bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4193: Treatment of malignant gliomas with systemic rapamycin and convection-enhanced delivery of nanoliposomal CPT-11
Authors: Marina Mendiburu-Eliçabe , Hadaczek Piotr , Forsayeth John , Bankiewicz Krystof 
Published: February 2011

Abstract
Combined therapy of rapamycin and nanoliposomal irinotecan (nLs-CPT-11) was used in the treatment of U87-MG intracranial brain tumor model looking for an improvement in the survival in comparison to animals that received only single-agent therapy.
The prognosis for patients with malignant gliomas has remained dismal, and the median survival for patients with glioblastomas is still less than one year after prognosis despite multidisciplinary use of surgery, chemotherapy and radiotherapy. Combination of two agents had start to be an encouraging option to treat glioblastomas giving better results when two different molecules implicate in tumor progress are inhibited instead than only one. Clinical trials with convection-enhanced delivery (CED) have opened a new window in neuro-oncology to the direct delivery of chemotherapeutics to the central nervous system (CNS), circumventing the blood-brain barrier (BBB) and reducing side effects. In this study, we evaluated a combination of nLs-CPT-11 and rapamycin to enhance efficacy in brain tumor xenograft models, and to establish a combination treatment (systemic rapamycin and CED nLs-CPT-11) capable of improving survival from malignant brain tumors. CPT-11 suppress activity of a key enzyme involved in tumor cell replication, topoisomerase I. Rapamycin inhibits PI3K/Akt/mTOR pathway implied in the regulation of the cell proliferation, cell growth, differentiation, migration and survival. In vitro toxicity experiments were carried out with U87-MG and U251-MG cells. An in vivo survival study was performed for intracranial brain tumor xenograft. The combination displayed excellent efficacy in a survival study 7 days after tumor implantation. Animals in the control group had a median survival of less than 20 days, whereas the combination group triplicates the median survival, surviving at least 70 days all the animals. We conclude that CED of nLs-CPT-11 and systemic rapamycin may be an effective treatment option for malignant gliomas.
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 4193.
Abstract 4199: A transgenic mouse for imaging caspase-dependent apoptosis within the skin
Authors: Hamilton Chritin A. , Khanna Divya , Bhojani Mahaveer S. , Lee Kuei C. , Dludosz Andrej , Ross Brian D. , Rehemtulla Alnawaz 
Published: February 2011

Abstract
Apoptosis is an essential process for the maintenance of normal physiology. The ability to non-invasively image apoptosis in living animals would provide unique insights into its role in normal and disease processes. Herein, a recombinant reporter consisting of LacZ gene flanked by two ER regulatory domains and intervening DEVD sequences was constructed to serve as a tool for invivo assessment of apoptotic activity. The results demonstrate that when expressed in its intact form, the hybrid reporter had undetectable β-galactosidase activity. Caspase-3 activation in response to an apoptotic stimulus resulted in cleavage of the reporter, and thereby reconstitution of β-galactosidase activity. Enzymatic activation of the reporter during an apoptotic event enabled non-invasive measurement of β-galactosidase activity in living cells, which correlated with traditional measures of apoptosis in a dose and time dependent manner. Furthermore, using a near-infrared fluorescent substrate of β-galactosidase (DDAOG), non-invasive in vivo imaging of apoptosis was achieved using a xenograft tumor model in response to pro-apoptotic therapy. Lastly, a transgenic mouse model was developed expressing the ER-LacZ-ER reporter within the skin. This reporter and transgenic mouse could serve as a unique tool for the study of apoptosis in living cells and animals especially in context of skin biology.
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 4199.
Abstract 420: Metastatic and neo-vasculature determinants as prognostic markers of thyroid cancer
Authors: Rajoria Shilpi , Suriano Robert , Shanmugam Arulkumaran , Megwalu Uchechukwu , Schantz Stimson P. , Geliebter Jan , Tiwari Raj K. 
Published: February 2011

