bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5520: Therapeutic vaccination with epitope-enhanced and wild-type TARP peptides in stage D0 prostate cancer
Authors: Wood Lauren V. , Dahut William , Gulley James L. , Madan Ravi A. , Arlen Philip , Parnes Howard L. , Roberson Brenda D. , Steinberg Seth M. , Terabe Masaki , Berzofsky Jay A. 
Published: June 2012

Abstract
Background: T-cell receptor alternate reading frame protein (TARP) is immunogenic, is expressed in ∼95% of prostate cancer specimens and hence is a good candidate for therapeutic vaccination. The immunogenicity of HLA-A*0201 binding TARP peptides can be improved through epitope-enhancement achieved by amino acid substitutions that result in increased HLA binding affinity and immunogenicity at least in mice. We conducted a pilot study to determine the safety and immunogenicity of TARP peptide vaccination and its impact on PSA doubling time (PSADT) in men with Stage D0 prostate cancer.
Methods: HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) or wild type (27-35) TARP peptides administered as a peptide emulsion with Montanide ISA 51VG plus GM-CSF (Arm A) or as an autologous peptide-pulsed dendritic cell vaccine (Arm B). Vaccines are administered q 3 weeks for a total of 5 vaccines with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria and a booster dose of vaccine for all patients at 48 weeks.
Results: 26 patients have enrolled in the study to date (n = 14 Arm A, n = 12 Arm B) with a mean on study duration of 7.5 months. Mean baseline cohort characteristics: age 63 yrs, PSA 4.43, PSADT 7.3 months and Gleason Score 6.7 with 19 of 26 s/p radical prostatectomy. TARP vaccination was safe and well tolerated with adverse events limited to local injection site reactions &lt; Grade 2. Nine of 18 patients (50%) reaching 24 weeks on study were documented to have an increase in their PSADT compared to baseline.
Mean Percent Increase/Prolongation in PSADT:

Surprisingly TARP-specific IFN-γ ELISPOT responses have been detected ex vivo in only 3 of 14 (21%) patients examined to date.
Conclusion: Vaccination with wild type and epitope-enhanced TARP peptides results in prolongation of PSADT in a substantial fraction of patients. The immunologic correlates responsible for PSADT lengthening are poorly understood and require additional study.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5520. doi:10.1158/1538-7445.AM2011-5520
Abstract 5533: A RT-PCR study of cytokine expression with macrophages and tumors
Authors: Syndergaard Chas , Knechtel Daniel C. , Clark Daniel N. , Keller Mary A. , O'Neill Kim , Robison Richard A. 
Published: June 2012

Abstract
Macrophages (MØ) are very important in initiating and directing an immune response. However, it has been noted that when MØ are in the presence of a tumor, they often undergo a change in phenotype. In this environment, MØ will be converted from an aggressive phenotype (M1) to one that promotes tissue remodeling and repair (M2) through a process that is not fully understood. The purpose of this study was to identify which cytokines, in both MØ and cancer cells, show altered expression when the two are in close proximity. To accomplish this, MCF-7 (breast cancer), MDA-MB-231 (breast cancer), MDA-MB-435 (melanoma), and HT29 (colon cancer) cell cultures were grown in prescribed media followed by a 48-hour co-incubation with whole blood MØ. Lipopolysaccharide (LPS) was used as a positive control of an M1-type stimulation. The cytokine levels of both the cancer cells and MØ were then analyzed by quantitative PCR (qPRC) for expression of interleukin-1beta (IL-1β), macrophage migration inhibition factor (MIF), and tumor necrosis factor-alpha (TNF-α). Mathematical calculations were analyzed using a Step One® comparative quantification program and the cytokine expression equation 2⁁-(Δct1- Δct2). MØ IL-1β showed a fold change of 2.76, 1.58, 0.95, 3.09, 10.11 when exposed to MCF-7, MDA-MB-231, MDA-MB-435, and HT29 cells and LPS respectively. These expressions correlated with the aggressiveness of the cancer. Aggressive MDA-MB-435's down regulated IL-1β. Fold change in MIF expression was 3.14, 1.33, 7.56, and 1.22 in MCF-7, MDA-MB-231, MDA-MB-435, and HT29 cells respectively. HT29's had the lowest expression levels suggesting one reason why it's been reported that infiltration of MØ happens properly in colon cancers. Fold expression in MØ expression of TNF-α was 1.34, 1.65, 1.10, and 0.85 with MCF-7, MDA-MB-231, MDA-MB-435, and HT29 cells respectively. An interesting finding that warrants further investigation was in regards to the colon cancer. We observed with interest that the colon cancer line, HT29, caused a decrease in expression of MØ TNF-α. These findings show that colon cancer HT29 decreases TNF-α expression whereas other tested cancer lines did not. This suggests that colon cancers might evade the immune system by regulating MØ TNF-α, an important factor in initiating the caspase-8 regulated apoptotic pathway. These findings suggest that each cancer has an individual method in managing it's microenvironment in respect to MØ.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5533. doi:10.1158/1538-7445.AM2011-5533
Abstract 5539: A predominant serrated pathway in hyperplastic polyposis syndrome generates microsatellite-stable and -unstable colorectal cancers
Authors: Noesel Carel V. 
Published: June 2012

