bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 457: Significance of angiotensin targeting on treatment of liver metastasis in colorectal cancer patients with diabetes
Authors: Kuniyasu Hiroki , Luo Yi , Chihara Yoshitomo , Ohmori Hitoshi , Fujii Kiyomu , Yoshikawa Motokiyo , Kuwata Masaomi , Fujimoto Kiyohide , Hirao Yoshihiko , Kitadai Yasuhiko 
Published: August 2012

Abstract
We examined the effects of hyperglycemic conditions on liver metastasis of colorectal cancer (CRC). Angiotensin (AT)-II increased growth, invasion, and anti-apoptotic survival in HT29 and CT26 cells. In contrast, angiotensinogen (ATG) increased these features in HT29 cells but not in CT26 cells. HT29 cells expressed AT-II type 1 receptor, chymase, and rennin, whereas CT26 cells did not express renin. Renin expression and ATG-induced cell growth, invasion, and survival induced and increased as glucose concentration increased in HT29 cells and also CT26 cells. An inhibitor of renin or chymase abrogated A-II production in both cells. Reduction of hepatic ATG production by knockdown suppressed liver metastasis of HT29 cells. An examination of 121 CRC patients showed that diabetes in CRC cases was associated with higher blood HbA1c, higher renin and AT-II concentrations in the primary tumors, and higher incidence of liver metastasis than in nondiabetic cases. These results suggest that diabetes-associated AT activation enhances liver metastasis of CRC. We then examined an antimetastatic therapy by anti-AT treatments in CRC. In a streptozotocin-induced BALB/c mouse diabetes model that was fed a high-calorie diet, the blood sugar level increased and was associated with enhanced CT26 liver metastases. In this diabetic mouse model, liver metastasis of CT26 cells was suppressed by anti-AT treatment with a chymase inhibitor, a renin inhibitor, and an AT-II receptor blocker. Moreover, concurrent hypoglycemic and anti-AT treatments showed a synergistic inhibitory effect on CT26 cell liver metastasis. These results suggest that AT activation ability associated with diabetic conditions enhances liver metastasis of colon cancer. Therefore, treatment with anti-AT and hypoglycemic agents might be relevant for suppressing liver metastasis. This scheme should be examined in a clinical setting.
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 457. doi:1538-7445.AM2012-457
Abstract 4572: Frequent MLL3 frameshift mutations in microsatellite-deficient colorectal cancer
Authors: Watanabe Yoshiyuki , Castoro Ryan J. , Kim Hyun Soo , Kleb Brittany , Oikawa Ritsuko , Hiraishi Tetsuya , Ahmed Saira S. , Chung Woonbok , Cho Mee-Yon , Toyota Minoru , Itoh Fumio , Estecio Marcos R. H. , Shen Lanlan , Jelinek Jaroslav , Issa Jean-Pierre J. 
Published: August 2012

Abstract
Background: MLL3 is a histone 3- lysine 4 methyltransferase with tumor-suppressor properties that belongs to a family of chromatin regulator genes potentially altered in neoplasia. Mutations in MLL3 were found in a whole genome analysis of colorectal cancer but have not been confirmed by a separate study. Methods & Results: We analyzed mutations of the coding region and promoter methylation in MLL3 using 126 cases of colorectal cancer. We found two isoforms of MLL3 and DNA sequencing revealed frameshift and other mutations affecting both isoforms of MLL3 in colorectal cancer cell lines and 19 of 134 (14%) primary colorectal samples analyzed. Moreover, frameshift mutations were more common in cases with microsatellite instability (31%) both in CRC cell lines and primary tumors. The largest isoform of MLL3 is transcribed from a CpG island-associated promoter that has highly homology with a pseudo-gene on chromosome 22 (psiTPTE22). Using an assay which measured both loci simultaneously we found prominent age related methylation in normal colon (from 21% in individuals less than 25 years old to 56% in individuals older than 70, R=0.88, p&lt;0.001) and frequent hypermethylation (83%) in both CRC cell lines and primary tumors. We next studied the two loci separately and found that age and cancer related methylation was solely a property of the pseudogene CpG island and that the MLL3 locus was unmethylated. Conclusions: We found that frameshift mutations of MLL3 in both CRC cells and primary tumor that were more common in cases with microsatellite instability. Moreover, we have shown that the CpG island-associated promoter of MLL3 gene has no DNA methylation in CRC cell lines but also primary tumors and normal colon, and this region is highly homologous to a pseudogene (psiTPTE22) that shows age-related DNA methylation.
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 4572. doi:1538-7445.AM2012-4572
Abstract 4575: Three-gene diagnostic classifier for ALK negative ALCL
Authors: Pellegrino Elisa , Mereu Elisabetta , Agnelli Luca , Limongi Tania , Kwee Ivo , Iqbal Javeed , Piccaluga Pier Paolo , Neri Antonino , Chan John C , Pileri Stefano , Bertoni Francesco , Inghirami Giorgio , Piva Roberto 
Published: August 2012

