bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3126: Intercellular communication in the urothelium: Evidence for a switch in gap junction regulation during differentiation
Authors: Hinley Jennifer S. , Kirkwood Lisa A. , Southgate Jennifer 
Published: June 2012

Abstract
Cells have a requirement for intercellular communication in order to maintain normal tissue polarity and homeostasis. Knowledge of the signaling molecules transferred through specific gap junctions is limited; however aberrant expression of connexins, the protein subunits of gap junctions, has been linked to many disorders including neoplastic transformation of brain and colorectal tissues. A number of reports have documented changes in connexin expression associated with bladder cancer.
The aims of this study were 1) to define the connexins expressed by the epithelial lining of the human urinary tract (urothelium) in situ and in vitro; 2) to determine if expressed connexins assemble into functional gap junctions and 3) the contribution of specific connexins to urothelial tissue physiology.
Established culture systems for normal human urothelial (NHU) cells were used to replicate proliferative (regenerative) or differentiated cell phenotypes. RT-PCR was used to screen normal urothelial tissue and NHU cell cultures for expression of connexin genes. Immunochemical techniques were employed to determine connexin expression and localization in situ and in vitro. Dye-transfer techniques were used on cultured cells to confirm that assembled gap junctions supported functional cell-cell communication.
Of the 20 human connexin genes, six were expressed in situ and by differentiated cultures, whilst two were expressed only in proliferative culture conditions. NHU cells were capable of dye transfer in both proliferative and differentiated cultures, indicating the presence of functional gap junctions. Immunofluorescence microscopy demonstrated that the switch in medium from a low (0.09mM) to near physiological (2mM) calcium concentration resulted in increased assembly of gap junctions containing connexin-43. Connexin-32 was only expressed by differentiated cultures, as shown by RT-PCR and immunochemistry, where it was localized to intercellular borders indicating a functional role.
This data represents the first systematic characterization of connexin family expression in the urothelium and provides evidence that urothelial cells alter their connexin expression upon differentiation to produce specific channels. Connexin-32 has been reported to be involved in terminal differentiation of human mammary gland and future work will focus on characterizing the role of connexins in defining the differentiated urothelial phenotype.
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 3126. doi:10.1158/1538-7445.AM2011-3126
Abstract 3141: Analysis of the endocrine treatment predictive protein HOXB13 in premenopausal breast cancer
Authors: Jerevall Piiha-Lotta , Jansson Agneta , Källström Ann-Christine , Landberg Göran , Fernö Mårten , Stål Olle 
Published: June 2012

Abstract
Homeobox B13 (HOXB13), part of the two-gene expression index H:I, has proven its capacity as a predictive factor of tamoxifen benefit in breast cancer. We have previously shown that in addition to mRNA expression, the protein shows predictive value in postmenopausal patients. High levels were associated with decreased tamoxifen (Tam) benefit and may indicate endocrine resistance, whereas Tam-treated patients with low expression had a longer recurrence-free survival. Here, we have analyzed HOXB13 protein expression in premenopausal breast cancer patients. We quantified the levels of HOXB13 with immunohistochemistry in tumor samples from 487 patients sampled in duplicates on tissue micro arrays. Patients were diagnosed with stage II invasive breast cancer and randomized to Tam or no endocrine treatment. HOXB13 protein analysis was successful in 367 patients. Data were correlated with clinicopathological variables. Using Kaplan Meier analysis to investigate Tam benefit in patients with tumors expressing estrogen receptor (ER) α, progesterone receptor, or both, patients with high HOXB13 levels unexpectedly benefited from Tam (hazard ratio for recurrences 0.43, 95% CI 0.28-1.01, p=0.053). Corresponding numbers for a lower expression were 0.69 (95% CI 0.44-1.07, p=0.1). For further analysis, we stratified the patients based on tumor ERβ status, which seemed to be an indicator of the performance of HOXB13 as a treatment predictive factor. Interaction between HOXB13 expression and benefit from Tam in the ERβ- group was close to significant (p=0.06), and corresponding p-value for the ERβ+ patients was 0.11. In conclusion, endocrine treatment prediction for premenopausal breast cancer patients using the protein levels of HOXB13 does not seem to be as straight forward as in postmenopausal patients. Based on our results, ERβ may be an additional determinant in predicting benefit from Tam-treatment using HOXB13 protein expression.

