75 NS Full-size table Table options View in workspace Download as CSV “
“EUS guided intratumoral therapy is a promising development in the treatment of pancreatic cancer. Intratumoral vaccination

is an emerging strategy for immunotherapy of tumors. Our laboratory was the first to demonstrate effective treatment of murine solid tumor models with intratumoral poxvirus vaccine. The recombinant pox viral vaccine “Panvac” encodes tumor antigens CEA and Muc-1 and 3 immune co-stimulatory antigens B7, LFA-3 and ICAM1. Intradermal and subcutaneous administration of this vaccine was previously studied for treatment of colorectal and pancreatic cancer. We present here, a human phase I trial of EUS guided intratumoral, and systemic administratation of Panvac for treatment of patients with locally advanced inoperable CYTH4 pancreatic adenocarcinoma. Thirteen patients

were enrolled at 2 dose levels of the intrapancreatic vaccine, Panvac-F (Fowlpox encoding MUC-1, CEA, TRICOM). Dose level 1 was 108 plaque-forming units (PFU); dose level 2 was 109 PFU. Systemic therapy consisted of subcutaneous Panvac-V (vaccinia, 2 X 108 PFU) and subcutaneous Panvac-F. Patients received a total of 2 EUS guided fine needle injections (EUS-FNI) given 2 weeks apart, 1 subcutaneous Panvac-V and 4 subcutaneous Panvac-F boosts given with GMCSF, extending to day 71. Patients were allowed to transition to standard care at day 35. EUS-FNI was performed with a standard 22 or 25 gauge needle. Procedural complications, toxicity, tumor progression, serum CA 19-9 and CEA levels were monitored. In the lower dose cohort, 2 out of 7 patients were removed from study after two weeks due to rapid disease progression locally, and died two and six months after trial initiation. One patient had mild pancreatitis that resolved allowing completion of protocol therapy. Two patients are alive at 15 and 30 months into follow up.

42 and 3 23 ng/mL, respectively (Table 3) The assay sensitivity

42 and 3.23 ng/mL, respectively (Table 3). The assay sensitivity was estimated as the assay cut point multiplied by the minimum sample dilution factor. The assay sensitivity was therefore estimated to be 28.3 and 64.5 ng/mL for anti-velaglucerase alfa and anti-imiglucerase

antibodies, respectively. This approach to determine the cut point is therefore supported by the assay sensitivities estimated for this assay, which are higher (28.3 ng/mL and 64.5 ng/mL) than the assay sensitivities of the antibody screening assay (33.4 ng/mL and 65.6 ng/mL). It is recognized that assay signal responses can vary over time and between assay runs (Mire-Sluis et al., 2004), particularly for assays utilizing radiolabeled reagents, and therefore the cut point CPM value for this assay may be adjusted to compensate for radiolabel decay. In MG132 order to normalize inter-assay variability, the cut point CPM can be adjusted, when necessary, relative to the calibration curve slope and y-intercept. The least squares line fit to the high-purity, monoclonal antibody-based calibration curve data, using well-characterized known concentrations of antibody, provides a reliable and consistent method for calculating the uncertainty in assay determinations. This procedure normalizes the cut point for inter-assay changes in CPM that may

occur from reagent radiolabel decay, radioautolysis and/or assay handling variability as well as allowing for changes in non-specific binding and for changing www.selleckchem.com/products/Avasimibe(CI-1011).html assay readouts over time. For all the confirmatory assays (IgA, IgM and IgE), Sitaxentan precision and linearity were determined according to guidelines (FDA, 2001, ICH, 2005 and EMEA, 2009) and are described in Table 4 and Table 5. The positive cut points for both the anti-velaglucerase alfa and anti-imiglucerase IgA and IgM confirmatory assays (Table 4 and Table 5) were determined from the mean blank (buffer only) result from 59 and 68 assays, respectively, for both velaglucerase alfa and imiglucerase. The positive cut points were calculated by the signal-to-noise approach

as 10 times the mean blank. Of note, these calculated cut point values were below or near the instrument limit of detection. A ratio of 2.0, indicating a 2-fold increase in signal over baseline, has been described in the literature as a clinically acceptable criterion for an anti-drug antibody-positive sample (Miller et al., 2001). Patient sera are therefore defined as positive for anti-velaglucerase alfa or imiglucerase IgA or IgM antibodies if the signal of the timepoint is greater than or equal to the respective cut point and if the ratio of the timepoint signal to the pre-infusion baseline signal is greater than or equal to 2.0. For the IgE assays, the assay cut point was established as the mean plus 1.645 standard deviation of assay values obtained from treatment-naïve patient serum samples as recommended by Mire-Sluis et al. (2004).

