bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5012: Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients
Authors: Liu Na , Cox Thomas R. , Cui Weiyingqi , Adell Gunnar , Holmlund Birgitta , Erler Janine T. , Sun Xiaofeng 
Published: July 2016

Abstract
Emerging evidence implies that the complex and seemingly paradoxical role of lysyl oxidase (LOX) in cancer may depend on its subcellular localization. LOX expression has been reported extracellularly, as well as intracellularly in both the cytoplasmic and nuclear compartments. In this study we analyze previously unreported LOX expression patterns in the nucleus of rectal cancer patient samples and determine the clinical significance of this expression.
LOX expression was examined by immunohistochemistry in 137 primary rectal cancer patients who participated in the randomized Swedish rectal cancer trial of preoperative radiotherapy between 1987 and 1990. Location and expression of LOX protein were detected by confocal microscopy and Western blot in three colon cancer cell lines.
LOX nuclear expression was high in normal mucosal and showed a significant decrease in primary rectal cancer (P&lt;0.001). Furthermore, a significant increase was observed from primary cancer to lymph node metastasis (P&lt;0.01). High nuclear LOX expression was correlated with a high rate of distant metastasis and total recurrence (P = 0.046, P = 0.048, respectively). It was also confirmed that LOX (50-kDa and 32-kDa isoforms) are located in the nucleus of in vitro colon cancer cells. High nuclear LOX expression was found in the metastatic cell line SW620 compared to the parental primary cancer cell line SW480. Radiotherapy had no effect on LOX expression and localization in cancer tissues as well as in in vitro culture. Moreover, multivariable analysis showed that high nuclear LOX expression correlated with poor overall survival (P = 0.003) and disease free survival (P = 0.006), independent of age, gender, TNM stage, differentiation and radiotherapy treatment. Nuclear LOX also correlated with other biological factors (such as NF-κB) known to be associated with patient survival suggesting a possible mechanism. Cytoplasmic LOX is high in primary cancer and metastasis compared with normal tissue, but not prognostic.
So here we firstly proved the nuclear expression of LOX enzyme both in patient rectal cancer tissues and in in vitro colon cancer cells. The strong correlation of nuclear LOX expression to survival offers a promising prognostic biomarker in rectal cancer.
Citation Format: Na Liu, Thomas R. Cox, Weiyingqi Cui, Gunnar Adell, Birgitta Holmlund, Janine T. Erler, Xiaofeng Sun. Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5012.
Abstract 5018: Immunohistochemical expression of lysyl oxidase in prostate cancer
Authors: Macias Virgilia , Delgado Santiago , Kajdacsy-Balla Andre A. 
Published: July 2016

Abstract
Background:
Lysyl oxydase (LOX) is a family of enzymes involved in catalyzing the cross-linking of collagen and elastin in the extracellular matrix, playing a crucial role in the building, strengthening and maintenance of tissues. Changes in its expression have been associated with many diseases. In oncology, these changes have been implicated in every step of tumor progression in different organs, with currently little existing data on prostate. The aim of this study is to analyze the nuclear expression of LOX in prostate tumor epithelial cells using a prostate cancer tissue array cohort.
Design:
PCa tumor samples were obtained from an outcome-based TMA set (5 tissue microarray blocks with 200 paired recurrence (R) and non-recurrence (NR) cases, 400 subjects total, each with quadruplicate 0.6 mm in diameter cores) from the Cooperative Prostate Cancer Tissue Resource (CPCTR). Each case was obtained from a PSA-recurrence subject matched to a non-recurrence subject based on age; race; interval since prostatectomy; Gleason sum-score and pTNM stage. All had at least 5 years follow up, and cases with known metastases were excluded. TMA sections were incubated with rabbit polyclonal anti-human LOX antibody (1:800, NB100-2527, Novus Biologicals) using the Bond™ polymer refine detection HRP (Leica Biosystems, DS9800). Nuclear LOX staining was scored semi-quantitatively as follows: 0, negative; 1+, weak; 2+, moderate; and 3+, strong. Percentage of positively stained cells at each intensity level was recorded to obtain a final h-score The Wilcoxon signed-rank test was used for the statistical analysis of the pair-matched dataset to assess the 2 groups (R vs. NR) for differences in LOX expression.
Results:
Data generated was available in 168 complete pairs. The Wilcoxon signed rank test showed no statistically significant differences for the h-score between the two groups (R vs. NR) (median = 2.15625 [range 0-3] vs. median = 2.2583333335 [range 0-3], p = 0.24604).
Conclusions:
The role of LOX in prostate cancer has not been fully established, and inhibitory and stimulatory effects have been reported. This is the first study in a case-control cohort evaluating the expression of LOX in prostate cancer. Based on our results we are now completing the analysis comparing expression of LOX in normal epithelium and cancer associated stroma.
Citation Format: Virgilia Macias, Santiago Delgado, Andre A. Kajdacsy-Balla. Immunohistochemical expression of lysyl oxidase in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5018.
Abstract 5029: The clinical prognostic factors of 889 patients with non-small cell lung cancer
Authors: Han Yiping 
Published: July 2016

