bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5523: Cost effectiveness of implementing a screening and treatment program for hepatitis C virus infection in Egypt
Authors: Kim David D. , Hutton David W. , Raouf Ahmed A. , Salama Mohsen , Hablas Ahmed , Seifeldin Ibrahim A. , Soliman Amr S. 
Published: August 2012

Abstract
Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) infection in the World. We estimated the cost-effectiveness of implementing a screening and treatment program for HCV infection among Egyptians. We developed a Markov decision analysis model of the natural history of HCV infection and treatment to evaluate cost-effectiveness of screening and treatment for asymptomatic average-risk Egyptian adults. We used HCV age-specific disease progression rates and prevalence for Egyptians. Lifetime costs of screening, treatment, disease progression, and health utilities have been used with 3% annual discounting. We used a societal perspective, local cost estimates, quality-adjusted life years (QALYs) gained, and calculated the incremental cost-effectiveness ratio of a hypothetical program of screening and treating Egyptians for HCV versus no screening. We conducted sensitivity analysis to test uncertainty in the model assumptions. Under base case assumptions, implementing the program for a 40-year-old, asymptomatic Egyptian adult would cost $1,856 for 19.192 QALYs, while non-screening would cost $1,807 for 19.164 QALYs for the 40 year time horizon. The incremental cost-effectiveness ratio (ICER) is $1,750/QALY (equivalent to about 10,392 LE, Egyptian pound/QALY). If applied to the population of 10-60 years old individuals, this program would lead to long-term costs of 2.15 billion dollars, but save one million life-years. Results were the most sensitive to change in disutility by being identified as HCV-positive after screening as well as the probability of receiving treatment after HCV positive diagnosis and probability of successful treatment. Comparing this model to international standards for cost-effectiveness, implementing a screening and treatment program for HCV in Egypt is very cost-effective. Therefore, we recommend implementing this program to reduce the burden of liver disease in Egypt.
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 5523. doi:1538-7445.AM2012-5523
Abstract 5524: Prostate cancer risk assessment model (PCRAM): a scoring model based on the Swedish Family-Cancer Database
Authors: Roudgari Hassan , Hemminki Kari , Brandt Andreas , Sundquist Jan , Fallah Mahdi 
Published: August 2012

Abstract
Background: Many prostate cancer (PC) risk assessment models have been developed, however almost none include familial history. We aimed to produce a risk assessment model for PC based on familial background of related cancers. Method: 976,859 independent index men aged &gt;=30 in year 1998 and their family members in the Swedish Family-Cancer Database (FCD 2010) were randomly divided into the development (60%) and the validation (40%) datasets (follow-up=10 years). The hazard ratio from Cox model for personal and family history was used to extrapolate risk scores. Results: Specified scores were for PC in situ at age&lt;60 years in index man, 5; PC at age&lt;60 in each first-degree relative (FDR), 15; PC at age&gt;=60 in each FDR, 10; PC at age&lt;60 in each second-degree relative, 5; breast cancer in each FDR, 2; oesophageal carcinoma in situ in index man, 2; and oesophagus cancer in each FDR, 2. The curve for score-group 26+ showed a sharp increasing slope from age 60-65 onward. The score-group 21-25 showed 15-40 times higher risk than the general population at age 38-45; ratio decreased to four-folds by age 60, and stayed about 3.5-times thereafter. The score-group 16-20 showed 10-fold increased risk at age&lt;=41; risk ratio 4-6 at age 42-54; and 2.5-3.5-fold thereafter. The curves for score 0-5 and population risk almost overlapped. Based on our findings, if the milestone age for a prostate cancer screening program was 60 years or more, the recommended starting age for the men with the score-group 6-10 would be 54 years; score-group 11-15, 52 years; score-group 16-20, 50 years; score-group 21-25, 44 years; and for the score-group 26+ it should start before age 40. The concordance index in both the development and the validation sets was 0.885 (95% CI=0.883-0.888). No significant difference was found between curves from the development and the validation datasets (internally-validated using two-fold validation and bootstrapping). Conclusion: Familial history of relevant malignancies can be used as risk factors to estimate a man's prior risk of developing prostate cancer. PCRAM could satisfactorily assess risk of developing 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 5524. doi:1538-7445.AM2012-5524
Abstract 5536: TP53 and MED12 mutations in uterine smooth muscle tumors
Authors: Kuhn Elisabetta , Yemelyanova Anna , Wang Tian-Li , Kurman Robert , Shih Ie-Ming 
Published: August 2012

