bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3744: Office cervicoscopy in the diagnosis of HPV infection
Authors: Darwish Atef 
Published: July 2017

Abstract
Introduction: Since the association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Searching for HPV became a basic step in all screening programs. Laboratory HPV testing is costly and unavailable in developing countries.
Objective: To compare the diagnostic indices of office cervicoscopy against cytology and punch biopsy for detection of underlying HPV lesions in women with suspicious cervix.
Design: An analytic cross-sectional research design
Setting: Early cervical cancer Detection Unit of the Women's Health University Hospital. Assiut, Egypt.
Patients and methods: A total of 274 non-pregnant women with clinical diagnosis of suspicious cervix were included in this study. After cervical smearing with Ayre's spatula, they were subjected to cervicoscopy utilizing 2.6 mm telescope and a 3.2 mm outer sheath office hysteroscope. Evaluation of the vulva, vagina, ectocervix, endocervical canal and the endometrial cavity were done. The cervix was then painted with saline, acetic acid and Schiller's iodine stains successively as used during colposcopic examination. Abnormal lesions were biopsied using punch biopsy forceps. Cytologic evaluation relied on both classic and non-classic (secondary) criteria for the diagnosis of HPV including "mild koilocytosis," mild dyskeratocytosis," hyperchromatic nuclei, bi- and multinucleation, and cleared cytoplasm. Punch biopsies were taken from every case based on cervicoscopic localization after staining.
Results:. The main complaint was abnormal vaginal discharge in 197 cases (71.4%) . Pap smear sampling was negative for HPV in 188 cases (68.6%) and positive in 86 cases (31.4%). Cervicoscopic findings suggestive of HPV infection were positive in 77 cases ( 28.1% ) and negative in 197 cases (71.9% ). Gold stand histopathology diagnosed HPV in 53 cases only (19.3%). All diagnostic indices of cervicoscopy significantly improved after combination with cytology positive results except false positive results..
Conclusions: Cervicoscopy as a simple, cheap and office procedure can be used as a quick screening tool of HPV infection in women with suspicious cervix. It has the advantage of screening of the rest of the genital tract. In the absence of laboratory HPV testing, cervicoscopy in conjunction with cytology screening of high-risk cases should be encouraged.
Note: This abstract was not presented at the meeting.
Citation Format: Atef Darwish. Office cervicoscopy in the diagnosis of HPV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3744. doi:10.1158/1538-7445.AM2017-3744
Abstract 3748: Development of anti-human mesothelin chimeric antigen receptor (CAR) messenger RNA (mRNA) transfected peripheral blood mononuclear cells (CARMA) for the treatment of mesothelin-expressing cancers
Authors: Hung Chien-Fu , Xu Xuequn , Li Linhong , Ma Ying , Jin Qiu , Viley Angelia , Allen Cornell , Natarajan Pachai , Shivakumar Rama , Peshwa Madhusudan V. , Emens Leisha A. 
Published: July 2017

