bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4297: mAbXcite: A novel immunotherapy platform that initiates a robust anti-cancer immune response by recruiting and activating neutrophils
Authors: Sansal-Castellano Isabelle , Carlson Mark , Armstrong Todd , Reznik Gabriel , Siedlecki James , Kane John , Dostalova Zuzana , Miao Hua , Jaffee Elizabeth , Rubin-Bejerano Ifat 
Published: August 2015

Abstract
The recent successes in the immunotherapy field demonstrate that a successful immune response to cancer can lead to meaningful anti-tumor responses. Antibodies blocking immune checkpoint molecules (e.g. CTLA4, and PD-1) lead to effective T cell responses especially in tumors that are immune active.
Immune cells that have not received as much attention in cancer immunotherapy are neutrophils. Neutrophils are the most abundant white blood cells, which protect us from microbial infections. They are the first line of innate defense: they arrive early on in the course of infection, phagocytose, and release the content of their granules, including reactive oxygen species and enzymes. Neutrophils also communicate with other immune cells, such as macrophages, dendritic cells, and T cells, by releasing cytokines and chemokines.
There has long been a call to recruit these professional killers to fight cancer. However, an approach that mediates the recruitment of neutrophils has to lead to acute as opposed to chronic inflammation to overcome the suppressive environment that tumors surround themselves with.
We have developed a novel immunotherapy platform technology, termed mAbXcite, which directs and activates neutrophils to kill cancer cells in a targeted manner. The targeting is achieved by using monoclonal antibodies that are chemically linked to beta-1,6-glucan, a saccharide found on the cell walls of fungal species which recruits and activates neutrophils. The resulting mAb construct attracts mediators of acute inflammation, notably neutrophils, leading to rapid destruction of cancer cells.
We will present proof-of concept of the mAbXcite technology using an anti-EGFR antibody and a syngeneic antibody. mAbXcite-cetuximab demonstrates significantly greater efficacy than the original antibody in resistant tumor models (BRAF and KRAS). Furthermore, mice that show complete regression or stasis do not grow tumors upon rechallenge, suggesting a lasting immune response that is initiated by neutrophils. We will also provide evidence for the involvement of T cells, suggesting that the immune memory is a result of neutrophils naturally leading to T cell activation.
Citation Format: Isabelle Sansal-Castellano, Mark Carlson, Todd Armstrong, Gabriel Reznik, James Siedlecki, John Kane, Zuzana Dostalova, Hua Miao, Elizabeth Jaffee, Ifat Rubin-Bejerano. mAbXcite: A novel immunotherapy platform that initiates a robust anti-cancer immune response by recruiting and activating neutrophils. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4297. doi:10.1158/1538-7445.AM2015-4297
Abstract 431: Active secretion of CXCL10 and CCL5 from colorectal cancer microenvironments associates with GranzymeB+ CD8+ T-cell infiltration
Authors: Zumwalt Timothy J. , Boland C. Richard , Goel Ajay 
Published: August 2015

Abstract
T-cell infiltration varies among colorectal tumors and directly impacts patient survival. Chemoattraction and infiltration of CD8+ T-cells are mediated by surface chemokine receptors CXCR3 and CCR5, and are associated with favorable prognosis. Transcriptional expression of these receptors’ cognate chemokines, as well as other inflammation-associated chemokines, correlate with prolonged disease-free survival (DFS). These findings, however, were derived from paraffin embedded tissues, thus little is known about the pattern of secreted T-cell targeting chemokines from colorectal tumors. Therefore, this investigation aimed to determine the secretion pattern of chemokines associated with DFS from immediately excised live tumor tissues. Our results demonstrate the first real functional analysis of chemokine activity in colorectal tumors beyond immunohistochemistry and real-time PCR. Forty-four colorectal tumors were procured immediately after surgery and categorized by transcriptional expression of two T-cell marker genes that represent the magnitude of type-1 T-cell activity. Tumors that more highly co-expressed IFNG and TBX21 consequently have a higher frequency of infiltrating GzmB+ CTLs and IFN-γ+ CD4+ helper T-cells and transcribe a unique pattern of DFS-associated chemokines when compared to normal mucosa. High co-expression of IFNG and TBX21 was bimodally distributed across the tumors collected. Tumors with higher co-expression more strongly secreted two DFS-associated chemokines, CXCR3 ligand, CXCL10 and CCR5 ligand, CCL5. Additional results demonstrate that tumors with higher co-expression are proportionally skewed towards early TMN stages and with mismatch repair-deficiency, confirming that infiltration of CD8+ T-cells are associated with early TNM stages and lack of metastasis. Secreted chemokines were detected using a novel immunoassay that may have implications for future development of immunopotentiating treatments in cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Timothy J. Zumwalt, C. Richard Boland, Ajay Goel. Active secretion of CXCL10 and CCL5 from colorectal cancer microenvironments associates with GranzymeB+ CD8+ T-cell infiltration. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 431. doi:10.1158/1538-7445.AM2015-431
Abstract 4316: hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2 overexpressing breast cancer cells
Authors: Trono Paola , Di Modugno Francesca , Circo Rita , Spada Sheila , Melchionna Roberta , Palermo Belinda , Panetta Mariangela , Matteoni Silvia , Soddu Silvia , De Maria Ruggero , Nisticò Paola 
Published: August 2015