Abstract
Anaplastic Large Cell Lymphomas (ALCL) comprise approximately 12% of all T-cell Non-Hodgkin's lymphomas (T-NHL), representing a heterogeneous group whose definition, origin and relationship with other T-NHL remains controversial. The notion that ALCL strongly express CD30, and display recurrent chromosomal translocations involving the Anaplastic Lymphoma Kinase (ALK) gene, led to recognition of two subsets, according to ALK expression. Although ALK positive ALCL can be readily diagnosed, ALK negative ALCL still lack unique genetic features and their distinction from other CD30 positive Peripheral T-Cell Lymphomas (PTCL) is not trivial. To unravel the regulatory network underlying lymphomagenesis of ALCL, and to discover new genomic classifiers for the recognition of ALK-positive and ALK-negative ALCL patients, we undertook a systematic approach of pathway discovery through a gene expression profiling meta-analysis of 309 cases, using data generated by five sets of experiments. In agreement with previous studies, unsupervised analyses were not able to distinguish ALCL from the other T-NHL categories. However, pathway discovery and prediction analyses defined a minimum set of genes useful for the stratification of ALK negative ALCL and strengthened the hypothesis that ALCL correspond to a distinctive pathological subgroup within T-NHL. Application of RT-qPCR in independent data sets of cryo-preserved and formalin-fixed paraffin embedded samples confirmed the gene expression profiling predictions and validated a simple model based on the measurement of three genes. These data suggest the possibility to translate RT-qPCR protocols to routine clinical settings as a new approach to precisely define T-NHL and to select more appropriate therapeutic protocols.
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 4575. doi:1538-7445.AM2012-4575
Abstract 4583: Comparison of repeated minor liver resection and major resection on lung metastasis growth in mice
Authors: Momiyama Masashi , Hiroshima Yukihiko , Suetsugu Atsushi , Tome Yasunori , Mii Sumiyuki , Yano Shuya , Bouvet Michael , Chishima Takashi , Endo Itaru , Hoffman Robert M. 
Published: August 2012

