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Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

Background: This study aimed to clarify the clinical associations between serum carcinoembryonic antigen (CEA) levels and whole-body metastatic distribution in stage IV NSCLC patients. Methods: This study analyzed 377 eligible patients between June 2007 and December 2012. All patients enrolled in the study were newly diagnosed with stage IV NSCLC and had records of pre-treatment serum CEA levels. The serum CEA levels were categorized as normal (< 5 ng/ml) or abnormal (≥ 5 ng/ml) to reveal clinically correlated factors with abnormal serum CEA levels. Results: The median age of the study cohort was 65 years old (range, 30-94), and 236 (62.6%) patients were male. Two hundred seventy-seven (73.5%) patients had tumors with a histology that is consistent with adenocarcinoma. The median serum CEA value was 8.2 ng/ml (range, 0.1-2872.7), and 218 (57.8%) patients had abnormal serum CEA levels. In multivariate analysis, abnormal serum CEA levels had statistically strong associations with non-squamous cell histology (P=0.002), bone (P=0.001), and brain metastases (P=0.005); and were also closely correlated with positive metastatic LN status (P=0.083) and pulmonary metastasis (P=0.065). Very high serum CEA levels (≥ 100 ng/ml) were additionally correlated with abdominal/pelvic metastasis (P < 0.001). Conclusions: Our findings suggested that abnormal serum CEA levels were strongly correlated with increased whole-body metastatic potential in advanced NSCLC. The results provided evidence for future exploratory anti-CEA targeting and intensive systemic assessment in advanced NSCLC patients with abnormal serum CEA levels.

We investigated the electrical transport characteristics of graphene transistors functionalized with a self-assembled monolayer (SAM) of cationic molecules. Contact-opened, channel-opened, and pristine graphene transistors were fabricated, and the changes in their electronic transport properties upon SAM functionalization were investigated. All three types of devices undergo a negative shift in the Dirac charge neutrality point (CNP), with the variation of the contact-opened device larger than that of the channel-opened device. This observation confirms that contact electrodes dope graphene through their work function, and that the work functions of metal electrodes can be modulated through the introduction of cationic SAMs.

Considering the protumorigenic roles of interleukin-6 (IL-6) transsignaling, we assessed the serum levels of IL-6, soluble interleukin-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in 143 patients with breast cancer. Serum levels of IL-6 were elevated with advanced T and N stage. Serum levels of sIL-6R were lower in patients with estrogen receptor-positive cancer. The median values of IL-6 and sgp130 did not differ between patients with recurrence and those without recurrence. However, higher serum levels of sIL-6R at diagnosis were associated with significantly shorter relapse-free survival in patients with estrogen receptor-positive breast cancer.

Few studies of systemic chemotherapy have focused on gastric cancer with peritoneal carcinomatosis (PC) without measurable lesions. In the present study, we characterized the outcomes of systemic chemotherapy and prognostic factors for gastric cancer with PC, particularly in patients without measurable disease.Clinical data from 211 gastric cancer patients with PC (137 without and 74 with measurable disease) who had received systemic chemotherapy between January 2003 and December 2010 at a single center were reviewed.The median overall survival (OS) rate of gastric cancer patients with PC with no measurable disease was significantly longer than that of patients with measurable disease (18.0 vs. 11.6 months, p = 0.010). On multivariate analysis, poor performance status [hazard ratio (HR) = 2.15, p 0.001], the presence of metastatic lymphadenopathy (HR = 2.17, p 0.001), and high-grade PC (HR = 1.83, p = 0.001) were associated with significantly decreased OS. When patients with low-grade PC were stratified by clinical PC grade, the median OS of those without measurable disease was 19.6 months. The median OS of patients with low-grade PC with no measurable disease was longer than those of patients with high-grade PC without measurable disease, patients with low-grade PC with measurable disease, and patients with high-grade PC with measurable disease (p = 0.001, p = 0.029, and p 0.001, respectively). Among the patients with low-grade PC, patients who received a gastrectomy had longer survival than patients who did not receive a gastrectomy (p 0.001).In our study, clinically low-grade PC without measurable disease was associated with better outcomes of systemic chemotherapy than the outcomes in the other groups examined. Clinical trials in patients with gastric cancer with PC should be stratified according to PC grade.

We retrospectively compared the efficacy and toxicity of gemcitabine combination with capecitabine or erlotinib in unresectable pancreatic cancer to know whether the combination with cytotoxic and target agent has more benefit comparing to combination of cytotoxic agents.Fifty-three patients with unresectable pancreatic cancer, treated with gemcitabine and capecitabine (GC) or gemcitabine and erlotinib (GE) as first line between October 2006 and July 2010, were reviewed. In GC group, patients were treated with gemcitabine 1,000 mg/m(2) on days 1, 8, and capecitabine 1,300 mg/m(2) bid was administered on days 1-14, repeated every 21 days. In GE group, gemcitabine was given at 1,000 mg/m(2) I.V for 30 min on days 1,8,15, and erlotinib was taken orally at 100 mg through days 1-28, repeated every 28 days.Response rate was similar, 23.5 % in GE and 21.1 % in GC, but GC had better disease control rate with 73.7 % than GE with 52.9 %. GC also showed longer PFS and OS (5.37 and 14.43 months) than GE (2.63 and 6.23 months) (p = 0.032 for PFS and 0.002 for OS). In toxicity profiles, GC had more hematologic toxicities and GE had more non-hematologic toxicities.The combination with cytotoxic agents seems to have better efficacy and clinical outcome than combination with cytotoxic agent and target agent. The new combination should be developed for the treatment for advanced pancreatic cancer.

