bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5353: Characterization of breast cancer stem cells (BCSCs) in Egyptian breast cancer patients through genetic profiling using the RT-PCR and quantitative real time microarray
Authors: Zekri Abdel-Rahman N. , Bahnassy Abeer A. , Ahmed Ola S. , Mourad Magda 
Published: August 2012

Abstract
Background: Stem cells (SC) are cells that can differentiate along distinct lineages through systemic differentiation steps. The concept of self renewal is crucial to understand cancer stem cells (CSC) and the mechanisms by which current therapies might evade the available treatment modalities. The aim of the present study was to characterize breast cancer stem cells (BCSC) by genetic profiling of properly isolated BCSCs at different stages using the recently developed quantitative real time microarray technology to understand the origin and contribution BCSCs to breast cancer development and progression. Material and Methods: 60 cases of BC were subjected to enzymatic digestion to obtain single cell suspension for: 1) flowcytometric characterization of cells, 2) mammosphere culture 3) magnetic separation of different subsets of BCSCs (CD44 and CD24), and 4) RNA extraction for RT-PCR and microarray using the SABiosciences's QC PCR profiler Arrays with SC panel of 84 genes (SC specific markers, SC differentiation markers, and signaling pathway markers for SC). Samples for the QC PCR profiler Arrays were categorized into groups: 1) normal breast tissue, 2) BC cells obtained from tumor samples, 3) cells from mammosphere cultures, 4)CD44+/CD24low/EpCAM- cells, 5) CD44+/ CD24low cells. ER, PR and Her-2 assessment was also performed. Results: Discrete mammospheres of different sizes were obtained from 10 cases and IHC of these samples confirmed the SC lineage. By FCM, cells expressing CD44+/CD24low ranged from 0.1% - 79%. MYC, MYST2, DHH, BTRC AND CXCL12 genes showed over-expression in the studied groups in comparison to normal breast tissue. Comparing all studied groups, we identified 5 candidate genes DVL1 and EP300 (Notch pathway), BTRC (Wnt Pathway), DHH (Chro-Chro Modulation), MYST2 (self Renewal), NCAM1 (Cell Adhesion Molecules) which could be used for characterization and molecular target therapy for breast cancerl. Conclusions: Our QC PCR profiler Arrays showed significant differences between the studied groups shedding light on the nature and helping in proper characterization of BCSCs. Correlation between prognostic factors of BC and the number of BCSCs in tumor biopsies together with the probability of mammoshpere formation in culture denotes the contribution of CSCS to the progression of BC.
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 5353. doi:1538-7445.AM2012-5353
Abstract 5370: Adjuvant breast cancer vaccine improves overall survival of patients with depressed immunity
Authors: Head Jonathan F. , Elliott Robert L. 
Published: August 2012

Abstract
Breast cancer patients were vaccinated in the adjuvant setting with a whole cell vaccine, containing autologous and allogeneic breast cancer cells, to evaluate the effect on host lymphocyte immunity and overall survival. We began preparing whole cell preparations for a breast cancer vaccine clinical trial in 1995. Stage I and II breast cancer patients had host lymphocyte immunity against tumors associated antigens evaluated before standard therapy. Those patients with depressed immunity determined by a lymphocyte blastogenesis assay (LBA) were offered the whole cell vaccine. Patients were given six intradermal injections (three weekly followed by three monthly). Ten weeks after the last injection the LBA was repeated. Thirty-seven patients were vaccinated in the adjuvant setting with the whole cell vaccine, containing autologous and allogeneic breast cancer cells. Some patients experienced slight pain and swelling at the injection site. There were no severe toxicities and the vaccine was well tolerated. There has been a ten year follow-up for all vaccinated patients. The survival data of the vaccinated patients with depressed immunity (79% survival at 10 years) compared to an historic control of unvaccinated patients with depressed immunity to their tumor associated antigens (59% survival at 10 years), demonstrates an improvement in overall survival of the vaccinated patients. This study confirms the importance of maintaining good host lymphocyte immunity after completion of standard therapy, and validates cancer immunotherapy in the adjuvant 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 5370. doi:1538-7445.AM2012-5370
Abstract 5404: Up-regulation of proliferative and migratory genes in regulatory T cells from patients with metastatic castration-resistant prostate cancer
Authors: Tucker Jo A. , Huen Ngar-Yee , Pang Alan LY , lee Tin-Lap , Vergati Matteo , Intrivici Chiara , Cereda Vittore , Jochems Caroline , Chan Wai-Yee , Rennert Owen , Gulley James L. , Schlom Jeffrey , Tsang Kwong-Yok 
Published: August 2012

