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Background and objectives Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation. Materials and methods To focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting. Results We identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy. Conclusion We propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents.

Background: Although various molecular subtypes of bladder cancer (BC) have been investigated, most of these studies have focused on muscle-invasive BC (MIBC). A few studies have investigated non-muscle-invasive BC (NMIBC) or NMIBC and MIBC together, but none has classified progressive NMIBC or immune checkpoint inhibitor (ICI)-based therapeutic responses in early-stage BC patients. Methods: A total of 1,934 samples from seven patient cohorts were used. We performed unsupervised hierarchical clustering to stratify patients into distinct subgroups and constructed a classifier by applying SAM/PAM algorithms. We then investigated the association between molecular subtypes and immunotherapy responsiveness using various statistical methods. Findings: We explored large-scale genomic datasets encompassing NMIBC and MIBC, redefining four distinct molecular subtypes, including a subgroup containing progressive NMIBC and MIBC with poor prognosis that would benefit from ICI treatment. This subgroup showed poor progression-free survival with the distinct features of high mutation load, activated cell cycle, and inhibited TGFβ signalling. Importantly, we verified that BC patients with this subtype were significantly responsive to an anti-PD-L1 agent in the IMvigor210 cohort. Interpretation: Our results reveal an immunotherapeutic option for ICI treatment of highly progressive NMIBC and MIBC with poor prognosis. Funding: This research was supported by the National Research Foundation of Korea grant funded by the Korean government, a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea, and a grant from the KRIBB Research Initiative Program. Keywords: Bladder cancer, Disease progression, Subtype, Immunotherapy, Genomic signature

Objective: To identify patterns of physical activity (PA) participation, exercise preference, and barriers of stage 2–3 prostate cancer survivors across cancer trajectories based on selected demogr...

Purpose Advanced stage clear cell renal cell carcinoma (ccRCC) involves a poor prognosis. Several studies have reported that dysfunctions in iron metabolism‒related proteins may cause tumor progression and metastasis of this carcinoma. In this study, we investigated the impact of the expression of iron metabolism‒related proteins on patient prognoses in advanced stage ccRCCs. Materials and methods All of 143 advanced stage ccRCC specimens were selected following validation with double blind reviews. Several clinicopathological parameters including nuclear grade, perirenal fat invasion, renal sinus fat invasion, vascular invasion, necrosis, and sarcomatoid/rhabdoid differentiation were compared with the expression of ferroportin (FPN), and F-Box and leucine rich repeat protein 5 (FBXL5), by immunohistochemistry. FPN and FBXL5 mRNA level of ccRCC from The Cancer Genome Atlas database were also analyzed for validation. Results FPN and FBXL5 immunohistochemistry showed membrane and cytoplasmic expression, respectively. Based on the H-score, cases were classified as low or high expression with a cut-off value of 20 for FPN and 15 for FBXL5, respectively. Low expression of FPN and FBXL5 were significantly associated with patient death (p=0.022 and p=0.005, respectively). In survival analyses, low expression of FPN and FBXL5 were significantly associated with shorter overall survival (p=0.003 and p=0.004, respectively). On multivariate analysis, low FPN expression (hazard ratio, 1.898; p=0.026) and low FBXL5 expression (hazard ratio, 1.851; p=0.022) were significantly associated with shorter overall survival. Conclusion FPN and FBXL5 can be used as potential prognostic markers and therapeutic targets for advanced stage ccRCC.

In this paper Hybrid Real Time HVDC Simulator for both operator's training and researching in Cheju-Haenam HVDC system is proposed and its performance is verified by RTDS(Real Time Digital Simulator), EMTDC(Electro-Magnetic Transient system for DC), PSS/E(Power System Simulator for Engineering), and experienced scenarios. The main objective of this paper is to represent the strategy in development of the KEPCO hybrid HVDC simulator for Cheju-Haenam HVDC system. This simulator consists of two DC stations, DC cables, external digital/analogue controllers, control desk for education, and AC networks. In cases of both startup/shutdown and normal state operations, the suitability of it for operator's education is tested. Also the dynamic performances of it are verified.

The authors studied the effect of hydrogen irradiation on the optical properties of ZnTe, ZnTe1−ySy (y=0.015) and ZnSe1−xOx (x=0.0023, 0.0057 and 0.009) epilayers. Photoluminescence measurements show the full passivation of O-related recombination bands in ZnTe and ZnTe0.985S0.015 samples unintentionally doped with oxygen. However, hydrogen irradiation does not affect the bandgap reduction following O incorporation in ZnSe1−xOx alloys. This lack of interaction between O and H in ZnSe1−xOx points toward a scarce localised character in the ZnSe1−xOx band edges, as supported by the study of the temperature dependence of the ZnSe1−xOx bandgap.

The ZnSe/GaAs epilayers grown by hot wall epitaxy have been investigated by means of Raman, and photocurrent (PC), and photoluminescence spectroscopy. Raman spectroscopy measurement showed that a plasmon-longitudinal optical phonon-coupling mode existed together with its characteristic longitudinal optical phonon. The temperature dependence of the energy band gap of the ZnSe/GaAs epilayer was found to be E g (T)=2.8210 eV −(9.11×10 −4 eV/K )T 2 /(298.1+T) based on PC measurement. Also, the energy band gap, Eg(T), at 300 K has been determined to be 2.6839 eV. From the photoluminescence spectra, two dominant peaks of 2.7988 and 2.7937 eV separated from the free exciton peak at 442.4 nm (2.8026 eV) have been found to be associated with the upper and the lower polariton peak of the exciton, I2 (Do, X), respectively. This polariton peak is attributed to the strain due to the lattice mismatch between the substrate and the ZnSe epilayer. On the basis of the obtained results, the donor-impurity binding energy is calculated to be 25.3 meV.

