bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1782: Recombinant B7-DCIg enhances Bacillus Calmette-Guérin (BCG)-induced Th1 and anti-bladder cancer immune responses in vitro and in vivo
Authors: Henning Jonathan R. , Knudson Matthew J. , Langermann Sol , O'Donnell Michael A. , Liu Linda , Luo Yi 
Published: August 2014

Abstract
Introduction and Objective: B7-DCIg, AMP-224, is a recombinant Fc fusion protein composed of the extracellular domain of B7-DC fused to the hinge and Fc domain of IgG. B7-DCIg interacts with PD-1, reduces the dysfunctional CD8+ T cells, and promotes an effective antitumor response. In vitro M. tuberculosis stimulation of human PBMC upregulates PD-1 expression in T cells. We proposed to test if B7-DCIg could enhance BCG-induced anti-bladder cancer immune responses.
Methods: For in vitro evaluation of B7-DCIg on BCG induction of immune responses, mouse splenocytes were prepared and cultured in the absence or presence of Pasteur strain BCG and/or different doses of B7-DCIg for 3 days, followed by ELISA analysis of interferon gamma (IFN-γ) in culture supernatants. For in vivo evaluation of B7-DCIg on BCG induction of immune responses, mice were treated twice weekly with intravesical (i.b.) PBS plus intraperitoneal (i.p.) PBS, i.b. BCG (0.1 OD/dose) plus i.p. IgG2a (400 μg/dose), or i.b. BCG (0.1 OD/dose) plus i.p. B7-DCIg (400 μg/dose). The bladders were collected after treatments 2, 4 and 6, and analyzed for IFN- γ as well as other mRNAs by RT-PCR. ImageJ software was used to quantify PCR products on agarose gels. To evaluate the effect of B7-DCIg on BCG treatment of bladder cancer, C57BL/6 mice were implanted i.b. with luciferase-expressing MB49 (MB49-Luc) bladder cancer cells at day 0 and treated with i.b. BCG (0.1 OD/dose) plus i.p. B7-DCIg (400 μg/dose) twice weekly starting at day 1 for a total of 6 treatments. Control mice were treated with i.b. PBS plus i.p. PBS or i.b. BCG plus i.p. IgG2a. Bioluminescence was measured with Xenogen IVIS imaging at days 7, 14, and 21. At day 23 mice were euthanized and bladder weights measured.
Results: B7-DCIg enhanced BCG-induced splenocyte IFN- γ production in a dose-dependent manner in vitro. B7-DCIg also enhanced BCG-induced bladder expression of IFN- γ and tumor necrosis factor related apoptosis-inducing ligand (TRAIL) mRNAs in vivo. In the orthotopic tumor model, BCG treatment reduced bladder weight by 53% (p = 0.0503 vs. PBS-treated group). Combination of BCG with B7-DCIg further reduced bladder weight by 5% (p = 0.0257 vs. PBS-treated group). In addition, the combination treatment also led to a delay in tumor growth by bioluminescence compared to BCG-treated group.
Conclusions: B7-DCIg enhanced BCG-induced Th1 and anti-bladder cancer immune responses in mice. B7-DCIg may serve as a potential agent in combination with BCG for the treatment of bladder cancer in humans.
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 1782. doi:10.1158/1538-7445.AM2011-1782
Abstract 1784: Comparing genetically engineered T cells for chimeric TCR versus CD16 + Herceptin for adoptive immunotherapy against HER2 positive breast carcinomas
Authors: Valsesia-Wittmann Sandrine , Clemenceau Béatrice , Jallas Anne-Catherine , Valladeau Jenny , Rousseau Raphael , Blay Jean-Yves , Caux Christophe , Vie Henri 
Published: August 2014

