bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-410: Phase I dose escalation study of MM-121, a fully human monoclonal antibody to ErbB3, in patients with advanced solid tumors
Authors: Denlinger Crystal S. , Keedy Vicki L. , Cleary James M. , Kubasek William , Onsum Matthew , Moulis Sharon , Garcia Gabriela , Schoeberl Birgit , MacBeath Gavin , Nering Rachel , Murray James , Moyo Victor , Wong Kwok-Kin , Shapiro Geoffrey 
Published: August 2014

Abstract
Introduction: ErbB3 has been identified as a key driver of the PI3K/AKT signaling pathway, resulting in cell growth and survival. MM-121 is a fully human monoclonal antibody targeting ErbB3. By binding to ErbB3, MM-121 blocks heregulin, thereby inhibiting ligand-induced ErbB3 heterodimerization and activation of receptors. Binding of MM-121 also induces downregulation of ErbB3 from the cell surface.
Methods: Patients ≥ 18 years with refractory advanced solid tumors were given MM-121 weekly in 4-week cycles at 6 dose levels. Dose escalation was based on dose limiting toxicities (DLTs) during cycle 1. Primary objectives were to determine the maximum tolerated dose (MTD) of MM-121 and describe any objective response and progression free survival. Secondary objectives were to describe the safety, pharmacokinetic (PK), and pharmacodynamic profile of MM-121. A dose expansion cohort at the highest dose cohort was also included for selected tumor types, with required pre- and post-treatment biopsies to assess MM-121 target effects, ErbB3 pathway markers, and guide dose schedule decisions.
Results: Between July 2008 to January 2011, 38 patients have been enrolled in the study. Twenty-five patients were enrolled in the dose escalation part of the study and treated until unacceptable toxicity or progression. Six cohorts were completed and an MTD was not reached. Grade 1/2 nausea, diarrhea, fatigue and rash were the most commonly observed adverse events. Grade 1 hypomagnesemia was observed in 4 patients at different doses. One patient experienced a DLT of confusion at the lowest dose, considered possibly related to MM-121 treatment but confounded by other comorbidities. No other treatment related serious AEs were reported. An additional 13 patients have been enrolled to date in an expansion cohort. The overall safety profile for patients in the expansion cohort is similar to that observed for the dose escalation cohorts.
Conclusion: In this single agent, first in human, dose escalation phase I study MM-121 was well tolerated with a favorable safety profile. Enrollment in the dose expansion cohort is ongoing.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-410. doi:10.1158/1538-7445.AM2011-LB-410
Abstract LB-416: Evaluation of phase 3 multicenter clinical data of receptor targeted (CD206) Tc99m-tilmanocept for sentinel node evaluation (ILM) in breast cancer and melanoma
Authors: Sondak Vernon K. , Wallace Anne M. 
Published: August 2014

Abstract
Background: Sentinel lymph node (SLN) mapping is widely used for staging clinically node-negative breast cancer and melanoma. [99mTc]tilmanocept is a new receptor-targeted (CD206) radiopharmaceutical designed for SLN mapping. The purpose of this review is to report the results of the Phase 3 clinical data designed to assess the concordance of [99mTc]tilmanocept with vital blue dye, considered the standard for identifying sentinel lymph nodes in these two malignancies.
Methods: The Phase 3 program was a multicenter, prospective, open label, evaluation of [99mTc]tilmanocept in patientswith clinically localized melanoma or breast cancer. Within the Intent-to-treat population, [99mTc]tilmanocept and vital blue dye were administered to patients and standard SLN mapping was performed, during which all identified radioactive and/or blue-stained lymph nodes were excised and histologically examined. The primary endpoint was concordance of [99mTc]tilmanocept with vital blue dye. The patient concordance rate was defined as the percentage of patients for whom all nodes detected by blue dye were also detected by [99mTc]tilmanocept.
Results: At least one blue-stained lymph node was exhibited by 91% patients and 98.0% had at least one “hot” node. The concordance of [99mTc]tilmanocept with vital blue dye was statistically significant with ∼98% concordant. Of the melanoma patients, ∼97% were concordant; and within the breast cancer patients, ∼99% were concordant. In contrast, vital blue dye had a concordance rate with [99mTc]tilmanocept of &lt;55%. No severe adverse events were related to the administration of [99mTc]tilmanocept.
Conclusions: [99mTc]Tilmanocept was well tolerated and effectively identifies sentinel nodes with a statistically significant degree of concordance to blue dye in either breast cancer or melanoma surgery. Additional outcomes will be presented. (Also refer to ClinicalTrials.gov, key word, tilmanocept)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-416. doi:10.1158/1538-7445.AM2011-LB-416
Abstract 101: Pilot study of oral microbiome and risk of pancreatic cancer.
Authors: Lin I-Hsin , Wu Jing , Cohen Steven M. , Chen Calvin , Bryk Darren , Marr Mollie , Melis Marcovalerio , Newman Elliot , Pachter H Leon , Alekseyenko Alexander V. , Hayes Richard B. , Ahn Jiyoung 
Published: August 2014