Abstract
Thyroid is amongst one of the most vascularized tissues of the human body and studies have demonstrated that neo-vascularization is critical for growth and metastasis of thyroid carcinoma with well differentiated thyroid carcinoma metastasizing to the lymph nodes of the neck in 50% of the patients. The perceived risk of thyroid proliferative diseases in women is one in eight, a risk similar to that of breast cancer, suggesting a possible role of female reproductive hormones such as estrogen in this epidemiological distribution. The identification of systemic modulators such as estrogen and markers of metastatic phenotype or neo-vascularization in thyroid cancer is a clinical need. We developed an in vitro thyroid cell culture model to study the effect of estrogen on metastatic phenotype of thyroid cells. We discovered that estradiol modulates metastatic properties of these thyroid cells as evidenced by an increase in in vitro migration, invasion and adhesion in presence of estradiol which correlates with a concomitant downregution of tumor suppressive protein, β-catenin. Restitution of cadherin/catenin complex by fulvestrant suppresses the metastatic phenotype of thyroid cells thus validating our findings of β-catenin as a significant metastatic phenotype marker. Furthermore, we developed an in vivo animal model so as to study the effect of estrogen on neo-vasculature in thyroid cancer. We found that estradiol acts as a mobilizing agent for bone marrow derived endothelial progenitor cells (BM-EPCs) resulting in homing of enhanced numbers of BM-EPCs to orthotopic tumor when ovariectomized mice were supplemented with estradiol pellets. We also discovered that thyroid cells secrete paracrine factors which results in enhanced migration of BM-EPCs as evidenced by in vitro experimental model suggesting that mobilization of BM-EPCs is tumor responsive. In conclusion, our data provides strong evidence that estradiol enhances the metastatic propensity of thyroid cells and mobilizes BM-EPCs to the thyroid tumor. These findings will allow for the possible development of anti-estrogenic compounds that target catenin mediated metastasis and/or stem cells mediated neo-vascularization of thyroid cancer.
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 420.
Abstract 4203: Plasma and tumor pharmacokinetics (PK) of carboplatin in Genetically Engineered Mouse Models of melanoma (GEMMs), murine melanoma, and in patients with cutaneous melanoma
Authors: Combest Austin J. , Roberts Patrick J. , Dillon Patrick J. , Habibi Sohrab , Eiseman Julie L. , Strychor Sandra , Hanna Suzan K. , Muller Markus , Brunner Matthias , Ross Charlene M. , Sharpless Norman E. , Zamboni Willam C. 
Published: February 2011

Abstract
Background: It is currently unclear what preclinical tumor model most accurately reflects the tumor disposition and antitumor response of an anticancer agent in patients with solid tumors. GEMMs of melanoma and other solid tumors may better predict drug distribution and antitumor response compared with flank tumor models by allowing for the development of tumor in situ which may more faithfully recapitulate human cancer. We compared the plasma and tumor disposition of carboplatin in a GEMM and murine models of melanoma and in patients with cutaneous melanoma.
Methods: Carboplatin was administered at 50mg/kg IV x 1 via a tail vein to a GEMM of melanoma [tyrosinase-H-RasG12V Ink4a/Arf−/− (TRIA)] and mice bearing B16 murine melanoma. Plasma total and ultrafiltrate conc were obtained (n = 3 mice per time point) from 0 to 6 h after administration. Microdialysis studies evaluating carboplatin in tumor extracellular fluid (ECF) were performed (n = 6 mice) from 0 to 4 h after administration. Six patients with cutaneous metastatic melanoma were administered carboplatin at 400mg/m2 IV over 20 minutes. Plasma total and tumor ECF, collected by microdialysis, were obtained from 0 to 6 h after administration. Platinum (Pt) conc were measured by ICP-MS, FAAS and FAAS in the GEMM, B16 and patient studies, respectively. Areas under the plasma conc versus time curves from 0 to infinity (AUC) of standard and allometrically scaled data were calculated.
Results: Results are in the table: UnitsHumanGEMMB16Standard / Unscaled Plasma Total Pt AUCµg/mL·h26.028.540.5Plasma Ultrafiltrate Pt AUCµg/mL·h—25.427.9Tumor ECF Pt AUCµg/mL·h15.38.61.9Allometrically Scaled Plasma Total Pt AUC(µg/mL)/(mg/kg)]·(h/kg)0.841.372.15Tumor ECF Pt AUC(µg/mL)/(mg/kg)]·(h/kg)0.490.410.10Ratio of Plasma Total pt AUC to Tumor ECF pt AUC 0.580.300.05
Conclusion: The tumor PK of carboplatin in GEMM models of melanoma more closely resembles the tumor disposition in patients with melanoma as compared with flank tumor models. GEMMs show promise in becoming an improved prediction model for drug PK and response in patient tumors. Studies are being conducted to determine the basis for differences in tumor drug delivery between GEMMs and transplanted tumors.
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 4203.
Abstract 4209: Organotypic multicellular glioma spheroids prepared from tissue fragments obtained by ultrasonic aspiration
Authors: Jensen Stine S. , Aaberg-Jessen Charlotte , Jabbari Javad , Andersen Claus , Schrøder Henrik D. , Kristensen Bjarne W. 
Published: February 2011