Abstract
Background and aims: Hyperplastic polyposis syndrome (HPS) is characterized by the presence of multiple colorectal serrated polyps and is associated with an increased colorectal cancer (CRC) risk. The mixture of distinct precursor lesion types and malignancies provides a unique model to study the canonical pathway and a proposed serrated CRC-pathway in humans.
Methods: To establish which CRC-pathways play a role in HPS and particularly to obtain new support for the serrated CRC pathway, we analyzed the molecular characteristics of polyps (n=84) and CRCs (n=19) in 17 HPS patients as compared to control groups of various sporadic polyps(n=59) and sporadic microsatellite-stable CRCs(n=16).
Results: In both HPS and sporadic polyps, APC mutations were exclusively identified in adenomas whereas BRAF mutations were confined to serrated polyps. Six of 19(32%) HPS CRCs were identified within a serrated polyp. Mutation analysis performed in both the CRC and the serrated component of these lesions showed identical BRAF mutations. One HPS CRC was located within an adenoma, both components harboring an identical APC mutation. Overall, 10/19(53%) HPS CRCs carried a BRAF mutation, compared to none in control group CRCs (p=0.001). Six of the BRAF-mutated HPS CRCs were microsatellite-unstable (MSI-high) due to MLH1 methylation.
Conclusion: Our findings provide novel supporting evidence for the existence of a serrated CRC pathway which predominates over the classical Wnt pathway of carcinogenesis in HPS.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5539. doi:10.1158/1538-7445.AM2011-5539
Abstract 5552: New models for prostate and colon carcinogenesis in PhIP-treated hCYP1A mice
Authors: Li Guang Xun , Cheung Connie , Loy Shea , Liu Anna B. , Yang Chung S. 
Published: June 2012

Abstract
The food mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP), is mainly metabolized by human CYP1A2 through N-CYP1A2 through N2-hydroxylation (activation) and by mouse Cyp1a2 through 4′-hydroxylation (detoxification). In order to mimic human PhIP carcinogenesis in mice, we treated hCYP1A mice (which express human CYP1A but not mouse Cyp1a) with PhIP by oral gavage. Following a dose of PhIP (200 mg/kg b.w.), low-grade prostate intraepithelial neoplasia (PIN) were observed after 20 weeks, high-grade PIN were observed after 30 weeks, and microinvasive carcinomas and adenocarcinomas in ventral, dorsolateral, and coagulating gland were observed after 40 and 50 weeks. Similar to human prostate carcinogenesis, higher than normal GSTP1 levels were observed in proliferative inflammatory atrophic lesions, and GSTP1 expression was lost in high-grade PIN and carcinomas. Under these experimental conditions, colon tumors were not observed. However, in mice that were treated with PhIP (200 mg/kg) and, a week later, followed by treatment with 1.5% dextran sodium sulfate (DSS) in drinking fluid for 1 week, colon tumors were observed after 6 weeks (with 85% tumor incidence and 3.75±0.70 tumors/mouse) and &gt;90% of the tumors were adenocarcinomas. The tumors had overexpressed β-catenin, c-myc, cyclinD1, iNOS and COX-2. In parallel studies with wild type mice treated with PhIP, or PhIP plus DSS, only low-grade PIN, but no colon tumors, were observed. Experiments are ongoing to study the effects of high-fat diet and other dietary factors in modulating carcinogenesis. These models, when fully characterized, could be very useful experimental systems to study diet and prostate/colon cancer (supported by NIH grants CA120915 and CA120915-S2).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5552. doi:10.1158/1538-7445.AM2011-5552
Abstract 5558: Persistent induction of cytochrome P450 (CYP)1A1 in human lung cell line, H358, by 3-methylcholanthrene: Implications for pulmonary carcinogenesis by polycyclic aromatic hydrocarbons
Authors: Moorthy Bhagavatula , Jiang Weiwu , Wang Lihua , Chu Chun 
Published: June 2012