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

A 31-yr-old man with abdominal pain was diagnosed with a pancreatic endocrine tumor and multiple hepatic metastases. Despite optimal treatment with interferon alpha, a somatostatin analog, local therapy with high-intensity focused ultrasound ablation for multiple hepatic metastases, and multiple lines of chemotherapy with etoposide/cisplatin combination chemotherapy and gemcitabine monotherapy, the tumor progressed. As few chemotherapeutic options were available for him, sorafenib (800 mg/day, daily) was administered as a salvage regimen. Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed tumor progression compared to the previous immunotherapy and chemotherapy. Serial computed tomography scans showed that the primary and metastatic tumors were stable. Thirteen months after beginning targeted therapy, and up to the time of this report, the patient is well without disease progression. We suggest that sorafenib is effective against pancreatic endocrine tumors.

Anticancer agents can induce sarcoidosis. Interferon-alpha, which is used for the treatment of malignant melanoma and renal cell cancer, is one causative agent of sarcoidosis. However, there are few reports of interferon-alpha-induced sarcoidosis in patients with malignant melanoma. Clinically, it is important to consider the possibility of sarcoidosis in such patients because it could be easily regarded as a metastatic lesion due to underlying malignancy and given unnecessary treatment. Here, we report on the first case of interferon-alpha-induced sarcoidosis in an Asian melanoma patient.

We have employed computer-aided furnace design and process simulation to optimize the conditions under which single-walled carbon nanotubes (SWCNTs) may be grown in high yields on 4 in. wafers for electronic device applications. Hydrokinetic simulations were performed to obtain optimized furnace structures and process conditions in terms of gas flow, temperature, and gas speed. Shower head structures and a flow isolation barrier were installed in an experimental 6 in. furnace, as suggested by the hydrokinetic simulations. To ensure clean surfaces and uniform catalyst islands, catalyst patterns were lifted off using Au films or polydimethylsiloxane. Photolithography was used to fabricate field-effect transistors with SWCNTs grown on 4 in. wafer substrates. The total yield of the nanotube devices increased from 30.5% to 96.4% after optimization.

To elucidate the effect of the work function on the position of the Dirac point, we fabricated graphene devices with asymmetric metal contacts. By measuring the peak position of the resistance for each pair of metal electrodes, we obtained the voltage of the Dirac pointVgDirac(V) from the gate response. We found that the position ofVgDirac(V) in the hybrid devices was significantly influenced by the type of metal electrode. The measured shifts inVgDirac(V) were closely related to the modified work functions of the metal-graphene complexes. Within a certain bias range, the Fermi level of one of the contacts aligned with the electron band and that of the other contact aligned with the hole band.

A mass fabrication scheme for carbon-nanotube (CNT)-based electronic devices is developed by combining the semiconductor wafer electrical sorting with selective burning of metallic CNT wires. By applying a millisecond electrical pulse to CNTs with the optimized logical scheme of voltage stress, we successfully removed the metallic CNTs but not the high-performance semiconductor CNTs. The fabrication scheme implemented with a probe card achieved a 100 % gross yield of CNT-based sensors with a short process time.

We have investigated the electrical transports of double-walled carbon nanotube field effect transistors (DWNT-FETs) with modified contacts. The CNT/Au metal contacts of DWNT-FETs were modified with a self-assembled monolayer of 2-aminoethanethiol molecules. In ambient air, the contact-modified DWNT-FETs showed a decreased conductance in the p-channel (negative gate voltages) and an increased conductance in the n-channel (positive gate voltages), while the original device showed p-type transport. In a vacuum, the n-channel current in the contact-modified DWNT-FET started to rise. We observed a clear n-type transport in the high vacuum. Almost no changes in the gate threshold voltages were observed by means of the contact-modification with a self-assembled monolayer. While the semiconducting DWNT-FET showed a clear transition from a p-type to n-type transistor with contact modification, no apparent changes were observed in semi-metallic DWNT devices.

