bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3525: IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma
Authors: Hassan Namir J. , Adams Katherine , Bossi Giovanna , Harper Jane , Buisson Sandrine , Paston Samantha , Liddy Nathaniel , Ashfield Rebecca , Gavarret Jessie , Bianchi Frayne , Baston Emma , Baker Debbie , Ladell Kristin , Sewell Andrew , Li Yi , Cameron Brian , Johnson Andrew , Vuidepot Annelise , Todorov Penio , Kalos Michael , June Carl , Karakousis Giorgos , Linette Gerry , Price David A. , Williams Daniel , McGrath Yvonne , Jakobsen Bent K. 
Published: August 2012

Abstract
In recent years significant advances in the treatment of metastatic melanoma have emerged. Small molecule drugs provide potent short-term responses for a significant proportion of the patient population; for a minority of patients, immunotherapy has elicited long-term responses with the promise of a cure. Despite these advances, long-term remission for the majority of patients remains elusive and much effort is focussed on combination therapies attempting to bring together the potency of small molecule drugs with the durability of immunotherapy. IMCgp100 is a novel bi-specific immunotherapy comprising a soluble, affinity- enhanced, T cell receptor (TCR) specific for the melanoma-associated antigen gp100, fused to an anti-CD3 specific antibody fragment (scfv). The engineered TCR portion of the drug targets the gp100 peptide 280-288 antigen, which is over- expressed and presented by HLA-A2 on the surface of melanoma cells, thereby effectively coating these cells with CD3-specific antibody fragments. The anti-CD3 scfv portion captures and redirects any T cells in physical contact with the melanoma cell to kill it. In vitro, IMCgp100 potently redirects T cells from the blood of late stage cancer patients to target melanoma cells exhibiting substantial HLA-down regulation, even in the presence of high numbers of regulatory T cells. Target cell killing is observed within hours, and is associated with the release of pro-inflammatory cytokines and dendritic cell cross-presentation of gp100 and other melanoma-specific antigens. Thus, IMCgp100 demonstrates the potential to elicit potent short-term responses and trigger longer-term anti melanoma durability in vivo (ref: paper to be published imminently in Nature Medicine). IMCgp100 is currently under investigation as part of a Phase 1 dose-finding study in patients with unresectable Stage III/Stage IV malignant melanoma. Safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity are assessed after intravenous infusion of IMCgp100, and the maximum tolerated dose (MTD) will be established. We also have a Phase 0 trial open, in which IMCgp100 is injected directly into tumours to assess pharmacodynamic activity in human lesions. Both studies are actively enrolling and preliminary clinical data 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 3525. doi:1538-7445.AM2012-3525
Abstract 3526: Subcutaneous administration of PSMA/CD3-bispecific BiTE antibody MT112/BAY 2010112 leads to complete remission of human prostate cancer xenografts in mice
Authors: Friedrich Matthias , Deegen Petra , Voelkel Markus , Wahl Joachim , Schuhmacher Joachim , Steinke Wolfram , Zopf Dieter , Harris Robert B. , Baeuerle Patrick A. , Kufer Peter , Rattel Benno 
Published: August 2012

Abstract
Blinatumomab, a CD19/CD3-bispecific BiTE antibody has shown high response rates and durable remissions in patients with relapsed or refractory acute lymphocytic leukemia and non-Hodgkin's lymphoma. For treatment of patients with prostate cancer (PCa), we have developed a novel BiTE antibody, MT112/BAY2010112, that is bispecific for prostate-specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex. MT112/BAY 2010112 binds PSMA and CD3 of human and macaque origin allowing for assessment of safety, pharmacodynamics and pharmacokinetics in a relevant animal species. PSMA expressing human PCa cell lines VCaP, 22Rv1, MDA PCa 2b, C4-2, PC3-PSMA and LNCaP were lysed by freshly isolated, unstimulated human T cells redirected by MT112/BAY2010112 at EC50 values ranging between 0.1 and 4 ng/ml (1.8-72 pM). Efficacy of lysis correlated with levels of surface expressed PSMA. No lysis was observed in PSMA-negative PCa cell lines PC3 and DU145, showing the target antigen-specific activity of MT112/BAY2010112. The relevance of cynomolgus monkeys for further nonclinical safety evaluation of MT112/BAY 2010112 was demonstrated by in vitro side-by-side comparison of the BiTE antibody's pharmacological characteristics in human and cynomolgus monkey assay systems. For studying the activity of MT112/BAY 2010112 after subcutaneous (s.c.) administration, human 22Rv1 PCa xenografts were grown s.c. in mice to sizes of &gt;200 mm3 in the absence of human T cells. Three days prior to treatment with BiTE, ex-vivo expanded human T cells were intraperitoneally injected. Animals were treated s.c. at 2.5 mg/kg/d or intravenously (i.v.) at 0.5 mg/kg/d for 28 consecutive days. S.c. administration of MT112/BAY 2010112 resulted in a similar drug exposure, rapid shrinkage and complete remission of established PCa xenografts as seen upon i.v. administration of the BiTE antibody. Treatment with human T cells or vehicle alone had no effect on tumor growth. Compared to i.v. administration, the relative bioavailability of the PSMA BiTE in serum after s.c. injection in mice was approximately 18%. Initial results will be presented showing that 14C-labeled MT112/BAY 2010112 accumulates in s.c. implanted LNCaP PCa tumors of mice after tail vein injection. Based on these preclinical in vivo pharmacology results, treatment of PCa patients with s.c. administered MT112/BAY2010112 appears to be justified.
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 3526. doi:1538-7445.AM2012-3526
Abstract 353: In vivo PET imaging of HER2 expression with GE226: An 18F-labelled affibody molecule
Authors: Hoppmann Susan , Danikas Antonios , Durrant Clare , Iveson Peter , Glaser Matthias , Indrevoll Bård , Hiscock Duncan 
Published: August 2012