Abstract
Most uterine smooth muscle tumors can be broadly subdivided into two groups: benign leiomyoma (including variant subtypes) and leiomyosarcoma based on cytologic atypia, mitotic activity and coagulative tumor cell necrosis. A small number defies classification into unequivocally benign and unequivocally malignant categories. These tumors, classified as “atypical leiomyoma” and “STUMP” (Smooth muscle Tumors of Uncertain Malignant Potential), generally behave in a benign fashion. Although p53 overexpression, as determined by immunohistochemical staining, has been reported in the atypical group and the leiomyosarcomas, it is uncertain whether they harbor TP53 mutations. In addition, a recent study has reported mutations in the mediator complex 12 (MED12) gene in the majority of benign uterine leiomyomas. We therefore performed a mutational analysis of uterine smooth muscle tumors to determine their TP53 and MED12 mutation status, in order to better understand their molecular genetic characteristics. A total of 9 uterine conventional leiomyomas, 27 atypical leiomyomas and 12 leiomyosarcomas from 40 patients were analyzed. DNA samples were sequenced and TP53 (from exons 4 to 9) and MED12 (exon 2) mutations were analyzed. Clinico-pathological data were collected. TP53 mutations were detected in 17 (63%) of 27 atypical leiomyomas and 8 (67%) of 12 leiomyosarcomas. MED12 mutations were identified in 6 (67%) of 9 conventional leiomyomas, 7 (26%) of 27 atypical leiomyomas and 1 (8%) of 12 leiomyosarcomas. Follow-up was available in 30 patients. None of the patients with atypical leiomyoma had recurrence or died of her disease (average follow-up 23 months). Seven patients with leiomyosarcoma, 4 of whom had TP53 mutations, died of their disease (average follow-up 42 months). The preliminary findings of this study indicate that the presence of TP53 mutations in uterine smooth muscle tumors is not sufficient to drive malignant behavior. Moreover, based on the presence of a MED12 mutation in one case of leiomyosarcoma, we postulate that at least some leiomyosarcomas develop from benign leiomyomas. Future correlated molecular genetic and clinicopathologic studies with a larger number of cases and long-term follow-up information are necessary to confirm this important finding.
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 5536. doi:1538-7445.AM2012-5536
Abstract 5538: Development of RNA quality control methods to improve BCR-ABL measurement in whole blood samples
Authors: Stanoszek Lauren M. , Crawford Erin L. , Blomquist Thomas , Willey Paige , Willey James C. 
Published: August 2012

Abstract
Measurement of BCR-ABL fusion transcripts in whole blood by quantitative, reverse-transcriptase PCR is a clinically validated method to monitor treatment response in patients with chronic myelogenous leukemia. For example, achieving a three-log or greater reduction in BCR-ABL expression from baseline is considered a Maximum Molecular Response (MMR). A 0.5-log increase from MMR signifies treatment failure sufficient to motivate change in treatment. The purpose of this study was to develop a BCR-ABL test with improved analytical performance characteristics including adequate quality control for RNA degradation or reverse transcription interference and reliable comparison of results across testing sites. To test whether RNA degradation could mask a 0.5-log increase in expression, an RNA degradation model was established by incubating whole blood from each of six individuals with K562 cells at room temperature for various times post-venipuncture. When data from six subjects were combined, the BCR-ABL/103 GUSB value trended down at 24h but was not significantly decreased until 48h (51% decrease, p = 0.004). To quantify the amount of whole blood RNA that can be loaded into an RT reaction without reducing RT efficiency, six different amounts of total RNA extracted from whole blood mixed with K562 cells were added into RT reactions. To measure RT efficiency, an RT Standards Mixture (RTSM) containing known copy numbers of External RNA Control Consortium (ERCC) 171 RNA and ERCC 113 cDNA was added to each RT reaction. RT efficiency was measured as the yield of PCR product from ERCC 171 RNA relative to ERCC 113 cDNA. Based on data from three subjects, compared to RT efficiency at reference concentration of 30 ng/µl RNA in RT, there was a 35% decrease (p = 0.043) at 167 ng/μl RNA and 82% reduction at 1000 ng/μl RNA. The maximum yield of BCR-ABL (molecules/μL cDNA) was observed at 300 ng/µl RNA/RT with a 3-fold increase (p=0.003) compared to 30 ng/µl RNA. Greater than 300 ng/µl RNA/RT did not further increase yield of BCR-ABL molecules/μL cDNA, likely due to reduced RT efficiency. We conclude that BCR-ABL/103 GUSB should be measured within 24 hours following blood collection. Because decreasing RT efficiency is associated with increasing RNA input into RT reactions, including 300 ng/µl RNA in RT reactions provides the maximum sensitivity in measuring BCR-ABL expression.
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 5538. doi:1538-7445.AM2012-5538
Abstract 5682: Modeling the pharmacological importance of endoxifen for the treatment of ER-positive breast cancer in premenopausal patients
Authors: Maximov Philipp Y. , McDaniel Russell E. , Jordan V. Craig , Brauch Hiltrud 
Published: August 2012

