bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5278: Mutation in protein tyrosine phosphatase receptor type K (PTPRK) enhances progression of colon cancer through WNT signaling
Authors: Tojo Masayuki , Konishi Kazuo , Shinjo Keiko , Ohka Fumiharu , Katushima Keisuke , Hatanaka Akira , Ichimura Norihisa , Nozawa Hisako , Shimazaki Tomoe , Yoshida Hitoshi , Kondo Yutaka 
Published: August 2015

Abstract
Recent comprehensive genome analyses revealed the accumulation of genetic alterations in colorectal cancers (CRCs). However, it is still unknown which genetic alterations are closely associated with certain phenotype of CRCs, such as tumors with highly invasive character regardless of its small size. Here we examined the small invasive CRCs using high-throughput sequencing in order to clarify the common molecular features in those CRCs.
Seven small invasive CRCs (types 0-IIa+IIc or 0-Is+IIc, less than 20mm in diameter and with submucosal massive invasion) were examined by exon sequencing. Seven thousands six variants (SNVs and indels) were detected. Among them, PTPRK was frequently mutated (3 cases, 43%; 1 nonsense and 2 missense mutations). We further examined public database (TCGA and COSMIC) and found that 50 of 617 (8.17%) CRCs contain PTPRK mutation. Those cases are frequent in proximal colon, extensively methylated (CIMP-H), microsatellite instability-high (MSI-H) and pathologically mucinous type. Consistent with clinical behavior, invasion assay in CRC cell lines revealed that CRCs with PTPRK domain D1 mutation showed high invasiveness via WNT signaling activity. These data indicate that PTPRK domain D1 mutation contributes to the invasiveness and progression of proximal CRCs, especially CIMP-H and MSI-H cases.
Citation Format: Masayuki Tojo, Kazuo Konishi, Keiko Shinjo, Fumiharu Ohka, Keisuke Katushima, Akira Hatanaka, Norihisa Ichimura, Hisako Nozawa, Tomoe Shimazaki, Hitoshi Yoshida, Yutaka Kondo. Mutation in protein tyrosine phosphatase receptor type K (PTPRK) enhances progression of colon cancer through WNT 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 5278. doi:10.1158/1538-7445.AM2015-5278
Abstract 5296: FOXP1 expression is associated with tumor progression and poor prognosis in cervical cancer
Authors: Cho Hanbyoul , Yang Woo Kyeom , Kim Sol , Shin Ha-Yeon , Lee Eun Ju , Kim Jae-Hoon 
Published: August 2015

Abstract
Background: The forkhead box protein 1 (FOXP1) is considered as both a tumor suppressor candidate and a potential oncogene. Here, we investigated FOXP1 expression in cervical cancer, and the clinical significance of FOXP1 and it's mechanism of action in cervical cancer.
Methods: To investigate the potential correlation between FOXP1 and various clinicopathologic parameters, we assessed the expression of FOXP1 in archival tumor tissue specimens from 158 patients with cervical cancer and 280 with cervical intraepithelial neoplasia as well as 378 matched nonadjacent normal tissues by immunohistochemical (IHC) staining. Subsequently, we studied the FOXP1's functional role by small interfering RNA (siRNA) approaches.
Results: IHC staining demonstrated that FOXP1 expression increased during the normal to tumor transition of cervical carcinoma (P&lt;0.001), and this increased expression was significantly associated with tumor stage (P = 0.009) and tumor grade (P&lt;0.001). In multivariate analysis, FOXP1+ (P = 0.031) and tumor stage (P = 0.032) were independent prognostic factors for overall survival. FOXP1 knockdown by siRNA decreased cell proliferation, migration, and tumorigenesis in HeLa and CaSki cells.
Conclusions: Taken together, our data indicate that FOXP1 has a crucial role in cervical cancer progression, and its overexpression is associated with poor prognosis, supporting that FOXP1 may be used as a promising novel target for therapeutic interventions.
Citation Format: Hanbyoul Cho, Woo Kyeom Yang, Sol Kim, Ha-Yeon Shin, Eun Ju Lee, Jae-Hoon Kim. FOXP1 expression is associated with tumor progression and poor prognosis in cervical 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 5296. doi:10.1158/1538-7445.AM2015-5296
Abstract 5297: Chromosomal instability as a prognostic marker in cervical cancer
Authors: How Christine , Bruce Jeff , So Jonathan , Pintilie Melania , Haibe-Kains Benjamin , Hui Angela , Clarke Blaise , Hedley David , Hill Richard , Milosevic Michael , Fyles Anthony , Yip Kenneth W. , Liu Fei-Fei 
Published: August 2015