Abstract
The HER2 receptor is overexpressed in 25% of breast cancers and is associated with poor prognosis. Herceptin, a monoclonal antibody targeting HER2 has been demonstrated to improve survival of HER2 overexpressing metastatic breast cancer. However, majority of patients who initially respond to Herceptin develop resistance within one year of treatment initiation, and in the adjuvant setting 15% of patients relapse after 5 years despite Herceptin-based therapy.
The goal of this project is to develop and compare efficiency of two adoptive immunotherapy approaches by genetically engineered T cells to overcome this resistance. For the first approach, we developed T lymphocytes armed with an anti-HER2 chimaeric TCR (CAR-CTL) to directly kill the HER2 positively cells.
For the second approach, we developed T lymphocytes armed with a high affinity IgG FcR (FcγRIIIα, CD16) linked to its transduction chain FC∈RIγ (CD16/γ). In this latter case, the HER2 antigen is pre-targeted by Herceptin Ab to induce a “two step killing” through Antibodies Dependant Cellular Cytotoxicity (ADCC).
Results obtained in vitro demonstrated the high direct killing efficiency of anti-HER2 chimaeric TCR CTL against HER2 amplified breast carcinoma cells BT474 or SKBR3 (&gt;75%). However, abnormal reactivity of these CTL against cells with low to undetectable HER2 expression was observed (15 to 30% of lysis). This constitutive non specific activation of chimaeric TCR might represent an important limitation point for clinical use.
On the other hand, “two step killing” with CD16/γ-CTL demonstrated a very specific cytotoxicity against HER2 positive cells through ADCC only in the presence of Herceptin. We demonstrated that efficacy of specific lysis is linked to levels of CD16/γ expression and appeared independent of HER2 targeted antigen level.
We are comparing in vivo efficacy of both approaches (“one step” TCR vs “two step”ADCC) to induce regression of HER2 + or – breast carcinoma xenograft in immunodeficient mice model NOD-SCID mβ2-/-. Our last results will be presented. Because the alteration of ADCC mechanisms during Herceptin treatment is one rational explanation for the acquired resistance, improving effectors might represent a safe adjuvant treatment to prevent resistance.
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 1784. doi:10.1158/1538-7445.AM2011-1784
Abstract 1855: Maternal consumption of long chain omega 3 fatty acids decreases risk for mammary gland cancer in the female C(3)1 TAg mouse
Authors: Ion Gabriela , Akinsete Juliana A. , Witte Theodore R. , Hardman W. Elaine 
Published: August 2014

Abstract
Omega 3 fatty acids have been shown to reduce incidence and slow growth of mammary gland cancer in rodent models. Omega 3 fatty acids in the maternal diet are important for normal fetal brain, eye and nervous system development. Since exposure to dietary components during the critical developmental times of gestation and lactation may alter risk for mammary gland cancer in females, we tested whether exposure to increased levels of long chain omega 3 fatty acids (from fish oils) would be preventive or promotional to mammary gland cancer in the offspring. Normal SV40 female mice were fed AIN 76 diets containing either 10% corn oil (control) or 5% of an omega 3 fatty acid concentrate + 5% canola oil. Females were then mated with C(3)1 TAg transgenic mice. Transgene hemizygous offspring were the experimental mice not the original SV40 female mice. On a normal diet the hemizygous mice are expected to have about 100% tumor incidence by 150 days of age. At weaning (3 weeks) pups were randomized to either the corn oil or the fish oil diet, 15-17 mice per group. At 140 days of age, mice never exposed to fish oil (C/C group) had a significantly higher incidence and multiplicity of mammary gland tumors than mice exposed to fish oil throughout life (F/F group). Mice exposed to fish oil during a portion of life (C/F or F/C) had intermediate incidences and multiplicities. Interestingly, omega 3 in the maternal diet alone decreased tumor multiplicity by 50% compared to no omega 3, even when the mouse received a control diet after weaning. If a mouse, developed a tumor the mean tumor masses were not significantly different though the F/F group had a much smaller mean tumor mass. Adequate omega 3 fatty acids in the maternal diet may reduce risk for mammary gland cancer in the offspring.
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 1855. doi:10.1158/1538-7445.AM2011-1855
Abstract 1857: Src: A novel target for chemoprevention of early stage ER- breast cancer
Authors: Jain Shalini , Shah Maitri , Li Ping , Wang Qingfei , Zhang Siyuan 
Published: August 2014

