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Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Background/Aims Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. Methods This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. Results Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. Conclusions Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.

Abstract Background This study investigated the prognostic effects of venous thromboembolism (VTE)-related factors in patients with metastatic pancreatic cancer receiving palliative chemotherapy. Predictive factors for VTE were also investigated. Methods A total of 216 patients diagnosed with metastatic pancreatic cancer who received gemcitabine-based palliative chemotherapy at our institution were retrospectively evaluated. Results VTE occurred in 51 (23.6%) patients during treatment and did not affect survival. However, patients who were diagnosed with VTE at the beginning of chemotherapy showed poor prognosis compared with patients diagnosed with VTE during chemotherapy: all patients (hazard ratio [HR] 1.897, p = 0.008); patients diagnosed with VTE (HR = 3.768, p = 0.001). Low serum sodium (Na) (

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3, RAB, RABL2B, and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.

The use of a millimeter-wave band defined as a 30–300 GHz range is significant element for improving performance of 5th generation (5G) mobile communication systems. However, since the millimeter-wave signal has peculiar propagation characteristics especially toward non-line-of-sight regions, the system architecture and antenna structure for 5G mobile communications should be designed to overcome these propagation limitations. For realization of the 5G mobile communications, electronics and telecommunications research institute (ETRI) is developing central network applying various massive antenna structures with beamforming. In this paper, we have introduced the central network and evaluated the system coverage and capacity through C++ language-based simulations with real geospatial information.

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

Background: Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib.Case Presentation: A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers.Conclusions: Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic liver disease (MLD) often progresses to life-threatening conditions. This study intends to describe the outcomes of liver transplantation (LTx) for MLD at a living donor-dominant transplantation center where potentially heterozygous carrier grafts are employed. Methods: We retrospectively evaluated the medical records of 54 patients with MLD who underwent LTx between November 1995 and February 2012 at Asan Medical Center in Seoul, Korea. The cumulative graft and patient survival rates were analyzed according to patient age, and living or deceased donor LTx. Recurrence of the original disease was also investigated. Results: The post-transplant cumulative patient survival rates at one, five, and 10 years were 90.7%, 87.5% and 87.5%, and the graft survival rates were 88.8%, 85.5%, and 85.5%, respectively. There were no differences in the patient survival rates according to the recipient age, human leukocyte antigen matching, and living or deceased donor LTx. There were also no differences in the patient survival rates between the MLD and the non-MLD groups for children. Recurrence of the original metabolic disease was not observed in any patient during the follow-up period. Conclusion: Our results suggest that the living donor-dominant transplantation program is well-tolerated in MLD without recurrence of the original MLD using all types of transplantation. [ABSTRACT FROM AUTHOR]

Standard endocrine therapy and chemotherapy can induce long-term remission in breast cancer patients; however, breast cancer can recur at any site. Pulmonary nodules with lymphadenopathy in advanced cancer patients are likely to be assumed as metastases. A 44-year-old woman with a history of breast cancer was presented to our institution with abnormal findings on 18-fluorodeoxyglucose positron emission tomography imaging, which suggested lung metastasis. She had previously been diagnosed with breast cancer (T1N2M0, Stage IIIa, intraductal carcinoma, triple negative cancer). Histological analysis of the mediastinal lymph node biopsy demonstrated sarcoidosis, showing a chronic, non-caseating, granulomatous inflammation. Our case highlights the need for non-malignant diagnoses in those with prior malignancies, and the need for histological evaluations in the event of first recurrence following potentially curative therapy. [ABSTRACT FROM AUTHOR]

Purpose: There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC. Materials and Methods: We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy. Results: The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death. Conclusion: Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment. [ABSTRACT FROM AUTHOR]