Abstract
Humans are constantly exposed to environmental carcinogenic polycyclic aromatic hydrocarbons (PAHs) through cigarette smoke, diesel exhausts, charcoal-broiled meats, etc. Cytochrome P4501A (CYP1A) enzymes play important roles in the activation of PAHs such as 3-methylcholanthrene (MC) to carcinogenic DNA-binding metabolites, which could in turn lead to pulpmnary carcinogenesis. We recently reported that MC elicits persistent induction of hepatic and pulmonary CYP1A1 in mice by mechanisms other than persistence of the parent MC, and that this phenomenon contributes to pulmonary carcinogenesis. The regulation of CYP1A1 in human lung is not well understood as MC fails to induce CYP1A1 in many lung cells lines, including A549 cells. In this study, we tested the hypothesis that MC elicits persistent induction of CYP1A1 in the human bronchoalveolar cell line, H358. H358 cells were exposed to MC (2.5 µM) dissolved in DMSO, or DMSO alone as controls. At different time points, CYP1A1 activities were determined by measuring the activities of ethoxyresorufin O-dethylase (EROD). CYP1A1 apoprotein and mRNA expression were determined by Western blotting and real time RT-PCR, respectively. MC induced CYP1A1 activities by 8-fold at 8 h, and this effect was persistent even at 72 h. This was accompanied by persistent expression of CYP1A1 apoprotein. Real-time RT-PCR showed that 8 h treatment with 2.5 µM MC induced mRNA of CYP1A1 by 850-fold, and the effect was persistent up to 72 h. These results suggest that the H358 cell line could be an excellent model to study the molecular mechanisms of CYP1A1 regulation by MC in the human lung. Since lung is a target organ for pulmonary carcinogenesis in humans exposed to environmental pollutants such as cigarette smoke, further studies could lead to improved understanding of the mechanisms of pulmonary carcinogenesis, which could in turn lead to the development of rational strategies for the prevention/treatment of lung cancers in humans. (Supported by NIH grant ES009132.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5558. doi:10.1158/1538-7445.AM2011-5558
Abstract 5567: Short-term pregnancy levels of estradiol delays Her-2 positive mammary tumor development by altering key signaling pathways
Authors: Parada Jacqueline , Arumugam Arunkumar , Myers Stephanie , Boopalan Thiyagarajan , Delgado Alejandro , Agullo Pamela , Lakshmanaswamy Rajkumar 
Published: June 2012

Abstract
Approximately 20-30% of all breast cancers overexpress the human epidermal growth factor receptor 2 (Her2). Breast cancers that overexpress Her2 have been associated with a more aggressive phenotype and decreased disease free survival. It has been demonstrated that uniparous Her2/neu transgenic mice developed smaller mammary tumors and these tumors had significantly decreased metastatic potential despite that this cancer type is phenotypically ER negative. We had earlier demonstrated that short-term treatment with pregnancy levels of estradiol was very effective in delaying tumor progression and decreasing tumor burden in activated Her2/neu transgenic mice. In this present investigation, we have attempted to understand the molecular mechanisms underlying this anti-tumor effect of short-term pregnancy levels of estradiol treatment against Her2/neu driven mammary carcinogenesis. Seven week old activated Her2/neu transgenic mice were treated for 3 weeks with 100micrograms of estradiol in silastic capsules. We have shown that this dose of estradiol treatment mimics pregnancy levels of the hormone in circulation. Control animals received empty silastic capsules for the same duration. Mice were palpated once every week for nine months to monitor the development of mammary cancer. Histopathological examination was performed to confirm the carcinomatous nature of the palpable tumors. A group (n=3) of mice were terminated from control and estradiol treated groups at 6 and 12 weeks post withdrawal of the treatment. Mammary tumors were excised, snap-frozen in liquid nitrogen and stored at -80 C. Protein and total RNA were extracted from these tissues. Pathway focused microarray analysis was done on the PI3K/AKT and P53 pathway. Results from the PI3K/AKT pathway demonstrate that, in estrogen treated mice, proteins and genes involved in tumor-suppression (Mtcp1,Rbl2,Srf and Ywhah) and immune response (Cd14,Tlr4) (which have been shown to play a role in reducing tumors by induction of apoptosis) were up-regulated. Many genes involved in promoting tumorigenesis were significantly down-regulated (Birc5,Ccnb2,Mdm2) while genes involved in cell cycle regulation and apoptosis were upregulated (Dapk1, Cul9, Sesn2).This trend in gene expression demonstrates that short-term pregnancy levels estrogen is altering key pathways leading to the delay and inhibition of Her-2 positive mammary cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5567. doi:10.1158/1538-7445.AM2011-5567
Abstract 5569: The association between statin use and risk of biochemical recurrence in men treated with radical prostatectomy in a cohort of men with inherited forms of prostate cancer
Authors: Ishak Miriam , Cooney Kathleen 
Published: June 2012