Abstract
Human Mena (hMENA), an actin regulatory protein of the ENA/VASP family, cooperates with ErbB receptor family signaling in breast cancer. It is overexpressed in high-risk preneoplastic lesions and in primary breast tumors where it correlates with HER2 overexpression and an activated status of AKT and MAPK. The concomitant overexpression of hMENA and HER2 identifies breast cancer patients with a worse prognosis. hMENA is expressed along with alternatively expressed isoforms, hMENA11a and hMENAΔv6 with opposite functions.
By Reverse Phase Protein Assay, we identified a novel role for the epithelial associated hMENA11a isoform in sustaining HER3 activation and pro-survival pathways in HER2 overexpressing breast luminal cancer cells. Since HER3 activation is crucial in mechanisms of cell resistance to PI3K inhibitors, we explored whether hMENA11a is involved in these resistance mechanisms. The specific hMENA11a depletion switched off the HER3-related pathway activated by PI3K inhibitors and impaired the nuclear accumulation of HER3 transcription factor FOXO3a induced by PI3K inhibitors. On the other hand, PI3K inhibitors activated hMENA11a phosphorylation and affected its localization. At the functional level, we found that hMENA11a sustains cell proliferation and survival in response to PI3K inhibitor treatment whereas hMENA11a silencing increases molecules involved in cancer cell apoptosis. As shown in three-dimensional cultured breast cancer cells hMENA11a contributes to cancer cells resistance to PI3K inhibition since the depletion of hMENA11a drastically reduced cell viability upon treatment with PI3K inhibitor BEZ235.
Altogether, these results indicate that hMENA11a in HER2 overexpressing breast cancer cells sustains HER3/AKT axis activation and contributes to HER3-mediated resistance mechanisms to PI3K inhibitors. Thus, hMENA11a expression can be proposed as a marker of HER3 activation and of resistance to PI3K inhibition therapies, to select patients who can benefit from these combined targeted treatments. hMENA11a activity may represent a new target for anti-proliferative therapies in breast cancer.
Citation Format: Paola Trono, Francesca Di Modugno, Rita Circo, Sheila Spada, Roberta Melchionna, Belinda Palermo, Mariangela Panetta, Silvia Matteoni, Silvia Soddu, Ruggero De Maria, Paola Nisticò. hMENA11a contributes to HER3-mediated resistance to PI3K inhibitors in HER2 overexpressing breast cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4316. doi:10.1158/1538-7445.AM2015-4316
Abstract 4318: Dexamethasone variably protects triple negative breast cancer cells against paclitaxel depending on relative cellular levels of glucocorticoid receptor alpha
Authors: Labbe Roselyne , Speyer Cecilia , Bukhsh Miriam , Belfiori Austin , Khansa Rafa , Patki Mudgha , Ratnam Manohar , Gorski David 
Published: August 2015