Purpose Activating mutation of the KRAS oncogene is an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, KRAS mutation as a prognostic factor of survival outcome remains controversial in CRC, independent of anti-EGFR therapies. Materials and Methods We conducted a retrospective analysis of 103 CRC patients who were available for evaluation of KRAS mutation status. None of the patients analyzed had received anti-EGFR therapies. The role of KRAS mutation status was evaluated as a predictive factor for oxaliplatin or irinotecan and as a prognostic factor in CRC patients who did not receive anti-EGFR therapies. Results Mutations in KRAS were observed in 48.5% of patients. The response for oxaliplatin-(p=0.664) and irinotecan-based (p=0.255) cytotoxic chemotherapy did not differ according to the KRAS mutation status. In addition, no significant difference in progression free survival (PFS; oxaliplatin, p=0.583 and irinotecan, p=0.426) and overall survival (OS; p=0.258) was observed between the wild and mutant type of the KRAS gene. In univariate and multivariate analyses, KRAS mutations did not have a major prognostic value regarding PFS (oxaliplatin: hazard ratio, 0.892; 95% confidence interval [CI], 0.590 to 1.347; p=0.586 and irinotecan: hazard ratio, 0.831; 95% CI, 0.524 to 1.319; p=0.433) or OS (hazard ratio, 0.754; 95% CI, 0.460 to 1.236; p=0.263). In addition, anti-vascular endothelial growth factor therapies did not affect PFS to oxaliplatin or irinotecan and OS. Conclusion KRAS mutation is not a prognostic marker for PFS to oxaliplatin or irinotecan and OS in CRC patients who did not receive anti-EGFR therapies. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to determine the efficacy and safety of treatment using gemcitabine and capecitabine for patients with advanced pancreatic cancer. Materials and Methods Patients with advanced unresectable pancreatic adenocarcinoma were enrolled in the study. Inclusion criteria included no prior systemic chemotherapy or radiation therapy, at least one radiographically documented and measurable tumor lesion, and adequate patient organ functions. The patients received 1,000 mg/m² gemcitabine intravenously on days 1,8 and 15, and 830 mg/m² of oral capecitabine twice a day on days 1-21 of a 28-day cycle. Results Fifty patients with a median age of 53 years (range, 39 to 76 years) were enrolled in the study. The median follow-up was 10.0 months. The objective response rate of the 50 patients was 48.0% (95% Cl, 22.5 to 57.1%). The median time to progression and overall survival were 6.5 months (95% Cl, 2.3 to 8.7 months) and 10.0 months (95% Cl, 5.7 to 16.7 months), respectively. Grade 3-4 toxicities associated with chemotherapy included neutropenia (22%), anemia (8%), thrombocytopenia (6%), and hand-foot syndrome (10%). Conclusion Combination chemotherapy using gemcitabine and capecitabine was well tolerated and demonstrated promising efficacy in the treatment of advanced pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose As the number of elderly patients diagnosed with non-small cell lung carcinoma (NSCLC) increases, the number of these patients receiving chemotherapy also increases. However, limited data exists regarding the use of chemotherapy in advanced NSCLC patients who are 75 years of age or older. Materials and Methods Between May 2002 and October 2008, data for 48 advanced NSCLC patients who were 75 years of age or older who had been treated with chemotherapy were retrospectively analyzed. Results The median age of study participants at the time of first line chemotherapy was 76 years (range, 75 to 87 years) and their median Charlson comorbidity index was 2 (range, 1 to 4). Of the total 48 patients, 43 patients (90%) were treated by platinum-based doublet as a first line chemotherapy regimen. Median progression free survival for first line chemotherapy was 5.7 months (95% confidence interval [CI], 4.93 to 6.47 months) with an overall response rate of 33.3%. After first line chemotherapy, only 14 of the 48 patients (29.2%) received second line chemotherapy. The median overall survival (OS) for these patients was 8.2 months (95% CI, 4.44 to 11.96 months). Multivariate analysis results indicated that female gender and having received second-line or more chemotherapy were independent prognostic factors for increased OS for all 48 patients. Charlson Index was not a significant independent prognostic factor for survival. There were 9 treatment related deaths due to infectious causes (18.8%). Conclusion Patients 75 years of age or older with advanced NSCLC may obtain clinical benefit from the administration of platinum-based doublet or single agent chemotherapy. However, oncologists must consider the aspect of safety in relation to the clinical benefits when managing this patient group. [ABSTRACT FROM AUTHOR]