Abstract
Immune suppression by regulatory T cells (Tregs) is associated with tumor evasion. An increase in the frequency and suppressive function of Tregs has been shown in a variety of solid tumors. The purpose of this study was to determine if the enhanced number and activity of these cells in prostate cancer patients could be due to tumor-induced changes in gene expression. CD4+CD25hiCD127lo Tregs were isolated from the peripheral blood of healthy donors and metastatic castration-resistant prostate cancer (mCRPC) patients. These samples were selected based on similar suppressive activity in a functional assay. A genome-wide expression array of 38, 500 genes was then performed to detect any effects in expression potentially induced by tumor. We found 384 genes had a three-fold or greater difference in expression between the groups. Differentially expressed genes were involved in cell cycle processes, cellular growth and proliferation, immune response, hematological system development and function, as well as the IL-2 and TGF-β pathways. Genes most up-regulated in the Tregs of mCRPC patients included C-FOS, C-JUN, DUSP1 and RGS1, which are crucial for regulation of T cell proliferation, activation and migration. We also observed increased expression of c-Jun protein in patient Tregs by flow cytometry. Patients had a significantly higher percentage of Tregs in their CD4+ population than the healthy donors, but interestingly, there was no difference in FoxP3 expression. These results indicate that tumor-derived factors may contribute to Treg mediated immune suppression by up-regulating genes that increase their proliferative and migratory capacities, allowing them to better home to the tumor and inhibit the host response.
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 5404. doi:1538-7445.AM2012-5404
Abstract 5411: Rb1 controls the differentiation of myeloid-derived suppressor cells subsets
Authors: Youn Je-In , Collazo Michelle , Kumar Vinit , Gabrilovich Dmitry I. 
Published: August 2012

Abstract
Myeloid derived suppressor cells (MDSC) consist of two distinct subsets, polymorphonuclear/granulocytic-MDSC (PMN-MDSC), and monocytic-MDSC (M-MDSC) that differ in morphology, phenotype and preferred suppression mechanisms. PMN-MDSC is the predominant subset of MDSC that accumulates in spleen, bone marrow, blood, and tumor tissues in various mouse tumor models. M-MDSC produced higher level of cytokines and chemokines including G-CSF, IL-1b, IL-6, TNF-a, MCP-1 and RANTES compared to PMN-MDSC. The current paradigm considers PMN-MDSC and M-MDSC to differentiate from different progenitors alongside different lineages (granulocytic and monocytic, respectively). M-MDSC differentiate into dendritic cells and macrophages, whereas PMN-MDSC are terminally differentiated cells. Our study demonstrated that in cancer M-MDSC represent highly proliferative population of cells that differentiate not only to DC and macrophages but also to PMN-MDSC. The retinoblastoma gene (Rb1), a central regulator of the cell cycle and cell differentiation, is known to be involved in monocytic and granulocytic lineage commitment. When examining Rb1 levels in freshly isolated cells, M-MDSC expressed high levels of Rb1 similar to those in dendritic cells, macrophages, and neutrophils isolated from naïve mice. In sharp contrast, PMN-MDSC had undetectable Rb1. Lack of Rb1 in mice with conditional deletion of the gene promoted an expansion of splenic CD11b+Ly6G+Ly6Clo cells, similar to the phenotype of PMN-MDSC in tumor-bearing mice. Lack of Rb1 in PMN-MDSC was caused by transcriptional repression of the gene. In culture with GM-CSF, Rb1 expression in M-MDSC remained the same while in PMN-MDSC it was increased over time to the level seen in control neutrophils. Inhibition of rb1 expression in PMN-MDSC correlated with the level of histone acetylation of rb1 promoter. Treatment of PMN-MDSC with inhibitors of histone deacetilases (HDAC) resulted in the increase in rb1 expression suggesting that it may be controlled by histone modification. HDAC inhibitors abrogated differentiation of M-MDSC to PMN-MDSC in the presence of tumor explants conditioned medium. These results suggest that down-regulation of Rb1 plays a major role in accumulation of MDSC in cancer by regulating PMN-MDSC differentiation from M-MDSC. HDAC may be considered as potential targets for therapeutic regulation of MDSC.
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 5411. doi:1538-7445.AM2012-5411
Abstract 5419: Targeting colon cancer stem cells using sulforaphane
Authors: Rangarajan Parthasarathy , Subramaniam Dharmaligam , Anant Shrikant , Dhar Animesh 
Published: August 2012

