bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 541: Cadmium activates translationally controlled tumor protein (TCTP) and p38 MAPK as possible pathways for prostate cancer cell aggressiveness
Authors: Munirathinam Gnasekar , Kajdacsy-Balla Andre A. , Kaul Sushma , Scumpu Andrei , Kucynda Terrie , Patel Purvi , Zheng Michelle , Lindholm Paul F. 
Published: August 2012

Abstract
Cadmium is a known cause of lung cancer, but in the prostate there is conflicting evidence for the role of cadmium as a causative agent in the prostate. Recent lines of evidence however suggest that cadmium overburden is associated with more aggressive prostate cancer. Since cadmium does not appear to cause direct genotoxic damage, its mechanism of action on cancer progression is not clear. Here we address the hypothesis that cadmium activates two key molecules: p38 MAP kinase and Translationally Controlled Tumor Protein (TCTP). The hypothesis was tested in in vitro with PC-3 prostate cancer cells and clinically relevant, sub micro molar concentrations of cadmium at various time points. Activation of p38 MAPK was analyzed using phospho- specific antibodies against p38 MAPK by western blot analysis. Results of this study showed that p38 MAPK was phosphorylated within 45 minutes following cadmium treatment. This activation of p38 MAPK by cadmium in PC-3 cells was inhibited TCTP in presence of a p38 MAPK inhibitor (SB203580). This inhibitor also markedly attenuated cadmium-induced invasion and migration of PC-3 cells in Boyden chamber experiments. In addition, our mechanistic studies show that treatment of PC-3 cells with cadmium activated a novel stress related gene, namelyTCTP, which was recently identified as an anti-apoptotic protein and target for tumor reversion process. The cadmium- mediated expression of TCTP in PC-3 cells was confirmed by real time PCR and western blot analysis. From our previous experiments, we know that overexpression of TCTP in LNCaP prostate cancer cells enhanced its migratory rates in a Transwell chamber assay and we are now testing the role of TCTP in cadmium-induced PC-3 cells invasion. Thus, results of our study suggest that TCTP and p38 MAPK may have a prominent role in cadmium mediated cell migration and prostate cancer progression.
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 541. doi:1538-7445.AM2012-541
Abstract 5414: Malignant monocytic AML cells trigger apoptosis in anti-leukemic lymphocytes: Role of NADPH oxidase gp91phox expression and PARP-1 activity
Authors: Aurelius Johan , Thoren Fredrik B. , Brune Mats , Palmqvist Lars , Hansson Markus , Hellstrand Kristoffer , Martner Anna 
Published: August 2012

Abstract
The dysfunction of natural killer (NK) cells and T cells in acute myeloid leukemia (AML) determines the course of disease, but only limited information is available on the mechanisms of lymphocyte inhibition. This study aimed to evaluate to what extent malignant AML cells utilize NADPH-oxidase derived reactive oxygen species (ROS) as an immune evasion strategy. We report that a subset of genetically defined malignant monocytic AML cells (FAB class M4/M5), recovered from blood or bone marrow of untreated AML patients at diagnosis, express gp91phox, a component of the NADPH oxidase. These AML cells produced large amounts of ROS upon activation and triggered PARP 1-dependent apoptosis in adjacent natural killer (NK) cells, CD4+ T cells, and cytotoxic T cells. In contrast, myeloblastic (FAB class M2) or immature (FAB class M1) AML cells did not express gp91phox, did not produce ROS, and did not trigger NK or T cell apoptosis. Our data are suggestive of a novel mechanism by which monocytic AML cells evade lymphocyte immunity.
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 5414. doi:1538-7445.AM2012-5414
Abstract 542: Camalexin, the phytoalexin from Cruciferous Plants, decreases cell proliferation and induces apoptosis in prostate cancer cells
Authors: Smith Basil A. 
Published: August 2012