Abstract
Long term adjuvant tamoxifen therapy for five years is the antiestrogenic standard of care for ER-positive breast cancer in premenopausal patients. The metabolic activation of tamoxifen by CYP2D6 to endoxifen remains controversial to plan the treatment of patients with breast cancer. However, all retrospective studies focus entirely on postmenopausal patients and no studies have been undertaken in the relevant premenopausal treatment population. We have addressed the issue of the pharmacological importance of endoxifen to control the estrogen-stimulated growth of four ER-positive breast cancer cell lines (MCF-7, T47-D, BT-474 and ZR-75). We have modeled the actual estrogen environment in the laboratory (estradiol plus estrone) based on previous data from premenopausal patients taking tamoxifen (Jordan et al, JNCI 2001; 83:1488-91). Our strategy was to evaluate the anti-proliferative actions of actual concentrations of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen combined, based on the actual measurements reported for these metabolites in patients who were extensive metabolizers (EM), intermediate metabolizers (IM) or poor metabolizers (PM) (Mürdter et al, Clin Pharmacol Ther 2011; 89:708-17). These data were then compared with similar anti-proliferative experiments in the four cell lines, using endoxifen obtained from four sources (Mayo Clinic, University of Indiana, Institut für Klinische Pharmakologie (IKP) and the Fox Chase Cancer Center). Each cell line was evaluated with the clinically relevant circulating levels of estrogen, with and without the inclusion of the different endoxifens at the published concentrations from EM, IM and PM. It is important to note that all synthetic endoxifen currently available is an impure mixture of geometric isomers. Therefore, results obtained are only an estimate of the efficacy of endoxifen in the patient. To address this issue, we have specifically synthesized the appropriate isomer of endoxifen as a fixed ring compound that can no longer isomerize. We have previously used this strategy to discover the actual pharmacology of the two geometric isomers of 4-hydroxytamoxifen (Murphy et al, Mol Pharm 1990; 38:737-43). The results demonstrate the essential requirement with the appropriate concentration of endoxifen necessary to block estrogen-mediated cell replication. Acknowledgements: This work (VCJ) was supported the subcontract under the SU2C (AACR) Grant number SU2C-AACR-DT0409; the Susan G Komen For The Cure Foundation under Award number SAC100009.
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 5682. doi:1538-7445.AM2012-5682
Abstract 5684: Sustained gene silencing by liposomal siRNA incorporated mesoporous silicon particles
Authors: Rodriguez-Aguayo Cristian , Shen Haifa , Deng Xiaoyong , Gonzalez-Villasana Vianey , Sakamoto Jason , Han Hee-Dong , Sood Anil K. , Ferrari Mauro , Lopez-Berestein Gabriel 
Published: August 2012