Recent advances in wireless communications and electronics has enabled the development of machine-to-machine (M2M) communications. This communication paradigm has been expected as an automated control and report solution for smart grid. The smart grid enables customers and operators to utilize the collected usage information from a large number of meters with transceivers for efficiency and safety. In this paper, we introduce architecture, requirements and challenges of M2M communications for smart grid. We extract technical issues that should be resolved in M2M communications to support the smart grid via third-generation partnership project (3GPP) cellular networks. We then present the current state of the art of research results to deal with such issues. Finally, we outline the open research issues. [ABSTRACT FROM AUTHOR]

Despite first-line therapy, most patients with advanced esophageal squamous cell carcinoma (ESCC) experience disease progression and may become eligible for second-line chemotherapy. Although commonly used, the role of salvage chemotherapy in patients with recurrent or metastatic ESCC has not yet been established. We analyzed 53 patients who had received second-line chemotherapy after the failure of cisplatin-based combination chemotherapy with or without radiotherapy as first-line therapy in ESCC between March 2000 and June 2008. Median progression-free survival (PFS) and overall survival (OS) for second-line chemotherapy were 2.4 and 5.2 months, respectively, with an overall response rate of 18.9%. In multivariate analysis, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2 or more and PFS under first-line therapy <4 months were independent prognostic factors for decreased OS. OS was estimated based on the number of adverse prognostic factors: 0 = good; 1 = intermediate, and 2 = poor. The median OS for the good, intermediate, and poor prognostic groups were 11.2, 4.5 and 4.3 months, respectively (p < 0.001). The good prognostic group showed better OS than the intermediate or poor groups (p < 0.001). Second-line chemotherapy may be beneficial for OS in ESCC patients with ECOG PS 0-1 and PFS under first-line therapy ≥4 months. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

There is no further treatment option for metastatic colon patients who are refractory to standard chemotherapy and to whom novel biological agents are not available. We evaluated the outcomes of mitomycin-C, 5-fluorouracil (5-FU) and leucovorin in patients with metastatic colon cancer previously treated with oxaliplatin/5-FU/leucovorin and irinotecan/5-FU/leucovorin. We retrospectively analyzed 46 patients who had received mitomycin-C/5FU/leucovorin between March 2008 and December 2009. All patients had failed prior first-line and second-line therapy containing oxaliplatin, irinotecan, and 5-FU. The median age of the patients was 57.0 years (range, 34.0-76.0) and their median Eastern Cooperative Oncology Group performance status was 1 (0-2). A complete or partial response was not observed in any patient and stable disease was observed in 19 patients (41.3%). The median duration of follow up was 29 weeks (range 8-87 weeks). Median progression-free survival was 10 weeks (95% CI 8-12) and median overall survival was 38 weeks (95% CI 32-44). Grade 3 and 4 hematological toxicities included neutropenia in five patients (10.8%) and thrombocytopenia in four patients (8.8%). Grade 3 or 4 non-hematologic toxicities included nausea and vomiting in two patients. There were no treatment-related deaths. The combination regimen of mitomycin-C/5-FU/leucovorin showed marginal activity and tolerable toxicity profiles in heavily pretreated metastatic colorectal cancer patients. [ABSTRACT FROM AUTHOR]

We present a simple process for the fabrication of high performance transparent conducting films that contain single-walled carbon nanotubes (SWCNTs) noncovalently coated with an ultrathin titania layer. The hydrophobic interactions between nanotube surfaces and the acetylacetone (acac) ligands used to stabilize the TiO2precursor provide an interesting alternative method for noncovalently coating the SWCNTs with a titania layer. The ultrathin titania layer on SWCNTs prevented the oxidation of functionalized SWCNTs at high temperatures, and protected against water molecule absorption. Moreover, the uniform and thin titania layer, formed viahydrophobic interactions, promoted the selective removal of amorphous carbonaceous materials upon heating to 300 °C as well as withdrawing electrons from the nanotubes. The noncovalent titania coating of the SWCNTs may potentially exhibit other interesting physical properties relevant to applications such as transparent conducting films, photo-catalysis, and sensor electrodes. [ABSTRACT FROM AUTHOR]