Abstract
Camalexin, the phytoalexin produced in the model plant Arabidopsis thaliana, accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. Besides moderate antibacterial and antifungal activity, camalexin was reported to also exhibit antiproliferative and cancer chemopreventive effects. We studied the effects of camalexin treatment on viability of several prostate cancer (PCa) cell lines and whether cytostatic/cytotoxic effects of camalexin-treated prostate cancer cells were due to reactive oxygen species (ROS) generation. As models, we utilized LNCaP and its aggressive subline, C4-2, as well as ARCaP cells stably transfected with empty vector (Neo) control or constitutively active Snail cDNA that represents an EMT model. Previous studies have shown that C4-2 and ARCaP-Snail cells express more ROS than LNCaP and ARCaP-Neo, respectively. We hypothesized that camalexin would decrease cell proliferation and increase apoptosis in PCa cell lines and that the more aggressive cell lines expressing more ROS would be more sensitive to camalexin. Our results showed that camalexin treatments led to higher ROS as shown spectrofluorometrically by the oxidation of H2DCFDA, and this was decreased by co-treatment with NAC. Cell viability using MTS proliferation assay indicated that camalexin treatments decreased cell proliferation more significantly in C4-2 and ARCaP-Snail cells, as compared to LNCaP and ARCaP-Neo cells, respectively, while PrEC normal prostate epithelial cells were unaffected. Conversely, camalexin treatments increased apoptosis and mitocasp activity, which assesses caspase3/7 activity. This was associated with increased p21 and p27 anti-proliferative markers and cleaved PARP apoptotic marker as shown by western blot analysis. NAC reduced camalexin-induced ROS in ARCaP-Snail cells and abrogated camalexin-mediated cell proliferation decrease and apoptosis increase, showing that camalexin is mediating its effects through ROS. In conclusion, camalexin retarded prostate cancer cell proliferation and induced apoptosis via increased ROS generation. Interestingly, it was more potent in aggressive PCa cells expressing higher levels of ROS and did not affect normal cells. Hence, this phytoalexin has a strong potential as a novel therapeutic agent for the treatment of especially metastatic prostate cancer cells that express high levels of ROS. Supported by grants P20MD002285-01 & G12RR003062-22.
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 542. doi:1538-7445.AM2012-542
Abstract 5422: Verification of the preventive effects of Lactobacillus casei Shirota and soymilk on breast cancer in animal model
Authors: Kano Mitsuyoshi , Kaga Chiaki , Takagi Akimitsu , Kado Shoichi , Nanno Masanobu , Sakai Masashi , Miyazaki Kouji , Toi Masakazu , Ohashi Yasuo 
Published: August 2012

Abstract
Breast cancer is the most prevalent cancer among women, and the incidence rate is increasing in Japan. There is a growing public awareness toward prevention and detection of breast cancer in Japan. We have previously shown in a case-control study that consumption of either soy isoflavone or fermented milk drink containing Lactobacillus casei strain Shirota (LcS) decreases the risk of developing breast cancer. To investigate the preventive effects of LcS and soy isoflavone against breast cancer, we next conducted an animal study. Female SD rats were treated with the heterocyclic amine PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine) under a diet containing LcS, soymilk, both LcS and soymilk or LcS-fermented soymilk (L-FSM), and changes were observed for 17 weeks. As a result, decrease in adenocarcinoma and tumor multiplicity was observed in the soymilk, LcS + soymilk and L-FSM groups. Suppression of tumor volume was observed in the LcS, LcS + soymilk and L-FSM groups. Results indicate the possibility that soymilk prevents adenocarcinoma formation, while LcS suppresses tumor growth.

