tbuckley/cabot-search huggingface dataset:
Abstract 5114: SRC-1 Up-regulates Integrin α5 Expression and Enhances Breast Cancer Metastasis
Authors: Li Qin, Michael Joseph Toneff, Xian Chen, Yelin Wu, Yi Li, Jianming Xu
Journal: Cancer Research (2010)

Abstract Steroid receptor coactivator-1 (SRC-1) is a member of the p160 SRC family, which also contains SRC-2 (TIF2/GRIP1) and SRC-3 (AIB1, p/CIP, ACTR, RAC3, TRAM-1). These molecules can interact with nuclear hormone receptors and certain other transcription factors to promote gene expression. In breast cancer, SRC-1 expression positively correlates with HER2 expression, disease recurrence and resistance to endocrine therapy. Our previous work has demonstrated that genetic ablation of SRC-1 in mice significantly suppresses breast cancer metastasis without affecting primary tumor initiation and growth in the MMTV-PyMT (polyoma middle T) mouse model. However, the mechanisms by which SRC-1 promotes breast cancer metastasis are unclear. To address the role of SRC-1 overexpression in breast cancer metastasis and mechanism, we generated MMTV-hSRC1 transgenic mice and found that MMTV-hSRC1 virgin mice exhibited normal mammary gland development. To take an advantage of the avian virus-mediated oncogene expression system, we crossed MMTV-hSRC1 mice to MMTV-tva mice and generated MMTV-hSRC1;MMTV-tva bi-transgenic mice. Intraductal injection of RCAS-PyMT avian viruses induced more metastasis in these bi-transgenic mice than in MMTV-tva mono-transgenic mice, suggesting that SRC-1 overexpression promotes lung metastasis. We also performed studies using MMTV-PyMT;SRC1−/− (KO) and MMTV-PyMT;SRC1+/+ (WT) cell lines derived from primary mouse mammary tumors. KO cells showed much lower migration and invasion capabilities than WT cells. KO cells also adhered much slowly to fibronectin and had reduced levels of active FAK, c-Src and Rac1. Mechanistic analyses revealed that SRC-1 was associated with a promoter region of integrin α5 with C/EBP and AP-1 binding sites and the integrin α5 gene might be a direct target of SRC-1. Accordingly, knockdown of integrin α5 in WT cells reduced cell adhesion and migration. Therefore, one of the pathways for SRC-1 to promote breast cancer cell migration and metastasis is to up-regulate integrin α5, leading to super activation of FAK, c-Src and Rac1. Our study provides a possibility to inhibit SRC-1-promoted breast cancer metastasis by targeting the integrin α5 function. 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 5114.
Double-Phase Tc-99m MIBI Scintigraphy as a Therapeutic Predictor in Patients with Non-Hodgkin’s Lymphoma
Authors: Ho-Chun Song, Je-Jung Lee, Hee-Seung Bom, Ik-Joo Chung, Hyeoung-Joon Kim, Young-Kyu Park, E Edmund Kim
Journal: Clinical Nuclear Medicine (2003)

Purpose Tc-99m MIBI is a promising agent for the functional characterization of P-glycoprotein expression and the prediction of therapeutic outcome in human tumors. The purpose of this study was to determine whether tumor clearance of Tc-99m MIBI may have a predictive value in the clinical outcome in patients with non-Hodgkin’s lymphoma. Methods Seventeen patients with histologically proved non-Hodgkin’s lymphoma underwent Tc-99m MIBI scintigraphy before starting chemotherapy. Early and late images were obtained after the injection of 740 MBq (20 mCi) Tc-99m MIBI. Tumor-to-normal soft tissue ratios were measured on early and late images, and the percentage retention (%R) was calculated. These findings were correlated with other prognostic factors. Results Of all 40 tumor lesions, 22 (55%) showed Tc-99m MIBI tumor uptake, whereas the other 18 (45%) lesions had no uptake. According to the location, the diagnostic accuracy of Tc-99m MIBI scans was 66.7% (12 of 18) for lesions of the head and neck, 66.7% (8 of 12) for those of the chest, and 20% (2 of 10) for those of subdiaphragmatic regions (P = 0.037). The mean %R of complete responders was 91.8 ± 14.8% and for partial responders or nonresponders it was 65.4 ± 17.7% (P = 0.014). The %R of Tc-99m MIBI showed a significant negative correlation with the serum lactate dehydrogenase level (r = -0.757), the score of the international prognostic index (r = -0.643), and the Ann Arbor stage (r = -0.733). Conclusion The slow tumor clearance of Tc-99m MIBI can predict a good response to chemotherapy in patients with non-Hodgkin’s lymphoma and differentiate responding and nonresponding tumors early in the course of chemotherapy.
Abstract 4355: Use of MnSOD tet on transgenic mice as a model for evaluating irradiation protection and mitigation
Authors: Michael W. Epperly, J. Richard Chaillet, Shaonan Cao, Xichen Zhang, Joel S. Greenberger
Journal: Cancer Research (2012)

