bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5: Frequency of FGFR2 gene amplification in gastric cancer
Authors: Matsumoto Kazuko , Arao Tokuzo , Hamaguchi Tetsuya , Shimada Yasuhiro , Kato Ken , Oda Ichiro , Taniguchi Hirokazu , Koizumi Fumiaki , Yanagihara Kazuyoshi , Sasaki Hiroki , Yamada Yasuhide , Nishio Kazuto 
Published: August 2012

Abstract
Background: FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. However, the frequency of FGFR2 amplification, its clinicopathological features, and the results of high throughput screening assays in a large cohort of gastric clinical samples remain largely unclear. Patients and methods: The expression levels of FGFR2 mRNA and proteins, the drug sensitivity to an FGFR inhibitor, and the genomic copy numbers of FGFR1-4 were evaluated in gastric cancer cell lines. The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay. For confirming the results, fluorescence in situ hybridization (FISH) was conducted. Results: All of the four gastric cancer cell lines with FGFR2 amplification were sensitive to an FGFR inhibitor. The above copy number assay and FISH analysis revealed that 4.1% (11/267) of the gastric cancers harbored FGFR2 amplification (intestinal type, n=2; diffuse type, n=8 and unclassified type, n=1). No amplification of the three other family members was detected. A FISH analysis showed that six of these seven cases were highly amplified, while the remaining one had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period. Conclusions: FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5. doi:1538-7445.AM2012-5
Abstract 5018: Genetic and epigenetic investigation of breast carcinoma arising in Lynch syndrome families
Authors: Lotsari Johanna E. , Gylling Annette , Abdel-Rahman Wael M. , Friman Marjukka , Aarnio Markku , Jarvinen Heikki J. , Mecklin Jukka-Pekka , Kuopio Teijo , Peltomaki Paivi 
Published: August 2012

Abstract
Breast carcinoma is the most common cancer type in females, but its incidence is generally not increased in Lynch syndrome (LS). Deficient DNA mismatch repair (MMR) is a hallmark of LS tumors that are unequivocal manifestations of the syndrome (e.g., colorectal and breast carcinoma). Because of controversial study results, it is unclear at present whether or not breast carcinoma is specifically associated with LS. We addressed this question by determining the genetic and epigenetic profiles for all available breast carcinomas from LS families from a nation-wide registry, including 24 tumors from MMR gene mutation carriers and 17 tumors from non-carriers. The average age at breast carcinoma diagnosis was similar in mutation carriers and non-carriers (56 years for each). Among breast carcinomas from mutation carriers, 43% showed loss of MMR protein corresponding to the germline mutation, and high-degree microsatellite instability (MSI-H) was present in 36%. Moreover, in mutation carriers, the age at diagnosis was lower for breast carcinomas that were MMR-deficient (by absent MMR protein and/or MSI present) compared to MMR proficient tumors (51 vs. 60 years, p= 0.031). Breast carcinomas showed frequent inactivation of tumor suppressor genes (TSG) by promoter methylation. The average number of methylated TSGs out of 24 per tumor was 3.1 for mutation carriers and 2.8 for non-carriers. The gene-specific distribution of methylation was also similar between the two breast tumor sets. In mutation carriers, the most frequently methylated TSGs were RASSF1 (77%), APC (45%), CDH13 (45%), GSTP1 (32%) and CDKN2B (27%). In non-carriers, the respective frequencies were 75%, 47%, 59%, 35%, and 29%. When compared to tumors arising in other organs from LS mutation carriers, methylation of CDKN2B was seen as a particular characteristic of breast tumorigenesis. Our investigation shows that TSG promoter methylation is a common characteristic of breast carcinomas arising in LS and affects mutation carriers and non-carriers with comparable overall rates and gene-specific distributions. Analysis of MMR protein expression and MSI revealed that while many breast carcinomas from LS mutation carriers follow MMR-driven tumorigenesis characteristic of tumors of the LS spectrum in general, a significant subset of breast tumors also exists that appears to arise and progress along separate pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5018. doi:1538-7445.AM2012-5018
Abstract 502: Schwann cells promote tumor cell invasion through regulation of the laminin receptorA6B1
Authors: Chopra Harsharon , Riquer Zyanya P. Espinosa , Cress Anne E. , Sroka Isis C. 
Published: August 2012

