bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5525: Influence of total dissected lymph node number on metastatic detection rate and survival in 10,382 esophageal cancer patients from the high incidence area for esophageal cancer in northern China
Authors: Wang Li Dong , Dong Jin Cheng , Zhang Peng , Zhou Fu You , Li Xue Min , Li Ai Li , Ji Ai Fang , Liu Zhi Cai , Song Xin , Zhao Xue Ke , Wang Xian Zeng 
Published: August 2012

Abstract
Lymph node (LN) metastasis has been recognized as one of the most important factors for poor prognosis of esophageal cancer (EC). However, the influence of dissected LN number on metastatic detection rate and survival in EC has not been well documented. The present study was undertaken to correlate the total number of dissected LN, metastatic detection rate and survival on 10,382 EC patients. All the patients had been performed surgical treatment and confirmed as esophageal squamous cell carcinoma (ESCC) by histopathological examination. The patients were from Henan, Hebei and Shanxi provinces, the high incidence areas for EC in northern China, including 6,375 males with a mean age of 58±9 and 4,007 females with a mean age of 59±9. Of the patients, 2,714 cases have been followed up by interview at home until July, 2010. Eight EC groups had been classified based on the total number of dissected LN (1-3, 4-5, 6-7, 8-9, 10-11, 12-13, 14-16 and ≥17). The results showed that the positive metastatic detection rate apparently increased with the total extended dissected LN number (P&lt; 0.05) until reaching the level with a total of 17 or more dissected LN. 5-year survival analysis showed that the patients without LN metastasis had a higher survival rate than those with LN metastasis in all seven groups (P&lt;0.05) except the group with ≥17. Interestingly, the survival rate was similar in the group of ≥17 between the patients with positive or negative LN (P&gt;0.05). We concluded that the total dissected LN number could affect the survival rate for EC and that a total of 10 to 16 dissected LN should be recommended for EC surgical treatment. (supported by Innovation Scientists and Technicians Troop Construction Projects of Henan Province).
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 5525. doi:1538-7445.AM2012-5525
Abstract 5532: Anti-cancer activities of tea epigallocatechin-3-gallate in breast cancer patients under radiotherapy
Authors: Wu Erxi 
Published: August 2012

Abstract
Abstract: The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment by radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radiotherapy alone, those given radiotherapy plus EGCG for an extended time period (two to eight weeks) showed significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 and metalloproteinase-2 (MMP9/MMP2). Addition of sera obtained from patients treated by combination of radiotherapy and EGCG feeding for 2-8 weeks to in vitro cultures of highly-metastatic human MDA-MB-231 breast cancer cells resulted in the following significant changes: (1) suppression of cell proliferation and invasion; (2) arrest of cell cycles at the G0/G1 phase; (3) reduction of activation of MMP9/MMP2, expressions of Bcl-2/Bax, c-Met receptor, NF-κB, and the phosphorylation of Akt. MDA-MB-231 cells exposed to 5-10 µM EGCG also showed significant augmentation of the apoptosis inducing effects of γ-radiation, concomitant with reduced NF-κB protein level and AKT phosphorylation. These results provide hitherto unreported evidence that EGCG potentiated efficacy of radiotherapy in breast cancer patients, and raise the possibility that this tea polyphenol has potential to be a therapeutic adjuvant against human metastatic breast cancer.
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 5532. doi:1538-7445.AM2012-5532
Abstract 5539: Snail expression is associated with epithelial to mesenchymal transition and a poor prognosis in malignant pleural mesotheliomas
Authors: Kobayashi Masashi , Huang Cheng-long , Sonobe Makoto , Kikuchi Ryutaro , Ishikawa Masashi , Imamura Naoto , Kitamura Jiro , Iwakiri Shotaro , Itoi Kazumi , Yasumizu Ryoji , Date Hiroshi 
Published: August 2012

