bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-435: Treatment decision-making for clinically localized Gleason score 6 prostate cancer: What younger men choose and why
Authors: Sidana Abhinav , Trock Bruce , Feng Zhaoyong , Hernandez David , Epstein Jonathan 
Published: February 2011

Abstract
Introduction: This study identifies various treatment related information sources used by young men with prostate cancer (&lt;50 years) and evaluates the association between decision making preferences and sociodemographic factors.
Methods: A survey was sent to 986 men under 50 years of age diagnosed with Gleason 6 prostate cancer from the consult service of one of the authors at Johns Hopkins Department of Pathology between 2001 and 2005.
Results: 488 completed questionnaires were received. Physicians and internet were two most common information sources used by the patients. Physicians were a more important information source for white men (p=0.04) and those with higher education (p=0.036). Family was an important information source in married men (p&lt;0.001) and those with higher education (p&lt;0.001). Three most important influential factors for treatment decision were doctor's recommendation, information from internet and spouse's advice. Most patients (88%) consulted more than 2 doctors while making a decision. Men with higher education (p=0.003) and higher income (p=0.003) tend to consult more doctors. Most respondents said that their doctor endorsed only one treatment, primarily surgery. 76% of the respondents said that their doctors recommended against watchful waiting. Men who underwent surgery considered doctor's recommendation as the most influential factor while those who had radiation considered information from internet, books and medical journals as most influential (p=0.018). Treatment choice was not influenced by PSA value at diagnosis. Subjects with higher education and higher income considered sexual function as a more influential factor while making a treatment choice. Better educated men preferred” informed decision making” over “complete reliance on doctor” (p=0.013). Non-married men found the decision more difficult to make (p=0.032), were more worried (p=0.0005) and experienced more distress (p=0.011) while making treatment decisions. Feeling of regret after treatment was experienced more by respondents with lower education (p=0.007) and lower income (p&lt;0.0001).
Conclusions: Patients younger than 50 years diagnosed with localized prostate cancer sought information from a wide range of sources but are influenced most by the doctor's recommendation.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-435.
Abstract LB-49: ABC transporters in the blood-brain barrier limit the brain penetration of the PARP inhibitor ABT-888
Authors: Fan Lin , de Gooijer Mark C. , Beumer Jan H. , Christner Susan M. , Beijnen Jos H. , van Tellingen Olaf 
Published: February 2011

Abstract
Introduction: ABT-888 is a potent poly(ADP-ribose) polymerase (PARP) inhibitor and is currently in phase 2 clinical trials. PARP inhibitors enhance the activity of DNA damaging therapies, due to the critical function of PARP-1 and PARP-2 in base excision repair. The combination of ABT-888 with chemo-radiation therapies for the treatment of glioma patients is receiving considerable interest because this combination has shown promise in preclinical models.
High-grade glioma patients have a very poor prognosis, in particular due to the inability to achieve complete surgical resection. Importantly, the residual tumor cells that have infiltrated surrounding normal brain tissue are using pre-existing brain vasculature and are thus protected by the blood-brain barrier (BBB). Consequently, the ability of potential chemotherapeutics to cross the BBB, including the role of ABC transporters in brain penetration, needs to be characterized.
Goal: To establish the impact of the BBB and the role of the ABC transporters ABCB1 and ABCG2 in the brain disposition of ABT-888. Methods: We performed in vitro transwell assays using polarized epithelial monolayers of parental vs ABC-transporter transduced cell lines. In vivo pharmacokinetic studies were conducted with wildtype (WT), single and compound ABC transporter knockout mice. Drug concentrations were determined by HPLC-UV and LC-MS.
Results: Transwell assays demonstrated basolateral-to-apical translocation in both Abcb1 expressing LLC-Mdr1a vs LLC-PK1 cells as in Abcg2 expressing MDCK-Bcrp1 vs MDCK-parent cells, which could be inhibited by zosuquidar and elacridar, respectively.
The plasma levels of ABT-888 in WT vs single Abcb1−/−, single Abcg2−/−, or compound Abcb1−/−;Abcg2−/− mice 1 h after i.v. administration of 10 mg/kg were not different. However, the brain-to-plasma ratios for WT, Abcb1−/−, Abcg2−/−, and Abcb1−/−;Abcg2−/−mice were 0.98, 4.46 ((p&lt;0.006*), 1.45 (p=NS*) and 7.47 (p&lt;0.001*, p=0.022**), respectively. Significance was assessed by ANOVA with Bonferroni post-hoc test (*relative to WT; **relative to Abcb1−/−).
Conclusions and Relevance: The brain penetration of ABT-888 is more than 7-fold reduced by the action of Abcb1 and Abcg2, with Abcb1 being the most important limiting factor. This information will aid in the interpretation of clinical trials in glioma. Disappointing efficacy of ABT-888 based therapy in glioma may merely reflect inadequate drug exposure, and could be improved by using inhibitors of selected ABC-transporters or by the development of PARP inhibitors with lesser affinities for ABC-transporters.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-49.
Abstract LB-5: RUNX3 targets estrogen receptor α for proteasome-mediated degradation suppressing breast cancer tumorigenesis
Authors: Huang Bo , Qu Zhaoxia , Victor Adrienne , Zhang Chen , Yang Xiao-dong , Ito Kosei , Xiao Gutian , Ito Yoshiaki , Shapiro David , Chen Lin-Feng 
Published: February 2011

