bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5305: Phosphorylations of Serine-10 and Tyrosine-198 residues in the cytoplasmic mislocalized p27 are critical to migration and invasion of osteosarcoma cells
Authors: Li Yiting , Flores Ricardo J. , Hicks John , Chintagumpala Murali , Lau Ching C. , Man Tsz Kwong 
Published: August 2012

Abstract
Osteosarcoma is the most common malignant bone tumor in adolescents and children. Metastasis is the major cause of death among osteosarcoma patients even with the advent of chemotherapy. Therefore, it is an urgent need to identify the key determinants of metastasis in osteosarcoma, so that new and effective therapeutic approaches can be developed to combat this deadly subtype of osteosarcoma. Recent studies have shown that the tumor suppressor protein p27 promotes metastasis when it is mislocalized from the nucleus to the cytoplasm in some solid tumors. However, the subcellular localization of the p27 protein in osteosarcoma and its role in metastasis are not known. In this study, we found that 82% human osteosarcoma cases harbored cytoplasmic staining of p27 using a tissue microarray. An immunohistochemistry analysis revealed that the p27 protein was localized in the nuclei of three pairs of non-metastatic osteosarcoma cell lines, but mislocalized in the cytoplasm of their metastatic sublines. Overexpression of a stable fusion construct of nuclear exporting sequence and p27 in a non-metastatic osteosarcoma cell line significantly increased tumor cell migration and invasion in vitro, suggesting that cytoplasmic p27 can promote metastatic potential in osteosarcoma cells. Site-directed mutagenesis on key phosphorylation sites of cytoplasmic p27 indicated that a mutation on Serine-10 or Tyrosine-198 residue abolished the promoting effects of p27 on cell motility and invasiveness, while a mutation on Tyrosine-157 had no effect. This result suggests that phosphorylations of these two residues are essential for tumor cell migration and invasion. Since mTOR signaling has been implicated in metastatic osteosarcoma, we tested if rapamycin, an mTOR inhibitor, can affect the subcellular localization of p27. We found that exogenous addition of the drug reversed the protein trafficking of p27 from the cytoplasm to the nuclei of metastatic osteosarcoma cells, suggesting that p27 may be a yet undiscovered player in the mTOR signaling of metastatic osteosarcoma. In summary, our results indicate that a novel relationship between p27 mislocalization and the metastatic potential of osteosarcoma cells. Therefore, further characterizations of the role of cytoplasmic p27 and its phosphorylations may lead to the development of a new therapeutic approach for metastatic osteosarcoma.
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 5305. doi:1538-7445.AM2012-5305
Abstract 5308: Id-1 gene and protein as novel therapeutic targets for metastatic cancer
Authors: Murase Ryuichi , Limbad Chandani , Murase Rumi , Soroceanu Liliana , McAllister Sean , Desprez Pierre Yves 
Published: August 2012