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 5422. doi:1538-7445.AM2012-5422
Abstract 5427: EGCG prevents hepatocellular carcinoma development in a diethylnitrosamine-induced rat model
Authors: Yamada Suguru , Fujii Tsutomu , Wei Lan , Hoshida Yujin , Lauwers Gregory Y. , Schmitt Anthony D. , Lanuti Michael , Tanabe Kenneth K. , Fuchs Bryan C. 
Published: August 2012

Abstract
Background: Hepatocellular carcinoma (HCC) is increasing in incidence and treatment is often unsuccessful. Thus, prevention in high-risk patients with established cirrhosis has been proposed as an alternative strategy. It has been suggested that the increased inflammation and fibrogenesis observed during cirrhosis predisposes the liver to future malignant transformation to HCC through a “field effect”. A growing body of evidence indicates that the green tea polyphenol, (-)-epigallocatechin gallate (EGCG), can reduce inflammation and fibrogenesis during chronic liver injury. Here, we test the hypothesis that physiological concentrations of EGCG administered in the setting of cirrhosis can prevent future HCC development. Methods: A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the efficacy of EGCG for inhibition of HCC formation in these cirrhotic livers. DEN (50 mg/kg) was administered weekly throughout the study while 0.02% EGCG was given in drinking water beginning at the onset of cirrhosis. At the end of the study, rats were sacrificed, livers were sectioned and stained to analyze disease progression and tumor nodules were counted. Liver function tests were performed to determine liver injury and overall liver function. Finally, genome-wide gene expression profiling on the surrounding, non-tumoral liver tissue was used to monitor the “field effect” in response to EGCG. Results: EGCG significantly (p &lt; 0.01) prevented the development of HCC tumor nodules from on average 18.8 in vehicle controls to on average 9.1 in EGCG-treated animals. EGCG also reduced liver injury and improved liver function as assessed by serum chemistry tests. Finally, a gene expression signature predictive of poor survival and HCC development in human cirrhosis patients was reversed in response to EGCG. Conclusions: Our data are consistent with the growing body of evidence suggesting that EGCG has protective effects in liver disease. Further, our results suggest that EGCG is a potentially effective HCC prevention strategy that can be monitored using gene expression signatures.
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 5427. doi:1538-7445.AM2012-5427
Abstract 5428: Consumption of S-allylcysteine inhibits tumor growth and progression in a mouse xenograft model of oral cancer
Authors: Tang Feng-Yao , Wang Fu-Yu , Pai Man-Hui 
Published: August 2012

Abstract
Oral cancer is a prevalent type of cancer in many countries. Although studies indicated that garlic extracts such as diallyl disulfide and diallyl trisulfide have anti-cancer effects, the chemopreventive effects of aqueous garlic extracts, S-allylcysteine (SAC), on oral cancer have not been studied yet. To this specific aim, we investigated the inhibitory effects of SAC on the proliferation and progression of oral cancer cells in both in vitro and in vivo models. In the present study, our results demonstrated that SAC dose-dependently inhibited the proliferation of human oral squamous cancer CAL-27 cells in vitro. The results indicated that SAC stabilized the adherent junction complex of E-cadherin/β-catenin and suppressed epithelial-mesenchymal transition (EMT) in oral cancer cells through suppression of MAPK/ERK signaling pathways. By study end (4th week), consumption of SAC (at doses of 5 and 40 mg / kg of body weight per day) significantly prevented tumor growth of oral cancer in a mouse xenograft model. Histopathological and immunohistochemical (IHC) staining results indicated that SAC could effectively suppress tumor progression including EMT of oral cancer in vivo. The chemopreventive effects of SAC were associated with decreases in cyclin D1 expression and suppression of Akt, mTOR, IκBα, and ERK 1/2 signaling cascades in tumor tissues. SAC consumption could inhibit the expression of cyclooxygenase-2 (COX-2), Vimentin, and nuclear NF-κB p65 (RelA) proteins. These results suggested that SAC could act as an effective agent to prevent tumor growth, progression, and EMT of oral 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 5428. doi:1538-7445.AM2012-5428
Abstract 5436: The role of reactive oxygen species in (-)-epigallocatechin-3-gallate (EGCG)-induced cell growth inhibition and apoptosis in oral cancer cells
Authors: Tao Ling , Forester Sarah C. , Lambert Joshua D. 
Published: August 2012