Abstract
The use of small interfering RNA (siRNA) technology has rapidly become an attractive revolutionary tool in silencing gene expression and holds potential as a therapeutic strategy in cancer and other diseases. However, for siRNA-based therapeutics to become a reality, an efficient method for in vivo systemic delivery is needed. Here, we demonstrate effective and sustained delivery of siRNA using mesoporous silicon particles (MSP). We first developed a novel variant of multistage MSP by tuning the size and shape properties, which can load dioleoyl phosphatidylcholine (DOPC) nanoliposomes containing siRNA. To test this concept, we targeted EphA2 oncoprotein, which is highly overexpressed in most cancers such as breast, lung, pancreas and ovarian carcinoma. MSP incorporated with EphA2 siRNA-DOPC (MSP-siEphA2-DOPC) resulted in effective gene silencing for up to 15 days after single i.v. injection into mice bearing either SKOV3ip1 or HeyA8.MDR ovarian tumors in the peritoneal cavity. In addition, with a single injection of MSP-siEphA2-DOPC given every 15 days during 6 weeks of treatment, there was significant reduction (83%, P** 0.0032, 64%, P* 0.028, 36%, P, ns 0.0032) of tumor weight and number of nodules in a dose dependent manner (15,10 and 5 µg/mice) respectively compared with control groups. Furthermore, when we administrated MSP-siEphA2-DOPC in combination with either paclitaxel or docetaxel, we observed 87% and 91% tumor reduction compared to the control group respectively. Taken together, MSP-siEphA2-DOPC provides a new approach for sustained release of siRNA into disease sites without repetition of injection.
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 5684. doi:1538-7445.AM2012-5684
Abstract 5700: Preparation and evaluation of glycosylated paclitaxel loaded in tastuzumab-immunoliposome
Authors: Murakami Masaharu , Kasai Tomonari , Okada Masashi , Mikuni Katsuhiko , Egashira Naoyoshi , Seno Masaharu , Hamada Hiroki 
Published: August 2012

Abstract
Targeted drug delivery is considered to enhance the therapeutic effects of anti-cancer agents because high amount could be administered with least side effects. However, water-insoluble hydrophobic chemical compounds such as paclitaxel are not suitable for efficient drug delivery. We conferred water-solubility of paclitaxel by coupling glucose at 7-OH to produce 7-alpha-glucosyloxyacetylpaclitaxel (7-GLG-PT). Although the 7-GLG-PT showed lower cytotoxicity than paclitaxel, encapsulation of 7-GLG-PT into liposomes was more efficient than that of paclitaxel. In our experiment, paclitaxel encapsulated liposomes was not detectable. Trastuzumab was then conjugated on the surface of 7-GLG-PT liposomes to prepare immunoliposome (GLG-PT-IL). The GLG-PT-IL exhibited cytotoxicity on SK-BR-3 cells overexpressing HER2. The IC50 values of paclitaxel, 7-GLG-PT, 7-GLG-PT liposome and GLG-PT-IL were 6, 126, 130 and 94 nM, respectively. From this evaluation, the concentration of each formula to suppress the cell growth completely was estimated around 30 to 300 nM. At these concentrations, the time required for each formula to suppress the growth at the half maximal level was evaluated. GLG-PT-IL showed the shortest time of 5 hours, which was one third of the others when compared with paclitaxel, 7-GLG-PT and 7-GLG-PT liposome. The specific targeting potential of the immunoliposome on SK-BR-3 cells was assessed. The accumulation on the cell surface was competitively inhibited by the excess amount of free tastuzumab. The endocytosis of the immunoliposomes was simultaneously confirmed by time-lapse imaging. Thus GLG-PT-IL has been successfully demonstrated to target the HER2-overexpressing cancer cells specifically suppressing their growth. Trastumab itself is considered to induce the antibody dependent cellular cytotoxicity, so that the endocytosis of HER2 may not be always necessary. However, HER2-mediated endocytosis was induced by the immunoliposomes while single trastuzumab did not show the endocytosis in SK-BR-3 cells. In this context together with the results demonstrated in this study, the 7-GLG-PT immunoliposome should be a promising candidate of highly efficient drug delivery system of cancer treatment targeting HER2.
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 5700. doi:1538-7445.AM2012-5700
Abstract 5714: Combination of glucagon-like-peptide-1 (GLP-1) receptor targeted therapy with anti-angiogenic compounds in a mouse model of neuroendocrine tumors
Authors: Wicki Andreas , Wild Damian , Orleth Annette , Rochlitz Christoph , Mamot Christoph , Christofori Gerhard 
Published: August 2012