Abstract
Previous studies showed that periodontitis and tooth loss are associated with increased risk of pancreatic cancer, suggesting possible role of oral bacteria in the pancreatic cancer etiology. We evaluated whether oral microbiome is associated with risk of pancreatic cancer and pancreatitis.
Oral wash samples were collected from 13 pancreatic cancer patients, 3 pancreatitis patients and 12 healthy controls at NYU Langone Medical Center, New York. Ribosomal 16S rRNA genes from oral wash DNA were amplified by universal primers, barcoded, and sequenced with 454 FLX technology. The bacterial 16S rRNA gene sequences were binned into operational taxonomic units (OTUs) with 97% identify and further classified by taxonomy. Non-parametric Wilcoxon Mann Whiteney U test and Kuskal-Wallis test were conducted to compare the relative abundance of taxa across pancreatic cancer, pancreatitis and control groups.
A total of 250,008 sequence reads (average 8,928 reads per sample) were observed. Firmicutes, Bacteroidetes, and Actinobacteria are major phyla, accounting for 96.5% of oral microbiota. We found that bacteroides genus was significantly more abundant in both pancreatic cancer patients (p = 0.002) and pancreatitis patients (p = 0.004) compared with control group. Further, BLAST search results indicate that the species most closely represented by the Bacteroides OTUs were oral pathogen. In addition, Corynebacterium (p = 0.033) and Aggregatibacter (p = 0.019) were less abundant in pancreatic cancer and pancretitis groups compared with controls.
Data from this pilot study of oral microbiome and pancreatic cancer suggest that the differential abundance in bacteriodates and possibly Corynebacterium and Aggregatibacter, are associated with risk of pancreatic cancer. Bacteroides, Gram-negative bacillus bacteria, plays an important role in oral inflammation, including periodontitis. Further larger studies are warranted to confirm these preliminary findings.
Citation Format: I-Hsin Lin, Jing Wu, Steven M. Cohen, Calvin Chen, Darren Bryk, Mollie Marr, Marcovalerio Melis, Elliot Newman, H Leon Pachter, Alexander V. Alekseyenko, Richard B. Hayes, Jiyoung Ahn. Pilot study of oral microbiome and risk of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 101. doi:10.1158/1538-7445.AM2013-101
Abstract 102: Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Men's Health Study.
Authors: Wu Jie , Cai Qiuyin , Li Honglan , Cai Hui , Gao Jing , Yang Gong , Zheng Wei , Xiang Yong-Bing , Shu Xiao-ou 
Published: August 2014