Abstract
Abstract Objective:To analyse the clinical characteristics and investigate the prognostic factors of the patients with non-small cell lung cancer. Method: We analysed the clinical characteristics of 889 cases with non-small cell lung cancer including age, gender, smoking history, TNM stage, Pathologic grade, the expression of Ki67 and p53, chemotherapy, radiotherapy and targeted therapy. Then, we identified the prognosis through the follow-up. The prognostic factors of the non-small cell lung cancer patients were analysed through survival analysis.We chose the Kaplan-Meier method for the univariate analysis and the Cox proportional hazard regression model for multivariate analysis.Results:The overall median survival time of the patients were 12.87 months,and 1-year,2-year,3-year survival rates were 49%, 26% and 12% respectively. Conclusion: Smoking history,TNM stage,Performance Status score, Pathologic grade, treatment and the expression of Ki67 were independent prognostic factors.
Citation Format: Yiping Han. The clinical prognostic factors of 889 patients with non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5029.
Abstract 5034: Overexpression of MYST4 induces tumor progression in hepatocellular carcinoma
Authors: Mao Tsui Lien , Sheu Jinn-Chyuan 
Published: July 2016

Abstract
MYST4 is a member of histone acetyltransferases which are involved in transcriptional activation of genes important for cellular growth and development. Our previous study revealed that overexpression of MYST4 in ovarian high-grade serous carcinoma correlated with worse survival. To further explore the role of MYST4 in human cancers, we selected hepatoma cell line Huh 7 due to its high level of MYST4 expression among various cancer cell lines tested. Immunohistochemical study showed that overexpression of MYST4 correlated with worse overall survival in hepatoceullular carcinoma (P = 0.02). Furthermore, tumor cells at invasion front and in lymphovascular spaces are frequently overexpressed. Knockdown of MYST4 in Huh 7 resulted in significantly reduced cellular growth, migration and perturbed cell cycle progression. Mouse xenograft model revealed that MYST4-knockdown Huh 7 cells had lower growth rate, consistent with the in vitro findings. Together, our studies suggest that MYST4 promotes cell growth, migration and lymphovascular spread in hepatocellular carcinoma. Thus, MYST4 may serve as a druggable target in treating hepatocellular carcinoma.
Citation Format: Tsui Lien Mao, Jinn-Chyuan Sheu. Overexpression of MYST4 induces tumor progression in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5034.
Abstract 5043: Molecular mechanism of resveratrol induced cell death in multidrug resistance prostate cancer
Authors: Singh Santosh K. , Banerjee Saswati , Lillard James W. , Singh Rajesh 
Published: July 2016

Abstract
In order to understanding the molecular mechanisms of drug resistance as well as enhancing the efficacy of docetaxel we established docetaxel-resistant prostate cancer (PCa) cells. The IC50 for docetaxel in PCa resistant cells was about 50-fold higher than parental PCa cells. In the current study we used resveratrol (RES), a natural compound with chemo preventive potential to test its ability to enhance the effectiveness of docetaxel on PCa as well as to explore the mechanism of acquired docetaxel resistance. PCa (PC3, C4-2B and DU145) cell lines treated with different dose of RES or DTX alone or in combination followed by analyzed cell proliferation (MTT assay), apoptosis (flow-cytometric analysis of annexin V/propidium iodide-stained cells and western blot methods).The expression of ABC transporter markers in the development of docetaxel resistance was examined using RT-PCR. Our result shows that the expression of 18 ABC transporter genes were down regulated in PCa cells at 48 and 72 hrs in RES treatment group. The up regulations of pro-apoptotic proteins (Bax, Bad, Bim) and down regulation of anti-apoptotic protein (Bcl2, Mcl1) further confirmed the effectiveness of RES or DTX alone or in combination with DTX. In conclusion these studies suggest that RES inhibits ABC gene expression and resensitizes docetaxel resistant PCa cells to DTX treatment with enhancing apoptotic cell death.
Citation Format: Santosh K. Singh, Saswati Banerjee, James W. Lillard, Rajesh Singh. Molecular mechanism of resveratrol induced cell death in multidrug resistance prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5043.
Abstract 5054: Role and signaling of desmosomal DSP and PKP1 in ovarian cancer
Authors: Xu Yan , Cai Qingchun 
Published: July 2016