Abstract
During normal development and embryogenesis, helix-loop-helix Id proteins regulate the differentiation programs of many tissues. Moreover, recent studies have shown that dysregulated Id expression contributes to cancer progression and metastasis. Specifically, we found high levels of one of the Id family members, Id-1, in breast, prostate, brain and head and neck tumor cells which were highly aggressive, and low levels of Id-1 in non-invasive tumor cells. Ectopic expression of Id-1 in non-aggressive human cancer cells rendered them highly proliferative and invasive, and induced high levels of matrix metalloproteinase (MMP) expression. Conversely, human metastatic cancer cells became significantly less proliferative and invasive in culture when Id-1 protein expression was decreased by antisense RNA or shRNA directed against the Id-1 gene. Next, we asked whether Id-1 could be exploited as a therapeutic target to treat metastatic cancers. Using tumor-bearing animals and systemic gene targeting technique, we showed that reduction of Id-1 levels, and consequently MMP expression, could significantly decrease the metastatic spread of cancer cells. Further, several molecular pathways underlying Id-1 effects on epithelial to mesenchymal transition (EMT) and neoangiogenesis were also identified in certain types of cancer. These results suggested that Id-1 gene and/or protein could be a promising target for development of therapeutic strategies to reduce cancer metastasis. Since Id-1 expression is scarce in most mature adult tissues, a majority of normal cells would not be affected by systemic therapy targeting this gene. We determined that a cannabinoid compound, CBD, could specifically inhibit the expression of the Id-1 gene and, as a result, cancer cell proliferation and invasion in culture and tumor metastasis in vivo. In tumor-bearing mice, we observed significant anti-metastatic effects after daily treatment with CBD. Id-1 expression in tumor cells from lung foci was significantly down-regulated as well as Ki67, a marker of cell proliferation. Finally, CBD prolonged the survival of tumor-bearing mice even though the treatment was initiated after the establishment of metastases. Overall, our data suggest that Id proteins act as key regulators of tumor metastasis and suggest the use of Id genes as novel therapeutic targets.
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 5308. doi:1538-7445.AM2012-5308
Abstract 5374: Significance of ADCC for the action of trastuzumab quantified by novel procedures
Authors: Kute Timothy E. , Stehle John , Ornelles David , Walker Natalie , Vaughn Jim 
Published: August 2012

Abstract
Background: The killing of Her2 + breast cancer cells by the antibody trastuzumab is an attractive therapy because of its specificity and limited side effects. However, many Her2 + positive patients have innate resistants or will become resistant to this treatment. Although Her2 status can be determined by immunohisochemistry or FISH, still only 30% of patients positive for high Her2 status will respond to trastuzumab alone. Improved methods to predict sensitivity to trastuzumab are greatly needed. Since trastuzumab is believed to work by antibody-dependent cell-mediated cytotoxicity (ADCC), we have developed a novel and reproducible bioassay to measure trastuzumab-dependent ADCC which may be predictive of patient response. Methods: Using both an xCELLigence platform (Roche Applied Science) and a flow cytometry assay (PanToXiLux from OncoImmunin, Inc), we measured the ability of mononuclear cells (MNCs) to kill four different breast cancer cell lines in the presence or absence of trastuzumab. Two cell lines used have resistance to trastuzumab and two cell lines have lower Her-2 expression. The xCELLigence platform measures killing in real time while the flow cytometry assay measures the transfer of granzyme B and upstream caspase activity from mononuclear cells to the tumor cells and the activation of cell death processes. The ability of mononuclear cells to bind tumor cells in the presence and absence of trastuzumab was evaluated by microscopy. Using miltenyi beads and immunofluroescence, we have measured which MNC population is most effective in ADCC activity. MNCs from patients with breast cancer and from individuals without disease were analyzed. Results: These studies provide a simple and reproducible assay for ADCC activity. Effective ADCC killing is directly related to Her2 expression on the tumor target. The degree of killing is directly related to the number of mononuclear cells added in the study when trastuzumab is added. Addition of trastuzumab alone to these cell lines results in little killing. MNCs from non-diseased individuals as well as those obtained from breast cancer patients display a broad range of ADCC killing efficiency per cell. Finally, our results demonstrate that NK cells are the major MNC population of effect killing. Conclusion: The two assays presented here and other specific studies show that trastuzumab can work with the immune system to increase cell killing of Her2 overexpressing cells by ADCC. A correlation between the results of these assays and the clinical response to trastuzumab will be presented.
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 5374. doi:1538-7445.AM2012-5374
Abstract 5382: Vascular endotelial growth factor and transforming growth factor-beta are enhanced in plasma of breast cancer patients resistant to endocrine therapy
Authors: Zavadova Eva , Konopásek Bohuslav , Vocka Michal , Fucikova Terezie , Petruzelka Luboš 
Published: August 2012