Abstract
Introduction: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. Regarding tumor histology, however, the survival has been reported to be lower in patients with non-epitheloid tumors than in those with epitheloid tumors. Therefore, in order to identify molecular targets for the treatment against MPM patients, we investigated several molecules associated with epithelial to mesenchymal transition, such as Snail, Twist, E-cadherin and N-cadherin. Methods: We studied one hundred and nine patients with MPMs, including 61 epitheloid tumors (55.9%), 21 sarcomatoid tumors (19.2%), 20 biphasic tumors (18.3%) and 7 desmoplastic tumors (6.4%). Immunohistochemical assays were performed to evaluate the intratumoral expressions of Snail, Twist, E-cadherin and N-cadherin. Results: Among 109 MPMs, 41 tumors (37.6%) were Snail-high tumors, 30 tumors (27.5%) were Twist-high tumors, 18 tumors (16.5%) were E-cadherin-positive tumors, and 35 tumors (32.1%) were N-cadherin-positive tumors. Regarding tumor histology, the nuclear expression of Snail expression was significantly higher in non-epithelioid tumors than in epitheloid tumors (P&lt;0.001). Furthermore, the E-cadherin expression was significantly lower in Snail-high tumors than in Snail-low tumors (P=0.046). As a result, the E-cadherin expression was significantly lower in non-epithelioid tumors than in epitheloid tumors (P=0.013). In addition, the Snail expression was significantly higher in Twist-high tumors than in Twist-low tumors (P=0.007). The frequency of N-cadherin-positive tumors was also significantly higher in Twist-high tumors than in Twist-low tumors (P=0.005). Regarding patient survival, the overall survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (P=0.002), especially among patients with non-epitheloid tumors (P=0.009). A multivariated analysis also demonstrated that the nuclear expression of Snail was a significantly factor of a poor prognosis in MPM patients (P=0.014). Conclusions: Snail expression is associated with epithelial to mesenchymal transition and a poor prognosis in MPMs. The Snail could be a potential molecular target for the treatment of MPM 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 5539. doi:1538-7445.AM2012-5539
Abstract 5694: Targeted photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres directed at EphB4 receptors
Authors: You Jian , Xiong Chiyi , Li Chun 
Published: August 2012

Abstract
Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. Doxorubicin (DOX)-loaded hollow gold nanospheres (DOX@HAuNS) mediated simultaneous PTA of cancer cells and local drug release, resulting in enhanced antitumor activity. EphB4, a member of the largest family of receptor tyrosine kinases, is overexpressed in numerous tumors. The purpose of this study was to synthesize DOX@HAuNS conjugated to an EphB4 receptor-binding peptide, and evaluate the pharmacokinetics, biodistribution, and antitumor efficacy of the resulting EphB4-targeting DOX@HAuNS. A cyclic 17-mer peptide [c(TNYL-RAW) with high binding affinity to EphB4 was conjugated to DOX@HAuNS through a PEG linker. The cell uptake of c(TNYL-RAW)-conjugated Dox@HAuNS was examined in human ovarian cancer Hey cells over-expressing EphB4. The biodistribution tumor uptake of c(TNYL-RAW)-Dox@HAuNS was assessed at 24 h after intravenous injection in nude mice bearing Hey and A2789 ovarian cancers, and in nude mice bearing human MDA-MB231 breast tumors. Near-infrared (NIR) light-triggered Dox release in tumor-bearing mice was evaluated using a dual tracer-autoradiography technique. Antitumor effect was evaluated by measuring the tumor grow delay in mice bearing Hey ovarian cancer. In vitro, c(TNYL-RAW)-Dox@HAuNS were selectively taken up by Hey cells. This resulted in increased tumor uptake of targeted nanoparticles in all three EphB4-positive tumor models evaluated. Significantly higher cell killing effect against EphB4(+) A2780 cells was shown with DOX@c(TNYL-RAW)-HAuNS cells than with free DOX or DOX@PEG-HAuNS. In vivo, conjugation of c(TNYL-RAW) onto PEG-HAuNS did not cause significant change on pharmacokinetic properties of the nanoaprticles. DOX@c(TNYL-RAW)-HAuNS and DOX@PEG-HAuNS were almost completely eliminated from the blood at 48 h after injection. Treatment with targeted c(TNYL-RAW)-Dox@HAuNS followed by near-infrared laser irradiation (combined PTA and DOX therapies) resulted in significantly increased tumor growth control as compared to treatments with DOX@PEG-HAuNS-plus-laser (combined PTA and DOX therapies) and with PEG-HAuNS-plus-laser (PTA therapy alone). Mice in all treatment groups did not show lost in body weight, whereas free DOX caused ∼20% body weight loss at the equivalent DOX dose level. Targeted photothermal-chemotherapy exemplified by a single-agent nanoconstruct c(TNYL-RAW)-DOX@HAuNS is a promising approach to effective anticancer therapy.
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 5694. doi:1538-7445.AM2012-5694
Abstract 5713: Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb-Trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice
Authors: Tan Zongqing , Chen Pingping , Schneider Nathan , Glover Samuel , Cui Lingling , Torgue Julien , Rixe Oliver , Spitz Henry B. , Dong Zhongyun 
Published: August 2012