Concomitant approach using cisplatin and 5-fluorouracil (5-FU) has shown an excellent local control rate and significantly reduced distant metastasis in patients with locally advanced nasopharyngeal carcinoma (NPC). However, optimal schedule and dosing of chemotherapy still need to be developed to reduce distant metastasis. This retrospective study was conducted to evaluate the efficacy, toxicity, and tolerability of a concurrent chemoradiation therapy (CCRT) regimen using cisplatin and 5-FU followed by adjuvant chemotherapy (AC) in patients with locoregioanlly advanced NPC. Forty-three NPC patients who had AJCC stage T3/T4 or N2/N3 and M0 disease were evaluated. The chemotherapy during CCRT consisted of cisplatin (75 mg/m2 on day 1) plus 5-FU (750 mg/m2/day on day 1–5), delivered every 4 weeks for two cycles. Three cycles of AC were given with cisplatin (75 mg/m2), epirubicin (37.5 mg/m2) on day 1, and bleomycin (7.5 mg/m2 bolus iv. on day 1 followed by 9 mg/m2 on day 1–5 by continuous infusion) every 3 weeks. The overall response rate after CCRT was 95% (22 CRs and 19 PRs in 43) and 100% (16 CRs and 8 PRs in 24) after AC. Grade 3/4 neutropenia, mucositis, and weight loss were observed during CCRT phase in 18, 44, and 26% of patients, respectively. AC caused grade 3/4 neutropenia and emesis in 12.5 and 20.8% of patients, respectively. CCRT regimen using cisplatin and 5-FU followed by three cycles of BEC chemotherapy was effective in locally advanced NPC patients, with acceptable and reversible acute toxicities. [ABSTRACT FROM AUTHOR]

Aim: Hepatocellular carcinoma (HCC) is one of the most commonly fatal malignancies in Asia but treatment options are limited. Methods: This multinational, nonrandomized phase II trial using the combination of irinotecan (Campto or CPT-11) and capecitabine (Xeloda) was conducted to determine efficacy and safety of this combination in Asian patients with advanced inoperable HCC. The starting dose was irinotecan 200 mg/m2 every 3 weeks followed by capecitabine 1000 mg/m2 orally twice daily for 14 days followed by a 7-day rest. The primary endpoint was tumor response rate, based on response evaluation criteria in solid tumors criteria. Secondary objectives included the safety and tolerability of the treatment combination, time to progression, duration of overall response, tumor growth control rate (complete response, partial response plus stable disease) and overall survival. Results: Of the 63 recruited patients, 47 were evaluable. Of these, three (6.4%) achieved a partial response (lasting 2.2, 3.4 and 8.0 months, respectively). The median overall survival was 4.5 months. Grade 4 diarrhea was reported in four patients. Hematologic grade 4 laboratory abnormalities observed in patients while on study treatment included neutropenia (5.2%) and anemia (1.7%). Seven patients (12.1%) had grade 4 elevations in their total bilirubin. Both irinotecan and capecitabine were generally well tolerated, with manageable and reversible toxicities. Conclusion: Combination therapy with irinotecan and capecitabine has limited efficacy in the treatment of advanced-stage HCC. Further investigation of this combination is not warranted. [ABSTRACT FROM AUTHOR]