Abstract
CD19-targeted chimeric antigen receptor (CAR)-engineered T/NK-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been less successful in solid cancers. This is partly due to specificity for shared tumor antigens also present on normal host tissues that leads to ‘on-target/off-tumor’ toxicity. We therefore developed a non-viral approach using repeated infusions of mesothelin-specific messenger RNA (mRNA) CAR-transfected T cells to permit prospective control of ‘on-target/off-tumor’ toxicity. Early trials provided preliminary evidence of the safety and anti-tumor activity of this strategy, but the ex vivo selection, activation and expansion of lymphocytes is laborious and expensive. We therefore explored the feasibility of using a rapid, automated, closed system for cGMP-compliant mRNA CAR transfection into freshly isolated peripheral blood mononuclear cells for clinical scale manufacture (CARMA). The resulting cryopreserved cellular product expressed CAR in &gt;95% of cells, and recognized and lysed tumor cells in an antigen-specific manner. Expression of CAR was detectable for 5-7 days in vitro, with a progressive decline of CAR expression related to in vitro cell expansion. In a murine ovarian cancer model, a single intra-peritoneal (IP) injection of CARMA resulted in the dose-dependent inhibition of tumor growth and prolonged the overall survival (OS) of mice. Multiple weekly IP injections of the optimal CARMA dose enhanced disease control and further prolonged OS, both of which improved with an increasing number of injections. No significant off-tumor toxicities were observed. These data support further investigation of serial IP CARMA administration as a potential treatment for ovarian cancer and other mesothelin-expressing tumors involving the peritoneum, and provide preclinical proof of principle of CARMA for solid tumors.
Citation Format: Chien-Fu Hung, Xuequn Xu, Linhong Li, Ying Ma, Qiu Jin, Angelia Viley, Cornell Allen, Pachai Natarajan, Rama Shivakumar, Madhusudan V. Peshwa, Leisha A. Emens. Development of anti-human mesothelin chimeric antigen receptor (CAR) messenger RNA (mRNA) transfected peripheral blood mononuclear cells (CARMA) for the treatment of mesothelin-expressing cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3748. doi:10.1158/1538-7445.AM2017-3748
Abstract 3762: Superior T cell activity of a membrane-proximal binding antibody when targeting Glypican-3 with an antibody-coupled T-cell receptor (ACTR) armed T cell
Authors: Motz Greg , Shin John , Whiteman Kathleen , Schultes Birgit , Pai Tapasya , Westendorf Lori , Ettenberg Seth , Biechele Travis , Sussman Django , Huet Heather 
Published: July 2017

Abstract
Glypican-3 (GPC3) is a GPI-anchored member of the heparan sulfate proteoglycan family. GPC3 is an oncofetal antigen expressed transiently during fetal development with re-expression during malignant transformation. GPC3 is an ideal tumor target as expression has been found in numerous epithelial malignancies, with highest expression in hepatocellular carcinoma (HCC) and non-small cell lung carcinoma (NSCLC), and normal tissue expression is highly restricted (Baumhoer D., Am J Clin Pathol, 2008.). Adoptive T-cell therapy with single-chain variable fragment (scFv)-derived chimeric antigen receptors (CARs) has transformed cancer therapy, but the broad applicability of this approach has been limited in part by safety concerns due the constitutive expression of a biologically active targeting receptor. The Antibody-Coupled T-cell Receptor (ACTR) platform is a universal, engineered T-cell therapy designed to engage the Fc domain of therapeutic antibodies opsonized to tumor cells to mediate anti-tumor activity. ACTR activity is therefore both regulatable and flexible, providing enhanced therapeutic control and improved safety of the T cell therapy.
Using both HCC and NSCLC tumor cell lines, we tested a panel of wild-type and afucosylated antibodies with similar binding affinities that bound to regions spanning the GPC3 protein across unique epitopes. We found that for GPC3 targeting antibodies, the greatest activity in a Jurkat-NFAT reporter assay was observed for the afucosylated antibody that bound GPC3 most proximal to the membrane. Further, the antibody that bound membrane proximal also had the most potent activity in primary ACTR T cell cytotoxicity and cytokine release assays. The physical distance between T cells and tumor targets has been previously determined to impact T cell activation for both peptide-MHC and CAR-T interactions. Similarly, our results demonstrate a potential relationship between spatial distance of tumor targets and T cells in determining the activity ACTR transduced T cells when targeting GPC3. Our data demonstrate that ACTR T cell activity is antibody-specific and dose-titratable, highlighting both efficacy and improved safety of the ACTR T cell platform when targeting GPC3+ solid tumor malignancies.
Citation Format: Greg Motz, John Shin, Kathleen Whiteman, Birgit Schultes, Tapasya Pai, Lori Westendorf, Seth Ettenberg, Travis Biechele, Django Sussman, Heather Huet. Superior T cell activity of a membrane-proximal binding antibody when targeting Glypican-3 with an antibody-coupled T-cell receptor (ACTR) armed T cell [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3762. doi:10.1158/1538-7445.AM2017-3762
Abstract 3764: Targeting GPR64 in pediatric sarcomas with CAR transgenic T cells
Authors: Schirmer David , Storz Isabel , Wisskirchen Karin , Feederle Regina , Schmidt Oxana , Abken Hinrich , Mackall Crystall , Protzer Ulrike , Burdach Stefan , Richter Günther H. 
Published: July 2017