Abstract
Ultrasonic aspirators are commonly used to resect brain tumors because they allow safe, rapid and accurate removal of dissected tissue. However, the tissue fragments removed by ultrasonic aspirators are used surprisingly little in daily diagnostics and in clinical research. Due to the increasing need for vital human tumor tissue for these purposes, which today require multidisciplinary approaches, the aim of this study was to investigate whether tissue fragments obtained by ultrasonic aspiration could be cultured as organotypic multicellular spheroids. These spheroids have earlier been shown to represent an important alternative to commercially available cell lines having multiple mutations and phenotypic changes. Fragments obtained by ultrasonic aspiration (sonocut) from one anaplastic astrocytoma and seven glioblastomas and tumor biopsy tissue from four of these glioblastomas were included in the present study. Sonocut and tumor biopsy tissue were mechanically dissociated into small tissue fragments and cultured in a serum containing medium on agar-coated plates. If excess tissue was available the fragments were also cultured in a serum-free medium. After 12-18 days of culturing the tissue fragments had formed spheroids which were fixated and paraffin embedded. Hematoxylin eosin staining was performed in order to investigate the viability and morphology of the spheroids. Part of the material was stained immunohistochemically for the astrocytic marker GFAP and the blood vessel markers VWF, CD31 and CD34. In the present study all sonocut cultures contained viable spheroids, whereas one of the cultures obtained from tumor biopsy tissue did not. The spheroids were able to survive and proliferate under both serum and serum-free conditions. The spheroids from both sonocut and tumor biopsy tissue contained malignant traits including high cellularity, cellular pleomorphism, mitoses and necrosis. Some spheroids consisted solely of GFAP positive tumor cells, while others contained preserved blood vessels confirmed by VWF, CD31 and CD34 immunohistochemistry. In conclusion, we found that it was possible to obtain viable spheroids from sonocut-material under both serum and serum-free conditions.
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 4209.
Abstract 4221: Pregnancy associated mammary gland micro-chimerism indicates fetal progenitor integration in breast cancer
Authors: Aziz-Zaman Sonya , Denes Viktoria , Pilichowska Monika , Geck Peter 
Published: February 2011