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 3141. doi:10.1158/1538-7445.AM2011-3141
Abstract 3146: The involvement of Foxp3 or CD34 expression and tumor lymphocyte infiltration in the prognosis of breast carcinoma patients
Authors: Rico María J. , Rozados Viviana R. , Alasino Carlos M. , Roggero Eduardo , Nocito Ana L. , Scharovsky O Graciela 
Published: June 2012

Abstract
Breast cancer is a heterogeneous disease with different known biological subclasses some of which are associated with immune cell infiltration. Studies in mice have shown that thymus-derived CD4+CD25+ regulatory T cells (Treg; FOXP3+ lymphocytes) inhibit the antitumor immune response. The presence of inflammatory cells may represent an immune response to the tumor, but could also potentially exhibit pro-tumor effects including stimulation of tumor invasion or angiogenesis. Angiogenesis has an important role in the progression of breast cancer. Microvessel density has been found to be strongly associated with features of tumor aggression as larger size and poor differentiation. It was observed that different characteristics of tumors like immune cells infiltration, number of Tregs and blood vessels density would be useful tools to anticipate the response to the therapy. The aim of this study was to analyze different cellular characteristics of primary tumors of patients with breast cancer and their relationship to the response to therapy. Samples of breast carcinomas (Stage I and II) (n=14) were analyzed. Foxp3 and CD34 expression was determined immunohistochemically on formalin-fixed, parafin-embedded tumor sections. Also, peritumor and intratumor lymphocytes infiltration was evaluated by hematoxylin-eosin staining. For quantification in 20 high magnification fields, a 0 (nule expression) to 6 (high expression) score was utilized. Confocal microcopy for Foxp3 was also used. Lymphocytes were mainly found in the intratumor (IT) area. Twelve over 14 patients (DF) that had a disease free survival of approximately 5 years showed an IT score for lymphocyte infiltration [median (range): 4 (2-6)] higher than that of 2/14 patients that relapsed (R) [2 (2-2)], p&lt;0.05. For Foxp3 expressing lymphocytes, the IT score was low in DF [2 (0-6)] and R [2 (2-2)] patients. Interestingly, some tumor cells were Foxp3+. Vascular density, evaluated through CD34 expression, was low [DF: 2 (1-4); R: (1-2)]. The relationship between the presence of Tregs cells, and the vascular density in the intratumor area, with prognosis is still controversial. Our present results show that Foxp3+ or CD34 IT expression could not predicts patients prognosis. Disease free patients showed higher intratumor lymphocyte infiltration than relapsed patients, a fact that could reflect the involvement of the host anti-tumor immune response.
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 3146. doi:10.1158/1538-7445.AM2011-3146
Abstract 3152: Distribution of hormone receptors (estrogen receptor, progesterone receptor and androgen receptor) in epithelial malignancies
Authors: Basu Gargi D. , Kemkes Ariane , Feldman Rebecca A. , Arguello David R. , Wright Alan , Loesch David , Ashfaq Raheela 
Published: June 2012

Abstract
The importance of steroid hormone receptors to the biology of breast cancer was recognized over 40 years ago. New insights into hormone receptor biology and the increasing array of proteins that can modify their function have already translated into better therapies for breast cancer. The responsiveness of a tumor to hormone therapy is an important parameter in cancer management. Besides breast cancer, other cancers also express steroid hormone receptors. Hence, the purpose of this study was to capture the relative distribution of hormone receptors in all types of cancer including breast cancer.
In a total cohort of 9,491 patient samples, hormone receptors ER, PR and AR were assayed by immunohistochemistry on a Ventana platform using antibodies ER (SP 1), PR (I E 2) and AR (AR 27). The slides were read manually by pathologists using the cutoff of (&gt;=1+ and &gt;=10% as positive) for AR, PR and ER. Based on these cutoffs, samples were deemed positive or negative.
Our preliminary observations indicate that the frequency of ER is highest in breast (40.8%), followed by ovary (25.0%), and uterus (14.9%), with marginal frequencies in lung (4.0%) and peritoneum (2.2%). The most common cancer types with negative ER expression are lung (14.7%), colon (13.3%), pancreas (10.5%), breast (9.4%) and skin (4.2%) The cancer distribution of PR mimics that of ER, albeit with a slightly lower prevalence (breast 25.5%, ovary 22.0%, uterus 13.3%, lung 5.6%, and pancreas 3.9%). The most common cancer types in which PR was negatively expressed are lung (14.0%), colon (12.6%), breast (12.2%), pancreas (9.5%) and ovary (7.6%) The frequency of AR, surprisingly, is higher in breast cancers (45.7%) as opposed to prostate cancer (5.8%). Other cancer types with overexpression of AR are ovary (18.5%), uterus (3.4%) and lung (3.0%). In contrast, low expression of AR is most often found in lung (14.3%), colon (12.0%), pancreas (9.7%), breast (9.6%), and skin (3.7%). All distributional differences by HR status were analyzed by Pearson's chi-square (χ2) test and showed statistical significance (p&lt; 0.001).
To our knowledge, this is the first study involving a large patient pool in which hormone receptors have been investigated in a single clinical laboratory with standardized IHC. Cancer is a heterogeneous disease with different molecular drivers regulating its growth, survival and response to therapy. This study shows that hormone receptors are frequently expressed in cancer types outside of breast, which merits the inclusion of therapeutic strategies using hormone therapy in such tumors.
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 3152. doi:10.1158/1538-7445.AM2011-3152
Abstract 3154: Human plasma, prostate and urine levels of α-, γ-, and Δ-tocopherols and their metabolites before and after supplementation with a γ-tocopherol rich vitamin E mixture
Authors: Goodin Susan , Lee Mao-Jung , Kim Isaak , DiPaola Robert , Yang Chung S. 
Published: June 2012