Abstract Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme responsible for the dismutation or reduction of superoxide produced by cellular respiration. Absence of MnSOD is lethal two to three days after birth. Following irradiation there is an increase in superoxide production which combined with nitric oxide can result in the formation of the highly reactive radical peroxynitrite. Increased expression of MnSOD in a cell increases survival by the reduction of superoxide produced following irradiation. Decreased MnSOD production has resulted in decreased survival following irradiation. To better understand the role of MnSOD in cellular respiration as well as protecting the cell from irradiation damage, we have developed a MnSOD tet on mouse which has no MnSOD activity. In the absence of doxycycline the homozygous MnSOD tet on mouse does not survive past 2 or 3 days after birth. If doxycycline (2 µg/ml) is added to the water of heterozygous mothers, the MnSOD tet on mice develop normally and are fertile as long as they remain on the doxycycline treated water. Long term bone marrow cultures (LTBMCs) were established from homozygous MnSOD tet on mice, heterozygous tet on mice and control C57BL/6J mice. The cultures from the control mice had more hematopoietic cell activity than the MnSOD tet on cultures. To determine when the MnSOD gene is turned on after addition of doxocycline, bone marrow stromal cell lines were developed from the LTBMCs were incubated in 1 µg doxocycline/ml media for time points up to 24 hr, RNA was extracted and RT-PCR for the MnSOD transgene was performed. By 12 hours there was an increase in MnSOD RNA expression in the MnSOD tet on cells. Removal of the doxycycline resulted in a decrease in MnSOD RNA by 1 hr in the MnSOD tet on cells as well as the heteroxyzous cells. This mouse model will be useful for testing new compounds for radiation protection and mitigation. 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 4355. doi:1538-7445.AM2012-4355
Fra-1 Expression in <i>In Situ</i> and Invasive Ductal Breast Carcinomas: Association with Worse Prognosis in Invasive Basaloid Tumors.
Authors: A. Logullo, M. Stiepcich, C. Toledo Osório, F. Pasini, F. Soares, S. Nonogaki, M. Brentani
Journal: Cancer Research (2009)

Abstract Background: Fos-related antigen 1 (Fra-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. A high level of Fra-1 expression is found in various tumors and tumorigenic cell lines, suggesting that Fra-1 may be involved in malignant progression. Objective: Evaluate the significance of Fra-1 expression in breast carcinogenesis and its possible help in sub typing and prognosis of breast carcinomas. Methods: Fra-1 expression was investigated by immunohistochemistry in a Tissue Microarray composed by neoplastic breast tissue from 85 in situ breast carcinomas lesions and 769 invasive ductal carcinomas NOS (IDC), ranging from early stage T1 N0M0 to very aggressive metastatic disease (TxN1-3M1). Positive and negative controls were present in each reaction. Nuclear staining were considered positive. Correlations of Fra-1 expression with other indicators of breast carcinoma prognosis (ER, PR TNM, survival) were analyzed. Results: IDC showed 22.8 % of positivity while in situ lesions maintained a 42.2% of reactive cases. In IDC samples, Fra-1 expression correlated with markers of invasiveness, as Node status, histological grade (P= 0.005 and 0.001, chi-square test) and marginally with presence of metastasis (P= 0.07). Fra-1 was also associated to Cytokeratin (CK) 14 (P= 0.043) and marginally to CK18 and her-2 status (P=0.063 and 0.05), and indirectly to estrogen receptor (P= 0.01). When we select basaloid (CK6 positive, ER negative) cases Fra-1 was associated to worse prognosis (P= 0. 013 - Log Rank test). Conclusions: The data shown here suggest that Fra-1 expression is progressively lost during cancer progression from DCIS to IDC. Fra-1 expression in IDC basaloid tumors confers a worse prognosis. Supported by FAPESP nº 04/04607-8. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2129.
Expression of P-Glycoprotein in High-Grade Osteosarcomas in Relation to Clinical Outcome
Authors: Nicola Baldini, Katia Scotlandi, Giovanni Barbanti-Bròdano, Maria Cristina Manara, Daniela Maurici, Gaetano Bacci, Franco Bertoni, Piero Picci, Sandra Sottili, Mario Campanacci, Massimo Serra
Journal: New England Journal of Medicine (1995)