Abstract
The PURPOSE of this work was to use Y chromosome markers to investigate the hypothesis that (i) post-pregnancy mammary glands are chimeras that integrate stem cells from the fetus and (ii) these immature progenitors have a critical role in breast cancer.
RATIONALE The exchange of fetal and maternal cells during pregnancy results in the integration of fetal, multipotent progenitors in the mother. The established fetomaternal microchimerism (MC) appears to be stable for life in most mothers. These cells, called Pregnancy Associated Progenitor Cells (PAPC) represent a surprising, third type of progenitor pool (in addition to embryonic- and adult stem cells), with major biological implications. Y chromosome markers (male fetus) detect the fetal lineage and were present in several maternal tissues. No data are available on fetal progenitors in the human mammary gland, although the hormonal regeneration-degeneration cycles render the mammary gland a prime target for the integration of circulating stem/progenitor cell.
HYPOTHESIS Based on the above, we postulated that the fetal progenitor lineage is highly represented in the mammary gland with a critical role in breast cancer. Two biological outcomes were considered: (i) PAPC integration may correctly rejuvenate the stem cell pool and protects from breast cancer; (ii) differentiation programs in the fetal progenitor lineages fail and progress to breast cancer. Our major OBJECTIVE was to investigate if breast cancer is microchimerism related by using Y-chromosome markers in breast cancer samples to establish correlations with breast cancer.
EXPERIMENTAL PROCEDURES We worked out the methodology for Y-marker detection in breast cancer samples from commercially available tissue-arrays. Methods for microdissection (laser and mechanical), DNA extraction and PCR for Y-specific sequences were optimized. We targeted two Y-specific genes: SRY (SOX3-unrelated regions) and DYS14 (a male marker for a TSPY pseudogene). We analyzed 65 samples mostly from invasive ductal breast carcinomas and 40 normal controls.
SUMMARY OF RESULTS We found low level Y-representation in 17.5 % (7/40) of normal breast samples. We detected increased levels of Y markers in 33.8 % (22/65) of breast cancer tissues (integrated SRY and DYS14 data). Further studies to analyze clinical correlations are in progress.
CONCLUSIONS The data suggest, for the first time, that fetal cells are able to integrate into the mammary gland. Furthermore, this integration event appears to coincide with breast cancer. The increased representation suggests potential involvement of fetal progenitor cells in the pathomechanisms of breast cancer.
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 4221.
Abstract 4222: CCN5 deficient MCF-7 side population exhibits stem cell like behavior and formed aggressive tumor in xenograft model
Authors: Dhar Kakali , Banerjee Snigdha , Slusser Joyce , Majumder Monami , Banerjee Sushanta K. 
Published: February 2011

Abstract
The side population (SP) has been identified in a variety of solid tumor cell lines including human breast cancer cell lines. This population of cells has been considered as cancer stem cells (CSCs). Cancer recurrence is currently thought to be due to non-dividing cancer stem/progenitor cells that are resistant to chemo- and radio-therapies. Different therapeutic approaches need to be considered for the elimination/transformation of the cancer stem cells. To reshape our therapeutic approach to breast cancer, we aimed this study and isolated the SP from MCF-7 breast cancer cell line. SP was confirmed by both positive and negative cell surface molecular markers. These include CD44, CD24, b-catenin, E-cadherin, Keratin 19, Oct-4, Notch-1 and Vimentin. Our studies showed that SP and non-SP exhibit differential expression of CCN5, an anti-invasive gene. CCN5 expression was undetected or barely expressed in SP. The comparative studies showed that the in vitro migratory property of SP was significantly higher as compared to non-SP. Moreover, the introduction of CCN5 in SP may enhance the epithelial properties as evidenced by differential expression of MET (mesenchymal-epithelial transition) molecular markers. SP shows higher tumorigenicity in immunodeficient mice. These findings indicate that CCN5 deficiency could be an essential molecular event for the development of a side population having invasive phenotype. Therefore, CCN5 can be used as a therapeutic reagent for advanced breast cancer.
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 4222.
Abstract 4224: Sox2 control breast cancer stem-like cells in a breast carcinoma cell line
Authors: Leis Olatz , Erika Lopez-Arribillaga , David Chrastek , Martin Angel G 
Published: February 2011