Abstract
In order to determine the blood/tissue levels of tocopherols and their metabolites, we analyzed samples from 5 prostate cancer patients who underwent prostatectomy by HPLC-ECD. These patients had a mean PSA of 6.37 (range 1.99 to 10.54) prior to surgery and a Gleason Score of 7. The plasma α-tocopherol (α-T) levels, 22.02 ± 3.85 μM (mean ± S.D., n = 10), were in the normal range. As expected, the levels of γ-T were lower and those of Δ-T were even lower. The prostate tocopherol levels were 6-14 times lower than plasma levels. Substantial amounts of carboxyethyl hydroxychromans (CEHC) and carboxymethylbutyl hydroxylchromans (CMBHC) were observed in the urine. These metabolites were also found at low levels in the plasma and prostate. In a pilot study, prostate cancer patients received no supplementation or 2 capsules of γ-TMT (a γ-T-rich dietary supplement, containing 128 mg α-T, 200 mg γ-T and 71 mg Δ-T per capsule) daily for 7 or 14 days before prostatectomy. Blood and urine samples were collected from each subject before γ-TMT supplementation and on the day of surgery. The plasma and prostate tocopherol/metabolite levels, especially those from γ-T and Δ-T, were increased in patients who received γ-TMT supplementation (but not in the patients who did not). The effect on the urine levels of tocopherol metabolites was even more evident; high levels of γ- and Δ- forms of CEHCs and CMBHCs were observed in patients who received γ-TMT supplementation. Tocopherols were not excreted in the urine even with supplementation. These results are consistent with our understanding that γ-T and Δ-T are more extensively metabolized than α-T. The rather high CEHC and CMBHC levels in the urine make them useful biomarkers for tocopherol intake and metabolism in future human studies (supported by NIH grants CA120915 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 3154. doi:10.1158/1538-7445.AM2011-3154
Abstract 3162: Assessing the therapeutic and diagnostic potential of human thymidine kinase 1 in leukemia
Authors: Estevez Dagoberto , Whitehurst Robert A. , Sharp Daniel W. , Robison Richard A. , O'Neill Kim L. 
Published: June 2012

Abstract
Thymidine Kinase 1 (TK1), a salvage pathway enzyme responsible for recycling thymine in cells for use in DNA replication and repair, is normally tightly regulated by the cell cycle; however research studies have shown that it is over-expressed and unregulated in cancer cells. Studies linking TK1 localization to the plasma membrane of lymphoma cells have suggested that this enzyme could also be used as a molecular target for cancer diagnosis and therapy. Previous research in our laboratory showed that TK1 located on the plasma membrane of different cancer cell lines had high enzymatic activity. This study was performed to support the eventual possibility of targeting TK1 for cancer diagnosis and immunotherapy in leukemias expressing high levels of TK1 on their plasma membrane. TK1 levels on plasma membrane were analyzed using a BD FACSCanto flow cytometry on lymphoblastoid cells derived from Burkitt's lymphoma (Raji cells), acute T cell leukemia (Jurkat cells), myeloblastic cells derived from promyelocytic leukemia (HL-60 cells), and normal lymphocytes from healthy individuals. Analysis was performed on unpermeabilized cells in exponential growth phase using both a mouse monoclonal anti-TK1 Ab and a rabbit polyclonal anti TK-1 Ab. Cells were incubated with human FcR blocking reagent to eliminate non-specific binding to Fc receptors. Permeabilized cells were excluded using propidium iodide staining. Using an IgG Isotype control we were able to select proper gating (0% binding). TK1 surface expression was compared to expression of sodium potassium ATPase, a common plasma membrane marker, and pan-leukocyte marker CD45. Results confirmed high levels of TK1 expression on cancer cell lines analyzed. Flow cytometry analysis showed that binding of the mouse monoclonal anti-TK1 Ab and rabbit polyclonal anti-TK1 Ab were 93.4% (SEM=1.05, N = 19) and 99.5 % (SEM=0.67, N=19) in Raji cells; 71.1% (SEM=3.41, N=19) and 89.4 % (SEM=2.74, N=19) in HL-60 cells; 63% (SEM=1.23, N=26) and 88.6% (SEM=1.81, N=27) in Jurkat cells. Lymphoblastoid cells showed significantly higher TK1 expression when compared to that of lymphocytes obtained from healthy individuals 9.9% (SEM=2.39, N=7) and 14.9% (SEM=2.43, N=3). When induced with pokeweed mitogen there was no increase in TK1 expression on the plasma membrane of normal dividing lymphocytes 7.9% (SEM=0.54, N=3) and 10.63% (SEM=2.89, N=3). Fluorescence microscopy observations provided more evidence of TK1 association with the plasma membrane of cancer cells. These results suggest that membrane-bound TK1 has potential for both diagnosis and immunotherapy in human leukemia.
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 3162. doi:10.1158/1538-7445.AM2011-3162
Abstract 3176: Preclinical validation of the sensitivity and specificity of a fluorescent nanobeacon for its application in colonoscopy-based imaging of colorectal cancer
Authors: Pham Wellington , Kumagai Hironori , Hiwatari Ken-Ichiro , Tachikawa Hiroyuki , Kimura Ryoji , Nakamura Kunio , Kataoka Makoto , Yamashita Shinji , Sakuma Shinji 
Published: June 2012