Abstract
Previous studies have demonstrated that chromosomal instability (CIN) is a consistent feature of the majority of solid tumors. In this current study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre (n = 79) and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients (n = 130). Patients with a high CIN70 score had a higher number of copy number alterations (Spearman's correlation coefficient (r) = 0.28, p&lt;0.001), and a higher percentage of genome altered (r = 0.19, p = 0.016). According to Kaplan-Meier analysis, the CIN70 signature achieved borderline significance for para-aortic nodal or distant relapse, with a hazard ratio of 3.02 and Wald p-value of 0.05, but not significant for overall, disease-free survival, or local relapse. In summary, these findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer.
Citation Format: Christine How, Jeff Bruce, Jonathan So, Melania Pintilie, Benjamin Haibe-Kains, Angela Hui, Blaise Clarke, David Hedley, Richard Hill, Michael Milosevic, Anthony Fyles, Kenneth W. Yip, Fei-Fei Liu. Chromosomal instability as a prognostic marker in cervical 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 5297. doi:10.1158/1538-7445.AM2015-5297
Abstract 5301: Integrative protein-marker prognostic model for early-stage endometrioid endometrial carcinoma
Authors: Liang Han ,   UT MD Anderson RPPA/TCGA working group
Published: August 2015

Abstract
Endometrioid endometrial carcinoma (EEC) is the major histological type of endometrial cancer, the most prevalent gynecologic malignancy in USA. EEC recurrence or metastasis is associated with an abysmal prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathological characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. We employed two large, independent EEC datasets as training and validation cohorts, and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. Using the training samples, we developed a predictive model containing two clinical factors and 18 protein markers and optimized the risk group classification. Kaplan-Meier survival analyses in the validation cohort confirmed an improved prognostic power. Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and optimizing their treatment strategies.
Note: This abstract was not presented at the meeting.
Citation Format: Han Liang, UT MD Anderson RPPA/TCGA working group. Integrative protein-marker prognostic model for early-stage endometrioid endometrial carcinoma. [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 5301. doi:10.1158/1538-7445.AM2015-5301
Abstract 5307: Analysis of telomere length in classic and variant hairy cell leukemia
Authors: Edelman Daniel C. , Arons Evgeny , Stevenson Holly , Gomez Allison , Petersen David , Zhou Hong , Wang Yonghong , Waterfall Joshua J. , Meltzer Paul S. , Kreitman Robert 
Published: August 2015

Abstract
Telomeres are ribonucleoprotein structures which protect the ends of chromosomes from aberrant recombination events and have been reported to be relatively short in several hematologic malignancies; adverse prognosis has been documented in chronic lymphocytic leukemia and several non-B-cell malignancies. However, their association with prognosis of classic and variant hairy cell leukemia (HCL and HCLv) has not been described. To study telomeres in HCL and HCLv, DNA from leukemic cells of patients was measured by monochrome multiplex quantitative PCR (MMQPCR) to determine relative telomere length (RTL). Of 46 patients in the cohort, 5 of 27 HCL (19%) vs. 12 of 19 HCLv (63%) patients had unmutated (&gt;98% homology to germline sequence) immunoglobulin rearrangements (p = 0.0045). IGHV4-34+ rearrangements were present in 12 of the 17 (70%) unmutated cases, including five HCL and seven HCLv. RTL was shown to be shorter in unmutated HCL (p = 0.03) and in patients who had died of their disease (p = 0.03). RTL negatively correlated with IGHV homology to germline sequence (r = -0.331; p = 0.025), and age (r = -0.315; p = 0.035). Shorter RTL was associated with death from disease in either HCL (p = 0.0063) or HCLv (p = 0.0034), in patients with mutated IGHV rearrangements (p = 0.005), or in all patients combined (p = 0.0008). Median survival from diagnosis was less in time in patients with shorter RTL (p = 0.016) and this significant difference persisted when examining just the 19 patients with HCLv (p = 0.029). Gene expression profiling identified several genes related to telomere maintenance with significantly different expression levels between mutated and unmutated cases. This first of kind study in HCL/HCLv suggests that telomeres play a role in the relative pathology of HCL and HCLv and RTL could be used as a prognostic biomarker in gauging the indolent course of these cancers.
Citation Format: Daniel C. Edelman, Evgeny Arons, Holly Stevenson, Allison Gomez, David Petersen, Hong Zhou, Yonghong Wang, Joshua J. Waterfall, Paul S. Meltzer, Robert Kreitman. Analysis of telomere length in classic and variant hairy cell leukemia. [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 5307. doi:10.1158/1538-7445.AM2015-5307
Abstract 5320: Targeting HER3 and EGFR in NRG1 positive and HER3 mutated lung squamous cell carcinoma
Authors: Pinzon-Ortiz Maria C. , Rong Xianhui , Versace Richard , Sheng Qing , Cao Z. Alexander 
Published: August 2015