Abstract
Colon cancer is a leading cause of cancer death in the United States, accounting for approximately 51,000 deaths each year. For patients with advanced colon cancer, the 5-year survival rate is less than 10%. Recent evidence suggests the existence of a small population of tumorigenic stem cells responsible for tumor initiation, metastasis and resistance to chemotherapy and radiation. Identification of the regulatory mechanisms and signalling pathways involved in cancer stem cells will help in designing novel agents to target this refractory cell population in colon cancers. We are currently investigating the mechanism by which sulforaphane, an isothiocyanate present in cruciferous vegetables such as broccoli, Brussels sprouts and cabbage inhibits growth of colon cancer cells. Our studies demonstrate that the compound had significant cytotoxicity against HCT116 colon cancer cells in both a dose- and time-dependent manner. Colon CSCs can be allowed to divide and grow in ultra-low binding tissue culture dishes to form multicellular spheroids called colospheres. Treatment with sulforaphane decreased the number and size of the primary and secondary colospheres in a dose dependent manner, suggesting that sulforaphane targets CSCs. To understand the mechanism of inhibition of colospheres, the signaling pathways affected by sulforaphane were dissected. Aberrant activation of Sonic Hedgehog signaling pathway has been associated with renewal of cancer stem cells, and in the development of several solid cancers. Sonic hedgehog (Shh) upon binding to its cognate receptor patched, allows smoothened to accumulate and activate Gli transcription factor. Treatment with sulforaphane inhibited the expression of both Shh and smoothened in the colon CSCs. Furthermore, it inhibited the expression of patched-1 and Gli-1, downstream targets of the hedgehog signalling pathway. Taken together, these data suggest that sulforaphane effectively inhibits colon cancer stem cells by down regulating the sonic hedgehog pathway, thereby inhibiting tumorigenesis (supported in-part by the US PHS grants CA 109269 and CA 135569 to SA and CA 151727 to AD).
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 5419. doi:1538-7445.AM2012-5419
Abstract 5433: Dietary factors and the risk of esophageal cancer: A population-based cohort study in Korea
Authors: Nam Byung-Ho , Bak Jeongin , Kim Jeongseon 
Published: August 2012