Abstract
Identification of driver genes/proteins in EOC tumorigenic processes is critical to increase the cure rate for late stage epithelial ovarian cancer (EOC), which has not been in improved over several decades. We have developed a highly aggressive EOC cell line (ID8-P1 or P1) from ID8-P0 (without in vivo passage, or P0) through in vivo passage in
C57BL6 mice. Two genes encode important desmosome components, desmoplakin (Dsp) and plakophilin 1 (Pkp1) were found to be significantly over-expressed in P1
vs. P0 cells, as well as human EOC cells. DSP is an obligate component of functional desmosomes that anchors intermediate filaments to desmosomal plaques. Pkp1 encodes a member of the arm-repeat (armadillo) and plakophilin (PKP) gene families. Our understanding of the functions of desmosomes in cancer is just emerging and the role of desmosomes in EOC is totally unknown. Our data showed the novel functions of DSP in anoikis-resistance and SRC activation using shRNA-mediated DSP-knocked down (KD) stable cell lines. In addition, we found that ID8-P1 cells formed spheroids and P0 cells tended to be single cells when they were cultured in suspension. KD-Dsp dissociated spheroids, suggesting that desmosomes play an important role in spheroid formation, which may be directly related to anoikis-, drug-resistance, and/or the cancer stem cell (CSC) concepts. Moreover, we found that enhanced glycolysis was involved in the increased anoikis-resistance of ID8-P1 cells and an inhibitor of glycolysis, shikonin (SHK) was a potent anoikis-resistance inhibitor and P1 cells gained more drug-resistance, when compared to P0 cells, with the IC50s were 1.7 and 7.4 μM for P0 and
P1 cells, respectively. Similarly, the IC50s were 2.4 and 8.1 μM for human EOC PE01 and PE04 cells, respectively. PE01 and PE04 cell lines are identified to represent high-grade serous ovarian cancer (HGSC), which were derived from the same patient before (PE01) and after (PE04) the onset of drug resistance to cis-platinum (CDDP), chlorambucil, and 5-fluorouracil. PP2 (a SRC nhibitor) and SHK were able to dissociate the cell-cells aggregates/spheroids in EOC cells. The previously unknown role of DSP and/or PKP1 in EOC may be related to their signaling activities outside desmosomes. Cells staining of PKP1 protein showed its cytosolic and perinuclear location, providing supporting and proof-of-concept data. Together, our data have suggested the novel links among DSP, PKP1, anoikis-resistance, SRC activation, cell-cell-aggregation, and
drug-resistance. These data provide a basis for developing new modalities for EOC treatment.
Citation Format: Yan Xu, Qingchun Cai. Role and signaling of desmosomal DSP and PKP1 in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5054.
Abstract 5056: RET-mediated invasion in three-dimensional microenvironment models
Authors: Maritan Sarah M. , Lian Eric Y. , Mulligan Lois M. 
Published: July 2016

Abstract
RET is a receptor tyrosine kinase expressed in cells derived from the neural crest. RET activation and signalling is mediated by soluble ligands of the Glial Cell-Derived Neurotrophic Factor (GDNF) family. RET signalling plays critical roles during embryogenesis, mediating directional cell migration, proliferation, and survival. In addition to its normal developmental roles, oncogenic mutations or aberrant expression of RET are also linked to tumor spread and metastasis in multiple human tumor types. Specifically, activating mutations of RET have been identified in multiple-endocrine neoplasia type 2, while expression of wildtype RET is linked to increased local invasion in breast and pancreatic tumors. Previous studies of RET-mediated invasion and metastasis have used standard 2D culture methodologies, which may not be reflective of the in vivo microenvironment. Here, we have developed an in vitro 3D model of tumor growth, invasion, and metastasis to characterize the signals critical to these processes.
Using SH-SY5Y cells, a neuroblastoma cell line that endogenously expresses RET, we assessed anchorage-independent growth and invasion into a surrounding collagen matrix in response to RET stimulation with GDNF. We have quantified the contributions of several RET downstream signalling pathways by individually blocking SRC, PI3K, FAK, STAT3, MEK, and integrin β-1 signals, for their effects on RET-mediated cell growth and invasion in 3D culture. Our data demonstrate that inhibiting either PI3K or MEK decreases the invasive potential of SH-SY5Y cells in response to RET activation, while inhibition of STAT3 had little effect. We have also shown that integrin β-1, FAK or SRC inhibition completely blocked invasion, consistent with an integrin dependent mode of invasion in SH-SY5Y cells. Additionally, we showed that FAK and SRC signalling were critical for SH-SY5Y survival in 3D microenvironments. While several RET-mediated signalling pathways have been implicated in cell motility and invasion in two-dimensional culture models, our findings suggest that specific signals may differ in their importance in a three-dimensional microenvironment. We are currently using our 3D models to further characterize the contributions of RET signalling to tumor cell invasiveness. These data may provide further insight into the role of RET expression in in vivo tumor spread.
Citation Format: Sarah M. Maritan, Eric Y. Lian, Lois M. Mulligan. RET-mediated invasion in three-dimensional microenvironment models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5056.
Abstract 5059: Cancer cell invasion dynamics in microchannels during stromal cell coculture
Authors: Holle Andrew W. , Kast Verena , Kemkemer Ralf , Spatz Joachim 
Published: July 2016