Abstract
This study examines the effects of types of liver resection on the growth of liver and lung metastasis. Experimental liver metastases were established by spleen injection of the Colon 26 murine adenocarcinoma cell line expressing GFP into transgenic nude mice expressing RFP. Experimental lung metastases were established by tail vein injection with Colon 26-GFP. Three days after cell injection, groups of mice underwent liver resection (35%+35% [repeated minor resection] vs. 70% [major resection]). Metastatic tumor growth was measured by color-coded fluorescence imaging of the GFP-expressing cancer cells and RFP-expressing stroma. Although major and repeated minor resection removed the same volume of liver parenchyma, the two procedures had very different effects on metastatic tumor growth: major resection, stimulated liver and lung metastatic growth as well as recruitment of host-derived stroma compared to repeated minor resection. Repeated minor resection did not stimulate metastasis or stromal recruitment. There was no significant difference in liver regeneration between the two groups. Host-derived stroma density, which is stimulated by major resection compared to repeated minor resection, may stimulate growth in the liver-metastatic tumor. TGF-β is also preferentially stimulated by major resection and may play a role in stroma and metastasis stimulation. The results of this study indicate that when liver resection is necessary, repeated minor liver resection is superior to major liver resection, since major resection, in contrast to repeated minor resection, stimulates metastasis, which should be taken into consideration in clinical situations indicating liver resection.
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 4583. doi:1538-7445.AM2012-4583
Abstract 4584: β-catenin (CTNNB1) and BRAF mutations in advanced hepatocellular carcinoma
Authors: Lu Li-Chun , Shao Yu-Yun , Hsieh Min-Shu , Huang Chien-Chung , Cheng Ann-Lii , Hsu Chih-Hung 
Published: August 2012

Abstract
Background: Specific mutations in Wnt/β-catenin and mitogen activated protein kinase pathways have been reported to have associations with tumorigenesis of hepatocellular carcinoma (HCC). The clinical implications of CTNNB1 (the coding gene for β-catenin) and BRAF mutations in advanced HCC and their associations with prognosis have not been well studied. Patients and Methods: We reviewed patients with HCC who were screened for enrollment in clinical trials of first-line molecular-targeted therapy for advanced diseases between Mar 2006 and Aug 2009 in a tertiary medical center. Only patients with adequate pathologic specimens obtained at the time of developing advanced disease were included. Direct sequencing of exon 3 of CTNNB1 and exon 15 of BRAF were performed to detect mutations. Associations between the specific mutations and clinicopathologic features or survival of the patients were analyzed. Results: Eighty-one patients were enrolled in the study, with the median age of 56.3 years. Among them, 55 (67.9%) patients were seropositive for hepatitis B virus (HBV) surface antigen; 19 (23.5%) patients were seropositive for antibody against hepatitis C virus (HCV); 77 (95.1%) patients had BCLC stage C; 42 (51.9%) patients had a CLIP score ≤ 3. Missense mutations of CTNNB1 were identified in 10 (12.3%) patients. BRAF mutations were found in 4 (4.9%) patients, including 3 missense and 1 silent mutations. The two gene mutations were mutually exclusive. The median overall survival of patients with and without CTNNB1 mutation were 7.5 and 6.5 months, respectively (P = 0.430). The median overall survival of patients with and without BRAF mutation were 2.8 and 6.6 months, respectively (p = 0.350). CTNNB1 or BRAF mutation had no statistically significant associations with the gender, the ECOG performance status, HBV infection, HCV infection, alpha-fetoprotein levels, prior local treatment, macrovascular invasion, extrahepatic metastasis, BCLC stages, Okuda stages or CLIP scores. Patients with CTNNB1 mutations were more likely to be &gt; 70 years old than patients without CTNNB1 mutations (40% vs. 11.3%, p = 0.017). Conclusions: CTNNB1 and BRAF mutations were relatively rare events in patients with advanced HCC. CTNNB1 mutations were associated with older ages in this specific population (This study was supported by the grant NTUHYLN005).
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 4584. doi:1538-7445.AM2012-4584
Abstract 4585: Expression of fibroblast growth factor-9 is associated with poor prognosis of resected non-small cell lung cancer patients
Authors: ohgino keiko , Soejima Kenzo , Arai Daisuke , Ishioka Kota , Sato Takashi , Terai Hideki , Ikemura Shinnosuke , Yoda Satoshi , Hamamoto Junko , Naoki Katsuhiko , Betsuyaku Tomoko 
Published: August 2012