23 However, the study was retrospective, and with <1000 cases lim

23 However, the study was retrospective, and with <1000 cases limiting its power. In contrast to the “extra PAF” we calculated, the adjusted PAFs in their article calculated the effect of each exposure in a pseudo-population with no other risk factors present, potentially overestimating the effect in the general population, in which a case can be caused by many risk factors. The second comparable paper of Gallerani et al found an association with comorbidity and a similar

2-fold increase in risk LBH589 mw in those exposed to NSAIDs to what we found in our peptic ulcer cohort.10 However, it was also a retrospective survey–based study potentially subject to recall bias, and had <1000 cases. Furthermore, the authors did not separate out gastrointestinal comorbidity from nongastrointestinal comorbidity and used hospital controls, therefore limiting comparisons with our population-based study. Other studies assessed higher alcohol intake,24H pylori, 25 smoking, 26 acute renal failure, 27 and acute myocardial infarction 28 and found associations with upper GIB. But these studies were in small selected hospitalised cohorts (n < 1000 bleeds) with limited assessments of individual comorbidity and no measure

of their PAFs. Our study has a number of important strengths when compared with these previous works because we set out specifically to assess the degree to which nongastrointestinal comorbidity predicts nonvariceal upper GIB after removing the effects of all the available known risk factors in a much larger general population. SB203580 mouse In addition, we used a method of defining cases and exposures that utilized information from both primary and secondary care, thereby Parvulin maximizing the evidence supporting each case while not excluding

severe events.14 Furthermore, due to the comprehensive coverage of the English primary care system, our study’s results are likely to be generalizable to the whole English population and, we believe, further afield. The linked dataset used for our study remained representative of the GPRD overall, as whole practices rather than individual patients declined or consented to the linkage. Consequently, we were able to estimate the additional attributable fraction for comorbidity in the English population that was not already attributable to other risk factors.19 As our study was one of the first to assess the effect of the burden of comorbidity as a risk factor for upper GIB, no measure of comorbidity had been specifically validated for this purpose. We decided to use the Charlson Index because it is a well-validated score for measuring comorbidity in many different contexts. Other comorbidity scores that could be used, such as the Elixhauser Index or a simple counts of diagnoses, have been used and validated less frequently and in fewer contexts.

Particular interesting genes, like sulfatases, were manually eval

Particular interesting genes, like sulfatases, were manually evaluated. The genome of R. sallentina SM41 features 6893 predicted

ORFs, of which 4825 are shared with other Rhodopirellula species. A rather high number of 138 ORFs was found to be shared with planctomycetes outside of the genus Rhodopirellula. Based on 16S rDNA similarities and ANI analyses, R. sallentina SM41 clusters together with and Rhodopirellula rubra SWK7 are rather distantly related to R. baltica SH1T. The type strain for R. rubra has been described by Bondoso et al. (in press). Like for all presented Rhodopirellula draft genomes, the number of GDC-0199 in vivo sulfatase encoding genes was exceptionally high ( Wegner et al., 2013) ( Table 1.). A tendency for sulfatase gene clustering was observed, although only few sulfatase maturation systems were identified. While all Rhodopirellula species harbor only few genes for peptidoglycan synthesis, one additional murA gene has been identified in the R. sallentina SM41 draft genome. This Whole Genome Shotgun project has been deposited in INSDC www.selleckchem.com/products/Dasatinib.html (DDBJ/EBI-ENA/GenBank) under the accession number ANOH00000000. The sequence associated contextual (meta)data are MIxS (Yilmaz et al., 2011) compliant. This study was supported by the German Federal Ministry of Education

and Research (BMBF) as part of the Microbial Interactions in Marine Systems (MIMAS) project (Grant No. 03F0480A). “
“Rhodopirellula belongs to the ubiquitous bacterial phylum Planctomycetes. Members of the Planctomycetes are abundant in particulate fractions of marine ecosystems and considered as important participants in the global carbon and nitrogen cycles. They convert substantial amounts of organic material, such as “marine snow” (aggregates of zooplankton, phytoplankton and protists), into carbon dioxide. Their importance in marine systems was recently discovered and documented in several publications ( Glöckner et al., 2003,

Winkelmann and Harder, 2009 and Winkelmann et al., 2010). A collection of 70 Rhodopirellula strains obtained from different European seas revealed 13 distinct operational taxonomic units (OTUs). These were Lepirudin defined by taxonomic studies with a combination of 16S ribosomal DNA (rDNA) sequence comparisons, DNA–DNA-hybridization (DDH) and a novel multi-locus sequence analysis (MLSA) approach that employed primers in putatively conserved regions of nine housekeeping genes ( Winkelmann et al., 2010). First evidence for a limited habitat spectrum of these sessile bacteria was detected by annotation and genome comparison of the strains. Here we report the permanent draft genome sequence of Rhodopirellula maiorica strain SM1 (= JCM 17615 = DSM 24050) which originated from sediment near Pt. Andratx, Mallorca, Spain (39.5446 N 2.3875 E) ( Winkelmann and Harder, 2009).