Recent advances in nanotechnology have enabled the development of nanoscale sensors that outperform conventional biosensors. This review summarizes the nanoscale biosensors that use aptamers as molecular recognition elements. The advantages of aptamers over antibodies as sensors are highlighted. These advantages are especially apparent with electrical sensors such as electrochemical sensors or those using field-effect transistors. Figure Feeling proteins with aptamer-functionalized carbon nanotubes

Alopecia areata (AA) is a common disease of patchy hair loss on the scalp that can progress to cover the entire scalp and eventually the entire body. Intralesional injection of corticosteroids is the first-line therapy for adult patients, however some patients do not respond to glucocorticoid treatment effectively. To delineate the molecular mechanism underlying glucocorticoid insensitivity, we examined the expression of glucocorticoid receptor (GR) and thioredoxin reductase 1 (TrxR1). In some case of glucocorticoid-resistant AA patients, the expression of TrxR1 was decreased in outer root sheath (ORS). We then investigated the effect of TrxR1 on GR activity using recombinant adenoviruses. Overexpression of TrxR1 markedly increased GR activity in ORS cells cultured in vitro. In addition, TrxR1 protected GR activity against H2O2. Finally, TrxR1-enhanced GR activity was significantly inhibited by the overexpression of dominant negative form of Trx (TrxC32S/C35S). These results suggest that decreased TrxR1 may be one putative cause for glucocorticoid resistance in AA, through the impact on intracellular redox system.

This paper presents a review of our current experimental research on GaP nanowires grown by a vapor deposition method. Their structural, electrical, opto-electric transport, and gas-adsorption properties are reviewed. Our structural studies showed that a GaP nanowire consisted of a core–shell structure with a single-crystalline GaP core and an outer Ga2O3 layer. The individual GaP nanowires exhibited n-type field effects. Their electron mobilities were in the range of about 6 to 22 cm2/V s at room temperature. When the nanowires were illuminated with an ultraviolet light source, an abrupt increase of conductance occurred resulting from carrier generation in the nanowire and de-adsorption of adsorbed OH- or O2 - ions on the Ga2O3 surface shell. Using an intrinsic Ga2O3 shell layer as a gate dielectric, top-gated GaP nanowire field-effect transistors were fabricated and characterized. Like other metal oxide nanowires, the carrier concentration and mobility of GaP nanowires were significantly affected by the surface molecular adsorption of OH or O2. The GaP nanowire devices were fabricated as sensors for NO2, NH3, and H2 gases by using a simple metal decoration technique.

BACKGROUND AIM: We evaluated the efficacy and toxicities of three induction chemotherapy regimens in locally advanced head and neck cancer and assessed the clinical significance of human papillomavirus (HPV) in induction chemotherapy.Fifty-two patients were retrospectively evaluated; 12 patients received 5-fluorouracil-plus-cisplatin (FP); 24 patients received docetaxel-plus-cisplatin (DP); 16 patients received docetaxel, cisplatin, and 5-fluorouracil (TPF).The TPF regimen showed a trend towards a higher overall response rate and pathological complete response and led to a significantly higher rate of metabolic complete response. Patients with HPV-positive tumors exhibited a significantly higher pathological complete response rate than those with HPV-negative tumors. In univariate analysis, the prognostic factors significantly affecting progression-free survival were lymph node stage, and metabolic and pathological complete response.TPF induction chemotherapy tended to improve clinical outcome, with manageable toxicity. Pathological complete response was positively correlated with HPV positivity.

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients. Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated. Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71–89) in the single regimen group (SG, 70 patients) and 73 years (range 71–81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85–5.95) and 4.1 months (95 % CI 2.62–5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17–9.08) and 7.6 months (95 % CI 5.50–9.69; P = 0.782), respectively. Hematologic (P

Background: 11q13 region is a frequently amplified locus in human malignancies. Among the genes located in this region, FADD is one of the alleged driving genes. Because amplification is not generally confined to a single gene and amplified genes may not show increased expression, we need to evaluate clinical significance of changes occurring in 11q13 region to understand their roles in carcinogenesis. Therefore, we screened expressions of FADD and closely located genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical significance in invasive ductal carcinoma of the breast. Methods: Ninety-eight cases of invasive ductal carcinoma of the breast were collected. Using archival tissues resected from the cases, we built a tissue microarray and used it in immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A expression scores with clinicopathological parameters, including disease-free survival. Results: FADD expression was associated with T stage (P = 0.046). The combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with perineural invasion (P = 0.022). Although individual gene expressions of TMEM16A, FADD, and PPFIA1 failed to show significant association with disease-free survival, combined gene expression scores did show association with disease-free survival (P = 0.034). Conclusions: FADD, TMEM16A, and PPFIA1 gene expressions as a whole were associated with disease-free survival in breast cancer.

Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC).The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins.Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270, P = 0.022, respectively).The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.

Background: To better understand the mechanisms of the SDC1 expression in invasive ductal carcinoma, we studied the correlations between SDC1 expression and related gene expressions (RSPO1, WNT1, WT1, and P16). Methods: Using 100 cases of invasive ductal carcinoma tissue, we screened expressions of RSPO1, WNT1, WT1, P16, and SDC1 using immunohistochemistry. We analyzed the association between the immunoreactivities and clinicopathological parameters. Results: WT1 expression was associated with tumor grade. RSPO1 expression was associated with progesterone receptor expression. Expressions of RSPO1, WT1, and P16 were significantly associated with disease-free survival. RSPO1 and P16 showed statistically significant hazard ratios. SDC1 ectodomain expression was significantly associated only with P16 expression. Immunoreactivity of SDC1 cytoplasmic domain was associated with WT1 and WNT1. However, WNT1 expression failed to show a significant association with disease-free survival. Conclusions: RSPO1 and P16 immunoreactivity was found to be an independent prognostic indicator in invasive ductal cancer. Cytoplasmic expression of SDC1 is positively correlated with tumor-prone proteins (WT1 and WNT1) and membranous expression of SDC1 is positively correlated with the tumor suppressor (P16).