Abstract
Purpose The purpose of this study was to determine therapeutic effects and systemic toxicity of 212Pb-Trastuzumab in an orthotopic model of human prostate cancer cells in nude mice. Experimental Design TCMC-Trastuzumab was radiolabeled with 212Pb. The activity and integrity of 212Pb-Trastuzumab was confirmed by a competitive binding assay and SDS-PAGE analysis. Therapeutic effects were determined in an orthotopic model of human prostate cancer in nude mice. Body weight, blood cell counts, serum alanine transaminase (ALT), blood urea nitrogen (BUN), and tissue histology were examined to evaluate systemic toxicity of 212Pb-Trastuzumab therapy. Results The 212Pb-Trastuzumab generated from the procedure was intact and had high binding affinity with a dissociation constant (Kd) of 3.9 ± 0.99 nM. PC-3MM2 cells, which expressed relatively a lower level of Her2 both in culture and in tumors, were used in the study. A single injection of 212Pb-Trastuzumab reduced tumor growth by 60-80%, reduced aortic lymph node metastasis, and prolonged the survival of tumor-bearing mice. Treatment with 212Pb-Trastuzumab did not cause significant changes in body weight, serum SGPT and BUN, hematological profiles, and histological morphology of several major organs of tumor-bearing mice. Conclusion The data presented in this report demonstrated that the 212Pb-Trastuzumab therapy did not cause significant systemic toxicity and was very effective in retarding tumor growth and prolonging survival of mice bearing tumors that express very low levels of Her2. These findings suggest that 212Pb-Trastuzumab, used alone or in combination with other means, could be an effective modality for management of advanced human prostate cancer.
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 5713. doi:1538-7445.AM2012-5713
Abstract 5719: Improvement of radiotherapy for glioblastoma by co-targeting PI3K and HSP90
Authors: Wachsberger Phyllis Rachelle , Lawrence Richard Y. , Liu Yi , Andersen Barbara , Dicker Adam P. 
Published: August 2012