Abstract
Objective: To date, there have been few prospective cohort studies that have investigated the association between dietary factors and the risk of esophageal cancer (EC). A large population-based cohort study was conducted to assess the effect of dietary factors on the risk of EC in Korean adults. Methods: The data for this study came from the National Health Insurance Corporation Study (NHICS), Korean Central Cancer Registry. The participants aged 30-80 years were 822,745 Korean men and 368,918 women, cancer-free at baseline in 1996 and 1997, and were followed up to December 31, 2007. The hazard ratio (HR) and 95% confidence interval (CI) of the HR were estimated using the Cox proportional hazards regression model. Results: During the follow-up period, crude incidence rates per 100,000 person-years for EC were 8.1 in overall total population, 11.1 in men, and 1.2 in women. In the total population, the estimated HRs (95% CI) for meat consumption of more than 4 times per week compared with consumption of less than once per week were 1.267 (1.018-1.577) with a p value of 0.0337. In men only groups, the HRs (95% CI) for those who had irregular meal patterns compared with those with regular meal patterns were 1.359 (1.087-1.699) with a p value of 0.0071. Conclusion: The present findings suggest that dietary factors may be associated with the risk of EC.
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 5433. doi:1538-7445.AM2012-5433
Abstract 5450: H-RASG12V transformation modulates antioxidant activities and enhances genotoxicity to arsenite in human urothelial cells
Authors: Liao Yi-Chun , Lai Kuo-chu , Lee Te-Chang 
Published: August 2012

Abstract
Inorganic arsenite (iAs) is a human carcinogen. Epidemiological evidence has revealed the strong association of chronic exposure to arsenic with increased incidences of cancers, including skin, lung, liver, bladder, etc. However, the exact carcinogenic mechanisms of iAs are not completely understood. Numerous studies have shown that mutation-activated H-Ras is frequently observed (about 30 ∼ 50%) in human urothelial carcinoma. In this study, we explored the gentoxic effects of iAs in human urothelial cells ectopically expressing H-RasG12V, an activated H-Ras oncogene. Our results showed that H-RasG12V-transformed human uroepithelial cells (HUC-RAS) were more susceptible to arsenite-induced cell death, DNA damage, micronuclei formation, and anchorage independent growth than control cells (HUC-neo). Furthermore, we found that iAs treatment induced higher intracellular levels of reactive oxygen species (ROS) in HUC-RAS cells than HUC-neo. In addition, iAs-induced genetic damages could be effectively suppressed by N-acetyl-L-cysteine (NAC). We therefore further determined the effects of iAs on antioxidant activities in these 2 cell lines. Our results showed that glutathione (GSH) and superoxide dismutase (SOD) activity were significantly elevated by treatment of HUC-neo cells with iAs, but not in HUC-RAS cells.Alternatively, catalase activity, 2-fold increase in HUC-RAS cells as compared to HUC-neo cells, was significantly suppressed by iAs. Taken together, we may infer that H-RasG12V expression disturbs redox homeostasis by increasing catalase activity. Since catalase activity is sensitive to iAs, it may account for the susceptibility of H-RAS transformed cells to iAs.
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 5450. doi:1538-7445.AM2012-5450
Abstract 5462: Single dose dermal irritation study of apaziquone in rabbits
Authors: Reddy Guru , Chawla Shanta , Fruchtman Steven 
Published: August 2012

Abstract
Introduction and Objectives: Apaziquone is a novel bioreductive alkylating agent in development for intravesical therapy of nonmuscle invasive bladder cancer (NMIBC). The standard dose of apaziquone in all ongoing clinical studies is 4 mg/ 40 mL (0.1mg/mL). For clinical use, lyophilized apaziquone is reconstituted with diluent and instilled in the bladder. During the preparation and handling of the product, there is a possibility of accidental dermal contact for the healthcare professionals. To date, dermal irritation potential of apaziquone has not been investigated. The purpose of this study was to evaluate the dermal irritation potential of apaziquone in rabbits. Materials & Methods: Apaziquone was administered topically on the skin (non-occlusive) to New Zealand White (NZW) rabbits as a single dose for 4 hours followed by removal of excess material, and skin examination for up to 72 hours after removal of excess material. Each male NZW rabbits (3/group; one group) had three identified treatment sites on the back: (1) untreated (2) vehicle (diluent for apaziquone) and (3) apaziquone (0.1 mg/mL). Animals were treated with a single non-occlusive dermal dose of apaziquone (0.5 mL of 0.1 mg/mL) and vehicle for 4 hours followed by removal of excess material. No test material or vehicle was applied to the site designated as untreated. The treatment sites were observed and scored at baseline and at various times (4, 24, 48, and 72 hours) after removal of excess test article and vehicle. The following parameters were evaluated: viability, clinical observations, and dermal observations/scoring by modified Draize method. Results: No clinical signs of toxicity were observed during the study and no signs of dermal irritation related to test article or vehicle/diluent were observed at any of the dose sites in any of animals. The Primary Dermal Irritation Index for apaziquone, administered at clinically relevant exposures, had a value of zero (0) indicating no irritation at the concentration and for the duration of exposure. Conclusion: Apaziquone did not cause any dermal irritation in rabbits at a clinically relevant concentration.
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 5462. doi:1538-7445.AM2012-5462
Abstract 5546: UVC irradiation inhibits superficial tumor growth in the brain of nude mice
Authors: Momiyama Masashi , Hiroshima Yukihiko , Suetsugu Atsushi , Tome Yasunori , Mii Sumiyuki , Yano Shuya , Chishima Takashi , Bouvet Michael , Endo Itaru , Hoffman Robert M. 
Published: August 2012