Abstract
Introduction: Triple negative breast cancer (TNBC) comprises 15-20% of all breast cancer cases and is unresponsive to the drugs used to treat ER+/PR+ or HER2+ breast cancers. The only treatment option for TNBC is chemotherapy with paclitaxel being a major component. However, many patients respond poorly and develop side effects that are routinely treated with dexamethasone. In certain cancers, dexamethasone attenuates chemotherapy response by inhibiting apoptosis or temporarily arresting cell growth. Dexamethasone's actions are mediated through glucocorticoid receptor alpha (GR alpha), which is ubiquitous. Here we examine the protective effect of dexamethasone in TNBC cells and the relationship of this effect to variability in cellular GR alpha levels.
Methods: GR alpha expression was measured in TNBC cell lines and related to dexamethasone's ability to affect their growth and resistance to paclitaxel. Cell lines analyzed included those expressing low levels of GR alpha and recombinant cells in which GR alpha expression was ectopically restored.
Results: A positive association was observed between endogenous GR alpha expression and dexamethasone's ability to protect TNBC cells against paclitaxel. Overexpression of GR alpha in cells expressing low endogenous GR alpha conferred protection against paclitaxel in the presence of dexamethasone. In contrast to reported observations in other cancer cell types, dexamethasone increased cell proliferation and transcriptional activation of thymidylate synthase, an S-phase enzyme. These results suggest the use of dexamethasone may be one factor responsible for the poor response of TNBC patients to traditional chemotherapy and suggest using GR alpha expression level as a biomarker for predicting which TNBC patients should be given traditional chemotherapy.
Citation Format: Roselyne Labbe, Cecilia Speyer, Miriam Bukhsh, Austin Belfiori, Rafa Khansa, Mudgha Patki, Manohar Ratnam, David Gorski. Dexamethasone variably protects triple negative breast cancer cells against paclitaxel depending on relative cellular levels of glucocorticoid receptor alpha. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4318. doi:10.1158/1538-7445.AM2015-4318
Abstract 4319: Clinical significance and possible role of GPNMB in patients with breast cancer
Authors: Futamura Manabu , Kanematsu Masako , Yamada Atsuko , Morimitsu Kasumi , Morikawa Akemi , Mori Ryutaro , Yoshida Kazuhiro 
Published: August 2015

Abstract
Glycoprotein non-metastatic B (GPNMB) is a type I transmembrane protein, which is isolated from differential expression assay using metastatic melanoma cells. The physiological function is very little known but may be supposed to be associated with cell invasion and motility particularly in breast cancer cells. Here we investigated the role of GPNMB in breast cancer. First we checked expression of GPNMB by RT-PCR and western blot in several cancer cell lines including breast, gastric, and colon cancer followed by establishment of GPNMB measurement by ELISA because it's reported that GPNMB is shed at extracellular domain by sheddase such as ADAM10. GPMNB expressed in breast (5/6:83%), gastric (3/6:50%), colon (1/7:14.3%) cancer cell lines. Of breast cancer cell lines, GPNMB was highly expressed in SK-BR3 (HER2 positive), BT474 (HER2/ER positive), MDA-MB-157 (Triple negative) cells. Shed GPNMB in culture medium was measurable and correlated with expression of each cell line. Next we evaluated serum GPNMB in patients with breast (n = 164; primary 119, metastatic 43), gastric (n = 38), and colorectal (n = 50) cancer in our institute from 2011.9-2014.2.) This study was approved by the central ethics committee of Gifu University. Serum GPNMBs were 9.403, 5.751, 6.550 ng/ml, respectively. GPNMB for breast cancer patients was statistically higher than those by colorectal cancer patients (p = 0.018). Of breast cancer patients, GPNMB for HER2-type patients was higher than those for Luminal type and DCIS patients (p = 0.0386, p = 0.0195, respectively). Those for triple negative patients was also higher than those for DCIS patients (p = 0.0459). Interestingly, serum GPNMB was dramatically reduced in accordance with chemotherapy in some patients. Based on these clinical observations, we further investigated relationship between GPNMP and HER2 in vitro. Blockage of GPNMB induced not only HER2 but also EGFR expression. On the other hand, inhibition of HER2 by trastuzumab increased expression of GPNMB. Depletion of GPNMB increased sensitivity of trastuzumab, suggesting that GPNMB may play an important role in crosstalk of signal transduction for breast cancer. These notions may suggest a novel therapeutic strategy to overcome HER2 positive breast cancer.
Citation Format: Manabu Futamura, Masako Kanematsu, Atsuko Yamada, Kasumi Morimitsu, Akemi Morikawa, Ryutaro Mori, Kazuhiro Yoshida. Clinical significance and possible role of GPNMB in patients with breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4319. doi:10.1158/1538-7445.AM2015-4319
Abstract 432: Macrophage promotes EMT in gastric cancer through activating CXCR2 signaling
Authors: Zhang Chang-Hua , Xia Guangkai 
Published: August 2015