Abstract
Background: Fibroblast growth factor (FGF)-9 is a member of the FGF family, which modulates cell proliferation, differentiation and motility. Recent studies show that activation of FGF signals including FGF-9 is associated with pathogenesis of several cancers, however its clinicopathological and biological significance in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study is to clarify the characteristics of FGF-9-expressing NSCLC. Methods: We evaluated expression of FGF-9 in completely resected NSCLC and corresponding non-tumorous lung samples using cDNA microarray combining with quantitative RT-PCR for confirmation, and compared with clinical pathological parameters and survival. We also evaluated altered gene expression patterns between FGF-9-high and -low NSCLCs. Results: The expression of FGF-9 increased compared with the corresponding non-cancerous lung tissues in 13 (13.2%) of 98 NSCLCs. Histologically, 10 out of 13 FGF9-high NSCLC were adenocarcinoma, while none of them were squamous cell carcinoma. The relationship between FGF-9 expression and sex, smoking history or clinical stage was not observed. On the other hand, postoperative recurrence rates and 3-year survival rates were 40% vs. 21% and 54% vs. 92% (p=0.002) for FGF9-high vs. -low NSCLC patients, respectively. The overall survival rate was also significantly worse in FGF9-high NSCLC (p=0.023). The specific gene expression pattern of FGF-9-high NSCLC will be also presented. Conclusion: Our data indicate that FGF-9 may be a novel unfavorable prognostic indicator and a candidate for therapeutic targets of NSCLC.
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 4585. doi:1538-7445.AM2012-4585
Abstract 4593: Expression of Ecdysoneless in breast cancer progression predicts poor outcome in breast cancer patients
Authors: Mirza Sameer , Zhao Xiangshan , Alshareeda Alaa , Zhang Ying , Gurumurthy Channabasavaiah Basavaraju , Bele Aditya , Kim Jun Hyun , Mohibi Shakur , Goswami Monica , Lele Subodh , West William , Qiu Fang , Ellis Ian O. , Green Andrew R. , Band Hamid , Band Vimla 
Published: August 2012

Abstract
Breast cancer is the most common type of cancer and second leading cause of cancer-related deaths in women in the United States. Our laboratory has identified the protein hEcd (human ortholog of Drosophila Ecdysoneless) as a novel regulator of cell cycle. Previous studies showed that Ecd regulates cell cycle by regulating the Rb-E2F pathway. Given the dysregulation of the cell cycle machinery in cancer, we examined expression of Ecd in normal, benign, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of breast. In first cohort, we showed while normal and hyperplasia of breast barely showed Ecd expression, high Ecd expression was observed in DCIS and IDC patient tissue specimens. In this cohort of 104 IDC patents, Ecd expression was positively associated with higher grade (p=0.04).We then analyzed Ecd expression in a second larger cohort (954) and observed similar results, where increased Ecd expression was associated with tumors of higher histological grade (p=0.013), mitotic count (p=0.032), and Nottingham Prognostic Index score (p=0.014). Notably, Ecd expression was positively associated with HER2/neu (p=0.002) overexpression. Significantly, a positive association between Ecd expression and shorter breast cancer specific survival (BCSS) (p=0.008) and disease-free survival (DFS) (p=0.003) was observed in HER2/neu overexpressing patients. Taken together, our results demonstrate Ecd expression as a novel marker for breast cancer progression that predicts tumor progression and the clinical outcome in breast cancer 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 4593. doi:1538-7445.AM2012-4593
Abstract 46: Microglial stimulation of glioblastoma invasion involves EGFR and CSF-1R signaling
Authors: Coniglio Salvatore J. , Eugenin Eliseo , Dobrenis Kostantin , West Brian , Symons Marc , Segall Jeffrey E. 
Published: August 2012