Abstract
Temozolomide and UVC light were used for induction of cancer cell apoptosis of cancer cells which was imaged in real time at the subcellular level in the brain. Temozolomide inhibited brain tumor growth (p &lt; 0.001). UVC irradiation inhibited superficial brain tumor growth (4.7-fold) (p &lt; 0.0001) and improved survival (39.0%) (p = 0.002). This model can be used to evaluate new treatment modalities of brain metastasis or brain cancer at the subcellular level. In order to visualize single cancer cell nuclear-cytoplasmic dynamics of cancer cells in the brain in real time, including mitosis and apoptosis, Lewis lung cancer cells or human U87 glioma cells were injected into the brain either stereotactically or via the carotid artery of nude mice. The cancer cells were labeled with GFP in the nucleus and RFP in the cytoplasm, such that mitosis and apoptosis could be clearly imaged. A craniotomy open window was made for real-time fluorescence imaging of the cancer cells growing in the brain. Mitosis as well as treatment-induced apoptosis of the individual cancer cells were imaged in real time. UVC irradiation was initiated 1 day after the cancer cell inoculation and tumors were irradiated for 120 seconds on days 1, 4, 7, and 10. The tumor volume and survival were compared with untreated mice. UVC irradiation inhibited 4.7-fold changes in the brain tumor growth (p &lt; 0.0001) and improved 39% higher survival (p = 0.002).
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 5546. doi:1538-7445.AM2012-5546
Abstract 5547: Oral delivery of tumor-targeting Salmonella typhimurium A1-R is effective therapeutically
Authors: Tome Yasunori , Zhang Yong , Momiyama Masashi , Maehara Hiroki , Kanaya Fuminori , Tomita Katsuro , Bouvet Michael , Hoffman Robert M. , Zhao Ming 
Published: August 2012

Abstract
The S. typhimurium A1-R mutant, which is auxotrophic for leu-arg to attenuate growth in normal tissue, and selected for high antitumor virulence, has been shown to be effective as monotherapy against human prostate, breast, pancreatic, and fibrosarcoma tumors. In the present study, we first administered A1-R to nude with subcutaneous murine colon cancer Colon-26 which expressed red fluorescent protein (RFP). S. typhimurium A1-R (1×107 cfu) was administered intravenously (i.v.) or intratumorally (i.t.) to the subcutaneous tumor as a positive control. The size of tumor was measured by weekly fluorescence imaging. Both i.v.- and i.t.-treated mice had smaller tumors and survived longer (p&lt;0.05) compared to the control group treated with PBS. When S. typhimurium A1-R was administered orally to nude mice with orthotopically-transplanted Colon-26 RFP, tumor growth was inhibited (p&lt;0.05) and animals survived longer than untreated controls (p&lt;0.05). Furthermore, orally-treated mice had no observable side effects suggesting oral delivery of tumor-targeting S. typhimurium A1-R is a promising route for bacterial therapy of 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 5547. doi:1538-7445.AM2012-5547