The role of 90K and galectin-3 in cell-to-extracellular matrix adhesion and tumor metastasis has been reported, but little is known about their role in the prognosis and extranodal involvement of diffuse large B-cell lymphomas (DLBCL). Thus, we measured serum 90K concentration by enzyme-linked immunosorbent assay and tissue expression of galectin-3 by immunohistochemistry in newly diagnosed DLBCL patients. The mean serum 90K concentration was higher in DLBCL than in healthy controls (1,408.81 ± 89.45 vs. 980.94 ± 58.69 ng/ml, p = 0.036). High serum 90K (median value ≥1,249.50 ng/ml) and high galectin-3 expression (grade 3 positive staining in >75% of cells) showed a significant association with stage III/IV, ≥2 extranodal involvements and risk of high/high-intermediate international prognostic index (p < 0.05). The complete response (CR) rate (86.9%, 20/23) in the low 90K group was higher than in the high 90K group (56.5%, 13/23). Among 14 patients with high galectin-3 expression, only 6 patients showed CR (42.9%). The time to progression and overall survival were shorter in the group with high 90K and galectin-3 expression (p < 0.05). In conclusion, serum 90K and galectin-3 expression might be useful markers to indicate the extent of lymphoma involvement and prognosis in DLBCL. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We performed a single-institution retrospective study to evaluate the efficacy and toxicities of oxaliplatin, 5-fluorouracil (5-FU), leucovorin (LV) combination chemotherapy as salvage treatment in patients with metastatic or advanced gastric cancer. Sixty-two patients with advanced gastric cancer previously treated were eligible for the study. Patients received oxaliplatin 100 mg/m2 and LV 100 mg/m2 (2-h intravenous infusion) followed by 5-FU 2,400 mg/m2 (46-h continuous infusion) every 2 weeks, and responses were assessed after every three cycles. Fifty-nine out of 62 patients were assessable for response. Among them, 46 patients had previously been treated with cisplatin based chemotherapy. Patients had a median age of 57 years (range 32–76 years), 72.6% had an Eastern Cooperative Oncology Group performance status of 0 or 1. Total 296 courses of chemotherapy were administered as second-line (67.7%) or third-line (27.4%), and the median courses per patient was three cycles. Out of 59 evaluable patients, 14 partial responses were observed (overall response rate, 22.6%). Stable disease was observed in 22 patients (35.5%), and progressive disease in 23 patients (37.1%). The median response duration, time to progression, and overall survival were 2.3, 3.0, and 8.0 months, respectively. The major toxicities were neutropenia, mucositis, and peripheral neuropathy. Grade 3 or 4 hematologic toxicities included neutropenia in nine patients (14.5%) and thrombocytopenia in one patient (1.6%). Other grade 3 or 4 toxicities included mucositis in one patient (1.6%) and vomiting in two patients (3.2%). Grade 1 or 2 peripheral neuropathy were observed in 18 patients (29.0%), however there were no cases of grade 3 or 4 peripheral neuropathy and no treatment-related deaths. The combination of oxaliplatin, 5-FU and LV was effective and safe salvage chemotherapy in advanced gastric cancer patients. [ABSTRACT FROM AUTHOR]

Clinical trials have reported conflicting results as to whether pre-operative aromatase inhibitors (AIs) improve outcome over pre-operative tamoxifen in postmenopausal women with hormone receptor-positive breast cancer. We performed a meta-analysis comparing primary and secondary end points of pre-operative AI and pre-operative tamoxifen. The event-based risk ratio (RR) with 95% confidence intervals (95% Cis) were derived, and a test of heterogeneity was applied. Four studies (1,160 patients) met the inclusion criteria for the analysis. Meta-analysis showed that pre-operative AI was more effective than pre-operative tamoxifen. Pooled results of clinical efficacy were as follows: clinical objective response rate (RR, 1.29; 95% CI, 1.14–1.47; P < 0.001), ultrasound objective response rate (RR, 1.29; 95% CI, 1.10–1.51; P = 0.002), and breast conserving surgery (BCS) rate (RR, 1.36; 95% CI, 1.16–1.59; P < 0.001). Hot flashes, nausea, and fatigue were not different between the pre-operative AI and pre-operative tamoxifen groups. Although headache was more frequent in the pre-operative AI group ( P = 0.011), it was a manageable toxicity and was not clinically relevant. Pre-operative AI has better BCS rate than tamoxifen and in terms of toxicities, is not inferior to tamoxifen; therefore, we could suggest pre-operative AI instead of tamoxifen for those postmenopausal patients with hormone receptor positive breast cancer, not eligible for chemotherapy. [ABSTRACT FROM AUTHOR]