Abstract
Background and aims: Macrophage as a member of the tumor microenvironment and chronic inflammation was considered as an important pro-tumoral factor in cancer. CXCR2 was an inflammation receptor and expressed in gastric cancer. But its’ association with macrophage remains unknown. We aimed to investigate the role of macrophage in the development of gastric cancer from inflammation.
Methods: Human GC cell lines AGS, BGC-823 were studied. Western Blot was used to detect the protein expression in gastric cancer cells. Migration of gastric cancer cells were tested by Transwell.
Results: Macrophages and gastric cancer cell lines can secret CXCR2′ ligands when coculutred with each other. CXCR2 knock down in gastric cancer cells can decrease migration and inhibit EMT. Macrophage promotes EMT of gastric cancer though CXCR2 signaling. CXCR2's ligands CXCL1 and CXCL5 can activate stat3 and promote the migration of gastric cancer cells. CXCL1 and CXCL5 are responsible for the EMT of gastric cancer.
Conclusion: Macrophage can promote gastric cancer EMT through activating CXCR2 signaling. CXCR2 ligands CXCL1 and CXCL5 are the crucial factors for promoting EMT in gastric cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Chang-Hua Zhang, Guangkai Xia. Macrophage promotes EMT in gastric cancer through activating CXCR2 signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 432. doi:10.1158/1538-7445.AM2015-432
Abstract 4333: Association of TP53 mutation status with clinical outcomes in patients with EGFR mutated non-small cell lung cancer (NSCLC)
Authors: Ahmed Saman , Aggarwal Charu , Mick Rosemarie , Bauml Joshua , Cohen Roger , Kadauke Stephan , Sterlicchi Trisha , Evans Tracey L. , Kucharczuk John C. , Desphande Charu , Morrissette Jennifer J D , Daber Robert , Langer Corey J. 
Published: August 2015

Abstract
Introduction:
Molecular characterization of tumors is critical in the modern treatment of NSCLC. Epidermal Growth Factor Receptor (EGFR) and p53 are commonly mutated genes in NSCLC with independent prognostic implications, but the significance of the co-existence of these mutations inpatients (pts) with Stage IV NSCLC is not well established. Herein, we describe the relationship of EGFR and TP53 mutations (MT) in pts with Stage 4 or recurrent NSCLC and their correlation with pt demographics and therapeutic outcomes.
Study Design:
We conducted a retrospective analysis of Stage 4 and recurrent EGFR MT (+) NSCLC pts with TP53 MT status determined by the Gene Sequence Analysis Panel obtained at the Abramson Cancer Center between 6/1/2012 and 2/1/2014. Overall survival (OS) and progression-free survival (PFS) were estimated for the TP53 MT (+) and wild type (WT) cohorts from the date of diagnosis.
Results:
Thirty-six EGFR (+) pts were identified, of whom 26 (72%) were TP53 MT (+). Pt characteristics were similar between cohorts, except for a higher rate of bone metastasis in pts with p53 WT (p = 0.07, Table 1). Median potential follow-up for OS was 15.1 mos. 60% of patients in TP53 WT group received TKI compared to 69% in TP53 MT (+). Of the 36 pts, 9 (25%). have died. A trend towards shorter median OS was seen in pts with p53 MT. (p = 0.08). PFS did not correlate with p53 MT status (p = 0.53).
Conclusion:
Coexistence of p53 MT and EGFR MT may be associated with shorter survival. Larger sample size and longer clinical follow up will be necessary to determine if these differences are statistically significant and whether TP53 MT status is an independent prognostic factor in EGFR MT NSCLC.
Citation Format: Saman Ahmed, Charu Aggarwal, Rosemarie Mick, Joshua Bauml, Roger Cohen, Stephan Kadauke, Trisha Sterlicchi, Tracey L. Evans, John C. Kucharczuk, Charu Desphande, Jennifer J D Morrissette, Robert Daber, Corey J. Langer. Association of TP53 mutation status with clinical outcomes in patients with EGFR mutated non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4333. doi:10.1158/1538-7445.AM2015-4333
Abstract 4336: Direct genotyping of CYP2A6 whole gene deletion: A new biomarker for prognosis of lung adenocarcinoma in Japanese smoking male
Authors: Okano Yasuko , Ichikawa Yasushi , Miyagi Yohei , Chishima Takashi , Natsumeda Yutaka 
Published: August 2015