5 or TALP > 960 U/l or both, as in the original case-series [2]

5 or TALP > 960 U/l or both, as in the original case-series [2]. RFU children were identified as having knock-knee, bow-leg or windswept deformity based on both the clinical examination and visual inspection of medical photographs. In order to investigate a genetic predisposition to rickets, the parent or guardian of RFU children were asked whether or not any other member of their family had learn more signs of rickets-like deformities. Standard anthropometry was conducted including weight, standing height and sitting height. Weight was measured to 0.1 kg using a calibrated electronic scale (model HD-314, Tanita B.V., Hoofddorp, The Netherlands). Height was measured to the nearest mm using a portable stadiometer (Leicester

Height Measure, SECA, Hamburg, Germany). In order to determine the calcium intake of the children a 2-day weighed dietary assessment was carried out by trained field-workers

at the homes of the children. Coding of the dietary records was performed using The Gambian Food Composition Tables [6] and an in-house analysis program adapted for use with Gambian foods was used to calculate nutrient intakes [7]. To consider the likelihood that calcium insufficiency was more prevalent in RFU children a yard stick of 200 mg of calcium a day was taken to represent the average bone calcium accretion rate across childhood [8]. The molar ratio of calcium/phosphorus (Ca/P) was determined using the molecular weight of calcium (40.08 g/mol) and phosphorus (30.97 g/mol). The Ca/P of 1 was used, as convention, to represent the optimal molar ratio of Ca/P in the diet [9]. Children were categorised as having a low dietary Ca/P if they had values < 0.33 [10]. An overnight-fasted, 2 h Raf inhibitor urine sample was collected between the hours of 07.00 and 09.00. Urinary dipstick tests (Multistix-SG, Bayer, Newbury, UK) for liver function (presence of bilirubin and urobilinogen) and kidney

function (presence of protein, haemoglobin, glucose, and leucocyte esterase) were performed on fresh 2 h urine collections. Acidified (HCl 10 μl/ml, laboratory reagent grade SD 1.18, Fisher Scientific) and non-acidified urine aliquots were stored at − 20 °C and then later transported frozen on dry ice to MRC HNR, Cambridge, UK where they were stored at − 80 °C until analysis. A fasting, antecubital venous blood sample IMP dehydrogenase (5–15 ml according to the age of the child) was collected 1 h after the start of the 2 h urine collection and was transferred to pre-cooled lithium heparin (LiHep) and EDTA-coated tubes. Blood ionised calcium (iCa) and haemoglobin (Hb) were measured in the LiHep sample (ABL77, Radiometer Medical, USA) within 10 min and pH 7.4 corrected values for iCa were used. The remainder of the blood was separated by centrifugation at 4 °C within 45 min and frozen at − 20 °C, and later transported frozen on dry ice to MRC HNR, Cambridge, UK where it was stored at − 80 °C until analysis. 24 h urine collections from the children were supervised by trained field-workers at their homes.

At some depth, the waves lose their stability and start to break,

At some depth, the waves lose their stability and start to break, running up and down on the beach surface, whereby a certain amount of water seeps into the permeable beach, generating a complex circulation in the porous medium. When waves break, their energy is dissipated and the spatial changes of the radiation stress give rise to changes in the mean sea level, known as the set-up. In the classic paper by Longuet-Higgins & Stewart (1964) the set-up was calculated using the linear model based on the shallow-water equation. Longuet-Higgins (1983) demonstrated that the mean onshore pressure gradient due to wave set-up

drives a groundwater circulation within the beach zone. Water infiltrates into the coastal aquifer on the upper part of the beach near Selleck Pirfenidone the maximum run-up, and exfiltration occurs on the lower part of the beach face near the breaking point. This paper presents a theoretical attempt to predict the groundwater circulation induced by the nonlinear wave set-up. The proposed solution is based on the theoretical concept of multiphase flows in the porous media of a beach. The basic value determined experimentally or calculated

in the model is pore pressure in the beach sand. The theoretical model is based on the Biot’s theory, which takes into account the deformation of the soil skeleton, the content of the air/gas dissolved in pore water, and the change in volume and direction of the pore water flow (Biot 1956), resulting from changes in vertical gradients and vertical pore pressure. It is assumed Regorafenib that the deformations of the soil