We describe the observation of photoconductivity and enhanced memory effects in graphene devices functionalized with clusters of alkylated C(60) molecules. The alkylated C(60) clusters were adsorbed on chemical vapor deposition-grown graphene devices from an aprotic medium. The resulting alkylated C(60)-graphene hybrid devices showed reproducible photoconductive behavior originating from the electron-accepting nature of the C(60) molecules. Significantly enhanced gate hysteresis was observed upon illumination with visible light, thereby enabling the use of C(60)-graphene hybrid devices in three-terminal photo-memory applications.

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

Background A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin. Methods We conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models. Results A total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group. Conclusions Green tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.

PURPOSE: The purpose of this study was to evaluate efficacy and toxicity of irinotecan, leucovorin and 5-fluorouracil (FOLFIRI) as second-line treatment after failure of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) for advanced gastric cancer. MATERIALS AND METHODS: Patients who received modified FOLFOX-4 as first-line treatment and then received sequential modified FOLFIRI for disease progression were included in this study. The modified FOLFIRI regimen consisted of irinotecan 150 mg/m(2) in a 90-minute intravenous infusion on day 1, leucovorin (LV) 20 mg/m(2) and 5-fluorouracil (5-FU) 400 mg/m(2) as a bolus followed by 600 mg/m(2) as a 22-hour infusion on days 1 and 2 with the same dose of 5-FU/LV of modified FOLFOX-4 every 2 weeks. RESULTS: A total of 32 patients received 126 courses of FOLFIRI chemotherapy. No complete response was achieved. Three patients (9.4%; 95% confidence interval [CI], 0 to 20.1%) achieved partial response, whereas 11 (34.4%; 95% CI, 17.0 to 51.8%) patients showed stable disease. Disease control rate (complete response, partial responses and stable diseases) was 43.8% (95% CI, 25.6 to 61.9%) and median follow up duration was 11.3 months (range, 2.23 to 37.9 months). Median time to progression was 2 months (95% CI, 1.49 to 2.51 months), and median overall survival from the start of FOLFIRI was 5.84 months (95% CI, 4.34 to 7.34 months). Toxicities were tolerable. CONCLUSION: Modified FOLFIRI as second-line chemotherapy after failure of the modified FOLFOX-4 in advanced gastric cancer was tolerable but showed a lower response rate. Further study about retrying 5-FU/LV with irinotecan after failure of the 5-FU/LV combined regimen is necessary in advanced gastric cancer.

Bridge deck is directly exposed to external environments and traffic loads. The deck can be more easily deteriorated than other bridge members and is often needed to be repaired or strengthened during the service life. Therefore, development of high strength and durable bridge deck that requires minimum maintenance during the service life is demanded. This study has been conducted to obtain basic data that are essential for the establishment of a fatigue design guideline of a steel-concrete composite bridge deck. The developed deck has high flexural rigidity compared to the conventional reinforced concrete deck. In this paper, the results of a detailed structural analysis and a fatigue test on the developed deck are presented. A guideline for the fatigue design of the developed deck is also proposed.

This study reports the electrical transport characteristics of Si(1-x)Gex (x=0-0.3) nanowires. Nanowires with diameters of 50-100 nm were grown on Si substrates. The valence band spectra from the nanowires indicate that energy band gap modulation is readily achievable using the Ge content. The structural characterization showed that the native oxide of the Si(1-x)Gex nanowires was dominated by SiO2; however, the interfaces between the nanowire and the SiO2 layer consisted of a mixture of Si and Ge oxides. The electrical characterization of a nanowire field effect transistor showed p-type behavior in all Si(1-x)Gex compositions due to the Ge-O and Si-O-Ge bonds at the interface and, accordingly, the accumulation of holes in the level filled with electrons. The interfacial bonds also dominate the mobility and on- and off-current ratio. The large interfacial area of the nanowire, together with the trapped negative interface charge, creates an appearance of p-type characteristics in the Si(1-x)Gex alloy system. Surface or interface structural control, as well as compositional modulation, would be critical in realizing high-performance Si(1-x)Gex nanowire devices.

This paper reports useful fabrication scheme customized for biosensing application by adopting the Collins approach of electrical breakdown (Collins, 2001) with some modification to improve the fabrication cost and reduce fabrication time.The electrical breakdown scheme was modified to increase the yield of electrical sorting and reduce sorting time, which is very important in real mass-production. CNTFETs were fabricated using the patterned catalyst growth technique, and source and drain electrodes were defined using photolithography and lift-off process. Then electrical sorting was performed in ambient condition.