Abstract
Selective ER modulators (SERMs) have shown significant efficacy for the prevention of ER-positive breast cancer, however, SERMs are not effective for patients whose tumors do not express ER. Therefore, novel agents are needed for prevention and intervention of high risk ER-breast cancers. The c-Src plays a pivotal role in the progression of EGFR- and HER2-dependent ER negative breast cancer. Thus, targeting Src using agents with minimal toxicity or in combination with other novel agents may prevent/intervene progression of early stage ER- breast cancer. In this study we used Saracatinib (AztraZeneca), a Src inhibitor well-tolerated in phase II clinical trials. We examined the effect of Src inhibition using Saracatinib alone or with other agents for cancer prevention using human mammary epithelial pre-malignant cell lines (MECs) and MMTV-neu mouse model. The MCF10A MECs stably overexpressing ErbB2 (10A.ErbB2 cells) form irregular (grape-like) acini in 3D culture condition. Saracatinib treatment prevents the progression of abnormal 3D acini growth as well reverses the abnormal 3D acini growth of 10A.ErbB2 cells to normal phenotype. Our reverse phase protein array data showed that Saracatinib induces the expression of cell cycle inhibitors and apoptosis related molecules, e.g. P27kip1, RAR beta, and PDCD4. Our 3D acini confocal microscopy experiment showed that it induces luminal apoptosis and suppresses cell proliferation in 10A.ErbB2 cells as detected by activated caspase-3 and ki-67 staining respectively. Next, we used MMTV-neu mouse model which develop ER negative lesions at early stage, to examine correlation between Src activation and ER negative mammary cancer progression. MMTV-neu mice mammary lesions exhibited super-activated Src which were negatively associated with estrogen receptor (ER) expression. Our preliminary data showed that Saracatinib-containing regimen inhibited MMTV-neu mice mammary lesions. Our study demonstrated that targeting Src by Saracatinib may be effective for the chemoprevention of early stage ER negative breast 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 1857. doi:10.1158/1538-7445.AM2011-1857
Abstract 1861: PPAR γ mediated involucrin induction in aerodigestive preneoplasia in vitro
Authors: Rosas Rolando R. , Handley Nathan R. , Gaffney Patrick M. , Wuertz Beverly R. , Ondrey Frank G. 
Published: August 2014

Abstract
Effective prevention and monitoring of head and neck malignancy is a critical component of disease control which is significantly underdeveloped. Currently, no validated biomarkers or therapies for human aerodigestive preneoplasia exist. We have increasing interest in PPARγ mediated therapy for oral leukoplakia reversal based on our preliminary clinical trial results. Involucrin expression is associated with squamous differentiation and we hypothesize involucrin would be involved with PPARγ upregulation in differentiation therapies.
In our present study we examined the use of involucrin as marker of PPARγ activity in response to treatment and effect of bexarotene on pioglitazone mediated PPARγ activation in oral leukoplakia. In an analysis of an Affymetrix database of human head and neck tumors (41 tumors compared to 13 normal oral mucosa samples), we found involucrin is expressed 5.6fold higher in normal versus tumor samples (P&lt;0.0001). We found pioglitazone upregulates PPARγ DNA binding activity and involucrin promoter activity via reporter gene assay. Bexarotene positively effects pioglitazone upregulation of these genes via reporter gene assay and increases protein expression via western blot analysis We conclude the PPARγ activator, pioglitazone, can activate involucrin, which may be useful in upregulating differentiation in oral preneoplasia in clinical trialsin combination with bexarotene. Also involucrin has potential use as a biomarker of disease response to treatment.
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 1861. doi:10.1158/1538-7445.AM2011-1861
Abstract 1866: (−)-Epigallocatechin gallate suppresses azoxymethane-induced colonic preneoplastic lesions in rats by inhibiting the expression and activation of indoleamine 2,3-dioxygenase
Authors: Ogawa Kengo , Hara Takeshi , Shimizu Masahito , Tsurumi Hisashi , Tanaka Takuji , Moriwaki Hisataka 
Published: August 2014