Abstract
Many solid tumors, including breast cancer, exhibit a functional hierarchy of cells of which only a small subpopulation of stem-like cells can give rise to the differentiated cells that make the bulk of the tumor. Recently, a method for the culture of undifferentiated human mammary epithelial cells in non-adherent “mammospheres” has been described. Mammospheres are enriched in stem/progenitor cells giving rise to all three mammary cell types. Although gene profiling was used to compare sphere cells to differentiated cells, no specific markers were described.
Three main transcription factors: Oct4, Sox2 and Nanog, have probed responsible for maintaining the undifferentiated state of stem cells, particularly embryonic stem cells. Ectopic introduction of these factors into differentiated cells is capable of reprogramming these cells into embryonic stem-like cells (called iPS, induced pluripotent stem cells). It has been shown recently that one of the main regulators of oncogenic transformation, the p53 tumor supressor, controls the induction of pluripotency, thus linking the process of reprogramming with the process of tumorigenesis.
By characterizing factors that control mammosphere formation in the breast carcinoma cell line MCF7 we have identified Sox2 as a gene that is up-regulated upon sphere formation. Besides, ectopic expression of Sox2 is capable of inducing augmented sphere formation, suggesting that expression of Sox2 is a key regulator of breast cancer stem cell phenotype. Up-regulation of Sox2 expression is transcriptionally controlled at the level of the RR1 Sox2 promoter enhancer which is also involved in regulation of Sox2 expression in pluripotent stem cell lines.
The recent observation that the tumor suppressor p53 pathway acts as a barrier for induced pluripotency reprogramming has lead to the speculation that cancer stem cells may arise through an altered reprogramming-like mechanism. Our data suggests that Sox2 expression may be such an event.
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 4224.
Abstract 423: Suppression of endometrial cancer cell migration, invasion, and colony formation by the putative tumor suppressor gene MIIP
Authors: Wang Yingmei , Ji Ping , Yang Da , Hu Limei , Cogdell David , Broaddus Russell , Xue Fengxia , Zhang Wei 
Published: February 2011

Abstract
Objective: Endometrial carcinoma (EC) is the leading cancer of the female genital tract in the United States and the fourth most common cancer among women after breast, lung, and colorectal cancer. Augmented cell motility, invasion, and proliferation are hallmarks of aggressive EC. We aim to determine whether the recently discovered migration and invasion inhibitory protein (MIIP) gene functions as an inhibitor for these hallmarks in endometrial cancer cells.
Methods: We measured MIIP expression by Western blot and quantitative RT-PCR. The effect of MIIP on cell motility and invasion was measured by wound healing and Boyden Chamber transwell assay. The potential anti-tumor function of MIIP was measured by colony formation assay. Whole-genome transcriptome was determined in MIIP overexpressing cells and KEGG pathway analysis was done to determine the key pathways regulated by MIIP.
Results: The levels of MIIP mRNA and protein expression were decreased in high-grade EC compared with normal EC tissues. MIIP protein is detectable at low level in the HEC1A cell line but undetectable in the AN3CA and HEC1B cell lines. Knockdown of MIIP expression with siRNA in HEC1A cells significantly increased cell migration when compared with control siRNA treated cells (71.17±3.82 vs. 30.12±1.94, P&lt;0.01). Elevated expression of the MIIP significantly decreased cell migration in AN3CA and HEC1B cells compared with control empty vector-transfected cells (AN3CA: 26.67±1.86 vs. 69.83±2.93, P&lt;0.01; HEC1B: 21.83±2.04 vs. 89.83±5.56, P&lt;0.01). The invasion of the MIIP-knocked-down HEC1A cells was significantly increased compared with control (50.67±1.86 vs.5.83±1.47, P&lt;0.01). Consistently, cell invasion was significantly decreased in MIIP overexpressed cells compared with control HEC1B cells (18.33±2.33 vs.43.17±4.07, P&lt;0.01). Overexpression of MIIP in EC cell lines led to reduced levels of matrix metalloprotease 2 and 9. Further, transfection with the MIIP expression vector significantly reduced colony formation by 73.6% in HEC1A compared with empty vector-transfected cells (52.25±3.30 vs.13.75±2.87, P&lt;0.01). Gene expression profiling of MIIP overexpressed AN3CA and HEC1B cells and their control cells followed by KEGG pathway analysis showed that MIIP expression regulates TP53 signaling, Jak-STAT signaling, and PI3K/Akt pathways.
Conclusions: MIIP may function as a tumor suppressor gene for endometrial cancer and loss of MIIP expression may contribute to increased cell growth and migration/invasion activities in endometrial cancer 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 423.