Abstract
Background: The assessment of HER2 expression in biopsies from primary lesions of breast cancer patients is a standard procedure to select patients for HER2-targeted therapies. However, in metastatic disease in which HER2 status can change, determination of HER2 expression is not standard procedure, which complicates patient management. Herein we report evidence for GE226 ([18F]FBA-ZHER2:2891), a highly specific HER2 targeted imaging agent that can determine HER2 expression levels in preclinical tumour models. We propose that GE226 can be progressed to clinical development for non-invasive determination of the HER2 status in recurrent breast cancer patients to improve the clinical management and therapy selection. Methods: The highly selective HER2 targeted 18F-labelled Affibody molecule GE226 was characterized in a murine dual tumour breast cancer model bearing NCI-N87 (high HER2 status) and A431 (low HER2 status) xenografts in separate flanks. Tumour-bearing mice were injected with 3 to 10 MBq of GE226, followed by biodistribution or positron emission tomography (PET) imaging analysis. Results: Biodistribution analysis demonstrated good differentiation of GE226 retention between high and low HER2 expressing tumours (8.4% ID/g and 3.4% ID/g respectively, 30 min post injection). GE226 cleared quickly from background tissue, including kidneys, with excellent ratios for tumour-to-muscle (8.9 for high HER2 status tumours and 3.6 for low HER2 status tumours, 30 min post injection) and tumour-to-blood (2.5 for high HER2 status tumours and 1.0 for low HER2 status tumours, 30 min post injection). PET imaging of GE226 in the dual tumour mouse model showed a marked difference in signal intensity between the two tumour types. Conclusions: The highly selective HER2 targeted Affibody molecule GE226 can image different levels of HER2 expression in a dual-tumour preclinical model of breast cancer with good target-to-background ratios. These data compare favourably with previous patient SPECT and PET studies using the 111In- or 68Ga-labelled HER2-binding Affibody molecule ABY-002 (Baum et al., J Nucl Med. 2010;51(6):892-7) which supports the efficacy of this class of Affibody tracer for visualization of HER2 expressing metastases. We plan to progress GE226 further to assess HER2 status in metastatic breast cancer patients in clinical PET studies.
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 353. doi:1538-7445.AM2012-353
Abstract 3564: A Phase II randomized trial of lycopene-rich tomato extract among men with high-grade prostatic intraepithelial neoplasia (HGPIN)
Authors: Gann Peter H. , Deaton Ryan , Enk Erika , van Breemen Richard B. , Han Misop , Lu Yi , Ananthanarayanan Viju 
Published: August 2012