Abstract
Although more than 2/3 of treated patients respond to the endocrine therapy, most patients with metastatic breast cancer will develop resistance. Estrogen modulate angiogenesis, in part, through the effects on VEGF. It appears that other factor contributing to the resistance may be a transforming factor-beta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates production of vascular endotelial growth factor /VEGF. Defects in the immune response correlated with poor prognosis and therefore in recent years, research focused on a precise description of the status and function of the immune system and its possible effect in cancer patients. The purpose of the study was to monitor immune responses in patients with hormone receptor positive breast cancer resistant to hormone therapy, particularly the examination of cellular (CD4, CD8, HLA-DR) as well as humoral immunity. TGF beta, and VEGF production was monitored and we analyzed the changes during hormonal treatment. Methods: 60 patients included in the research project were implemented routine cancer teratment with hormonal therapy. Basic parameters (histological type and grade, the degree of expression of ER and PR, HER2, and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta, VEGF were mesured by ELISA and anti-tumor cellular immunity (CD4, CD8, antigen presenting cells) will be measured by flow cytometry. Results In patients with resistance to hormone therapy mainly depression in cellular immunity was found.Immunglobulin plasma level was dicreased as well (mainly IgG4 subtype). Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections) TGF beta as well as VEGF plasma level were increased. Significant increase of autoantibodies production was found, particulary in those, involved into blood coagulacion process/anti phospholipide and anti cardiolipin autoantibodies. Conclusion Correlation of these factors with resistance to hormonal therapy, and the state of anticancer immunity could help in the future with the the prediction of resistance to hotmonal therapy and contribute to the selection of targeted immune therapy in cancer patients. Dedication: This project was supported by grant IGA NT11168-3/2010
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 5382. doi:1538-7445.AM2012-5382
Abstract 5398: Direct interaction of inhibitory molecules LAG-3 and PD-1 in murine CD8+ T cell signaling
Authors: Huang Ruea-Yea , Eppolito Cheryl , Matsuzaki Junko , Odunsi Kunle 
Published: August 2012

Abstract
Chronic stimulation by tumor antigens results in exhaustion of antigen-specific T cells and loss of ability to produce key cytokines that are critical for the maintenance of T cell function. We have previously demonstrated that a subset of tumor antigen-specific CD8+ T cells coexpressing LAG-3 and PD-1 are impaired in IFN-γ and TNF-α production and that simultaneous blockade of LAG-3 and PD-1 restores effector function of ovarian tumor antigen-specific T cells in humans. Recently, others have reported that dual blocade of LAG-3 and PD-1 via either by antibodies or gene knockout leads to severe autoimmunity and enhanced immunity to tumors in mice. However, direct evidence of molecular interaction between LAG-3 and PD-1 in T cell signaling is lacking. The signaling molecules downstream of LAG3 are also unknown. Using a combination of ImageStream and confocal microscopy analyses, here we demonstrate that LAG-3 and PD-1 molecules co-localize in approximately 10-15% of activated murine antigen specific CD8+ T cells. Co-localization also occurred with trans-Golgi vesicles, microtubule organizing center, and early/recycling endosomes. Reciprocal immunoprecipitation with specific antibodies for LAG-3 and PD-1 revealed a physical association between LAG-3 and PD-1 and this interaction was abolished in T cells isolated from LAG3- and PD-1 knockout mice. The recruitment of Src family tyrosine kinases and phosphatases to the LAG-3 and PD-1 interaction complex are also implicated. Our data reveal a potential molecular mechanism by which LAG3 and PD-1 co-regulate T cell function.
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 5398. doi:1538-7445.AM2012-5398
Abstract 5472: Role of Harvey Ras (HRAS) mutations in head and neck squamous cell carcinoma (HNSCC)
Authors: Endhardt Katharina U. , Khattri Arun , Keck Michaela , Braegelmann Johannes , Mahmutoglu Derya , Leung Kelley , Dinali Mohamed El , Rieke Damian , Cohen Ezra , Seiwert Tanguy 
Published: August 2012