Increased levels of P-glycoprotein occur in some osteosarcomas. In this study we determined the relation between P-glycoprotein status and outcome in patients with high-grade osteosarcoma.
AB1023 Hepatic osteodystrophy during chronic viral hepatitis
Authors: L. Mnif, M. Medhioub, M. Boudabbous, L. Chtourou, A. Amouri, N. Tahri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Metabolic bone disease is common among patients with chronic liver disease. It is known as hepatic osteodystrophy. Osteoporosis is the most common complication; its incidence varies between 20 and 100% depending on the series. <h3>Objectives</h3> the aim of this study was to assess the prevalence and risk factors of hepatic osteodystrophy in patients with chronic viral hepatitis. <h3>Methods</h3> The study was carried out in 47 patients with chronic viral hepatitis B or C. Bone mineral density (BMD, g/cm) was assessed by dual X-ray absorptiometry. Osteoporosis was diagnosed when BMD was 2.5 standard deviations below the mean peak value in young adults (T score, 22.5 SD). Patients with other pathology that may change the bone metabolism were excluded. <h3>Results</h3> This is a prospective study including 47 patients (16 women and 31 men), with a mean age of 49.8 years (19-80 years). Thirteen patients had hepatitis C (28%) and thirty four were carriers of hepatitis B (72%). Liver cirrhosis was found in 38, 3% of patients (Child A: n=5, Child B: n=8, child C: n=5). No patient was taking calcium supplements, four of them had a history of fractures, and only three had a family history of osteoporosis. Almost a third of our patients were smokers and 10% of them were alcohol drinkers. Among patients with hepatitis C, 4 had osteoporosis and 3 had osteopenia. For those with hepatitis B, five had osteoporosis and 13 osteopenia. Osteoporosis was associated with female sex (p=0.022). Patients with bone loss had respectively a body mass index and albumin levels lower than patients with normal bone density 26.3 vs 23 kg/m<sup>2</sup>; p=0.05 and 38.2 VS 33.2 g/l; p=0.03 respectively. There were no significant differences between the two groups regarding the nature of hepatitis, disease duration, sex, cytolysis, cholestasis and cirrhosis. <h3>Conclusions</h3> Bone loss must be systematically sought in chronic viral hepatitis. Female sex, low body mass index and low albumin level are risk factors of hepatic osteodystrophy in patients with viral hepatitis. <h3>Disclosure of Interest</h3> None Declared
False-Positive 123I-FP-CIT Scintigraphy and Suggested Dopamine Transporter Upregulation Due to Chronic Modafinil Treatment
Authors: Per Borghammer, Karoline Knudsen, Erik Danielsen, Karen Østergaard
Journal: Clinical Nuclear Medicine (2013)

A 76-year-old man with movement disorder had a I-FP-CIT (DaTSCAN) SPECT exam demonstrating universally decreased striatal uptake. It was later determined that he had taken modafinil, and the scintigraphy was interpreted as false positive. Because of progressive symptoms, DaTSCAN was repeated 43 months later, with modafinil withheld for 7 days. Striatal uptake values were nearly doubled compared with the modafinil state and were now above normal upper limit. This suggests pharmacological upregulation of dopamine transport capacity by chronic modafinil treatment. In this setting, I-FP-CIT striatal uptake values should be interpreted with caution.
Abstract 973: The NCI Biospecimen Research Network
Authors: Sherilyn Sawyer, Helen M. Moore, Mark David Lim, Jimmie Vaught, Carolyn C. Compton
Journal: Cancer Research (2010)