Abstract
Immune escape is involved in the development and progression of several types of tumors. Indoleamine 2,3-dioxygenase (IDO) plays a critical role in the induction of immune tolerance. (−)-Epigallocatechin gallate (EGCG), the major biologically active component of green tea, exerts cancer chemopreventive and anti-carcinogenic effects in various organs. In the present study, we examined the effects of EGCG and 1-methyl-tryptophan (1-MT), an IDO inhibitor, on the development of azoxymethane (AOM)-induced colonic preneoplastic lesions in F344 rats by focusing on the inhibition of IDO activation. To induce colonic premalignant lesions, male F344 rats were given two weekly subcutaneous injections of AOM (20 mg/kg body weight). They also received drinking water containing 0.1% EGCG or 0.2% 1-MT for 4 weeks, starting 1 week before the first dose of AOM. At sacrifice, drinking water with EGCG and 1-MT significantly decreased the total number of aberrant crypt foci and β-catenin accumulated crypts, which overexpresses IDO protein, compared with the control untreated-rats. Drinking EGCG decreased the expression levels of IDO mRNA on the colonic mucosa of experimental rats. In addition, the enzyme activity of IDO, which was estimated by measuring the serum concentration of kynurenine and tryptophan, was also significantly inhibited by treatment with EGCG and 1-MT. These findings suggest that the up-regulation of IDO is associated with colon carcinogenesis and EGCG prevents this carcinogenesis by inhibiting the expression and activation of IDO. Targeting IDO by using EGCG or IDO inhibitor might be, therefore, a promising strategy for the prevention of colon 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 1866. doi:10.1158/1538-7445.AM2011-1866
Abstract 1870: Green tea polyphenol EGCG upregulates mir-210 expression in lung cancer cells by transiently stabilizing HIF1α
Authors: Wang Hong , Bian Shengjie , Yang Chung S. 
Published: August 2014

Abstract
Epigallocatechin-3-gallate (EGCG) has been reported to affect many cellular regulatory pathways. This study aims to determine whether EGCG could target microRNA, one of the mechanisms for cells to achieve subtle change in multiple targets. We found that, in both human and mouse lung cancer cells in culture, EGCG specifically upregulated the expression of mir-210, a major microRNA regulated by HIF1α. Furthermore, we found that overexpression of mir-210 led to reduced cell proliferation rate and anchorage-independent growth as well as reduced sensitivity to EGCG. To explore the mechanisms of mir-210 regulation by EGCG, we demonstrated that the regulation was mediated through hypoxia-response element in mir-210 promoter. Consistently, the upregulation of mir-210 was found to be correlated with the transiently stabilized HIF1α in lung cancer cell lines after EGCG treatment. Such stabilization was further shown by the stabilization of HA-tagged HIF1α, but not the P402A/P564A mutated HIF1α, by EGCG, suggesting that EGCG targets the oxygen-dependent degradation (ODD) domain. Direct evidence was obtained by affinity binding assay showing that EGCG specifically binds HIF1α with a Kd=3.47 μM. This result implies that EGCG binding interferes with the hydroxylation of key Pro residues in the ODD domain, preventing HIF1α from the Pro hydroxylation-induced ubiquitination and subsequent proteosome-mediated degradation. In summary, our results demonstrate the elevation of mir-210 by EGCG and this is mediated by the stabilization of HIF1α. This event may contribute to the anti-cancer activity of EGCG (Supported by NIH grant CA 122474 and CA133021).
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 1870. doi:10.1158/1538-7445.AM2011-1870
Abstract 1872: A prospective cohort study of shift work and pancreatic cancer risk in Japanese men
Authors: Lin Yingsong , Kikuchi Shogo , Yagyu Kiyoko , Kurosawa Michiko , Tamakoshi Akiko 
Published: August 2014