Abstract
Background: Harvey Ras (HRAS) was recently reported being mutated in head and neck squamous cell carcinomas (HNSCC) and likely plays an important role as an oncogene. The precise role of HRAS mutations for signaling and carcinogenesis of HNSCC remains to be determined. Methods: We completed mutational screening (Sanger Sequencing) for tissues and cell lines focused on the known hotspot mutations G12X and Q61X. Furthermore we performed viability testing for various cell lines and visualized the signaling-effects by itself, in presence of PI3K-, EGFR inhibitors and likewise in combination, by immunoblotting. After suppression of HRAS using siRNA, we determined the cell-viability. Results: In our study we sequenced 100 HNSCC tumor tissues and HNSCC cell lines and identified several canonical HRAS mutations. One cell line contained a G12D HRAS mutation and was further examined. Additional two cell lines with atypical HRAS variants were identified and compared to the classic hotspot mutated cell line. The viability for the mentioned cell lines were indicative of resistance to EGFR inhibition to different degrees. The protein activation levels in important signaling pathways (PI3K/MAPK) confirmed our viability data. HRAS signaling was primarily via PI3K/AKT. Silencing HRAS showed significantly decreased viability. Conclusions: Previous studies have shown that EGFR-targeting agents remain insufficient as single targeted therapy. HRAS appears to contribute to the EGFR-resistance of HNSCC. The canonical mutation G12D appears to signal primarily via PI3K and PI3K inhibitors may be effective. The G12D cell line model indicates a central role of mutated HRAS for signaling and viability consistent with role as a driver mutation.
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 5472. doi:1538-7445.AM2012-5472
Abstract 5482: Sun exposure and prostate cancer risk in New South Wales, Australia: A case control study
Authors: Nair-Shalliker Visalini , Smith David P. , Egger Sam , Hughes Ann Marie , Clements Mark , Kricker Anne , Armstrong Bruce K. 
Published: August 2012

Abstract
Background Ultraviolet-B radiation in sunlight may influence risk of developing prostate cancer. Method We examined the relationship between individual solar UV exposure and risk for prostate cancer in a case control study combining the New South Wales (Australia) Prostate Cancer Care and Outcome (cases) and Non-Hodgkin Lymphoma (controls) studies. Results There was evidence that increasing solar UV exposure increased prostate cancer risk (adjusted OR for highest vs. lowest quartiles of average weekly, warmer months sun exposure 2.07 95% CI: 1.36-3.16) and that this increased risk was most evident with weekend sun exposure (adjusted OR 5.54 95%CI: 2.94-10.43). Increased sun sensitivity was also associated with increased risk of prostate cancer (adjusted OR 1.63 95% CI: 1.09-2.44 for very high sun sensitivity). Conclusion Our results suggest that increasing solar UV exposure increases prostate cancer risk in a high ambient solar UV environment. Impact Given that previous studies conducted mainly in low solar UV environments found either no evidence of an association or evidence of a negative association; our findings suggest the possibility of a U-shaped dose effect relationship between exposure to solar UV and prostate cancer. Further studies are needed to test the hypothesis that high solar UV exposure is a risk factor for prostate cancer and to explore possible mechanisms for such an association.
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 5482. doi:1538-7445.AM2012-5482
Abstract 5499: A descriptive epidemiological study of lobular carcinoma of the breast and the effects of normal lobular regression at menopause
Authors: Yu Anna , Shah Amy , Henson Donald 
Published: August 2012