Aim: For patients with NSq-NSCLC, pemetrexed(A) plus cisplatin(P) was superior to gemcitabine(G) plus cisplatin(P) in terms of efficacy and toxicity. However, there have been no prospective phase III trial directly comparing the efficacy of AP with docetaxel + cisplatin (DP) in NSq-NSCLC. The objective of this study is to prove the non-inferiority of progression free survival (PFS) of DP compared to AP. Methods: We undertook an open-label phase III trial with recruitment between August 2011, and December 2013, at 14 centers in Korea. Patients with chemotherapy-naive NSq-NSCLC were randomized into 3 weekly cisplatin 70 mg/m2 with either docetaxel 60mg/m2 (DP) or pemetrexed 500mg/m2 (AP) for up to 4 cycles with stratification strata of performance status and sex. The primary objective was to assess PFS and the secondary endpoints were response rate, overall survival (OS) and safety. Treatment response was evaluated according to RECIST version 1.1. Results: After 149 patients were randomized into AP (n = 77) and DP (n = 72) arm, study team finished enrollment because of approval and popular use of maintenance pemetrexed treatment in Korea. Clinical characteristics including sex, age, and performance status were well balanced between the arms. Number of cycles and relative dose intensity were not significantly different between the arms. Partial remission was observed in 24 (31.2%) and 24 (33.3%) cases of AP and DP group, respectively. Median PFS was 4.7 months (95% confidence interval, CI 4.4 ∼ 5.1) in AP arm and 4.6 months (3.7 ∼ 5.6) in DP arm. Rate of grade 3 or 4 neutropenia and febrile neutropenia, number of serious adverse events were significantly higher in DP compared to AP arm (Table 1). Conclusions: Although both regimens showed similar PFS and response rate, more frequent adverse events and higher toxicities were observed in DP arm. (ClinicalTrials.gov Identifier: NCT01282151) Disclosure: Y. Kim: This study was funded by Sanofi Aventis Korea. All other authors have declared no conflicts of interest. Comparison of treatment, response, and adverse events. Pemetrexed/Cisplatin (n = 77) Docetaxel/Cisplatin (n = 72) Age, mean(SD) 63.0 ± 8.9 63.8 ± 9.8 Sex 53/24 50/22 ECOG PS (0/1/2) 14/55/8 17/48/7 Histology ADC/LCC/NSCLC 75/0/2 69/1/2 Stage (IIIB/IV) 5/72 3/69 Cycles (1/2/3/4/6) 7/16/2/49/3 11/14/1/45/1 Cycles mean(range) 3.4 (1-6) 3.2 (1-6) Total number of Cycles 259 228 Cycles delayed 17 (6.7%) 18 (7.9%) Doses reduced 16 (6.3%) 21 (9.3%) Relative dose-intensity (%) 97.6 ± 5.7 96.2 ± 6.9 Response (PR/SD/PD/NE) 24/33/10/10 24/25/15/8 PFS (m) 4.7 (4.4-5.1) 4.6 (3.7-5.6) Overall survival (m) 19.7 (10.8-28.6) 28.0 (7.5-48.5) Neutropenia grade 3/4 1 (1.3%) 10 (13.9%) ** Febrile Neutropenia 1 (1.3%) 8 (11.1%) * Total number of SAE 42 (16.2%) 70 (30.7%) *** SAE cases 17 (22.1%) 29 (40.3%) * * p

Aim: Oropharyngeal cancer (OPC) associated with human papilloma virus (HPV) shows better treatment outcomes than non-HPV OPC. We investigated the expression of p53, b-tubulin, bcl-2 and ERCC 1 according to p16 status in OPC patients receiving induction chemotherapy followed by concurrent chemoradiotherapy. Methods: Patients who were treated with at least 2 cycles of induction chemotherapy for locally advanced oropharyngeal cancer from 2004 to 2011 were reviewed. Immunohistochemical staining of p53, b-tubulin, bcl-2, ERCC, which are well known to be associated with chemotherapy response, and p16, as a surrogate marker for HPV, was done in paraffin-embedded tumor tissue. We analyzed the response for chemotherapy and survival outcomes according to p16 expression. Results: Seventy-four patients were enrolled for this study. All patients received induction chemotherapy with docetaxel, 5-FU, cisplatin (n = 72) or 5-FU and cisplatin (n = 2). One patient received a salvage operation and eight patients were not given radiotherapy due to poor general condition after induction chemotherapy. Therefore, 65 patients received chemoradiotherapy subsequently (total radiation dose; ≥60Gy n = 54, Conclusions: OPC associated with HPV (HPV OPC) showed lower expression of p53, beta tubulin and higher expression of bcl-2 than non-HPV OPC. In addition, the expressions of p53 and beta tubulin were prognostic factors for OPC. This result suggested the underlying mechanism of better response to chemotherapy in case of HPV OPC than non-HPV OPC and de-escalation of treatment in patients with HPV OPC could be considered based on clinical trial results. Disclosure: All authors have declared no conflicts of interest.