7523 Background: To assess the role of mutant EGFR and C-MET in survival benefit obtained from platinum-based adjuvant chemotherapy (PBAC) among resected lung adenocarcinoma (RLADC) patients. Metho...

we have fabricated field effect transistors (FETs) by using high quality Si 1-x Ge x alloy nanowires. To obtain stable contacts between Si 1-x Gex alloy nanowire and Ni/Au electrodes, we annealed the samples at 300 °C furnace with Ar atmosphere or RTA at 400 °C [4] Three different Si 1-x Ge x alloy nanowires (x=5, 15, 30) were used for the fabrication of field effect transistors, and p-type gating effect observed from Si 1x Ge x alloy nanowire devices. Among them, pronounced p-type transistor behavior, with on/off ratios as high as 106 observed from Si 0.7 Ge 0.3 nanowire field effect transistor.

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.

1540 Background: Activating EGFR mutations are strongly predictive of EGFR tyrosine kinase inhibitor (TKI) activity in NSCLCs, however, some patients having wild type EGFRdo not infrequently show clinically favorable outcome to EGFR TKIs. The key proapoptotic proteins have been reported to be involved in TKI-induced cell death. The up-regulation of BIM, a pro-apoptotic protein of BCL2 family, is required for TKIs to induce apoptosis in cancers. Methods: For 150 advanced or metastatic NSCLC pts. receiving gefitinib or erlotinib, we assayed mutation status of EGFR in paraffin embedded tumor tissue using PNA clamping (PANAGENE, Korea) and direct sequencing. Six different genetic variants of EGFR (-191C>A, -216 G>T, CA repeat number, R497K, 2607G>A, and D994D) and BIMdeletion in genomic DNA extracted from peripheral blood were analyzed. Results: M:F ratio was 72:78 and median age was 63 (35~82). Histological subtypes are as follows: 131 adenocarcinoma (87.3%), 16 squamous cell ca. (10.7%) and 3 large cell ca. (1.3%). Objective tumor response (CR+PR) was observed in 60 pts. (40.0%) and SD in 44 pts. (29.3%). Median PFS and OS were 4.3 (0.4~67.4) and 18.6 (0.9~78.1) months, respectively. Of 129 pts. in whom EGFR mutation could be analyzed, 41 pts. (31.8%) had activating EGFR mutation. In univariate analysis, only gender was associated with objective response to EGFR TKI in activating EGFR mutant group (P=0.048). In wild type EGFR group (n=88), R497K (P=0.04) and BIM (P=0.04) as well as gender (P=0.05) were significantly correlated with objective response. In addition, multivariate analysis demonstrated that gender, R497K and BIM were associated with objective response to EGFR TKIs in wild type EGFR group with statistical significance (P=0.023, 0.027 and 0.018, repectively). Neither six EGFR polymorphisms nor BIM was correlated with PFS and OS in activating EGFR mutant group. Meanwhile, in wild type EGFR group, R497K was significantly associated with OS (P=0.028). Conclusions: Taken together, our data suggest that R497K of EGFR and BIM deletion polymorphisms are useful pharmacogenetic biomarkers to predict objective tumor response for EGFR TKIs in advanced NSCLC pts. harboing wild type EGFR.

Background: This study is desiged to evaluate biomarkers that are correlated with the efficacy of pemetrexed in patients with non-small-cell lung cancer (NSCLC). Methods: Patients with stage III or IV NSCLC who received pemetrexed monotherapy after failure of one or more chemotherapy regimen between January 2003 and August 2011 were included. Polymorphism of reduced folate carrier gene (SLC19A, rs1051298), 5,10-methylenetetrahydroflate reductase (MTHFR, rs1801133) and thymidylate synthase (TS, rs45445694, rs16430) gene were analyzed by PCR and direct sequencing method using peripheral blood. Results: Total 123 patients were included. The median age was 61 years (range 35-82). Fifty eight (47.2%) patients were female. Predominant histology was adenocarcinoma (92.7%). Metastatic diseases were 114 (80.5%) patients. Patients received one or more lines of systemic therapy before pemetrexed therapy, one line in 53 (43.1%) patients, two in 51(41.5%), three in 14 (11.02%), and four in 4 (3.3%). Median 4 cycles of chemotherapy were given (range 1-44). Response rate was 22.7% (CR, n=2, PR, n=26) and stable disease was detected in 54 patients (43.9%). Median follow up duration was 28.7months (range 4.07-84.33months). Median progression free survival (PFS) was 4.2 months (95% CI: 2.9-5.6) and median overall survival (OS) was 18.9 months (95% CI: 13.3-24.6). Clinical factors like, sex, histology of tumor (adenocarcinoma vs, nonadenocarcinoma), differentiation, smoking status and EGFR mutation status (active mutation vs. other mutation vs. wild type) did not have any significant difference on response and PFS. Only polymorphisms of TS promoter enhancer region (TSER) were related with PFS. 2R/2R repeat in the TSER (2R/2R vs 2R/3R, 3R/3R 1.0m vs 4.3m, p Conclusions: This study suggests that polymorphisms of TSER associated PFS in pemetrexed treatment. Further prospective studies will be needed to validate these polymorphism as a useful biomarker of pemetrexed treatment in NSCLC patients. Citation Format: Hiun S. Chae, Yoon Ho Ko, Eun Kyoung Jeon, Sook Hee Hong, Jeong-Oh Kim, Seung Joon Kim, Kyo Young Lee, Young Kyoon Kim, HoonKyo Kim, Seok young Park, In Sook Woo, Jin Hyoung Kang. Predictive markers in patients with non-small cell lung cancer with pemetrexed treatment. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2372. doi:10.1158/1538-7445.AM2013-2372