Abstract
(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea (Camellia sinensis L.). Recently, it has been reported to have cancer chemotherapeutic and chemopreventive effects. However, the mechanisms are incompletely understood. We found that EGCG induced both extracellular and intracellular reactive oxygen species (ROS) in SCC-25 and SCC-9 human oral squamous carcinoma cells. Extracellular ROS was produced rapidly in the DMEM/F12 (1:1) cell culture medium, but was also quenched very rapidly (t1/2 = 1.7 h). By contrast, the level of intracellular ROS increased more slowly and was increasing even after EGCG could no longer be detected in either the cytosol or the cell culture medium. We observed that EGCG treatment decreased the mitochondrial membrane potential suggesting that EGCG induced dysfunction of electron transport chain in the mitochondria of treated cells. This may explain the continuous ROS production in the cells even after EGCG levels have dropped to below the limit of detection. EGCG treatment for 72 hr reduced cell viability significantly (IC50=127 µM in SCC-25 cells and IC50=83 µM in SCC-9 cells). Effects on cell viability were modulated by inclusion of N-acetylcysteine, a thiol-antioxidant, indicating a role for EGCG-induced ROS in the reduction of cell viability. EGCG treatment also arrested cell cycle progression in the G2/M phase of cell cycle, and induced apoptosis (increased TUNEL positivity and annexin V staining). Based on the present studies, it appears that EGCG-induced oxidative stress and mitochondrial dysfunction play a role in its anti-oral cancer effects in cell culture. Ongoing studies in our laboratory are focused on the mechanism by which EGCG induces mitochondrial dysfunction, and the relevance of this mechanism to oral cancer prevention in vivo.
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 5436. doi:1538-7445.AM2012-5436
Abstract 5440: Upregulation of prostaglandin E2 and TGF-alpha by linoleic acid enhances pro-oncogenic signaling in models of human lung and breast cancer
Authors: Martins Clarissa R. , Pardini Ronald S. , Kikawa Keith D. 
Published: August 2012

Abstract
The omega-6 polyunsaturated fatty acid (PUFA), linoleic acid (LA), has been reported to have adverse affects in the growth and metastasis of a variety of cancer cell models. However, there has been some controversy over how much these models relate to human disease. In the current study, a novel cascade of actions behind the LA-induced upregulation of cell proliferation has been identified. It is well established that PUFAs serves as precursors for eicosanoids, and LA supplementation was found to significantly increase the levels of Prostaglandin E2 (PGE2) in a variety of lung and breast cancer cell lines. These increases in PGE2 are associated with elevations in the activity of Cyclooxygenase-2 (COX-2), increased levels of Tumor Growth Factor-alpha (TGF-alpha) and specific pro-proliferative signaling pathways. These findings were corroborated in animal xenografts derived from the same cell lines used for the in vitro studies, with serum levels of PGE2 showing significant increases in PGE2 in animals fed diets high in LA. Moreover, the omega-3 PUFA, docosahexaenoic acid (DHA), was found to have an opposing affect on PGE2 production by upregulating Thromboxane B2 (TXB2), a stable metabolite of Thromboxane A2 (TXA2), which inhibits COX-2 activity. These findings present specific mechanisms behind the upregulation of cancer cell growth due to LA supplementation that may contribute to a resolution in determining its role in human disease.
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 5440. doi:1538-7445.AM2012-5440
Abstract 5444: In vitro modeling for breast cancer prevention - omega-3 ethyl esters functioning as preventive agents in 21T series models
Authors: Chen Ching Hui , Fabian Carol , Hursting Stephen , deGraffenried Linda 
Published: August 2012