Abstract
Chronic inflammation has been implicated in the pathogenesis of colorectal cancer. C-reactive protein (CRP), a biomarker of systemic inflammation, has been investigated in various populations for its association with colorectal cancer risk, but results have been inconsistent. We examined pre-diagnostic circulating levels of CRP with colorectal cancer risk among 288 colorectal cancer cases and 576 frequency-matched controls nested within the Shanghai Men's Health Study (2002-2006), a population-based cohort study of 61,483 men. Baseline plasma CRP levels were 47% higher among men who subsequently developed colorectal cancer than among those who remained free of the disease (1.12 μg/ml vs. 0.76 μg/ml; P&lt;0.001). Multivariate analyses showed a dose-dependent relationship between CRP and colorectal cancer risk (P-trend=0.001); men in the highest tertile with CRP &gt;1.19 μg/ml had 1.88-fold (95%CI: 1.24-2.86) increased odds of developing colorectal cancer compared with men in the lowest tertile with CRP &lt;0.45 μg/ml. The association was observed for both colon and rectal cancers, became stronger after excluding subjects who took any antibiotics during past 7 days, and was restricted to cancer cases diagnosed within 4 years of blood collection (ORs for the highest tertile being 3.28 (95%CI: 1.28-8.37), 3.68 (95%CI: 1.62-8.38), and 1.05 (95%CI: 056-1.97), respectively for cases diagnosed within 2, 2-4 and 4 years after blood draw). The findings from our study suggest that circulating CRP level is positively associated with colorectal cancer risk in Chinese men, and this association, at least in part, is explained by inflammation related to cancerous or precancerous processes.
Citation Format: Jie Wu, Qiuyin Cai, Honglan Li, Hui Cai, Jing Gao, Gong Yang, Wei Zheng, Yong-Bing Xiang, Xiao-ou Shu. Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Men's Health Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 102. doi:10.1158/1538-7445.AM2013-102
Abstract 1049: PIM2 inhibitor as a targeted therapy for the treatment of multiple myeloma patients with specific genetic signatures.
Authors: Baldino Carmen M. , Caserta Justin , Dumas Stephane , Flanders Yvonne , Nair Jayakumar , Lee Kelvin P. 
Published: August 2014

Abstract
Jasco Pharmaceuticals has developed a novel and selective pan-PIM inhibitor (JP_11646) that has demonstrated biochemical IC50s of 24, 0.5 and 1 nM for PIM1, PIM2 and PIM3 respectively. Jasco also developed an engineered cell line to measure PIM2 transphosphorylation by over-expressing human PIM2 in human HEK293 cells together with human BAD as the substrate. The cell based assay measures the phosphorylation levels of BAD at Ser112 attributed solely to PIM2. JP_11646 exhibited a 590 nM IC50 in this cell based PIM2 assay confirming the MOA. JP_11646 increases apoptosis and decreases cell viability in multiple myeloma cell lines with the t(14;16) and t(4;14) translocations, which are known markers for poor prognosis. JP_11646 is orally bioavailable and has demonstrated in vivo efficacy, inhibiting tumor growth by &gt;80% in a MM1.S tumor xenograft study. These data provide solid rationale for further development of JP_11646 as a targeted therapy for specific population of multiple myeloma patients that exhibit these genetic markers.
Citation Format: Carmen M. Baldino, Justin Caserta, Stephane Dumas, Yvonne Flanders, Jayakumar Nair, Kelvin P. Lee. PIM2 inhibitor as a targeted therapy for the treatment of multiple myeloma patients with specific genetic signatures. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1049. doi:10.1158/1538-7445.AM2013-1049
Abstract 105: Serum retinol and risk of head and neck cancer.
Authors: Chang Jeffrey S. , Hsiao Jenn-Ren , Ou Chun-Yen , Wong Tung-Yiu , Tsai Sen-Tien , Lo Hung-I , Huang Cheng-Chih , Lee Wei-Ting , Chen Ken-Chung , Huang Jehn-Shyun , Wang Yi-Hui , Weng Ya-Ling , Yang Han-Chien 
Published: August 2014