skeleton conform to the law of linear elasticity. The major issue being examined is the fact that when waves break, they inject air and gases into the porous medium. In addition, gases are produced by organisms living in the sand. Hence, we are dealing with a three-phase medium consisting of a soil skeleton, pore water and gas/air. As a result, the elastic modulus of buy Temsirolimus pore water E′w depends on the degree of water saturation with air ( Verruijt 1969). Analysis of the results of a laboratory experiment showed that in the case where fine sand is saturated with air or gas, the rigidity of the soil is much greater than that of the pore water. The equation for the water pressure in the soil pores can be written in the form (Massel et al. 2005): equation(1) ∇2p−γnKfEw′∂p∂t=0, where Kf – coefficient of permeability, The solution of equation (1) is the following function: equation(2) pxzt=ℜρwgcoshkhcoshψz+hncoshψhn−hexpiφ)ζxt, where equation(3) ψ2=k21−inγωk2KfEw′, where n   is a measure of the porosity (the ratio of free pore volume to total volume), ℜℜ is the real part of a complex number. According to the solution, the presence of air in the porous medium causes a phase delay ϕ between the deflection of the free surface and the pore pressure. Massel et al.

Early clinical studies failed to confirm that adjuvant chemothera

Early clinical studies failed to confirm that adjuvant chemotherapy prolongs survival. In 2009, a meta-analysis of 12 randomized clinical trials analyzed 3809 patients [7]. The hazard ratio for OS was 0.78 (95% CI = 0.71-0.85) in favor of chemotherapy. The most recently published meta-analysis evaluated data from 34 randomized trials that compared adjuvant systemic chemotherapy to surgery

alone and were conducted in both Asian and Western populations [8]. The risk of death among patients receiving adjuvant chemotherapy was reduced by 15% [hazard ratio (HR) = 0.85). To date, two large-scale phase III clinical trials have demonstrated a benefit of adjuvant chemotherapy in patients with gastric cancer who underwent curative surgery with D2 lymphadenectomy. One selleck chemicals llc was the Japanese adjuvant chemotherapy trial of TS-1 for gastric cancer (ACTS-GC) trial [9]. In the ACTS-GC trial, 1059 patients with stage II or III gastric cancer who had undergone a D2 lymphadenectomy were randomly assigned to 6 months of S-1 versus surgery Selleckchem LY2109761 alone. Five-year OS was significantly better with S-1 (72% vs 61%). Another study was the Asian multicenter capecitabine and oxaliplatin adjuvant study in stomach cancer

(CLASSIC) trial, in which 1035 patients with stage II/III gastric cancer were randomly assigned to capecitabine plus oxaliplatin (XELOX) or observation after a D2 gastrectomy [10]. Adjuvant chemotherapy was associated with a significant improvement in 3-year DFS (74% vs 59%; HR = 0.56) and OS (78% vs 69%; HR = 0.66) [11]. The optimal adjuvant chemotherapy regimen has not yet been established. There are several choices, including S-1 (used in the ACTS-GC trial) [10], XELOX (used in the CLASSIC trial) [11], capecitabine plus

cisplatin (used in the adjuvant Bay 11-7085 chemoradiation therapy in stomach cancer trial) [12] or epirubicin, cisplatin, and infused fluorouracil (used in the Medical Research Council Adjuvant Gastric Infusional chemotherapy trial) [13]. However, it is unclear which regimen is best or whether a superior alternative approach exists. Docetaxel is a novel antitumor drug that promotes microtubule assembly from tubulin dimers and inhibits the depolymerization of tubulin, thereby stabilizing microtubules in the cell. This results in the inhibition of DNA, RNA, and protein synthesis [14]. The efficacy of docetaxel monotherapy in AGC is only 15% to 24% [15]. The response rate of 5-FU/platinum-based treatment is approximately 22% to 65% [16]. Cisplatin and 5-FU synergize with docetaxel. The DCF regimen was first shown to have efficacy for the treatment of patients with AGC in a multinational TAX-325 trial [17]. On the basis of these results, docetaxel was approved in the United States and Europe for AGC. The role of the DCF regimen in the adjuvant treatment of gastric cancer is not clear. In this study, we show that the DCF regimen may also have a survival benefit when used as adjuvant chemotherapy in gastric cancer.