Abstract
Colorectal cancer is the third most commonly diagnosed type of cancer and the second leading cause of cancer-related death in the U.S. Currently, the key element in the control, prevention, and treatment of this disease is recognition of its early symptoms. In this work, we describe the development and validation of a specific fluorescent nanobeacon that targets the Thomsen-Friedenreich (Tf) antigen, potential biomarkers of this disease, via the terminal carbohydrate Gal-β(1-3)GalNAc.
The imaging agent is comprised of a submicron-sized polystyrene nanosphere encapsulated with a hydrophobic fluorescent dye. The surface of the nanosphere was modified with the peanut agglutinin (PNA) and poly(N-vinylacetamide (PNVA) moieties. The former binds to Gal-β(1-3)GalNAc with high affinity, while the latter enhances the specificity of PNA for the carbohydrates. This nanobeacon detects colorectal tumors by recognizing the tumor-specific antigen through the surface-immobilized PNA, and identification is made via the fluorescence signal obtained from the coumarin-6 encapsulated in the nanosphere's core. Biorecognition by the probe has been demonstrated in cell lines and orthotopic mouse models.
Here, we assessed the sensitivity and specificity of the probe in a pre-clinical MUC1 transgenic mouse model. Of note, the probe reported that the Tf antigen expression level is high in the colon and intestine of that model compared to wild- type mice. Data obtained by fluorescence imaging using this probe correlates well with those obtained via immunohistochemistry. Most importantly, the probe was not absorbed systemically upon topical application in the host. As a result, no registered toxicity is associated with the probe.
Using the Tf antigen imaging approach, we are evaluating the binding specificity of the nanobeacon in panel of human colorectal cancer tissues. Thus far, the study has indicated quantitatively a 5-fold enhancement of the Tf expression in colon cancer tissue versus the control tissue. In sum, these data demonstrate the potential for the use of this novel nanobeacon in imaging the Tf antigen as a biomarker for the early detection and prediction of the progression of colorectal cancer. Currently, several probe optimization processes are presently being carried out in our laboratory, including the incorporation of near-infrared fluorescent dyes to enhance the signal-to-noise ratio. Detailed results of the biometric validation of the nanobeacon will be reported in a timely manner.
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 3176. doi:10.1158/1538-7445.AM2011-3176
Abstract 3180: Mutation detection in circulating free DNA using mutant-enriched PCR and digital PCR
Authors: Huw Ling-Yuh , Spoerke Jill , Patel Rajesh , Liu Weiqun , Raja Rajiv , Amler Lukas , Hampton Garret , Punnoose Elizabeth , Lackner Mark 
Published: June 2012

Abstract
Mutations in oncogenes such as EGFR, KRAS and PIK3CA, have been shown to have profound effects on pathway signaling and tumor growth. These genetic aberrations are potentially valuable predictors for patient stratification and therapeutic responses to targeted therapies directed against these signaling pathways. Here we evaluate the utility of circulating tumor DNA as a “liquid biopsy” for predictive diagnostics and real-time monitoring of disease. A fundamental challenge with this approach is that, due to the low frequency of the mutant tumor DNA in circulation, a highly sensitive assay is required to detect the single base pair alterations. We have designed and investigated several assay formats, including TaqMan and scorpion-ARM assays for mutation detection using a digital PCR platform. We also employed LNA/PNA blockers and thermostable restriction digestion in PCR reaction to enrich the mutant DNA. The combination of the biased amplification and digital PCR dramatically increased mutation detection 10-100 fold. To assess clinical utility of the technology, data on PIK3CA mutation screening of matched patient tumor and plasma samples from a phase I clinical trial will also be reported.
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 3180. doi:10.1158/1538-7445.AM2011-3180