Abstract The National Cancer Institute's (NCI) Office of Biorepositories and Biospecimen Research (OBBR) initiated the Biospecimen Research Network (BRN) in early 2006 to coordinate and support systematic investigation into how collection, processing, and storage of human biospecimens affect subsequent analysis. To support this goal, the BRN sponsors, conducts and collaborates on studies to evaluate the effects of biospecimen pre-analytical variables on the outcomes of molecular assays for cancer diagnosis and research. BRN supported findings will contribute to the development of evidence-based best practices for the collection, processing, storage and transport of biospecimens; building on the “NCI Best Practices for Biospecimen Resources.” Currently the BRN sponsors a variety of initiatives aimed to develop and support the research efforts of the biospecimen science community. Through its newly launched extramural research program the BRN supports a portfolio of projects addressing biospecimen pre-analytical variables and biospecimen integrity. Furthermore, the BRN aims to significantly improve biospecimen-based diagnostic and research capabilities by communicating the results of such research to the scientific and clinical communities. The Biospecimen Research Database and the annual BRN symposium, Advancing Cancer Research Through Biospecimen Science are forums established for effective exchange of biospecimen research results. The BRN also supports new research and innovation through its collaborations with other NCI programs such as NCI Innovative Molecular Analysis Technologies (IMAT), the NCI Small Business Innovation Research Development Center (SBIR), the Clinical Proteomics Technologies for Cancer (CPTC) and the Cancer Genome Atlas (TCGA). Through these partnerships, the BRN serves as a resource for program awardees and presents new opportunities for research. 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 973.
A6.12 Lateral Epicondyle Tendon Lesions Treatment with Platelet Growth Factors
Authors: P González-Moreno, R Santos Sanabria, R Hernández-Sánchez, JL Marenco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic painful tendon disorders are common and difficult to treat. Recently, research has focused on regenerative therapies based in the injections with autologous platelet growth factors (PGRF). Two randomised clinical trials involving patients with tendinopathy receiving autologous PGRF showed conflicting results. However, better outcomes were observed among individuals randomised to PGRF injections in the trial randomising patents with lateral epicondyle tendon lesion. The potential benefit of PGRF injections in patients without response to standard therapy is not established. <h3>Objectives</h3> To evaluate the efficacy and safety of local injections with autologous PGRF to treat epicondylitis in patients refractory to standard therapy. <h3>Methods</h3> Patients with epicondylitis who had received standard therapy including corticosteroid local injections and NSAIDS, with or without local ice or orthesis, were included in this prospective study. Patients being treated with physiotherapy were excluded. Patients were treated with one PGRF injection per month during three months. Symptoms, side effects of injections, visual analogic scale (VAS) were recorded in every visit. Fried man test was applied to compare VAS among visits. <h3>Results</h3> 17 patients were included, 12 (57%) of whom were men. The median age was 52 (range: 42–61) years. 8 individuals have completed the scheduled therapy, 17 have reached 1 month. Median (RIQ) VAS were: at baseline 7 (6–9); at 1 month 6 (4–8); at 2 months 5 (3–9.5) (p &lt; 0.001). An improvement in VAS was observed in 14 (82%) patients at 1 month, and 6 (75%) at 2 month. No significant side effects were observed. <h3>Conclusions</h3> Local PGRF injections were efficacious to treat lateral epicondyle tendon lesions in patients without response to previous standard therapy. Local PGRF injections were well-tolerated.
Clonality in Nodular Lymphocyte-Predominant Hodgkin's Disease
Authors: Toshiyuki Ohno, Judith A. Stribley, Gang Wu, Steven H. Hinrichs, Dennis D. Weisenburger, Wing C. Chan
Journal: New England Journal of Medicine (1997)

There is general agreement that lymphocytic and histiocytic (L&H) cells, the variants of Reed–Sternberg cells in nodular lymphocyte-predominant Hodgkin's disease, belong to the B-cell lineage. However, the clonality of L&H cells remains controversial.
P16.35 * DELAYED CONTRAST MRI FOR DIFFERENTIATING TUMOR FROM TREATMENT EFFECTS IN CONVENTIONAL AND ANTI-ANGIOGENIC TREATMENTS
Authors: D. Daniels, D. Guez, D. Last, L. Zach, Y. Mardor, T. a. group
Journal: Neuro-Oncology (2014)