Abstract
Evidence from observational epidemiology, animal models and cell culture experiments suggest that tomato foods or other sources of lycopene might inhibit the development of prostate cancer. Clinical trial data, however, is thus far sparse, especially in relation to effects on benign prostate tissue. We conducted a 6-month repeat biopsy trial in men with HGPIN who were randomly assigned to consume either placebo or capsules of Lyco-Mato®, a tomato oleoresin containing 30 mg/day of lycopene. All participants were encouraged to avoid lycopene containing foods and supplements while on-study. Here we report results for serum lycopene, PSA and IGF proteins, and initial results for immunohistochemical analysis of markers for proliferation (minichromosome maintenance protein 2, MCM-2) and cell cycle inhibition (p27). Biopsy slides were stained using monoclonal antibodies for both markers and scoring was performed using an Aperio whole-slide digital microscope and scoring algorithms plus Genie® pattern recognition software for defining the epithelial compartment. Serum lycopene was determined by LC-MS-MS; PSA, IGF-1 and IGFBP3 were measured by enzyme immunoassay. Primary analyses compared treatment groups using a paired t test for the change in each endpoint. A total of 58 men completed the trial (26 active, 32 placebo); assignment groups were equivalent at baseline in terms of age, race, serum lycopene, PSA, IGF-1 and IGFBP3. Serum lycopene increased by 0.550 μmol/L (77%) in the active treatment group and declined by 0.288 μmol/L (19%) in the placebo group. We observed no meaningful differences in serum PSA, IGF-1 or IGFBP3 concentrations between groups. There were also no differences between groups in the percentages of epithelial nuclei expressing MCM-2 or the scoring index combining percentage with nuclear stain intensity. Similar null results were seen for staining with the CDK2 inhibitor p27. We conclude that despite a large difference in serum lycopene concentrations following intervention, no effects were apparent at 6 months on PSA or IGF proteins. The IHC results, although preliminary, suggest that treatment had no effect on epithelial cell proliferation or cell cycle inhibition via p27. Further analyses, including analysis of additional IHC markers, are currently underway.
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 3564. doi:1538-7445.AM2012-3564
Abstract 3570: Cervical cancer screening practices among Hispanic migrant and seasonal farmworkers of Michigan
Authors: Knoff Jayne S. , Soliman Amr S. , Harlow Sioban D. , Yassine May , Barnhardt Kelly 
Published: August 2012

Abstract
Cervical cancer incidence among all racial/ethnic groups in the United States is highest among Hispanics. Previous studies have found that migrant and seasonal farmworkers have limited access to health care and may therefore be less likely to follow screening recommendations for early cervical cancer detection. The objective of this study was to describe Pap test utilization and identify barriers, attitudes and knowledge regarding cervical cancer screening among Hispanic migrant and seasonal farmworkers served by Northwest Michigan Health Services, Inc (NMHSI) in Shelby and Traverse City, Michigan. This cross-sectional study surveyed the patient population of NMHSI. A questionnaire addressing knowledge, attitude and practice of cervical cancer screening was administered to 309 participants in NMHSI clinics or in participants’ residences. The Hispanic study population included 184 seasonal and 125 migrant farmworkers. Of all Hispanics surveyed (mean age 38.7), 94.2% had ever received a Pap test. Comparatively, 87.7% had received a Pap test recently (in the last two years for 21-29 year olds, in the last three years for those over 30) and 14.5% had an abnormal Pap test result in the last ten years. There was no significant difference between migrant and seasonal farmworkers in terms of ever having had a Pap test or having had a recent Pap test (p-value 0.88 for both comparisons). Consistent with these findings, participants reported that they understood the benefits of and experienced few barriers to getting Pap tests. These findings suggest that migrant farmworkers may not experience more difficulty in receiving Pap tests than seasonal farmworkers in Michigan. Farmworkers in general recognize the importance of receiving Pap tests even though both groups of women have low levels of acculturation. Furthermore, findings suggest that recent efforts to increase cervical cancer screening have been effective. While cervical cancer screening rates are high, knowledge is low and this continuing research will aid in identifying specific gaps in cervical cancer screening knowledge and attitudes to address in future interventions.
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 3570. doi:1538-7445.AM2012-3570
Abstract 3575: The effects of selection bias by lung cancer screening
Authors: Aerts Joachim 
Published: August 2012

Abstract
Background: Lung cancer is the most common cause of cancer mortality worldwide. The five-year survival rate of lung cancer is still extremely poor: only 16%. This is mainly due to the fact that most patients present with an advanced stage of the disease. Recent studies showed that screening of high risk persons is very effective in reducing the mortality from lung cancer. However, the inclusion criteria for these studies are rather strict. For instance the study by The National Lung Screening Trial Research Team Persons only included people with more than 30 pack-years (PY) and aged between 55 and 74 years at time. Aim: To evaluate the effects of selection bias in lung cancer screenings studies as the The National Lung Screening Trial. Methods: The inclusion criteria of The National Lung Screening Trial were extrapolated to our population based cohort: The Rotterdam Study. The Rotterdam Study is an ongoing prospective cohort study in Rotterdam, the Netherlands, in which all inhabitants of the Rotterdam suburb Ommoord aged ≤ 55 years were invited to participate in the study. A total of 7,983 participants (78%) were included between 1990-1993 in the first cohort. Up to 2009, 208 deaths due to incident lung cancer were found in this cohort. Results: In our cohort, only 62 cases (29.8%) complied with the criteria of the screening trial (persons with unknown smoking history were included in the &gt;30 PY group). 12.5% of the lung cancer cases between 55-74 years of age were never smokers or had a history of &lt;30 PY at baseline and the remaining 57.7% were above 74 years. Consequently, 70.2% of cases would not have been included. A relative reduction in mortality of 20%, as found in the screening trial, would lead to a reduction in mortality in the Rotterdam Study population of lung cancer of 6.0% (i.e. 0.2*62 = 12.4 persons out of the 208 would have been saved from mortality by lung cancer). Conclusion: Screening of lung cancer with the present inclusion criteria reduces lung cancer death rate compared to standard of care, but because only a minority of lung cancer patients comply with these criteria, we should be cautious in generalizing findings to the total population of such patients. In addition, mortality reduction may be different in countries with other demographics and health care systems.
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 3575. doi:1538-7445.AM2012-3575
Abstract 3579: Prognostic and predictive role of JWA and XRCC1 expression in gastric cancer
Authors: Zhou Jianwei , Wang Shouyu 
Published: August 2012