We have investigated the electromechanical properties of single-walled carbon nanotubes (SWNTs) by constructing carbon nanotube transistors on micro-cantilevers. SWNTs and ultra-long carbon nanotubes (UNTs) were grown on free-standing Si3N4 membranes by using chemical vapor deposition, and electrical contacts were generated with electron beam lithography and lift-off. The cantilevers bearing SWNT devices were micromachined so that hybrid cantilevers with various spring constants were fabricated. To measure the electromechanical properties of the SWNTs, precisely controlled forces were generated by a microbalance and applied to the hybrid cantilever devices. Upon bending, the conductances of the metallic and large-gap semiconducting UNTs showed no notable change, whereas the conductances of the small-gap semiconducting UNTs and networks of SWNTs increased. Numerical simulations of bended SWNT made using a multiscale simulator supported the hypothesis that the small-gap semiconducting SWNTs undergo a metallic transformation upon bending.

Background Platinum agents and oral fluoropyrimidines are widely used in the treatment of advanced gastric cancer. This study was aimed to evaluate the efficacy and safety of two combination regimens (capecitabine plus cisplatin [XP] vs S-1 plus cisplatin [SP]) in patients with untreated recurrent or metastatic gastric cancer. Methods Patients diagnosed as untreated recurrent or metastatic gastric cancer were randomly assigned to either capecitabine (2500 mg/BSA/day; day 1-14) plus cisplatin (60 mg/BSA/day; day 1), every 3 weeks or TS-1 (80-120 mg/day; day 1-14) plus cisplatin (60 mg/BSA/day; day 1), every 3 weeks. Primary end point was overall response rate (ORR), accessed by RECIST criteria (ver. 1.0). The secondary end point was progression free survival (PFS), overall survival (OS), and toxicities. Results 86 patients were anticipated to be enrolled, but 51 patients were randomized to XP (25 patients) arm or SP (26 patients) arm because enrollment was slower than expected. ORR of XP and SP was 52% (13 of 25 assessable patients) vs. 44% (15 of 25 assessable patients), and no significant differences were found (P = 0.778). OS of XP vs. SP was 10.3 months (95% CI; 4.8-15.8) vs. 12 months (95% CI; 9.5-14.5), with no differences (P = 0.785). PFS was 4.6 months (95% CI; 4.6-5.2), 4.4 months (95% CI; 2.2-6.6) each (P = 0.68). The incidence of grade 3-4 neutropenia of XP vs. SP was 40% vs. 43.2%. There were no febrile neutropenia in XP arm, but 7.7% in SP arm. Grade 3-4 thrombocytopenia was 12%, 3.8% each. Other grade 3-4 toxicities were; Nausea (4% vs. 0%), Stomatitis (12% vs. 3.8%), Hand-foot syndrome (16% vs. 0%), Diarrhea (0% vs. 3.8%). Median relative dose intensity of capecitabine vs. TS-1 was 78.7% (range 51.9-116.7%), 87.5% (range 57.1-166.7%). Conclusion There were no significant differences in ORR, OS, and PFS between XP vs. SP arm. The incidence of grade 3-4 neutropenia was similar in both arms, but thrombocytopenia was relatively more common in XP arm. SP was more tolerable than XP in non-hematologic toxicities. Considering the usual dosage of capecitabine in monotherapy is 2500 mg/BSA/day, capecitabine 2500 mg/BSA/day combined with cisplatin 60 mg/BSA may be overdosed, and higher rate of non-hematologic toxicity can be explained. Dosage of capecitabine when combined with cisplatin, needs to be further adjusted for routine use. Disclosure All authors have declared no conflicts of interest.

Introduction Autophagy is a critical intracellular pathway for removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins on clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods The expression of five autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results Of the 73 patients, autophagy-related proteins expression frequencies were 49.3% (36/73) for ATG 5, 63.9% (46/72) for ambra 1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for bif-1. The correlation between the expressions of autophagy-related proteins was statistically significant in all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P=0.059). Multivariate analysis revealed that beclin 1 overexpression or increases in alteration of autophagy-related proteins wereindependently associated with poor prognosis (hazard ratio 5.365, P=0.001 and hazard ratio 5.270, P=0.022, respectively). Conclusion The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The awareness and inhibition of autophagy offer a potential therapeutic target for PDAC.

e14634 Background: Autophagy is a critical intracellular pathway for removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins on clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: The expression of five autophagy-related proteins in the PDCA tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results: Of the 73 patients, autophagy-related proteins expression frequencies were 49.3% (36/73) for ATG5, 63.9% (46/72) for Ambra 1, 47.9% (35/73) for Beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was statistically significant in all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (p = 0.059). Multivariate analysis revealed that Beclin 1 overexpression or increases in alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio 5.365, p=0.001 and hazard ratio 5.270, p=0.022, respectively). Conclusions: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDCA. The awareness and inhibition of autophagy offer a potential therapeutic target for PDCA.