Abstract
The ability of glioma tumor cells to infiltrate the surrounding brain parenchyma makes complete removal of these tumors nearly impossible. We investigated how microglia, the resident macrophages of the brain, stimulate glioma cell invasion. Coculture with microglia stimulates the invasion of GL261 glioma cells in-vitro. Pharmacological inhibition of EGFR using Iressa completely inhibits microglia-stimulated invasion and sequestration of EGF using an EGF-specific function-blocking antibody also fully inhibits microglia-stimulated glioma invasion. Furthermore, we demonstrate using novel CSF-1R (c-fms) inhibitors that CSF-1R signaling is also required for microglial enhancement of glioma invasion. GL261 cells were found to constitutively secrete CSF-1, the levels of which are unaffected by EGF stimulation, EGFR inhibition or coculture with microglia. In addition, GL261 tumors orthotopically injected into the brains of C57 mice fed with PLX3397 were compromised in their ability to recruit microglia/macrophages. Interestingly, tumors from these animals also showed a 50% reduction in invasion into the parenchyma. These data indicate that during invasion, glioma and microglia cells signal to each other using EGF and CSF-1 similar to what has been observed in breast cancer models. The results of this study indicate the possibility of inhibiting glioblastoma invasion by targeting functions of tumor-associated microglia in addition to glioma 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 46. doi:1538-7445.AM2012-46
Abstract 4618: Response post first autologous stem cell transplantation (ASCT) for multiple myeloma identify patients who may benefit from tandem transplants: A single center prospective phase II study
Authors: Moreb Jan S. , Salmasinia Donya , Leather Helen , Davis Amy , Hsu Jack , Wiggins Laura , Cogle Christopher R. , Chang Myron N. , Wingard John R. 
Published: August 2012

Abstract
The role of tandem transplants as well as a later salvage second transplant has been in the center of interest for many myeloma investigators. Also, the need for tandem ASCT in patients (pts) achieving very good partial remission (VGPR) or complete remission has not been studied prospectively. We conducted a prospective phase II clinical trial in which enrolled myeloma pts are assessed after the first ASCT and offered either 2nd tandem ASCT if they achieve ≤ PR or maintenance if they achieve ≤ VGPR. These latter pts received 2nd salvage transplant after relapse. The conditioning regimens used were different for the two ASCT: Busulfan 0.75 mg/kg PO q 6 hr days –8 through –5, Cyclophosphamide (CP) 60 mg/kg IV days –3 and –2, and Etoposide 10 mg/kg IV days –4 to –2 for the first ASCT, and 96 hr (days –6 to –3) continuous IV CP 6 gr/m2 and total body irradiation (TBI) 600 cGy (days –2 and –1) for the second ASCT. Etoposide was omitted if pts were ≤ 65 year old, and TBI was substituted by melphalan 140 mg/m2 if prior radiation did not allow TBI. Between the years 2001-2009, 76 pts were enrolled. Of the 31 pts planned to have tandem ASCT, 20 received tandem ASCT, 2 additional pts had tandem auto-allo transplants and one patient had progressive disease. The primary reasons for not receiving the planned tandem ASCT were lack of socioeconomic resources and physical co-morbidities. Maintenance treatment was offered to both groups of pts. There were no treatment related mortalities in the ASCT pts. We compared the progression-free (PFS) and overall (OS) survival following the first ASCT between pts who received tandem ASCT (n=20) and pts who received single ASCT (n=54). The median PFS for tandem pts was 27 mo (range, 10-93) versus 28 mo for single ASCT (range, 4-99) (P=0.889); the OS was 38 mo (range, 11-120) versus 72 mo (range, 5-136), respectively (P=0.293). At the present time, a total of 7 (35%) and 30 (55%) pts are still alive in the tandem and single ASCT groups, respectively. Among the tandem pts, 2 underwent salvage ASCT and one non-myeloablative allogeneic transplant (allo-SCT); while in the single ASCT group 6 had salvage ASCT and 6 had allo-SCT. All salvage transplants were done at a median of 37 mo (range, 8-91) from 1st ASCT. In conclusion, pts who achieve ≤ VGPR after 1st ASCT have similar PFS and may be better OS than pts who had tandem ASCT. Thus, the use of such response criteria may identify a group of lower risk pts that will do well without the upfront tandem ASCT.
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 4618. doi:1538-7445.AM2012-4618