Abstract
Purpose: Polymorphisms in the DNA repair genes JWA and XRCC1 have recently been reported to increase susceptibility for gastric cancer, but the expression pattern and significance of these genes in gastric cancer is unknown. Experimental Design: Expression of JWA and XRCC1 were assessed by immunohistochemistry in three independent tissue microarray sets of gastric carcinoma (total n=1227), and paired adjacent non-tumoral tissues (n=80) with minimum five years follow-up time. Prognostic value of JWA and XRCC1 and of clinicopathologic factors, were evaluated in patients treated only with surgery. The predictive role of JWA and XRCC1 expression status in cases treated with adjuvant chemotherapy compared with surgery alone was analyzed. Results: JWA and XRCC1 protein levels were significantly downregulated in gastric cancer lesions compared with adjacent non-cancerous tissues (P &lt; 0.001 for all correlations). Low tumoral JWA or XRCC1 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients without adjuvant treatment. Multivariate regression analysis showed that low JWA and XRCC1 expression, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P = 0.01), however, this effect was evident only in the JWA or XRCC1 low expression group (HR = 0.44; 95% CI = 0.26-0.73; P = 0.002, and HR = 0.44; 95% CI = 0.26-0.75; P = 0.002, respectively). Conclusions: JWA and XRCC1 protein expression in tumor are novel candidate prognostic markers and predictive factors for benefit from adjuvant FLO chemotherapy in resectable human gastric carcinoma. Acknowledgements: This study was supported in part by the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China (30930080, 81001231), the Foundation of Cancer Center of Nanjing Medical University (08ZLKF08), and the Postdoctoral Science Foundation of China (20100481165).
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 3579. doi:1538-7445.AM2012-3579
Abstract 3581: Long-term results of organ sparing surgical treatments of precancerous cervical lesions in Mongolia
Authors: Damdin Avirmed , Jazag Amarsanaa 
Published: August 2012

Abstract
Background: Cervical cancer is the most common cancer in female reproductive system. Since introduction of diagnostic modalities like Pap-tests, the detection pre-cancerous cervical lesions CIN1, CIN2 and CIN3 have increased dramatically. Early detection of pre-cancerous lesions enables performance of organ sparing treatments like LEEP, conization and cryotherapy. Aim: Since there are no studies in the field of organ sparing treatment of cervical cancer, we decided analyze the results of such treatments and calculate the: 1. Five year survival of patients underwent organ sparing surgical procedures 2. Fertility and reproductive function of these patients Method: LEEP (n-63), knife conization (n-22) and trachelectomy (total removal of cervix) (n-15) was performed in women of reproductive age (25-35 years old) at National Cancer Center. The treatment results were followed for 5 years and statistical analysis of survival and reproductive function were analyzed. Results: 87.7% of patients with CINI lesions had LEEP, 12.3 % had knife conization and 0% had trachelectomy. 44.4% of patients with CINI lesions had LEEP, 55.6 % had knife conization and 0% had trachelectomies respectively. For CINIII 6.2% of patients had LEEP, 0% had knife conization and 93% had trachelectomy. We performed organ sparing treatment in 100 patients, out of which 10% had cancer recurrence in LEEP treatment, 9.1% in knife conization and 0% in trachelectomy. Complications of hemorrhage were observed in 14% of patients, cervical tube obstruction in 3% and deterioration of chronic inflammations in 13% respectively. After the organ sparing treatment, menstrual cycle was normal in 75% of the all patients, 65% reached pregnancy. 9.2% of patients who reached pregnancy had stillbirth, 12.3% had abortion, and 78.5% had normal delivery. 80.4% of patients with pregnancy had natural labors, while19.6% of patients had caesarean sections respectively. Conclusion: in Mongolia, LEEP, knife conization and trachelectomy methods are used since 2000. But the treatment results were not reported so far. 10% of patients treated by LEEP and 9.1% of patients treated by knife conization had tumor recurrence. Thus our treatment efficiency is above 90%. Up to 20% of patients had complications ranging from bleeding to cervical tube obstruction. We conclude that organ sparing cancer treatment allows better QOL (quality of life) for the patients and provides opportunity to have children.
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 3581. doi:1538-7445.AM2012-3581