Abstract
Background: Head and neck cancer (HNC), including cancer of the oral cavity, pharynx, and larynx, is one of the leading cancers in the world. The known risk factors, including alcohol, betel quid, and cigarette, account for the majority of the HNC cases. However, the biological mechanisms regarding the carcinogenic effects of these agents in the development of HNC are not completely understood. Retinoic acid is involved in cell growth, differentiation, and apoptosis, which when dysregulated may lead to the development of cancer. Studies have shown that alcohol, betel quid, and cigarette can affect either the metabolism or the function of retinoic acid pathway. The current analysis evaluated the association between serum retinol and HNC risk and assessed whether this association can be modified by alcohol, betel quid, or cigarette.
Methods: 93 incident cases of HNC and 79 sex- and age- frequency matched controls were recruited from the department of otolaryngology and department of stomatology. Information on the use of alcohol, betel quid, and cigarette was collected by in-person interviews. Serum retinol levels were measured using high performance liquid chromatography. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with serum retinol levels. Additional analyses were performed stratified by alcohol, betel quid, and cigarette.
Results: Compared to controls, HNC cases had a lower level of serum retinol (Median for HNC cases: 811 ug/l vs. median for controls: 901 ug/l, Wilcoxon rank-sum P = 0.04). For every 100 ug/l increase, the risk of HNC was reduced by 8% (OR = 0.92, 95% CI: 0.83-1.02). The OR was 0.5 (95% CI: 0.24-1.06) comparing the highest tertile of serum retinol level to the lowest tertile. A lower HNC risk associated with higher serum retinol levels was observed among never alcohol drinkers (For every 100 ug/l increment, OR = 0.80, 95% CI: 0.66-0.96) but not among regular alcohol drinkers (For every 100 ug/l increment, OR = 0.98, 95% CI: 0.86-1.13).
Conclusion: Higher levels of serum retinol are associated with a reduced risk of HNC. Alcohol consumption obliterates the inverse association between serum retinol and HNC risk, possibly by disrupting the metabolism of retinoic acid pathway.
Citation Format: Jeffrey S. Chang, Jenn-Ren Hsiao, Chun-Yen Ou, Tung-Yiu Wong, Sen-Tien Tsai, Hung-I Lo, Cheng-Chih Huang, Wei-Ting Lee, Ken-Chung Chen, Jehn-Shyun Huang, Yi-Hui Wang, Ya-Ling Weng, Han-Chien Yang. Serum retinol and risk of head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 105. doi:10.1158/1538-7445.AM2013-105
Abstract 1064: The combined activation of MET signaling and PKCα is sufficient to induce tumors in mouse skin.
Authors: Cataisson Christophe , Liu Fan , Wright Lisa N. , Zhuang Anne , Merlino Glenn , Yuspa Stuart H. 
Published: August 2014

Abstract
Aberrant activation of MET signaling has been identified in multiple cancers but its relation to cancer-associated inflammation has not been explored. To address this issue in the context of skin carcinogenesis, a double transgenic mouse model (MT1-HGF/ K5-PKCα or DT) was generated. K5-PKCα mice that overexpress PKCα in basal keratinocytes develop a strong neutrophilic cutaneous inflammatory response upon topical TPA (12-tetradecanoylphorbol-13-acetate) application. These mice were crossed with MT1-HGF mice that overexpress HGF under a metallothionein promoter to create MT1-HGF/ K5-PKCα double transgenic (DT) mice and their respective controls. We observed that DT animals were very sensitive to squamous carcinogenesis. Using a low promoting dose of TPA that primarily activates PKCα in K5-PKCα or DT mice yielded an average of 6 tumors per mouse in the DT group; single transgenic K5-PKCα or MT-HGF mice developed an average of 1 tumor while WT developed none at this TPA dose. We hypothesize that in DT mice, keratinocyte-derived HGF synergizes with PKCα to drive tumor promotion and increase tumor growth. Primary keratinocytes derived from MT1-HGF or DT mice display a phenotype reminiscent of EGFR activated cells: increased expression of pro-inflammatory factors, upregulation of Keratin 8 (K8) and downregulation of K1 and K10 mRNAs. Indeed western blot analysis shows that EGFR is transactivated in MT1-HGF and DT keratinocytes and cell proliferation is elevated as well but not in K5-PKCα or WT keratinocytes. The release of CXCL1,a hallmark of RAS transformation, is augmented in RAS-keratinocyte cell culture supernatants with MT1-HGF and DT keratinocytes producing the most in the absence of RAS-transduction. Blockade of EGFR or IL-1 activity can mitigate the HGF-induced RAS-phenotype. K5-PKCα and DT mice exhibit the same acute inflammatory response and regenerative epidermal hyperplasia following low dose TPA treatment. When promoted for 10 weeks with TPA, 100% of DT mice but none of the single transgenic controls developed squamous papillomas in the absence of DMBA-mediated initiation. Our data suggest that the synergistic activity of Met and PKCα can substitute for the lack of RAS mutation during skin carcinogenesis. It remains to be determined if that mechanism could provide an alternate route to transformation in human skin tumors lacking RAS mutations.
Citation Format: Christophe Cataisson, Fan Liu, Lisa N. Wright, Anne Zhuang, Glenn Merlino, Stuart H. Yuspa. The combined activation of MET signaling and PKCα is sufficient to induce tumors in mouse skin. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1064. doi:10.1158/1538-7445.AM2013-1064
Abstract 1107: β2-integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis.
Authors: Oellerich Thomas , Oellerich Mark , Engelke Michael , Muench Silvia , Mohr Sebastian , Hsiao He-Hsuan , Zhang Jing , Bohnenberger Hanibal , Berg Tobias , Rieger Michael , Wienands Juergen , Bug Gesine , Brandts Christian , Urlaub Henning , Serve Hubert 
Published: August 2014