Abstract
Transcription factor RUNX3 is inactivated in a number of malignancies including breast cancer and is suggested to function as a tumor suppressor. However, the exact mechanism for its tumor suppressor function in breast cancer remains elusive. Here we demonstrate that RUNX3 interacts with estrogen receptor α (ERα) and reduces ERα-mediated transactivation by stimulating the ubiquitination and proteasome-mediated degradation of ER. Consistent with its ability to reduce levels of ERα, expression of RUNX3 inhibits the estrogen-dependent proliferation and transformation potential of ER -positive MCF-7 breast cancer cells in liquid culture and in soft agar and suppresses the tumorigenicity of MCF-7 cells in mice. Thus, these studies reveal modulation of ERα stability as a novel mechanism by which RUNX3 functions as a tumor suppressor in ERα-positive breast cancer.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-5.
Abstract LB-50: Overexpression of PBX1 is associated with recurrence and worse clinical outcome in patients with recurrent ovarian high-grade serous carcinoma
Authors: Kuhn Elisabetta , Park Joon T. , Davidson Ben , Kurman Robert J. , Shih Ie-Ming , Wang Tian-Li 
Published: February 2011

Abstract
PBX1 has been initially identified as a proto-oncogene in human leukemia in a form of the E2A-PBX1 fusion protein. PBX1 is currently known as a regulator of self renewal of stem cells which contributes to maintenance of a “stemness” phenotype mainly through TGF-ß signaling. PBX1 was recently shown to be elevated in ovarian cancer and its locus was found to be frequently amplified in many cancer types including ovarian carcinoma.
In order to further understand the clinicopathological and prognostic significance of PBX1 in ovarian carcinoma, we investigated the gene expression of PBX1 in patients with ovarian high-grade serous carcinoma (HGSC). PBX1 mRNA levels were analyzed in a panel of 78 ascites from patients with HGSC (including 36 primaries and 42 recurrences) by quantitative RT-PCR. Moreover, we performed immunohistochemical staining for PBX1 in 25 pairs of matched primary and recurrent HGSCs from the same patients. The results were correlated with clinicopathological data.
Kaplan-Meier analysis demonstrated higher PBX1 levels in ascites from patients with recurrent/chemoresistant HGSC and an association with worse overall survival (p=0.026) as well as disease-free survival (p=0.024). Patients’ effusions with high PBX1 levels (based on median cut-off, n=22) had a mean overall survival of 26 months vs. 39 months for patients whose effusions showed low PBX1 expression (n=20). Patients’ effusions with high PBX1 expression (n=21) also had a mean progression-free survival of 4 months vs. 10 months for patients whose effusions showed low PBX1 levels (n=20). Furthermore, we found more intense PBX1 immunoreactivity in recurrent HGSCs than in matched primaries (Paired t test, p=0.024). Finally, PBX1 expression in primary HGSCs did not demonstrate any significant correlation with patients’ clinical outcome.
This study is the first one demonstrating that PBX1 expression correlates with recurrent disease and is associated with worse clinical outcome in patients who develop recurrent HGSC. Future studies will aim at determining the usefulness of PBX1 immunoreactivity as a biomarker to predict patient treatment response and whether it can be a potential molecule for drug-targeted treatment in patients with recurrent HGSC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-50.
Abstract LB-55: Histone deacetylase inhibitor causes DNA damage and apoptosis by downregulation of repair enzymes in cancer but not normal cells: Basis of resistance of normal cells to HDACi
Authors: Lee Juhee , Choy Megan L. , Ngo Lang , Foster Steven , Xu Weisheng , Petrini John H. , Marks Paul A. 
Published: February 2011