Conventional MRI is unable to differentiate progression from treatment effects (TEs) in brain tumor (BT) patients. We have applied a novel technique, based on MR images acquired with a delay of >1 hour, enabling high resolution complete separation between tumor (contrast clearance at the delayed time point) and TEs (contrast accumulation) with no overlap. 496 maps were calculated for 151 patients with primary/metastatic BTs recruited/followed on study. The maps were validated by comparing pre-surgical maps of 51 resected patients with histology, resulting in 100% sensitivity and 93% specificity to active tumor regions (ATRs). Following initial validation, the maps were used for making 232 clinical decisions. In 67 cases the decision was to continue follow-up and in 165 to change treatment (surgery, chemoradiation, radiation treatments, switch to Avastin, etc). The incidence of decisions to change treatment was significantly higher in primary BTs (83%) than in metastatic BTs (54%). The application to Avastin was studied in 20 recurrent GBM patients and 2 patients with breast cancer brain metastases scanned pre/during Avastin. 90% of the GBM patients demonstrated significant reduction in TEs 1 month (58 ± 16% of original volume, p < 0.03) and up to 3 months (55 ± 19%, p < 0.04) post treatment. 80% demonstrated a reduction in ATRs 1 month post treatment (56 ± 18% of original volume, p<0.04), however, at 3 months ATRs re-grew to near baseline volumes. Only 3 patients demonstrated response >5 months post treatment. This data suggests that Avastin may induce antineoplastic effects (mostly short term), and not only reduction in TEs/edema, as previously suggested. In 10 GBM patients who reached progression, the change in ATRs 1 month post treatment was found to correlate significantly with patients' PFS. The correlation calculated from the maps (r2 = 0.9, p < 0.0001) was significantly higher than those calculated from T1-Gd (r2= 0.65, p < 0.009) and FLAIR (r2 = 0.55, p < 0.02), suggesting the maps provide additional information regarding response to Avastin. A subgroup of 6 patients underwent re-irradiation during Avastin. All showed significant radiological response in the maps (ATRs decreased to 62 ± 10% of original volume while TEs increased to 296 ± 72%), in agreement with clinical stabilization, while conventional MRI showed radiological deterioration (T1-Gd/FLAIR showed stable/increased enhancing volumes reaching 92 ± 21%/155 ± 18% of original volumes). 2 patients with 4 breast cancer metastases showed significant response as well (ATRs decreased to 10 ± 3% of original volumes). In summary, our high resolution, easy to interpret, model-independent maps provide clear differentiation between tumor/non-tumor tissues in BT patients undergoing conventional treatments. Initial experience with Avastin suggests that the maps may also be valuable in assessing response to antiangiogenic treatments.
Abstract 620: Development of a dual protein farnesyltransferase -geranylgeranyltransferase-I inhibitor with antitumor activity against human cancer cells
Authors: Aslamuzzaman Kazi, Yunting Luo, Norbert Berndt, Steven Fletcher, Christopher Cummings, Harshani Lawrence, Andrew D. Hamilton, Said M. Sebti
Journal: Cancer Research (2011)

Abstract Many low molecular weight GTPases such as Ras, Ral and Rho require posttranslational farnestylation or geranylgeranylation for mediating malignant transformation. This prompted the development of farnesyltransferase (FT) inhibitors (FTI) and geranylgeranyltransferase-I (GGT-1) inhibitors (GGTI) as potential anticancer agents. However, when cancer cells are treated with FTIs, K-Ras becomes geranylgeranylated suggesting that inhibition of both FT and GGT-1 may be required to inhibit tumors harboring K-Ras mutations. Recently our group has developed a series of dual FT and GGT-1 inhibitors based on an ethylenediamine scaffold. Among these dual inhibitors FGTI-2734 was most potent in vitro (FT IC50 = 250±190 nM and GGT-1 IC50 = 520±90 nM). In human cancer cells FGTI-2734 inhibits potently HDJ-2 farnesylation, Rap 1A geranylgeranylation and K-Ras prenylation. Furthermore, FGTI-2734 inhibits the phosphorylation of Erk1/2, Akt and S6K, induces p27 accumulation and inhibits potently tumor cell growth. Finally, FGTI-2734 significantly reduces survivin protein levels, and reduction of survivin levels is associated with induction of apoptosis. Thus, this single molecule with dual FT and GGT-1 inhibitory activities may have distinct advantage over selective FTIs and GGTIs and warrants further advanced pre-clinical studies. 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 620. doi:10.1158/1538-7445.AM2011-620