Abstract
Metastasizing cancer cells must escape their tumor microenvironment and invade into surrounding healthy stromal tissue. During this process, they must balance intercellular crosstalk with ECM degradation, physical force generation, and cytoskeletal rearrangement. To mimic this process in vitro, PDMS microchannels fabricated with photolithography and replica molding were used to examine the interaction of cancer cells with healthy stromal cells during physical confinement in three dimensional environments. A focus was placed on understanding the variations in invasion behavior between healthy cells and cancer cells, then attempting to explain these differences by cell mechanical properties and gene expression. Distinct differences in cancer cell invasion characteristics were observed between wide 10 μm channels and narrow 3 μm channels, with the latter exhibiting smooth velocity profiles and increased channel permeation. Live cell actin staining, ECM protein alteration, and chemical inhibition of both Rac1 and RhoA mechanical pathways were all used to better understand these differences, leading to the conclusion that the actin cytoskeleton is greatly altered during invasion into very confined channels. To better understand the role of stromal cells in this process, both indirect and direct coculture of MDA MB-231 basal breast cancer cells and stromal cells were performed in microchannel chips with the aid of live cell permeable tracking dyes. To reflect a diverse range of stromal cell types, cocultures were performed with MCF 10A non-tumorigenic breast epithelial cells, macrophage-differentiated THP-1 monocytes, and HN-CAFs (head and neck carcinoma-associated fibroblasts). Both the cancer cells and the stromal cells exhibited increases in invasion speed upon direct co-culture of the two cancer cell lines, both in wide and narrow channels. The use of stromal cell-conditioned media as well as observed differences in migration speed and persistence when unconfined provided further understanding of the complex processes underlying cancer cell and stromal cell invasion.
Citation Format: Andrew W. Holle, Verena Kast, Ralf Kemkemer, Joachim Spatz. Cancer cell invasion dynamics in microchannels during stromal cell coculture. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5059.
Abstract 5064: CORO1B amplification and expression status identifies an aggressive subset of chromosome 11q13 amplified HNSCC
Authors: Allen Jessica L. , Walk Elyse L. , Rhodes Kristen L. , Beatty Colleen J. , Markwell Steven M. , Papenberg Brenen W. , Interval Erik T. , Wu Hong , Varella Garcia Marileila , Bear James E. , Weed Scott A. 
Published: July 2016

Abstract
Head and neck squamous cell carcinoma (HNSCC) is highly invasive cancer type that occurs with greater incidence in West Virginia and the rest of Appalachia. The chromosome 11q13 region is amplified in approximately 30% of late stage HNSCC cases and is associated with a poor patient prognosis. The core 11q13 region encodes the well-studied tumor genes CCND1 (cyclin D1) and CTTN (cortactin). The CORO1B (coronin 1B) gene flanks the 11q13 core and is amplified in 9-14% of all HNSCC, but how CORO1B amplification contributes to HNSCC is unknown. Coronin 1B governs cell motility by negatively regulating F-actin stability through displacement of cortactin at actin related protein 2/3 (Arp 2/3) branch points, generating dynamic turnover of Arp2/3-F-actin networks required for productive cell movement. Kaplan-Meier analysis of two independent patient cohorts indicates that HNSCC cases with CORO1B amplification have significantly reduced overall survival. Cox hazard ratios also indicate the CORO1B amplification is strongly associated with increased mortality in both cohorts. Automated quantitative analysis (AQUA) of coronin 1B expression in HNSCC tissue microarrays indicates that coronin 1B overexpression decreases median survival of HNSCC patients from 81 to 29 months. Reduced expression of coronin 1B by RNAi-mediated knockdown in established HNSCC cell lines decreases several actin-mediated invasive processes, including invadopodia formation and extracelluar matrix degradation. Collectively these results suggest that elevated coronin 1B expression levels in HNSCC function to enhance tumor invasion, potentially through accelerated downregulation of cortactin stabilizing activity at Arp2/3-F-actin junctions. Importantly, CORO1B amplification and coronin 1B expression status may serve a role as a precision biomarker for identification of a subset of late-stage HNSCC patients that would benefit from more aggressive forms of initial clinical treatment.
Citation Format: Jessica L. Allen, Elyse L. Walk, Kristen L. Rhodes, Colleen J. Beatty, Steven M. Markwell, Brenen W. Papenberg, Erik T. Interval, Hong Wu, Marileila Varella Garcia, James E. Bear, Scott A. Weed. CORO1B amplification and expression status identifies an aggressive subset of chromosome 11q13 amplified HNSCC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5064.