Abstract
Histone deacetylase inhibitors (HDACi) developed as anti-cancer agents have a high degree of selectivity for killing cancer cells. HDACi induce acetylation of histones and many non-histone proteins, affecting gene expression, cell cycle progression, cell migration and cell death. The mechanism of the tumor selective action of HDACi is unclear. Here we show that the HDACi, SAHA (Suberoylanilide hydroxamic acid, vorinostat), induces DNA DSB (double strand break) in normal (HFS) and cancer (LNCaP, A549) cells, but normal cells in contrast to cancer cells repair the DSB despite continued culture with SAHA.
In transformed cells, H2AX levels increased with continued culture with SAHA, while in normal cells, this marker of DNA DSB tended to decrease with time. To define the capacity of normal and transformed cells for repair of SAHA induced DNA DSB, cells were cultured for 24hr with SAHA, washed and continued culture without HDACi. In normal cells, the H2AX was undetectable by 2hr (presumably reflecting repair of DNA DSB), while persisting in transformed for duration of culture (presumably reflecting failure to repair DNA DSB) with consequent transformed cell death. Further, we found that SAHA suppressed DNA DSB repair proteins, e.g., RAD50, MRE11, Tip60 and PP2A, in cancer (LNCaP, A549) but not in normal cells (HFS).
These findings indicate that the HDACi induces DNA damage in cancer and normal cells, but normal cells have the capacity to repair the DNA DSB, while cancer cells do not owing in part at least to suppression of DNA DSB repair proteins. This selective action of SAHA in inducing transformed cell death points to potential effective therapeutic strategies for combination therapy with HDACi with agents that suppress DNA damage repair proteins.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-55.
Abstract LB-61: Comparative study of different diagnostic techniques (AI, MLPA, FISH) in breast cancer patients with 1q25.3 alterations
Authors: Wiechec Emilia , Kjeldsen Tina , Overgaard Jens , Kjeldsen Eigil , Hansen Lise Lotte 
Published: February 2011

Abstract
Background: Breast cancer is the most frequently diagnosed malignancy among women and is the leading cause of cancer related death worldwide. Molecular genetic studies have revealed many subgroups of breast cancer within which the genomic alterations affecting chromosome arm 1q are considered to be an early event in breast carcinogenesis and are correlated with favorable prognosis for the patients.
We have found a high percentage of concordance between the AI and MLPA assays pointing towards gain of the 1q25.3 region in breast cancer.
Aims: Our main objective was to compare the sensitivity and specificity of AI and synthetic probe-based MLPA with other cytogenetic method (FISH) in breast cancer patients with or without previously confirmed alterations within 1q25.3.
Methods: FISH was performed on formalin-fixed paraffin-embedded tumor material in order to verify previous findings and assess the level of genetic alterations of 1q25.3 in breast cancer. The 1q25.3 test and 1p35 reference probes labeled with different fluorochromes were utilized for analysis.
Results: A total of 70 nuclei from each breast cancer case were examined and scored for the percentage of 1q25.3 alterations. The non-tumorigenic nuclei obtained from healthy individuals served as adequate cut-off for the 1q25.3-specific changes. The overall FISH results are consistent with results obtained from previous analysis in the majority of analysed cases. Furthermore, FISH resolved the level of 1q25.3 alterations in few cases that were uncertain by AI and MLPA analysis.
Conclusion: This study shows that both AI and MLPA assays are able to map regions of copy number changes in the cancer genome and are in concordance with molecular cytogenetics. These three techniques proved to be an efficient tool for diagnosis of 1q25.3 alterations, however, confusing results in AI and MLPA analysis might be obtained while using non-microdissected tumor DNA as a template.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-61.
Abstract LB-62: Direct visualization of circulating sarcoma cells by whole-blood fluorescence in-situ hybridization
Authors: Morozov Alexei , Leversha Margaret , Keohan Mary-Louise , D'Adamo David R. , Schwartz Gary K. , Meyers Paul , Maki Robert G. , Moore Malcolm A.S. 
Published: February 2011