Abstract
HER3 is a member of the ErbB family of receptor tyrosine kinases. Aberrant activation of HER3 as a result of HER2 amplification or neuregulin 1 (NRG1) over-expression has been demonstrated to mediate constitutive activation of downstream oncogenic signals. LJM716 is a fully human IgG1 anti-HER3 monoclonal antibody. It locks HER3 in an inactive conformation and prevents HER3 dimerization with other ErbB family members. This unique mode of action enables LJM716 to block both ligand dependent and ligand independent HER3 activation. In search of new indications that may benefit from anti-HER3 therapies, we noted that squamous cell carcinomas (SCC) tend to have relatively higher NRG1 expression as compared to their adenocarcinoma counterparts. Highest NRG1 expression was observed in the lung SCC cell lines in cell line encyclopedia (CLE). A subset of the lung SCC cell lines with high NRG1 expression are moderately sensitive to LJM716, with HER3 activation detected in all of the sensitive lines. Additionally, EGFR activation is consistently observed in our panel of squamous lung carcinoma models. In some cases, activation of HER2 and/or HER3 is also noted. We hypothesize that squamous lung carcinomas may be dependent on signaling through EGFR, HER2 and HER3. To completely block EGFR, HER2-HER3 signaling, we set to test the treatment of LJM716 and Cetixumab in a number of NGR 1 positive squamous lung carcinomas tumor models. Enhanced anti tumor activity of LJM716 and Cetixumab is observed in four out nine tumor models. Analysis of broad activation status of receptor tyrosine kinases (RTK) reveals that a subset of responsive models have activated pEGFR, pHER2 and pHER3. These data suggest that activated HER3 signaling may be important in a subset of lung squamous cell carcinoma. Combination of anti-HER3 and anti EGFR treatment is effective at inhibiting growth in these tumors.
Note: This abstract was not presented at the meeting.
Citation Format: Maria C. Pinzon-Ortiz, Xianhui Rong, Richard Versace, Qing Sheng, Z. Alexander Cao. Targeting HER3 and EGFR in NRG1 positive and HER3 mutated lung squamous cell carcinoma. [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 5320. doi:10.1158/1538-7445.AM2015-5320
Abstract 5322: Englerin-A prevents invasive phenotypes of renal cell carcinoma by reprogramming mesenchymal to epithelial transition: A key mechanism of its anticancer properties
Authors: Haque Inamul , Banerjee Snigdha , Beutler John A. , Banerjee Sushanta K. 
Published: August 2015