Abstract
Constitutive activation of certain kinase-dependent signal transduction pathways is critical for the pathogenesis of acute myeloid leukemia (AML). Apart from FLT3-ITD the spleen tyrosine kinase (Syk) induces cell survival and proliferation in a high proportion of AML blasts, but the underlying molecular events of Syk signaling have not been investigated so far. Using a phosphoproteomic approach we elucidated the AML-specific phosphorylation state of Syk and found that the kinase is constitutively phosphorylated at all known activation inducing tyrosine residues. Moreover, we have identified the multi-protein complex that is nucleated by constitutively active Syk in AML cells by quantitative proteomic techniques. This complex differs from the B lymphoid Syk interactome regarding several proteins, in particular the
β2-integrin receptor Mac-1 and also the oncogenic transcription factors STAT3 and STAT5. Our functional studies in primary AML cell cultures revealed that tonic signals derived from the integrin-associated Fc-γ chain lead to Syk-dependent activation of STAT3 and STAT5 that in turn induces AML cell proliferation. Moreover, stimulation of Mac-1 intensifies the constitutive Syk-mediated STAT3/5 activation in AML cells, a scenario likely to take place in the bone marrow niche. In accordance with these findings, we observed that β2-integrins including Mac-1 induce proliferation of AML cells in an AML cell/stroma co-culture model. Taken together, we identified an oncogenic integrin/Syk/STAT signaling axis that might serve as a therapeutic target of AML in the future.
Citation Format: Thomas Oellerich, Mark Oellerich, Michael Engelke, Silvia Muench, Sebastian Mohr, He-Hsuan Hsiao, Jing Zhang, Hanibal Bohnenberger, Tobias Berg, Michael Rieger, Juergen Wienands, Gesine Bug, Christian Brandts, Henning Urlaub, Hubert Serve. β2-integrin-derived signals induce cell survival and proliferation of AML blasts by activating a Syk/STAT signaling axis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1107. doi:10.1158/1538-7445.AM2013-1107
Abstract 1111: Whole genome bisulfite sequencing reveals tissue-specific DNA methylation in a normal mouse.
Authors: Hon Gary C. , Shen Yin , McCleary David F. , Edsall Lee , Kuan Samantha , Ren Bing 
Published: August 2014

Abstract
Epigenetic alteration is a hallmark of cancer. In particular, compared to normal cells, the DNA methylomes of cancer cells often exhibit two contrasting phenomena: 1) hypomethylation of large regions of the genome, notably at regions of late replicating DNA; and 2) hypermethylation of focal sites, frequently at CpG-island containing promoters. While this epigenetic variation between cancer cells and normal counterparts has been well documented, the variation between different normal cell types is still unknown. In an effort to better understand the epigenetic variation of a normal individual, we profiled DNA methylation using whole genome bisulfite sequencing in 16 tissues isolated from an individual mouse. We observed a unique distribution of CpG methylation for each tissue, which cluster based on cell lineage and type. Most somatic tissues exhibit a small but consistent decrease in methylation at late-replicating regions of the genome, suggesting the beginnings of global hypomethylation. Our global analysis identified only one-eighth of the genome as tissue-specific differentially methylated regions. Remarkably, the vast majority of these regions exhibit hallmarks of cis-regulatory activity, including: small size (&lt;500 bp), DNase I hypersensitivity, enhancer chromatin modifications (H3K4me1/H3K27ac), and evolutionary conservation. Our results reveal that most somatic cells are primed for global hypomethylation in regions of the genome that are typically hypomethylated in cancer cells, supporting previous observations that hypomethylation may be an indicator of cell age. In addition, our results in normal tissue suggest that hypomethylation in cancer cells could alter transcriptional regulation through disruption of cis-regulatory activity.
Citation Format: Gary C. Hon, Yin Shen, David F. McCleary, Lee Edsall, Samantha Kuan, Bing Ren. Whole genome bisulfite sequencing reveals tissue-specific DNA methylation in a normal mouse. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1111. doi:10.1158/1538-7445.AM2013-1111