e18050 Background: The EGFR mutation on particular exons has been known as a strong predictive biomarker to EGFR TKIs (tyrosine kinase inhibitors) in NSCLC pts. However, some pts having wild type EGFR do not infrequently show clinically favorable outcome to EGFR TKIs. Accordingly, we hypothesized that clinical outcome and skin toxicity to EGFR TKIs might be related to specific single nucleotide polymorphisms regulating the expression of EGFR gene as well as EGFR sensitive mutation. Methods: In 211 advanced or metastatic NSCLC pts receiving gefitinib or erlotinib, we assayed mutation status of EGFR in paraffin embedded tumor tissue using PNA clamping method and direct sequencing. Six different SNPs in genomic DNA extracted from peripheral blood were analyzed; promoter 191C>A, 216 G>T, CA repeat number, exon 13 R497K, exon 20 2607G>A, and exon 25 D994D. Results: M:F ratio was 106:105 and mean age was 63.2 (35.0-82.0). Histological subtypes are as follows: 175 adenocarcinoma, 32 squamous cell ca. and 3 large cell ca. Objective response (CR+PR) was observed in 78 pts (36.9%) and SD in 69 pts (32.7%). Median PFS and OS were 8.7 ± 11.3 and 15.9 ± 14.8 months, respectively. Of 167 pts in whom EGFR mutation was analyzed, 68 pts (40.7%) had EGFR harboring sensitive mutation. In R497K, wild type (RR) was 35 (21.0%) and K alleles (RK + KK) were 132 (79.0%). In D994D, wild type (GG) was 76 (45.5%) and heterozygote and homozygote variants (GA+AA) were 91(54.5%). Statistically significant differences of PFS and OS were observed between wild and hetero-/homozygote variants of R497K (11.9 m vs. 36.2 m, p=0.037 and 23.7 m vs. 39.1 m, p=0.054, respectively) in the pts harboring mutant type EGFR. Meanwhile, in the pts harboring wild type EGFR, GA+ AA genotype of D994D demonstrated much longer PFS and OS compared with GG genotype (PFS: 18.5 vs. 3.7 m, p=0.013 and 37.6 vs. 15.2 m, p=0.035, respectively). In addition, skin rash showed statistically significant association with R497K polymorphism (P=0.031). Conclusions: Our data suggest that two germline genetic variations of EGFR gene, R497K and D994D, be useful pharmacogenetic biomarker to predict longer PFS and OS for EGFR TKIs in advanced NSCLC pts harboring mutant type and wild type EGFR, respectively.

BACKGROUND: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiotherapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. METHODS: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions. We evaluated the extent of LC3-II, as an autophagosome marker, by Western blotting to measure the hypoxia- or chemotherapy-induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Finally, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed.RESULTS: Compared with normoxia, gemcitabine-induced cell death was significantly decreased under hypoxia, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia. However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4107. doi:1538-7445.AM2012-4107

Recently, there is growing evidence to support that oral cavity and oropharyngeal squamous cell carcinoma are two distinct diseases with different etiology. The aim of this study was to evaluate the expression of EGFR, PI3K/Akt/mTOR pathway, and PTEN in oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Mary's Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used for assessment of human papillomaviruses (HPV). Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and 2 of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression were significantly higher in oray cavity cancer than in oropharyngeal cancer. Loss of PTEN was significantly higher in oral cavity cancer than in oropharyngeal cancer. There were no significant differences in PIK3CA, mTOR, and p53 expressions. HPV-negative tumors overexpressed more EGFR and pAkt than HPV-positive tumors. Loss of PTEN expression was more frequent in HPV-negative tumors than in HPV-positive tumors. In multivariate cox regression analysis, pAkt expression showed a significant impact on relapse-free survival. There was a significantly negative correlation between PTEN and pAkt expression, and positive correlation between pAkt and mTOR expression. We concluded that there were differences in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity cancer. It was attributed to etiologic role of human papillomaviruses in oropharyngeal cancer. The expression of pAkt may be a prognostic marker for relapse-free survival in oropharyngeal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B21.

7592 Background: It has been well known that EGFR mutation on particular exons is a strong predictive biomarker to EGFR TKIs (tyrosine kinase inhibitors) in NSCLC pts. However, some pts having wild...