Abstract
Background: Evidence exists that statin medications are associated with decreased risk of advanced prostate cancer. The risk factors for prostate cancer are increasing age, African-American race and family history of the disease. To date, studies of the association between statin medication and risk of prostate cancer have not considered men with familial or hereditary prostate cancer.
Methods: Men enrolled in the University of Michigan Prostate Cancer Genetics Project (PCGP) who had been previously diagnosed with prostate cancer and treated with radical prostatectomy were surveyed as to their past and current statin medication use status, type of statin medication, duration of statin medication use and their incidence of biochemical recurrence. PCGP is a large, family-based study of inherited forms of prostate cancer. The PCGP enrollment criteria included families with two or more living-affected family members in a first-degree or second-degree relationship. The risk of biochemical recurrence (BCR) was modeled using logistic regression models and odds ratios and 95% confidence intervals were calculated.
Results: Of 595 unrelated men with past radical prostatectomy surveyed, 91 men experienced BCR. At time of survey, 40% of men were current statin users. Median follow-up time was 67 months for statin users was 75 months for non-statin users. Current statin-use at time of recurrence was associated with a decreased risk of BCR (OR = 0.685; 95% C.I.:0.438 – 1.072; p=0.09); while ever statin-use was not associated with risk of BCR in multivariate models adjusted for age and BMI.
Discussion: This represents the only study to date to assess statin medication use and the risk of biochemical recurrence in men with familial and hereditary prostate cancer. Given the importance of family history as a risk factor for prostate cancer, these findings should be confirmed in other studies and may implicate subgroups of men at risk for prostate cancer who may benefit from statin medication use.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5569. doi:10.1158/1538-7445.AM2011-5569
Abstract 5575: Tetrandrine blocks emergence of castrate resistant phenotype in prostate cancer by promoting apoptosis and sensitizing prostate cancer cells to androgen deprivation
Authors: Koul Sweaty , Koul Hari K. 
Published: June 2012

Abstract
Prostate cancer (PCa) is the second leading cause of cancer deaths in men, and the majority of prostate cancer deaths are a result of emergence of castrate resistant phenotype. One of the six hallmarks of cancer is resistance to apoptosis, and we hypothesized that resistance to apoptosis is in part responsible for emergence of castrate resistant phenotype in prostate cancer. Specifically we investigated the effects of Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the root of Stephania tetrandra, on apoptosis of PCa cells in vitro. TET decreased viability of PCa cells. Long-term treatment with TET resulted in a dramatic increase in sub G0/G1 cell population suggestive of apoptosis. Treatment with TET resulted in decrease in anti-apoptotic proteins (Bcl-xl and survivin) and concomitant activation of caspase 3 and PARP cleavage. Moreover, Tet treatment induced DNA fragmentation and nuclear condensation, all hallmarks of apoptosis. We also observed that pretreatment with Tet sensitized LNCaP cells to androgen depletion and prevented emergence of castrate resistant phenotype in vitro culture. Moreover, Tet induced apoptosis in LNCaP C-4 and C4-B (AR positive castrate resistant prostate cancer) cells, indicated effectiveness against established castrate resistant phenotypes in prostate cancer. These results show that Tet by promoting apoptosis of prostate cancer cells and by sensitizing prostate cancer cells to androgen depletion may serve as a chemopreventive/ therapeutic agent in prostate cancer. If these results hold true in additional in vivo studies, Tet may serve as a mechanism based agent against emergence of castrate resistant prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5575. doi:10.1158/1538-7445.AM2011-5575
Abstract 558: Targeting tumour heparanase activity using fully human monoclonal antibodies
Authors: Rathanaswami Palaniswami , Pan Oscar , Ross Sarah , King Chadwick , Foltz Ian N. , Elvin Paul 
Published: June 2012

Abstract
Modification of heparan sulfate proteoglycans (HSPG) in the tumour microenvironment can have a significant influence on tumour cell behavior, tumour growth and metastasis. HSPG play an important role in shaping the integrity of the extracellular matrix, and cell surface HSPG are determinants of cell-cell interactions and receptor function. Heparanase (Hpa1), an endoglycosidase, cleaves the glycosidic bonds within heparan sulfate domains resulting in HSPG with impaired or altered functionality. Elevated expression of heparanase has been correlated with disease progression and poor survival in a number of human cancers. Using Xenomouse™ technology and immunising with recombinant human Hpa1, we have generated fully human monoclonal antibodies that bind to heparanase with high affinity (&lt;100pM). A number of antibodies were shown to inhibit recombinant human, murine and cynomolgus heparanase activity in a HTRF (homogeneous time resolved fluorescence) heparan sulfate degradation assay with IC50s in the nM range (0.2-3nM) for human Hpa1. The antibodies also inhibited cell surface localised heparanase activity and appeared to interfere with secretion and activation of heparanase. Targeting heparanase activity with an inhibitory therapeutic antibody may be a promising alternative strategy to the use of heparan sulfate mimetics.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 558. doi:10.1158/1538-7445.AM2011-558