Abstract
Introduction: Glioblastoma (GBM) tumors frequently contain mutations in the tumor suppressor gene, PTEN, leading to loss of PTEN activity. PTEN loss causes overactivation of the PI3K pathway, inducing inhibition of apoptosis and radioresistance. Heat-shock protein 90 (HSP90) is a molecular chaperone that is over-expressed in GBM and that has among its client proteins, PI3K and Akt. It was hypothesized that dual inhibition of Hsp90 and PI3K signaling would additively or synergistically radiosensitize GBM through inhibition of radiation-induced PI3K/Akt signaling, leading to enhanced apoptosis. This study investigated the radiosensitizing effect of the HSP 90 inhibitor, HSP990 in combination with the PI3K inhibitor, BKM-120 in U87 GBM xenografts. Methods: Human U87 (GBM) cells, null for PTEN, were studied. Radiosensitivity was determined by apoptotic assays (Annexin V kit) in vitro and by tumor growth delay studies in vivo. Immunoblots were performed to assess pAkt levels. HSP990 and BKM 120 were provided by Novartis Pharmaceuticals. Results: Apoptotic assays revealed the following percentages of cells undergoing apoptosis 48 hrs after treatments: radiation alone: 57%; HSP990 alone: 75%; HSP990 + radiation (RT): 86%; BKM120 alone: 59%; BKM120+ RT: 42%. The combination of BKM120 + HSP990 induced the highest percentage of apoptosis (89% of cell population). The addition of radiation to the combined drug treatment did not increase the percentage of cells undergoing apoptosis (66% for triple modality treatment vs. 89% for HSP990 + BKM120 treatment). In vivo, each individual treatment (RT, HSP990 or BKM120) slowed the rate of tumor growth compared with the control group and all pairs of treatments performed better than either of the component treatments alone (p&lt;0.0001 for all comparisons). The combination of all three treatments performed significantly better than BKM+RTX and HSP+RTX (p=0.01 for both) but was not significantly better than BKM+HSP (p=0.06). Conclusions: The response of U87 glioblastoma to radiotherapy was enhanced in the presence of BKM120 and HSP990. Enhanced apoptosis contributed to the mechanism of cell death. This work was supported by a grant from Novartis Pharmaceuticals.
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 5719. doi:1538-7445.AM2012-5719
Abstract 572: Induction of NAD(P)H-Quinone oxidoreductase 1 by antioxidants in female ACI rats is associated with decrease in oxidative DNA damage and inhibition of estrogen-induced breast cancer
Authors: Bhat Hari K. , Singh Bhupendra 
Published: August 2012

Abstract
Exact mechanisms underlying the initiation and progression of estrogen-related cancers are not clear. Literature evidence and our studies strongly support the role of estrogen metabolism-mediated oxidative stress in estrogen-induced breast carcinogenesis. We have recently demonstrated that antioxidants vitamin C and butylated hydroxyanisole (BHA) or estrogen metabolism inhibitor α-naphthoflavone (ANF) inhibit 17β-estradiol (E2)-induced mammary tumorigenesis in female ACI rats. The objective of the current study was to identify the mechanism of antioxidant-mediated protection against E2-induced DNA damage and mammary tumorigenesis. Female ACI rats were treated with E2 in the presence or absence of vitamin C or BHA or ANF for up to 240 days. Nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H-Quinone oxidoreductase 1 (NQO1) mRNA and protein levels were suppressed in E2-exposed mammary tissue and in mammary tumors after treatment of rats with E2 for 240 days. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. Vitamin C and BHA significantly increased NQO1 levels after 120 days. 8-Hydroxydeoxyguanosine (8-OHdG) levels were higher in E2-exposed mammary tissue and in mammary tumors compared to age-matched controls. Vitamin C or BHA treatment significantly decreased E2-mediated increase in 8-OHdG levels in the mammary tissue. In vitro studies using silencer RNA confirmed the role of NQO1 in prevention of oxidative DNA damage. Our studies further demonstrate that NQO1 upregulation by antioxidants is mediated through NRF2.
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 572. doi:1538-7445.AM2012-572
Abstract 5721: Garcinol, a histone acetyltransferase inhibitor, radiosensitizes cancer cells by inhibiting non-homologous end joining
Authors: Oike Takahiro , Ogiwara Hideaki , Nakano Takashi , Yokota Jun , Kohno Takashi 
Published: August 2012