329 Background: We compared the efficacy and toxicity of gemcitabine with capecitabine (GX), and gemcitabine with erlotinib (GT) chemotherapy for recurrent or advanced pancreatic cancer by retrospective analysis. Methods: Between October 2006 and June 2010, 44 patients with recurrent or advanced pancreatic cancer, diagnosed at Seoul St. Mary's hospital were enrolled. In GT group, gemcitabine 1000mg/m2 was administered on days 1, 8, 15, 22, 29, 36, 43 followed by a 1-week rest in first treatment cycle (8 weeks), and then D1, 8, 15 followed by a 1-week rest. Erlotinib was taken orally at 150mg daily through the entire cycle. In GX group, gemcitabine 1000mg/m2 was administered on days 1 and 8. Capecitabine was taken orally at 650mg/m2 twice daily on day 1-14 of a 21-day cycle. Results: In 44 patients, 26 patients were treated with GT, and 18 patients treated with GX. The median age was 56.58 years in GT and 57.67 years in GX. Median number of cycle was 3.04 in GT and 3.57 in GX, and the dose reduction was significantly more common in GX than GT (50% vs. 19%, p=0.031). No complete response was achieved in either group. In GT, partial response and stable disease were achieved in 6 (23.1%) and 8 (30.8%) patients. In GX, partial response and stable disease were shown in 4 (22.2%) and 7 (38.9%) patients, respectively. No significant differences in two patients groups (p=0.442). GX had more favorable clinical outcome of the time to progression (6.1 months vs. 3.0 months, p=0.002) and the overall survival (11.13 months vs. 6.1 months, p=0.012) than GT. The most common grade 3 or 4 toxicity in GT and GX treatment were hematologic toxicity: anemia (8.3%:0%), neutropenia (34.6%:38.8%), thrombocytopenia (15.4%:11.1%). Grade 3 or 4 hand-foot-syndrome of GX was reported in only one patient. Conclusions: GX showed better time to progression and overall survival outcome than GT, but dose reduction was more common. Although there was no significant difference in response rate, and the less dose intensity, GX regimen may be more effective than GT in advanced pancreatic cancer. Further prospective, randomized trials would be warranted in large scale. No significant financial relationships to disclose.

5546 Background: HPV infection has been known to be one of the important risk factors for carcinogenesis of head and neck squamous cell carcinoma (HNSCC). The over-expression of epidermal growth fa...

5120 Background: Platinum based neoadjuvant chemotherapy (NAC) for locally advanced uterine cervix cancer has some benefits to the patients who responded to the chemotherapy, but there is no validated clinical or biologic predictor of response to the chemotherapy. Methods: We used immunohistochemical analysis to determine the expression of the excision repair cross-complementation group1 (ERCC1) protein in pretreatment uterine cervical biopsy tissue. 42 patients only stage IIB had been enrolled in the previous etoposide and cisplatin NAC phase II clinical trial, thereby allowing comparison of the effect of cisplatin based NAC on response according to ERCC1 expression. Results: Among 42 patients, ERCC1 was positive in 33 (78.6%) and negative in 9 (21.4%). Response to chemotherapy (by RECIST criteria) was observed in all patients with negative ERCC1 expression. With logistic regression analysis, ERCC1 negatively continued to be an independent predictor for responsiveness of NAC (p = 0.007). Also, regression...

Background: Sorafenib (BAY 43-9006) is a multi-kinase inhibitor that targets a serine-threonine kinase, B-Raf as well as several tyrosine kinases. Given the numerous molecular targets of sorafenib, several potential mechanisms of its inhibitory activity on tumor cell proliferation, angiogenesis and anti-apoptosis have been proposed. Paclitaxel exhibits unique and potent anti-cancer activity in the treatment of non-small cell lung cancer (NSCLC). Our aim of this study, is to examine the anti-proliferative, anti-angiogenesis effect and apoptosis induction when sorafenib combined with paclitaxel in NSCLC tumor model. Methods: We investigated sorafenib's effect on cell proliferation, cell cycle distribution, ERK phosphorylation in A549 NSCLC cell line using SRB assay, flow cytometry, and Western blot analysis, respectively. In vivo, A549 tumor cells were implanted in the Balb/c nu/nu mice. Five different combination schedules of sorafenib and paclitaxel were applied with their single treatment. PPS and PSS combination therapy. Tumor volume and body weight was measured at two times per week. Intratumoral molecular changes were studied on paraffin-embedded tumor tissue block from xenograft mice using immunohistochemistry and the apoptotic change was measured with TUNEL assay. Result: In vitro study, single treatment of sorafenib or paclitaxel inhibited cell proliferation in A549 cells with dose-dependent manner. Sorafenib effectively inhibited the phosphorylation of ERK and induced G0/G1 arrest of cell cycle. When these two agents were combined with different schedules, schedule-dependent cytotoxicity and cell cycle arrest were observed. In A549 xenograft model, combination of sorafenib and paclitaxel more significantly suppressed tumor growth than their single treatment. However, PSS combination caused profound body weight loss compared with other treatment schedules. In immunohistochemistry study, greater inhibition of Ki-67 as well as pAKT and pERK, and CD31 were observed in PPS combination compared with single treatment. In TUNEL assay, significant apoptosis was observed in combination treatment. Conclusion: Taken together, sorafenib, paclitaxel, and their combination effectivity inhibited tumor growth and angiogenesis via down regulation of pAKT and pERK signaling and apoptosis induction in NSCLC tumor model. The PPS and PSS combination schedule demonstrated more potent antitumor activity including anti-proliferation, anti-angiogenesis, and apoptosis compared to other combination schedules. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A81.