Abstract
Background: Lobular carcinoma (LC) is a distinctive neoplasm originating in the milk producing glands and constituting about 12% of all breast cancer cases. LC differs from the more common invasive ductal carcinoma (IDC) by morphology and biology. We report the results of a descriptive epidemiological study of LC and a comparison of the pathogenesis of lobular and ductal carcinoma of the breast. Methods: A total of 86,846 cases of invasive LC (ILC) from women, aged 20 to 85, were obtained from NCI's SEER Program for the years 1973-2008 in the United States. There were 20,512 cases of LC in-situ (LCIS) and 66,634 cases of ILC. For comparison, 692,201 cases of IDC and 61,569 cases of ductal carcinoma in situ (DCIS) were collected. The analysis compared trends, age specific rates, log-log plots, age frequencies and relative survival rates. Results: From 1973-2008, the age-adjusted rate of LC progressively increased from 5.8 to 16.4/ 100,000 women. In an age frequency analysis of age versus rate, LCIS increased to 0.22/ 100,000 women at age 50, and then declined to 0.02/100,000 women at age 80. ILC increased to 0.11/100,000 women at age 50, and then plateaued after menopause but did not decline. Log-log plots revealed parallel curves between ILC and IDC in both pre-menopausal and post-menopausal age groups. At age 50, the age specific rate of LCIS increased to 11.3/100,000 women then progressively decreased. In contrast, the age specific rate of DCIS was 22.1/100,000 women at age 50 and continued to increase after menopause. Conclusions: At menopause, the incidence of LCIS decreases as a result of lobular involution of the breast. In contrast, DCIS continues to increase. ILC does not decline but plateaus suggesting that the initiation of ILC occurs before menopause, but the tumor becomes clinically apparent only after menopause. Although morphologically different, parallel log-log plots of age specific rates and age frequency analysis suggest a similar pathogenesis for IDC and ILC even though epidemiological patterns are different.
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 5499. doi:1538-7445.AM2012-5499
Abstract 5519: Prevalence of three types of cancers in southern part of Nigeria
Authors: Nwosu Chinelo Jacinta , Anyangwe Njwen 
Published: August 2012

Abstract
There is an increase in the incidence of various cancers globally. It is estimated that ten (10) million new cases of cancers are diagnosed every year and fifty (50%) of this figure is from developing countries. As death toll from infectious diseases decline globally, cancer is becoming the most potent cause of death led by heart and cardiac diseases. This study was carried out to establish the prevalence of three common cancers that affect mainly women using the Southern parts of Nigeria as a case study. Three age groups of women were used for this study: those below forty (40) years, those between forty (40) and sixty (60) years and those from sixty one (61) and above. The review checked major government owned hospital records from 2006 to 2011 and the results are presented. It was observed that 15% of women from 61 years and above suffered from breast cancer within the period under review. About fifty five (55) % of breast cancer cases occurred in women of age forty (40) years and below while thirty (30) % of cases occurred in the age group forty (40) and sixty (60) years. About four (4) % of breast cancer cases occurred in men. Cervical cancer was more prevalent in women between ages 40-60 years followed by those in age group 61and above. The percentage of women who were diagnosed of cervical cancer in the age group 40-60 years was 37%, percentage of those in age bracket of forty (40) years and below was 16% and those in the age bracket of sixty one (61) years and above that suffered from cervical cancer were 22%. The prevalence of uterine cancer within the period under review was about nine (9) % and distributed in these order; age group forty (40) years and below was 2%, 40-60 years, 3% and 61 years and above was 4%. Thus the study shows that breast cancer was more prevalent in women of 40 years and below, cervical cancer was more prevalent in women of 40 years and above while uterine cancer was low in all age groups. Studies have shown that incidence of breast cancer is rising more in populations that hitherto enjoyed a low incidence rate like many parts of Africa. However there is significant under reporting of diagnosed cancer cases as well late reporting of cancer cases as a result of illiteracy. It was suggested that increase in cancer occurrences in the Southern part of Nigeria is largely due to lack of adequate education and awareness on early detection, and life style of patients. Early detection and treatment have been proven to be effective against cancer proliferation and helps in a better prognosis for patients.
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 5519. doi:1538-7445.AM2012-5519