Abstract
The etiology of pancreatic cancer remains largely unknown. The lack of effective screening tools coupled with the dismal prognosis make it crucial to identify modifiable risk factors that can be incorporated into a prevention strategy for pancreatic cancer. Approximately 15-20% of the working population in industrialized countries engages in night-shift work, drawing considerable interest in the effect of such work patterns on health, including on the formation of cancers. We analyzed data from a large-scale, prospective cohort study of middle-aged and elderly Japanese individuals (the JACC Study) to test the hypothesis that rotating shift work might be associated with an increased risk of pancreatic cancer. Our analysis was restricted to 18,745 men who were 40-60 years of age at baseline (1988-1990) and who reported working full-time or were self-employed. Information on occupation and lifestyle factors was collected using a self-administered questionnaire. Mortality from pancreatic cancer was ascertained from the causes of death recorded on death certificates. The Cox proportional hazards model was used to estimate relative risk (RR) and confidence interval (CI) for the association between shift work and pancreatic cancer risk. A total of 70 pancreatic cancer deaths were observed until Dec 31, 2008. Overall, we found no statistically significant increase in the risk of death from pancreatic cancer associated with rotating shift work. As compared to day-shift workers, the RRs were 0.89 (95%CI: 0.40-1.96) for rotating shift workers and 0.27 (0.04-1.93) for fixed night-shift workers, after adjustment for potential confounding factors. In conclusion, shift work is not associated with the risk of death from pancreatic cancer in this cohort of Japanese men.
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 1872. doi:10.1158/1538-7445.AM2011-1872
Abstract 1873: Low-dose radiation exposure and the risk of developing acoustic neuroma
Authors: Han Yueh-Ying , Berkowitz Oren , Donovan Maryann , Talbott Evelyn 
Published: August 2014

Abstract
Aside from the rare hereditary syndrome of Neurofibromatosis type 2 or high-dose ionizing radiation exposure, the causes of the vast majority of acoustic neuroma development remain unclear. A hospital-based case-control study was conducted to investigate the roles of exposure to commonly used diagnostic tools and phone technology that emit low dose ionizing and non-ionizing radiation in the etiology of acoustic neuroma.
A total of 353 cases were recruited from a cohort of individuals who underwent Gamma Knife Radiosurgery as primary or adjuvant management of acoustic neuroma between the years 1997-2007 at the Center for Image Guided Neurosurgery, University of Pittsburgh Medical Center (UPMC). Matched by age and gender, 353 controls without brain tumor history were recruited from the Neurosurgery spine and pain clinics at UPMC. Information on demographic characteristics, medical exposure to radiation, use of cell phone, and other potential risk factors of acoustic neuroma were collected via questionnaire by trained interviewers at clinics. Conditional multivariate logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to assess risk of acoustic neuroma associated with low-dose radiation exposure.
Adjusted for education, smoking, drinking, occupational exposure to noise, previous history of head injury, and family history of cancer, exposure to dental x-ray every 2-3 years and at least once a year was significantly associated with development of acoustic neuroma compared to individuals exposed to dental x-ray less than once every five years (OR=3.57, 95% CI = 1.54-8.23 and OR=2.31, 95% CI=1.06-5.04, respectively). History of full mouth or panorax X-ray exam (OR=1.35, 95% CI=0.76-2.41), CAT or CT scan of head or neck (OR=0.61, 95% CI=0.30-1.23), and other X-ray exam of head or neck (OR=0.77, 95% CI=0.41-1.45) were not found to be related to development of acoustic neuroma. Use of cell phones or cordless phones for more than 10 years was not significantly associated with development of acoustic neuroma (OR=1.30, 95% CI=0.53-3.20 and OR=1.20, 95% CI=0.43-3.37, respectively).
We found that frequent exposure to dental X-rays may contribute the development of acoustic neuroma, although does-response effect was not found. Further epidemiologic studies are necessary to confirm the association of diagnostic dental X-rays exposure and development of acoustic neuroma.
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 1873. doi:10.1158/1538-7445.AM2011-1873