The tumor suppressor gene, TP53, is located on chromosome 17p13.1 and is critical for DNA repair, cell-cycle control, and apoptosis. TP53 also plays a crucial function in the tumorigenesis of lung cancer. Inactivation of TP53 via genetic alterations such as missense mutations is often associated with lung cancer. In this study, potential association of TP53 polymorphisms with the risk of lung cancer was examined in a Korean population. A total of 299 Korean lung cancer patients and 296 control subjects were recruited into this study. Direct DNA sequencing and TaqMan analysis were employed, and logistic regression analyses were conducted to characterize the association between TP53 polymorphisms and lung cancer risk. Through direct sequencing in 24 Korean individuals, 13 sequence variants were identified, and five of these polymorphisms were selected for a larger-scale genotyping ( n = 595). Statistical analyses revealed that polymorphisms and haplotypes in the TP53 gene, including Arg72Pro, were not significantly associated with lung cancer in a Korean population. [ABSTRACT FROM AUTHOR]

The aim of this phase II study was to evaluate the response rate to gemcitabine combined with cisplatin in patients with locally advanced, metastatic or recurrent biliary tract cancer who had received no prior chemotherapy. The treatment consisted of cisplatin 70 mg/m2 in intravenous infusion followed by gemcitabine 1,250 mg/m2 in 30-min intravenous infusion on days 1 and 8, repeated every 3 weeks until disease progression, unacceptable toxicity, patient’s refusal or up to 8 cycles. Thirty-nine patients with advanced biliary cancer were enrolled between March 2003 and August 2003. Fourteen patients (40%) had gall bladder cancer and 20 patients (57%) had cholangiocarcinoma. Thirty-two patients (91%) had metastatic disease at study entry with liver being the most commonly involved site of metastasis. About 84.5 and 94.2% of the initially planned dose were administered for gemcitabine and cisplatin, respectively. In the ITT population ( n = 35), six partial responses were observed for an objective response rate of 17.1% (95% CI; 4.7–29.6%). Ten patients (28.6%) had stable disease, 16 (45.7%) progressed, and three (8.6%) were not evaluable. For the 35 patients in the ITT population, the median overall survival time was 8.6 months (95% CI; 6.1–10.4 months). The median time to disease progression was 3.2 months (95% CI; 2.3–4.9 months) and the median time to treatment failure was 3.1 months (95% CI; 1.9–4.1 months). Among the six tumor responders, the median duration of tumor response was 7.3 months (95% CI; 5.6–11.0 months). The most common grade 3/4 maximum toxicities were nausea (3.4%) and vomiting (2.7%). The combination chemotherapy with gemcitabine and cisplatin in this trial demonstrated moderate antitumor activity with favorable toxicity profile. [ABSTRACT FROM AUTHOR]

The article deals with a study which reveals that mesenchymal stem cells (MSC) derived from human chorionic plate may promote hematopoietic differentiation of the human embryonic stem (hES) cell line SNUhES3. Two human placentas from two healthy pregnant women during normal full-term delivery were obtained. It is concluded that co-culture of hES cells with human MSC might be a feasible way to induce hematopoietic differentiation of hES cells.