Abstract
Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Recently, Englerin A (Eng A), a molecule of herb (Phyllanthus engleri) extracts, shows selective toxic effect on RCCs through the National Cancer
Institute Drug Discovery panel using human cell lines as well as in vitro angiogenesis. Eng A has been reported to possess certain anticancer properties. However, whether Eng A could suppress RCC metastasis has not been fully elucidated. The epithelial-mesenchymal transition (EMT) is followed by invasion is a hallmark of metastasis malignancies including renal cancer. The aim of the present study was to examine the effects of Eng A in preventing the migration and invasion of
RCCs (Caki-1 and 786-0), as well as to investigate whether Eng A may inhibit the molecular changes associated with EMT induced by transforming growth factor-beta1 (TGF-β1). We also aimed to see whether Eng A suppresses the cancer stem cell markers and spheroid formation. The investigation demonstrated that Eng A suppressed the migration and invasion of these cells under non-cytotoxic concentrations. Eng A inhibited molecular changes associated with TGF-β1-induced
EMT by upregulating the epithelial markers and downregulating the mesenchymal markers. Eng A significantly reduced the levels of Twist protein, a master regulator of EMT. Eng A also inhibits the stem cell markers, i.e., CD44, ABCG2 and ALDH1 and spheroid formation. We also found that Eng A inhibits TGF-β1-induced angiogenesis. This study indicated that Eng A may serve as a potential candidate for the treatment of renal cancer metastasis.
Citation Format: Inamul Haque, Snigdha Banerjee, John A. Beutler, Sushanta K. Banerjee. Englerin-A prevents invasive phenotypes of renal cell carcinoma by reprogramming mesenchymal to epithelial transition: A key mechanism of its anticancer properties. [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 5322. doi:10.1158/1538-7445.AM2015-5322
Abstract 5326: Intracellular bacterial delivery of a NIPP1-peptide kills tumor cells
Authors: Van Dessel Nele , Forbes Neil S. 
Published: August 2015

Abstract
Protein phosphatase-1 (PP1) is a cancer target because it is involved in many cell signaling pathways. Its activity is tightly regulated by its interaction partners, mainly via the RVxF-binding motif. RVxF-containing peptides deregulate PP1 and have therapeutic potential as antagonists of increased cancer kinase signaling. Because PP1 is responsible for more than half of the dephosphorylations on Ser/Thr sites, it is essential in all eukaryotic cells and it is difficult to target systemically. Moreover, delivering peptides to cells extracellularly is inefficient because of poor cell permeability and proteolytic instability.
To specifically transport therapeutic peptides into cancer cells, we engineered bacteria to be intracellular delivery vectors. A bacterial delivery system (BDS) was designed by creating a strain that lyses after cell invasion and releases its contents into the cytoplasm of cancer cells. A BDS strain was then manipulated to express a peptide containing the RVxF motif of Nuclear Inhibitor of PP1 (NIPP1; AA 142-224). The therapeutic potential of this strain was tested on MCF-7 cell monolayers and on 3D tumor tissue.
The BDS was cloned by inserting the bacterial phage lysis gene E under the control of the sseJ promoter, a Salmonella promoter that is activated after cell invasion. The specificity of the sseJ promoter was tested by inserting GFP under its control and infecting MCF-7 cancer cells with Salmonella containing the plasmid. All intracellular bacteria expressed GPF after 4 hours of infection, while no fluorescence was measured in the bacteria outside the mammalian cells. After infection, the created BDS lysed in 78% of invaded cells. BDS delivery of the NIPP1-peptide to MCF-7 cancer cells killed 41% of infected cells while infection with control, empty BDS did not result in any death. When treating tumor tissue with BDS expressing NIPP1-peptide, 39% of tumor tissue was killed after 9.5 hours, compared to 8% when treated with BDS alone. These results indicate that targeting phosphatases with intracellular peptide delivery by bacteria is feasible and reduces tumor tissue viability.
Citation Format: Nele Van Dessel, Neil S. Forbes. Intracellular bacterial delivery of a NIPP1-peptide kills tumor 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 5326. doi:10.1158/1538-7445.AM2015-5326
Abstract 5339: Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo
Authors: Zhang Yuanhui , Wang Yuan , Wang Lina , Aslanidi George , Srivastava Arun , Ling Changquan , Ling Chen 
Published: August 2015