Abstract
Tumor cell migration and invasion of nerves, a process known as perineural nerve invasion (PNI), is a major metastatic route for neurotropic cancers including prostate and pancreatic cancer. The laminin family of extracellular matrix glycoproteins derived from myelinating Schwann cells coat nerve axons and play a prominent role in the development and maintenance of the peripheral nervous system. Tumor cells undergoing PNI utilize the laminin rich nerves as they migrate and invade during metastasis. Evidence has shown that the A6B1 laminin receptor promotes tumor cell migration and invasion following cleavage of the receptor to form the variant A6pB1 by the serine protease urokinase plasminogen activator (uPA). Here we demonstrate Schwann cell regulation of A6pB1 formation on prostate and pancreatic tumor cell lines. Conditioned medium from the S16 and S16Y cell lines, which are immortalized Schwann cells of the myelinating and non-myelinating phenotype, respectively was provided to the prostate and pancreatic tumor cell lines. It was observed that S16Y conditioned medium inhibited A6 conversion to A6p while the myelinating S16 cells increased cleavage of the receptor in DU-145, CF-PAC1 and PC-3 cancer cells. This effect was reversible as replenishing standard media conditions following a 24 hour treatment with S16 or S16Y media brought integrin cleavage levels back to steady state levels by 24 hours. Further, conditioned medium from S16 cells significantly increased pancreatic tumor cell invasion while S16Y conditioned medium decreased invasion in a modified Boyden chamber Matrigel assay. The increased invasion mediated by myelinating Schwann cells was dependent on A6 since a function blocking antibody targeting A6 inhibited invasion. Taken together these results suggest that myelinating Schwann cells (S16Y) in the pancreatic and prostatic nerve environment promote A6B1 and A6pB1 receptor dependent tumor cell invasion during PNI. (Supported in part by NIH CA23074 and CA159406 and HHMI Grant 52005889)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 502. doi:1538-7445.AM2012-502
Abstract 5027: MicroRNA profiling of diagnostic fine needle aspirates of pancreatic cancer preserved as formalin-fixed paraffin-embedded cell blocks
Authors: Ali Shadan S. , Saleh Husain , Sethi Seema , Sarkar Fazlul H. , Philip Philip A. 
Published: August 2012

Abstract
MicroRNA (miRNA) expression profiling and quantitative real-time PCR (qRT-PCR) from fine needle aspirates (FNA) of formalin-fixed paraffin-embedded cell blocks (FFPE) could be a major improvement for prognosis and predicting treatment response in inoperable tumors of pancreatic cancer (PC). MicroRNA (miRNA) profiling provides a more comprehensive molecular interrogation of tumors. In the present study, miRNA expression profiling was performed on formalin-fixed paraffin-embedded cell blocks (FFPE) from FNA of suspicious pancreatic masses. Subjects were retrospectively studied and included those who had a pathological diagnosis of pancreatic adenocarcinoma and others with no histological proof of any cancer. We compared the expression profile of miRNAs in the pooled samples of FNA blocks from patients diagnosed with PC (n=29) with normal controls (n=15). MicroRNA profiling confirmed the deregulation of over 228 miRNAs of which, the top seven were validated by qRT-PCR. The expression of let-7c, let-7f, and miR-200c were significantly lower in almost all of the 29 patients compared to normal samples. On the contrary, the expression level of miR-486-5p, and miR-451 were significantly higher in all PC samples. Interestingly, two of the miRNAs, let-7d and miR-423-5p, that showed significant down-regulation or up-regulation in pooled sample showed a differential expression between the samples with individual qRT-PCR. These results suggest that identifying seven-miRNA signatures for PC in FNA cell blocks and validating with qRT-PCR can provide a strategy for improving the diagnosis of PC by using minimally invasive procedures.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5027. doi:1538-7445.AM2012-5027
Abstract 5038: Non-cording microRNA hsa-miR-199a expression in hepatocellular carcinoma correlates with patient survival
Authors: Nakajima Go , Kuramochi Hidekazu , Kondo Yurin , Okuyama Ryuji , Yamamoto Masakazu , Kanemura Toshinori , Hayashi Kazuhiko 
Published: August 2012

Abstract
[Aim] MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level. Previous study from our group identified forty nine miRNAs that are expressed differentially by comparing 26 pair samples of hepatocellular carcinoma (HCC) tumor tissue and non-tumor liver tissue using next-generation sequencer system. In this study, the expression of hsa-miR-199a and hsa-miR-199b, one of the extracted targets from our study, were investigated by real-time PCR using validation set HCC samples, and were examined the correlation between the miRNA expression and clinical data. [Patients and Methods] Forty-eight patients diagnosed as HCC had undergone surgical removal from 1991 to 1997 at the Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Japan. The formalin-fixed paraffin embedded samples were prepared using the standard protocol. The paraffin blocks were cut into 10μm sections, and the tumor samples were collected using Laser-captured microdissection and total RNA including miRNA fraction were isolated. After synthesized cDNA using miRNA specific primer, real-time PCR was performed using miRNA specific primer/probe. [Results] The expression level of hsa-miR-199a and hsa-miR-199b were down-regulated in tumor compared to non-tumor (P&lt;0.0001, P=0.0002, respectively). The patients were divided into two groups, higher/lower expression of each miRNA, the group of the higher hsa-miR-199a expression was significantly longer overall survival time compared to the lower expression group (P=0.0303). However, hsa-miR-199b was not significant difference (P=0.3801). [Conclusion] The hsa-miR-199a may be potential prognostic factor for HCC patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5038. doi:1538-7445.AM2012-5038
Abstract 504: Metformin potently inhibits cell proliferation, adhesion and invasion in ovarian cancer cells
Authors: Suri Anuj , Schuler Kevin , Zhou Chunxiao , Malloy Kim , Dickens Hallum , Steplowski Tara , Huh Gene , Gehrig Paola A. , Bae-Jump Victoria 
Published: August 2012