Abstract
Background: Several sarcoma subtypes are characterized by well-defined genetic events such as chromosomal translocations or gene amplification. In translocation-associated sarcomas, the presence of the fusion transcript can be detected in peripheral blood by RT-PCR. However, sarcoma cells have never been directly visualized in peripheral blood due to the absence of specific immunocytochemical markers.
Methods: We developed a novel method to examine large numbers of peripheral blood cells for the presence of sarcoma-associated genetic changes. Using an IRB-approved biospecimen collection protocol, peripheral blood was collected from 20 patients with translocation-associated sarcomas or well-differentiated/dedifferentiated liposarcomas (WD/DD LS), which are characterized by MDM2 amplification. In this exploratory phase, the analysis was limited to patients with high burden of disease, evidence of disease progression or recurrence. Immuno-FISH was performed using CD45 immunostaining to identify hematopoietic cells and the corresponding FISH probe, either a break-apart probe (SYT, DDIT3) or MDM2 probe to detect amplification.
Results: ADW2-amplified cells were detected in a subset of WD/DD LS peripheral blood samples, while translocation-positive cells were detected in samples of synovial sarcoma (using the SYT breakapart probe) and myxoid/round cell liposarcoma (using the DDIT3 breakapart probe). We are currently developing the techniques to quantitate the frequencies of such CD45(-) Probe(+) cells.
Conclusions: To our knowledge this is the first report of direct visualization of sarcoma cells in peripheral blood using whole-blood FISH analysis. We are currently characterizing these cells morphologically and immunocytochemically. In addition, we are developing tools necessary to perform quantitative analysis of circulating tumor cell frequencies in peripheral blood samples, to begin to establish whether the levels of circulating tumor cells correlate with tumor burden and response to therapy. This method may be applicable to other tumors where defined genetic lesions exist that are amenable to FISH analysis, such as chromosomal translocations or genomic gains or losses. The goal is to use such genotype-based analysis to explore the phenotypic diversity of circulating tumor cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-62.
Abstract LB-64: Synuclein gamma inhibits BubR1 function and renders resistance to antimicrotubule drug
Authors: Shi Yuenian Eric , Wu Kejing , Liu Yiliang Ellie , DelRowe John , Chen Yiding 
Published: February 2011

Abstract
The microtubule (MT) cytoskeleton is an effective and validated target for cancer chemotherapeutic drugs. Currently, anti-MT drug taxane, e.g. docetaxel, is the first-line chemotherapeutic agent to treat patients with locally advanced or metastatic breast cancer and is also one of the most effective chemotherapeutic agents in clinical use in six different cancers (breast, ovarian, non-small cell lung, prostate, gastric, and head and neck). Nearly half of the treated breast and ovarian cancer patients, however, do not respond to chemotherapy. Although general mechanisms of drug resistance may apply to docetaxel resistance, more specifically, the current research paradigm on docetaxel resistance focus on acquired -tubulin mutations and altered expression of β-tubulin isotypes that interfere with drug target binding. Synuclein gamma (SNCG) is a new unfavorable prognostic marker for breast cancer and a potential target for cancer treatment. At the cellular level, SNCG increases metastasis and promotes genetic instability. At the molecular level, SNCG functions like a tumor specific chaperone and regulates many pathways in growth and progression of cancer, including an interaction with mitotic checkpoint kinase BubR1. Here, we show that expression of SNCG is sufficient to induce specific resistance to docetaxel-caused mitotic arrest and apoptosis in breast cancer cells and in breast cancer xenografts. SNCG binds to spindle checkpoint kinase BubR1, interferes with its interaction with other checkpoint proteins of p55cdc20-APC and Mda2, reduces BubR1's kinase activity, and thus attenuates docetaxel-caused mitotic cell death. The working mechanism of anti-MT drugs heavily relies on the normal function of the checkpoint machinery in which BubR1 is a critical component, this inhibitory effect of SNCG on BubR1 function may lead to the inactivation of checkpoint and thus renders docetaxel resistance. To test the clinical relevance, in a pilot neoadjuvant trial, 20 women with histological proven locally advanced breast cancer were treated with 3 cycles of neoadjuvant TE regimen (docetaxel + epirubicin). SNCG-positive tumors are resistant to anticancer effect of neoadjuvant therapy as assayed by reduction in primary tumor size, an increase in apoptotic index, and a decrease in Ki67 proliferation index. These data show that SNCG renders docetaxel resistance by inhibiting BubR1 activity and is new biomarker for predicting anti-MT drug resistance.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-64.
Abstract LB-67: Global DNA methylation in fetal human germ cells and germ cell tumors: correlation with differentiation and cisplatin resistance
Authors: Looijenga Leendert H.J , Wermann Hendrik , Gillis Ad , Honecker Friedemann , Ammerpohl Ole , Richter Julie , Oosterhuis Wolter , Bokemeyer Carsten 
Published: February 2011

Abstract
Differences in the global methylation pattern, i.e. hyper- as well as hypomethylation, are observed in cancer, including germ cell tumors (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n=103) and GCTs (n=251) by immunohistochemical staining for 5-mCytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, while female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, carcinoma in situ and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumors, choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam-2 before and after demethylation using 5-azacytidine. Exposure to 5-azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell specific marker VASA showed increased expression. Upon treatment with 5-azacytidine, TCam-2 cells were analyzed by high throughput methylation screen for changes in methylation sites of 14,000 genes. Among the genes revealing changes, interesting targets were identified, i.e. demethylation of KLF11, a putative tumor suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-67.