Abstract
Neuroendocrine tumors are well vascularized and express specific cell surface markers, such as somatostatin receptors and glucagon-like peptide-1 receptors (GLP-1R). Using the Rip1Tag2 transgenic mouse model of pancreatic neuroendocrine tumors, we have investigated the potential benefit of a combination of anti-angiogenic treatment with targeted internal radiotherapy. To this end, [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4, a radiopeptide that selectively binds to GLP-1R expressed on insulinoma and other neuroendocrine tumor cells, was co-administered with PTK787, an inhibitor of vascular endothelial growth factors (VEGFR). For biodistribution, Rip1Tag2 mice were pre-treated with PTK787 for 0, 3, 5 or 7 days. Subsequently, [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 was administered and the biodistribution assessed after 4 hours. For therapy, mice were injected with 1.1 MBq [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 and treated with PTK787 orally for another 7 days. Tumor volume, tumor cell apoptosis and proliferation, and microvessel density were quantified. Combination of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 and PTK787 was significantly more effective than single treatments (p&lt;0.05) and reduced the tumor volume by 97% in the absence of organ damage. Pre-treatment of mice with PTK787 led to a reduction in the tumor uptake of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4, indicating that concomitant administration of PTK787 and the radiopeptide was the best approach. Thus, combination of targeted radionuclide therapy with an anti-angiogenic compound inhibiting VEGF signaling had a synergistic effect on therapy efficacy. The combination of 1.1 MBq of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 with PTK787 had the same effect on a neuroendocrine tumor as the injection of 28 MBq of the radiopeptide alone, but without any apparent side-effects, such as radiation damage of the kidneys.
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 5714. doi:1538-7445.AM2012-5714
Abstract 5729: The Wnt transcription factor TCF4 mediates resistance of colorectal cancer cells to (chemo-) radiotherapy in a β-catenin-independent manner
Authors: Grade Marian , Eimer Christine , Emons Georg , Kendziorra Emil , Spitzner Melanie , Gaedcke Jochen , Wolff Hendrik , Beissbarth Tim , Ried Thomas , Pukrop Tobias , Ghadimi Michael 
Published: August 2012

Abstract
Background: We recently demonstrated that the Wnt transcription factor TCF4 is over-expressed in rectal cancers that were resistant to preoperative chemoradiotherapy. Because the association between Wnt signaling and chemoradioresistance is a novel finding, we aimed to investigate whether this over-expression is functionally relevant. Methods: Three colorectal cancer cell lines were transfected with two shRNA-vectors targeting TCF4. Stable single-cell clone (SCC) populations were established, and selected clones were irradiated at 0, 1, 2, 4, 6 and 8 Gy. γH2AX staining was used to evaluate DNA double strand repair after irradiation, and changes in cell cycle distribution were analyzed before and after radiation. Finally, β-catenin activity was inhibited using both siRNAs and the small molecule inhibitor XAV939. Results: Silencing of TCF4 led to a significant radiosensitization in SW837 and SW480, whereas there was no effect in HT-29. Well-fitting, we observed significantly more γH2AX foci 24 hrs after radiation in SW837 SCCs compared to HT-29 SCCs, pointing to an impaired DNA damage repair in SW837. Furthermore, in SW837 SCCs, but not in HT-29 SCCs, we noticed a change in the cell cycle distribution towards radiosensitive cell cycle phases before radiation, and compromised cell cycle control after radiation. Finally, both siRNA- and small molecule-mediated inhibition of β-catenin activity did not influence the sensitivity to chemoradiotherapy. Conclusion: Our results indicate a novel mechanism through which the Wnt transcription factor TCF4 mediates chemoradioresistance in a β-catenin-independent manner. Moreover, they suggest that TCF4 is a potential molecular target to sensitize resistant tumor cells to (chemo-) radiotherapy.
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 5729. doi:1538-7445.AM2012-5729