Abstract
Traditional Chinese medicine (TCM) has held, and still holds, an important position in primary health care in China, especially in the rural areas. However, scientific evidence of its mechanism is, for the most part, limited and additional better-designed laboratory research is needed. To date, numerous leading chemical compounds from TCM drugs have been identified and evaluated for their anti-tumor effects. However, little effort has been made on the protein-encoding genes isolated from TCM drugs, and the delivery of these genes into malignant cells through recombinant adeno-associated viral (rAAV) vectors has not been attempted. For example, Trichosanthin (TCS), an antiviral plant defense protein found in the root tuber of a TCM herb, Trichosanthes kirilowii, has been used in anti-HIV clinical trials in the USA. Its enzymatic activities were recognized as type I ribosome-inactivating protein. Although the nucleotide sequence of the TCS gene was determined more than 20 years ago, to date, there was little report to deliver TCS-encoding gene into malignant cells. In the present studies, we synthesized the cDNAs of five known cytotoxic proteins isolated from TCM drugs and the FLAG epitope-tagged cDNAs were subcloned into a rAAV plasmid vector. The expression of mRNA was confirmed by RT-PCR and protein expression by Western blot assays against the FLAG tag, respectively. Among these genes, TCS gene yielded the most promising results for the inhibition of cancer cell growth in vitro. The over-expressed TCS functioned as a type I ribosome inactivating protein, followed by inducing apoptosis that is associated with the Bcl-PARP signaling pathway. Next, rAAV vectors containing the TCS gene driven by a liver cancer specific promoter, α-fetoprotein promoter (AFPp) were generated and tested. The results indicated that rAAV-AFPp-TCS vectors significantly inhibited the growth of hHCC cell lines in vitro as well as hHCC tumor growth in vivo following intra-tumor injections in a murine xenograft model. These studies suggest that the use of TCM cytotoxic genes may prove to be a useful therapeutic strategy for treating human cancers in general, and liver tumors in particular.
Note: This abstract was not presented at the meeting.
Citation Format: Yuanhui Zhang, Yuan Wang, Lina Wang, George Aslanidi, Arun Srivastava, Changquan Ling, Chen Ling. Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo. [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 5339. doi:10.1158/1538-7445.AM2015-5339
Abstract 5351: Oral delivery of doxorubicin using bile enhancer for metronomic maintenance chemotherapy
Authors: Kweon Seho , K.A. Mahmud Foyez , Chang Hyo Won , Nam Have Yoon , Kim Mi Ra , Park Jung Je , Byun Youngro , Kim Sang Yoon 
Published: August 2015

Abstract
Conventional chemotherapy requires therapy holiday due to their toxic adverse effects. However, the therapy holiday has been allowing cancer cell to relapse and caused secondary metastasis to occur in other tissue. On the contrast, metronomic maintenance chemotherapy (MMC) treats anticancer drugs frequently to reduce the adverse effects from normal tissues by maintaining low concentration in the blood. In this context, an oral route is more suitable for MMC than a parenteral route. Our oral delivery system that uses electrochemical property of bile acid derivatives increases bioavailability of doxorubicin (DOX) from below 5% to 26% by eluding p-gp. The antitumor studies showed that 5mg/kg/day oral DOX complex inhibited 70% of tumor volume in C3H mice model bearing SCC7 tumor. The H&E staining of intestines and liver and the blood analysis proved that there were no histological and hematological toxicities. In addition, low dose of the DOX complex affects cell cycle regulation to arrest cancer cells. The concentration of 10nM, 30nM of DOX restricted the cell cycle at checkpoints in G1 phase of MCF-7 cells which are p-53 wild type and checkpoints in G2-M phase of MDA-MB 231 cells which are p-53 disruptive type. When MK8776, a inhibitor of cell cycle checkpoints, is treated with the low concentration of DOX, the cancer cells went through apoptosis or senescence depending on a type of cancer. In conclusion, our oral delivery of doxorubicin can offer safe and effective chemotherapy.
Note: This abstract was not presented at the meeting.
Citation Format: Seho Kweon, Foyez K.A. Mahmud, Hyo Won Chang, Have Yoon Nam, Mi Ra Kim, Jung Je Park, Youngro Byun, Sang Yoon Kim. Oral delivery of doxorubicin using bile enhancer for metronomic maintenance chemotherapy. [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 5351. doi:10.1158/1538-7445.AM2015-5351