Abstract
Over the past few decades, multiple trials have warranted the benefits of using prevention as an effective strategy for lowering breast cancer incidence. The Breast Cancer Prevention Trial (BCPT) and Study of Tamoxifen and Raloxifene (STAR) conducted by National Cancer Institute demonstrated the effectiveness of tamoxifen and raloxifene as preventive agents in reducing diagnoses of invasive breast cancer. Another prevention study the VITAL cohort study demonstrated that omega-3 supplementation reduces breast cancer incidence in postmenopausal women. In vivo studies have produced results that demonstrated a delay in onset of breast cancer in transgenic mice model. However, current in vitro effort did not have a system that closely resembles the linear progression of breast cancer and therefore stalls the molecular investigation of breast cancer prevention. Majority of in vitro preventive studies have been conducted using cancer cell lines that do not represent precancerous status of mammary tissues and do not mirror the observation of delayed onset or reduced incidence in in vivo and clinical trials. A recent report has suggested the use of a new series of mammary cells that represent hyperplasia, ductal carcinoma in situ (DCIS) and invasive carcinoma in nude mice. In this study we propose the use of 21T series breast cancer cells as a model for breast cancer prevention study using omega-3 ethyl esters. Preliminary data using this model has shown that omega-3 ethyl esters derived from Omacor® reduce proliferation only in 21NT (DCIS) and 21MT-1 (Invasive Carcinoma) and not in 21PT cells (hyperplasic). Suppression of proliferation is most optimal in the presence of estrogen. Survival of cells is inhibited in all cell lines and Ki67 index is reduced in the presence of treatments. Targets of omega-3 ethyl esters may include Akt, ER and NF-kB. Current studies are conducted to investigate the effect of omega-3 ethyl esters on these targets.
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 5444. doi:1538-7445.AM2012-5444
Abstract 5445: Polyphenolic phytochemical curcumin suppresses HER-2 protein phosphorylation and gene expression in breast cancer cells
Authors: Thomas T. J. , Venkiteswaran Sripriya 
Published: August 2012

Abstract
Curcumin (diferuloylmethane) is the major pigment ingredient of turmeric, a plant native to South Asia, belonging to ginger family. Turmeric is used in Oriental cuisine and is believed to exert anti-inflammatory, anti-oxidant and anti-carcinogenic properties. Curcumin has apoptotic activity against different types of cancer, including colon cancer, stomach and skin tumors, breast cancer and prostate cancer, and has been the subject of several clinical studies. Curcumin disrupts different stages of carcinogenesis, including cell proliferation, survival, angiogenesis and metastasis in preclinical models. In order to understand the mechanism of action of curcumin in HER-2 positive breast cancer, we investigated the effects of different concentrations of curcumin on SK-BR-3, an HER-2 positive human breast cancer cell line. Curcumin inhibited the growth of SK-BR-3 cells in a concentration- and time-dependent manner, with an IC50 value of 5 ± 1 µg. A significant 80% cells underwent apoptosis in the presence of 25 µM curcumin at the 24 hour of treatment, as determined by APO-BRDU assay. At 25 µM concentration, curcumin suppressed the expression of HER-2 gene by a significant 70% (P ≤ 0.005, compared to untreated control) at 24 hours of treatment, as measured by real-time qPCR assay. In addition, curcumin suppressed the expression of cyclin A, cyclin B1, cyclin D1 and cyclin E by 30 to 70%. In contrast, 10, 25 and 50 µM concentrations of curcumin increased the expression of p21 by 4-, 3-, and 2-fold, respectively, at 16 hours of treatment. Comparable increase in p21 level was evident at 24 hours of treatment also. Curcumin arrested cells in the G2/M phase (38 ± 3% compared to 22 ± 2 % control at the same time point; P &lt; 0.001; n = 3). Curcumin suppressed HER-2 phosphorylation in a concentration- and time-dependent manner, suggesting a possible mechanism of action. Pre-treatment of cells with an anti-oxidant, glutathione partially reversed apoptosis induced by curcumin, and restored HER-2 and cyclin D1 protein levels. These results suggest the involvement of redox pathway also in the action of curcumin. Taken together, our data indicate multiple pathways in the mechanism of action of curcumin in HER-2 positive breast cancer cells, and suggest possible preventive strategies with this natural plant product.
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 5445. doi:1538-7445.AM2012-5445