Rather than these, health problems may arise because of the consi

Rather than these, health problems may arise because of the considerable quantity of asbestos-containing wastes that were spread

all over the affected area from the fire retardant coatings, heat, fire, and acid resistant gaskets, Bioactive Compound Library datasheet pipe insulation, ceiling insulation, flooring, roofing, etc. of the damaged buildings. Large quantities of many chemicals from various other sources might have been spread in the tsunami hit areas and also reached the nearby coastal environment. For example, as per the Law Concerning Special Measures against PCB waste which was enforced in Japan on 15th July 2001 (http://www.jesconet.co.jp/e.g./pcblaw.htm), PCB waste holders are to dispose of all PCB wastes by July 2016. Since the deadline is five years away from now, considerable quantities of PCB wastes might have been

in stock in the tsunami hit areas, and thus washed away and Ion Channel Ligand Library clinical trial spread all over. Small stocks of pharmaceutical and personal care products (PPCPs) and also various medicinal chemicals which were kept at the hospitals and commercial establishments in the tsunami washed areas are now in the environment of northeastern Japan, posing a complicated threat. Many industries in the area, involved in manufacturing processes using hundreds of organic and inorganic chemicals, were also inundated by tsunami waters

releasing them into the surrounding marine environment. Part of all the above wastes reached the coastal environment when the seawater receded to the sea. These materials, nearly before and after settlement to the seafloor will get decomposed and may release considerable quantities of the chemicals into the water for a long period of time, thus leading to bioaccumulation and biomagnification. This may lead to toxic implications in marine life especially fish and those in the apex of the marine food chain. For example, cetaceans can biomagnify chemicals like PCBs to 107 times than in the ambient water as they have high lipid stores and weak metabolic capacity for chemicals like PCBs when compared with terrestrial mammals (Tanabe et al., 1984). Scientists are now worrying about a possible build-up of radioactive material in edible marine and terrestrial biota of the tsunami hit area that may reach humans. Along with that, there is also concern about a variety of other chemicals which can have short and long term effects on wildlife and humans. Long term survey of the soil, sediment, water and biota including human should be carried out on the build-up of many toxic chemicals, to avoid any possible catastrophe by such chemicals.

53%) of the combination group and in four patients (23 53%) of th

53%) of the combination group and in four patients (23.53%) of the chemotherapy group. No significant difference was found between the two groups (23.53% selleck chemicals vs 23.53%; P > 0.05). No serious adverse events were observed ( Table 3). The results of our study suggest that CT-PFNECII combined with second-line chemotherapy produced a higher response rate and improved survival than second-line chemotherapy in platinum-pretreated stage IV NSCLC. In addition, side effects of this combination

therapy were generally well tolerated. Compared with ORR of 11.76% and DCR of 35.29% in the chemotherapy group, the combination therapy provided an ORR of 23.53% and a DCR of 58.82% in platinum-pretreated stage IV NSCLC. Of note, one complete tumor regression was achieved in a patient by two cycles of combination treatment. More importantly, all patients who had lung tumor–related chest pain or dyspnea before our treatment achieved significant symptom relief even within 72 hours after CT-PFNECII treatment. Our pilot

study suggests that CT-PFNECII combined with second-line selleck products chemotherapy has potent antitumor activity against platinum-pretreated NSCLC tumors. The benefit of our combination treatment in terms of survival outcomes was also quite encouraging. Considering that 29.41% of patients in our study population were platinum resistant (five patients in each arm) and 58.82% of the patients (10 of 17) received CT-PFNECII two times, the PFS of 5.4 months and OS of 9.5 months by our combination treatment were more valuable. The side effects of CT-PFNECII such as transient mild pain and cough in patients with lung cancer were minimal and well tolerated because only quite small amount of cisplatin and quite low concentration of ethanol were injected intratumorally. In addition, mild pneumothorax Digestive enzyme and mild hemoptysis relating to the procedure were uncommon because we used a 22-gauge fine needle under the precise guidance of CT. Furthermore, combination of CT-PFNECII with second-line chemotherapy did not worsen common side effects of chemotherapy. No significant differences in chemotherapy-related adverse events in the two groups

were noted, indicating clinical safety of CT-PFNECII. We previously found that 5% ethanol could potently inhibit ABCG2 pump, which is a major drug transporter in protecting platinum-resistant NSCLC cells from cytotoxic agents. We also found that 5% ethanol-cisplatin injected intratumorally could eradicate cisplatin-resistant lung tumors by killing chemoresistant lung CSCs and normal lung cancer cells [10]. We speculate that the residual unkilled but damaged tumor cells in the 5% ethanol-cisplatin treatment group might be more fragile and sensitive to second-line chemotherapy agents. As a result, we speculate that CT-PFNECII treatment might have synergistic effects with systemic second-line chemotherapies, such as docetaxel or pemetrexed, in controlling platinum-pretreated NSCLC.