Abstract
Purpose: Non-homologous end joining (NHEJ), a major pathway to repair DNA double-strand breaks (DSBs) generated by ionizing radiation (IR), requires chromatin remodeling at DSB sites through acetylation of histones by histone acetyltransferases (HATs). However, effects of compounds with HAT inhibitory activities on DNA damage response (DDR), including NHEJ and cell cycle checkpoint, as well as on the radiosensitivity of cancer cells remain largely unclear. Here, we investigated whether garcinol, an HAT inhibitor found in the rinds of Garcinia indica fruit (called mangosteens), has effects on DDR and whether it can be used for radiosensitization. Methods and Materials: The ability of garcinol to inhibit DSB repair, including NHEJ, was examined by two assays; the conventional neutral comet assay and a cell-based assay recently developed by us, in which the activity of NHEJ against DSBs on chromosomal DNA was evaluated. The effects on cell cycle checkpoint after IR were assessed by phosphorylation levels of checkpoint kinases CHK1 and CHK2, and histone H3. The radiosensitizing effect was assessed by clonogenic survival assay. The effects on apoptosis and senescence were examined by annexin V and Senescence-associated β-galactosidase (SA-β-Gal) staining, respectively. Results: Garcinol was shown to inhibit DSB repair, including NHEJ, without affecting cell cycle checkpoint. Garcinol radiosensitized A549 lung and HeLa cervical carcinoma cells with a dose enhancement ratio at 10% surviving fraction of 1.6 and 1.5, respectively. Cellular senescence induced by IR was enhanced by garcinol. Conclusion: These results suggest that garcinol is a radiosensitizer that inhibits NHEJ and facilitates senescence, without impairing activation of cell cycle checkpoint.
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 5721. doi:1538-7445.AM2012-5721
Abstract 5724: HER2-mediated resistance of breast cancer stem cells in HER2-negative/low breast cancer
Authors: Candas Demet , Fan Ming , Duru Nadire , Menaa Cheikh , Wen Yunfei , Xiao Kai , Eldridge Angela , Chromy Brett A. , Li Shiyong , Spitz Douglas R. , Lam Kit S. , Max Max S. , Li Jian Jian 
Published: August 2012

Abstract
Despite a recent trend toward improvement, breast cancer (BC) mortality remains high due to resistance of recurrent tumors. A major cause of recurrence is likely a micro-metastatic seeding of cells that developed resistance by activating intrinsic or acquired survival pathways. In this regard, HER2 expression and cancer stem cells (CSCs) are the major cause for recurrence and targeting HER2 is well considered in therapeutic regiments. However, clinical data showed that anti-HER2 also benifit HER2−/low BC patients, suggesting that tumor cells may acquire HER2 gene activation to survive. We have previously reported that NF-κB mediates radioresistance by controlling HER2 gene. Herein, we identified HER2-expressing BC stem cells (HER2+/CD44+/CD24−/low) in radiation-resistant HER2−/low BC cells, MCF7/C6. Matrigel invasion, tumor sphere formation and radioresistance were enhanced in the HER2 mediating radioresistant cells. About 10% of the CD44+/CD24−/low cells sorted from MCF7/C6 cells or irradiated xenografts showed co-expression of HER2/CD44, ALDH and high tumorigenicity compared to HER2−/CD44+/CD24−/low cells, suggesting that the induction of HER2 expression further increased the BCSC aggressiveness. In fact, clinical data indicates that cells co-expressing HER2/CD44 were increased in recurrent tumors (84.6%) compared to the primary tumors (57.1%). Proteomics analysis identified a unique profile of proteins including DNA repair, mitochondrial function, redox, mTOR pathways that may govern the resistance of HER2+/CD44+/CD24−/low CSCs. These results demonstrate that HER2-mediated BC resistance can develop at the level of BCSC. Thus, HER2-expressing BCSCs may serve as an effective target to treat BC recurrence even from primary HER2−/low tumors.
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 5724. doi:1538-7445.AM2012-5724