A 39-year-old woman presented with acute onset of arthralgia in both wrists. Although her primary gastric cancer was in remission after previous treatment, carcinomatous arthritis was suggested by the osteolytic radiographic findings and refractoriness to nonsteroidal anti-inflammatory drugs, which was then confirmed by synovial fluid cytopathology. In view of the high incidence of gastric cancer in Korea, gastric cancer involving the carpal bones should be considered when we encounter a patient presenting with inflammatory peripheral joint arthritis, which might be the first sign of recurrence. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Because HCC usually presents as an advanced disease and occurs in the background of liver cirrhosis, most patients are not suitable for treatment with curative intent, thus effective systemic chemotherapy is required. However, the outcome of systemic chemotherapy has been disappointing in advanced HCC. This study was conducted to test the efficacy and toxicity of the combined regimen of epirubicin, cisplatin, and UFT moderated by leucovorin in advanced or recurrent HCC. Patients and methods: All 53 patients received epirubicin (50 mg/m2 i.v.) on day 1 and cisplatin (60 mg/m2 i.v.) after epirubicin administration. Oral UFT 400–600 mg/day, determined by body surface area, and leucovorin 75 mg/day were administered for 21 consecutive days, followed by a 7-day drug free interval. Results: Nine had a partial response, representing 16.9% of response rate (95% confidence interval rate; 7.0–26.8%) with median response duration of 17.1 weeks (95% CI; 5.0–29.3 weeks, range; 7.1–51.7 weeks). Fifteen patients had stable disease and the disease progressed in 26 patients. The median overall survival for the patients was 24.6 weeks (95% CI; 17.3–31.9 weeks, range; 3.0–131.3 weeks). The main toxicities were hematologic toxicities including neutropenia, which reached grade 3/4 in 17 patients (38.5%), and grade 3 or 4 thrombocytopenia in five patients (9.4%). Conclusion: The combination of epirubicin, cisplatin, and UFT moderated by leucovorin showed modest anti-tumor activity with relatively tolerable toxicities. However, a randomized phase III trial based on this regimen is warranted to clarify its survival benefit in patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Urokinase plasminogen activator receptor (uPAR) plays a major role in cancer invasion and metastasis and uPAR expression is correlated with a poor prognosis in various cancer types. Moreover, the expression of uPAR is increased under hypoxic conditions. Nitric oxide (NO) and its metabolites produced by inducible nitric oxide synthase (iNOS) are important products of hypoxic stress, and NO may activate or modulate extracellular signal regulated kinase (ERK). Here, we evaluated uPA, uPAR, and activated ERK levels under hypoxic conditions, and the modulatory effects of iNOS and NO in the MDA-MB-231 human breast cancer cell line. Cells were incubated in a hypoxic or normoxic incubator and treated with PD98059 (a MEK 1/2 inhibitor, which abrogates ERK phosphorylation) and aminoguanidine (a selective iNOS inhibitor). uPAR expression, ERK phosphorylation, and uPA activity were found to be increased under hypoxic conditions. Moreover, when cells were treated with PD98059 under hypoxic conditions, uPAR was downregulated, whereas aminoguanidine markedly increased ERK phosphorylation in a dose dependent manner. Furthermore, aminoguanidine increased uPAR expression and prevented the inhibition of uPAR expression by PD98059. These results demonstrated that uPAR is induced by hypoxia and that increased uPAR expression is mediated by ERK phosphorylation, which in turn is modulated by iNOS/NO in MDA-MB-231 cells. We conclude that iNOS/NO downregulates the expression of uPAR under hypoxic conditions via ERK pathway modulation.Cell Research (2006) 16: 75–81. doi:10.1038/sj.cr.7310010; published online 16 January 2006 [ABSTRACT FROM AUTHOR]

The chemotherapeutic effects of all-trans-retinoic acid (atRA) are mediated by the retinoic acid receptor β (RARβ), but RARβ expression is reduced in a number of head and neck carcinoma (HNSCC) cells which causes resistance to RA treatment in half the patients with HNSCC. The possible mechanism for the reduced RARβ expression has been suggested as the methylation of the CpG islands adjacent to the RA response elements (RARE) in the RARβ promoter and the loss of histone acetylation. The suppressed RARβ expression can be reactivated by a demethylating agent (5-aza-2′-deoxycytidine, 5-AzaC) or a histone deacetylase inhibitor (trichostatin A, TSA). Therefore, we sought to determine if the restoration of RARβ activity, or a combination of these drugs, could restore the sensitivity to RA in RARβ-negative HNSCC cells with an epigenetically methylated RARβ promoter region. SqCC/Y1 cells resistant to atRA showed methylated and unmethylated forms in the RARβ promoter region. RARβ expression of these cells was restored by 5-AzaC or TSA treatment. Also, treatment with TSA and atRA combined synergistically increased the growth-inhibitory effect and highly induced the transcriptional activation of the RARβ promoter compared to atRA treatment in HNSCC cells. Additionally, TSA alone and the combination 5-AzaC and TSA increased lysine-9 (Lys-9) acetylation and Lys-4 methylation of the first exon at the RARβ gene, while decreasing the methylation of Lys-9 in the HNSCC cells. [ABSTRACT FROM AUTHOR]