Abstract
ABSTRACT Objectives: Metformin is an anti-diabetic drug that has been shown to have anti-tumorgenic effects by behaving as a novel mTOR inhibitor. Metformin has been shown to suppress cancer cell growth, but little is known of its potential to halt metastatic spread. Thus, our goal was to assess the effect of metformin on proliferation, adhesion and invasion in ovarian cancer cell lines. Methods: Four ovarian cancer cell lines, SKOV3, CAOV3, OVCAR3 and IGROV1 were used. Cell proliferation was assessed by MTT assay after exposure to metformin. Cell cycle progression was evaluated by flow cytometry. Apoptosis was assessed by Annexin V-FITC assay. hTERT expression was determined by real-time RT-PCR. Western immunoblotting was performed to determine the expression of the downstream targets of metformin, including AMPK and the ribosomal protein S6. Inhibition of adhesion and invasion by metformin was assessed by in vitro adhesion assay and ChemoTx® invasion assay. Results: Metformin potently inhibited growth in a dose-dependent manner in all four ovarian cancer cell lines (IC50 of 0.1-1 mM) (p=0.00001-0.0121). Treatment with metformin resulted in G1 arrest, induction of apoptosis and decreased hTERT expression. Western immunoblot analysis demonstrated that metformin induced phosphorylation of AMPK, its immediate downstream mediator, and decreased phosphorylation of the S6 protein, a key target of the mTOR pathway, within 24 hours of exposure. Metformin inhibited cellular adhesion in the ovarian cancer cell lines by 10-23% at 1 mM (p=0.04-0.00001) and 25-35% at 10 mM (p=0.05-0.00001). In addition, metformin decreased invasion by 7-21% at 1 mM (p=0.03-0.0009) and 29-42% at 10 mM (p=0.03-0.0012). Conclusions: We report that metformin is a potent inhibitor of cell proliferation and exhibits anti-metastatic effects in ovarian cancer cells. Thus, metformin may have potential as a targeted chemotherapeutic agent in the treatment of ovarian cancer. More work is needed to determine if metformin will be universally beneficial in all ovarian cancer patients versus selectively efficacious in a subset of ovarian cancer patients, such as those women who are obese and/or diabetic.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 504. doi:1538-7445.AM2012-504
Abstract 5191: Periostin signaling in breast cancer stem cells
Authors: Lambert Arthur W. , Ozturk Sait , Thiagalingam Sam 
Published: August 2012

Abstract
Recent evidence suggests that the molecular heterogeneity inherent to breast cancer, which underlies metastasis, resistance to treatment and disease recurrence, can be driven by a distinct subpopulation of tumor cells referred to as cancer stem cells. Breast cancer stem cells are associated with epithelial-mesenchymal transition (EMT) and the basal-like molecular subtype of tumors, exhibit a CD44+/CD24- expression profile and have an enhanced capacity to form mammospheres. However, the extracellular cues and intracellular pathways that cancer stem cells rely on remain unclear. Using a cell line model of breast cancer progression we found a carcinoma line that was enriched for cancer stem cells. Using microarray expression profiling we identified periostin, a secreted extracellular matrix protein, to be overexpressed in this cell line and numerous other basal-like cell lines. Periostin was also overexpressed in populations that were enriched for cancer stem cells through other means such as cell sorting or growth as mammospheres. Furthermore, cancer stem cell-like populations displayed increased surface levels of the alpha-v beta-3 integrin heterodimer, a known receptor for periostin, suggesting that hyperactivation of periostin signaling may be a common feature of the cancer stem cell state. In support of this, cells with high levels of alpha-v beta-3 integrin form significantly more mammospheres and exhibit an enhanced capacity for growth on soft agar, a surrogate marker of tumorigenesis. Conversely, treatment of cells with an alpha-V beta-3 inhibitory antibody decreased mammosphere formation in a dose-dependent manner. Knockdown of periostin expression does not seem to alter the proportion of CD44+/CD24- cells but it does influence their ability to grow as mammospheres and the activity of aldehyde dehydrogenase (ALDH), another marker of cancer stem cells. Finally, as periostin is a TGF-beta inducible gene, we are currently testing the role of periostin in TGF-beta induced EMT and have seen evidence for an attenuation of this process. Ongoing studies are aimed at characterizing the intracellular pathways regulated by periostin and determining the effect of periostin expression on chemotherapeutic resistance and metastasis, two properties which may be enhanced by the presence of cancer stem cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5191. doi:1538-7445.AM2012-5191
Abstract 5193: The importance of primo vascular system (PVS) on cancer metastasis and therapeutic intervention: A new dimension of cancer stem cell
Authors: Islam Ashraful , Thomas Shelia D. , Sedoris Kara J. , Miller Donald M. 
Published: August 2012