Abstract
Purpose: Cytochrome P450 (CYP2A6) is known as an enzyme responsible for the metabolism of activation of tobacco-specific nitrosamines to their ultimate carcinogenic forms and metabolism of nicotine. We here report that the genetic polymorphisms of human CYP2A6*4 is associated with primary lung cancer and their overall survival.
Experimental Design: We prepared genomic DNA samples from 387 Japanese patients with primary lung cancer and the genetic polymorphisms of human CYP2A6*4 (whole gene deletion) by the rapid genetic testing method we developed in this study. We analyzed the association between the CYP2A6*4 gene, NRF2 gene and overall survival.
Results: Patients harboring wild-type CYP2A6*1 and whole gene deletion CYP2A6*4/*4 numbered 380 (98.2%) and 7 (1.8%), respectively. Its frequency was four-fold higher in male patients than in female (P = 0.038).Multivariate logistic regression models revealed that the genetic polymorphisms of human CYP2A6*4 were significantly related to gender and smoking behavior. Interestingly, lung cancer patients carrying CYP2A6*4/*4 (whole gene deletion), the NRF2 SNP heterozygous (c.-617C/A) and wild-type homozygous (c.-617C/C) exhibited remarkable survival over 1,500 days after surgical operation.
Conclusion: CYP2A6*4/*4 whole gene is considered to be a prognostic biomarker for assessing both the gender-related risk of lung adenocarcinoma in the smoking sub-population and their overall survival.
Citation Format: Yasuko Okano, Yasushi Ichikawa, Yohei Miyagi, Takashi Chishima, Yutaka Natsumeda. Direct genotyping of CYP2A6 whole gene deletion: A new biomarker for prognosis of lung adenocarcinoma in Japanese smoking male. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4336. doi:10.1158/1538-7445.AM2015-4336
Abstract 4337: Comprehensive analysis of genetic variations of genes involved in DNA damage response pathways or cell cycle checkpoints and treatment outcome in non-small cell lung cancer patients treated with platinum doublets
Authors: Ryu Jeong Seon , Yi Bo-Rim , Lee Seul-Ki , Hong Soon-Sun 
Published: August 2015

Abstract
Genes involved in DNA damage response (DDR) pathways or cell cycles checkpoints (CCC) are thought to be closely related to effect of platinum doublets, backbone in treatment for lung cancer patients. We tried to evaluate validity of germ-line variations of all genes related to DDR or CCC as potential predictive biomarker of treatment outcome in non-small-cell lung cancer (NSCLC) patients treated with platinum doublets. A total of 967 NSCLC patients treated with platinum doublets as front line chemotherapy was enrolled and divided randomly into three sets: screening, training and validation. For screening set, whole exons, -1,000 bps upstreams, and splicing junctions in the 170 genes related to DDR or CCC were analyzed using next generation sequencing, then genetic variations were selected with several criterions such as minor allele frequency &gt; 5%, call rate &gt; 90%, p value for HWE &gt; 0.001, and impact of genetic variation. Their effects on progression free survival or response to platinum doublets were evaluated in two phases: training and validation process. Clinical characteristics were not different between training (n = 372) and validation (n = 381) cohorts. A total of 4,697 genetic variations and 7 In/Del were identified in screening set, then 232 genetic variations and 7 In/Del from 118 genes were finally selected with predefined criterions. In training cohort, 29 genetic variations were found to be associated with progression free survival or response. However, the effects of these genetic variations were not failed to be validated. In subgroup analysis with non-adenocarcinoma patients, CLSPN (rs79083467), MSH3 (rs32952), and RAD51C (rs12946397) were shown to be associated with progression free survival of the patients (cox p values for CLSPN, MSH3, RAD51C: 0.028, 0.022, 0.035 in training cohort; 0.046, 0.026, 0.008, respectively in validation cohort). In this study, we have failed to show validity of the germ-line variations in predicting treatment outcome of NSCLC patients treated with platinum doublets. This result show germ-line variations related to pharmacodynamics have a limited value in predicting platinum effect.
Note: This abstract was not presented at the meeting.
Citation Format: Jeong Seon Ryu, Bo-Rim Yi, Seul-Ki Lee, Soon-Sun Hong. Comprehensive analysis of genetic variations of genes involved in DNA damage response pathways or cell cycle checkpoints and treatment outcome in non-small cell lung cancer patients treated with platinum doublets. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4337. doi:10.1158/1538-7445.AM2015-4337