Abstract
The ability of cancer cells especially immature and multi-potent cancer stem cells to escape from conventional therapeutic intervention has been long investigated. The exact mechanisms and safe harboring of this population of cells have yet to be identified. The primo vascular system (PVS) which is composed of new types of micro-conduits named primo-vessels (PV) and primo-nodes (PN) has recently emerged as a third component of circulatory system. In this study, we have shown the existence of PVS and their networks in murine xenograft of human histiocytic lymphoma cells (U937) using trypan blue. These PVs are thread-like, elastic, multi-lumen structure and appears to radiate from PN, perpendicular of the conventional venuoles-arteriols and reside in close proximity to the tumor. PNs are about 500-600 μM membranous sac-like structures, containing numerous tiny cells evident by DAPI staining. Isolation of RNA from PVS signifies the presence of intact transcriptional machinery in the cells. Hematoxylin and Eosin (H&E) staining of PVS shows the presence of loose and abortive structure lined by fibroblast but filled with lightly dense fibers, cells, lacuna and nerve-like structures. To further characterize the origin and type of cells within the PVS, immunostaining with antibodies for CD68, CD45 and lysozyme has revealed the cells are same immunophenotype as of U937. RT-PCR arrays demonstrates a hundred to thousand fold up regulation of human cancer stem cell specific transcription factors most notably KLF4, an upstream regulator of NANOG which maintain the pluripotent and undifferentiated state of stem cells. These results suggest that PVS close to the tumor could be the safe haven for a selective population of cancer stem cell. Further understanding of the biological properties and responsiveness to therapy of these cells will shed light on new dimensions of anti-cancer interventions.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5193. doi:1538-7445.AM2012-5193
Abstract 5196: CDF inhibits cell migration by inactivating cancer stem cell markers, and expression of VEGF, IL-6 and miR-21 in human pancreatic and prostate cancer cells under hypoxic condition
Authors: Bao Bin , Ali Shadan , Ahmad Aamir , Azmi Asfar S. , Banerjee Sanjeev , Kong Dejuan , Li Yiwei , Padhye Subhash , Sarkar Fazlul H. 
Published: August 2012

Abstract
Hypoxia has been well recognized to cause therapeutic resistance associated with solid tumors and considered to play critical roles in other of biological events including cell growth and proliferation, cell survival, angiogenesis, immunosurveillance, tumor invasion and metastasis. Hypoxia-inducible factor (HIF) 1α, a master transcription factor that regulates hypoxia responsive genes, plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Tumor hypoxia and over-expression of HIF-1α have been reportedly associated with resistance to radiation therapy and chemotherapy, increased risk of invasion and metastasis and poor clinical prognosis, all of which leads to higher mortality of patients diagnosed with solid tumors. Emerging evidence suggest that hypoxia and HIF signaling pathways leads to the acquisition of epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cell (CSC) functions, and causing inflammatory tumor microenvironment, which contributes to therapeutic resistance; however, the exact mechanisms by which hypoxia/HIF regulates these events are not fully understood. Here, we demonstrates that hypoxia increases the productions of VEGF and IL-6, and increased expression of CSC marker genes such as Nanog, Oct4, EZH2 as well as miR-21, an oncogenic miRNA, in human pancreatic cancer (AsPC-1 and MiaPaCa-2) and prostate cancer (PC-3 and LNCaP) cells. The treatment of these cells with CDF, a novel curcumin analog that was previously shown to be biologically superior than curcumin as an anti-tumor agent both in vitro and in vivo, inhibited the productions of VEGF, IL-6, Nanog, Oct4 and EZH2 mRNAs, as well as down regulated the expression of miR-21 in these cells under hypoxic condition. CDF also decreased cell migration in pancreatic and prostate cancer cells under hypoxic condition as documented by wound healing assay. Taken together, these data suggest for the first time that the anti-tumor effect of CDF could in part be due to inhibition of tumor hypoxic pathways including the inhibition of CSC markers and thereby reconditioning the tumor microenvironment, which would be useful for overcoming therapeutic resistance.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5196. doi:1538-7445.AM2012-5196