Abstract
Introduction: Ewing Sarcoma (ES) is the second most common bone malignancy in children and young adolescents with a high potential of dissemination into lung and bones. Patients with disseminated disease into the bone have an approximate long-term survival rate of only 10%, compelling the search for new therapeutic treatment modalities like engineered T cell therapy. Here the therapeutic potential of chimeric antigen receptor (CAR) transgenic T cells directed against G-protein coupled receptor 64 (GPR64) was examined.
Experimental procedure: Two different monoclonal antibodies (mAb) directed against the extracellular region of GPR64 were generated and characterized. Subsequently, retroviral constructs containing second generation CARs together with the scFv fragments of the respective mAbs were designed. Constructs consisting of different spacers and co-stimulatory elements were compared (dIgG1-CD28-CD3z vs. CD8a-4-1BB-CD3z). Primary lymphocytes were transduced and tested in vitro via flow cytometry, ELISpot and xCelligence assay as well as in immunodeficient xenograft mice.
Results: Antibodies specifically stained ES cells as determined by flow cytometry and immune histology. The signal intensity was reduced after RNAi mediated down-regulation of GPR64 in ES cell lines confirming specificity of the isolated mAbs. Following sequence determination of those mAbs two different CAR constructs were designed. Retroviruses containing such CARs transduced primary lymphocytes with high efficiency. The CAR transgenic T cells were enriched for CD8+CAR+ cells via microbead isolation and demonstrated strong proliferative capacities in vitro. Furthermore, target structures were specifically recognized as determined by ELISpot and xCelligence assays but dIgG1-CD28 CAR T cells derived from one hybridoma revealed hints of early exhaustion via auto-activation.
Conclusion: CAR transgenic T cells targeting GPR64 show a promising approach to transfer the success of CARs in hematological malignancies to solid tumors. The cells generated in this study show strong specificity towards GPR64 and are able to control tumor cell growth. Since GPR64 expression is not restricted to ES but also up-regulated in a number of carcinomas derived from prostate, kidney or lung, GPR64-specific CARs may also be a future treatment option for other tumor entities.
Citation Format: David Schirmer, Isabel Storz, Karin Wisskirchen, Regina Feederle, Oxana Schmidt, Hinrich Abken, Crystall Mackall, Ulrike Protzer, Stefan Burdach, Günther H. Richter. Targeting GPR64 in pediatric sarcomas with CAR transgenic T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3764. doi:10.1158/1538-7445.AM2017-3764
Abstract 3776: Examination of ERCC1 status in circulating tumor cells as a prognostic tool for patients with nasopharyngeal carcinoma
Authors: Hui Edwin P. , Ma Brigette BY , Chan KC Allen , Chan Charles ML , Wong SC Cesar , To Ka Fai , Loong Herbert HF , Mo Frankie KF , Ngan Roger KC , Chan Anthony TC 
Published: July 2017

Abstract
Investigation of the expression pattern of DNA-repair protein excision repair cross-complementation group 1 (ERCC1) has been reported to allow selection of patients with non-small cell lung cancer who are likely to benefit from cisplatin-based therapy. Recent evidence suggests that ERCC1 expression may also find prognostic use in patients with nasopharyngeal carcinoma (NPC). We evaluated ERCC1 expression and genotype from NPC tissues and peripheral blood mononuclear cells of patients with NPC. ERCC1 expression was detected in 61/77 cases (79.2%) with varying intensities, where high ERCC1 expression significantly associated with worse relapse-free survival (RFS) (HR 2.34, 1.06-5.16, p=0.036). In addition, the presence of ERCC1 C118T genotype was significantly associated with favorable RFS and overall survival (OS) in a subgroup of patients with undetectable post-treatment plasma EBV DNA. These findings support a prognostic role for ERCC1 examination in NPC. However, the invasive nature of obtaining biopsy samples for tumor marker studies is a major hindrance of this approach. To facilitate the investigation of ERCC1 expression in a noninvasive manner, we have developed a negative selection immunomagnetic method for isolating circulating tumor cells from patient blood. Cell line spike-in experiments reveal a mean recovery rate of 66% for NPC cells with greater than 99% removal of non-targeted blood cells. Specificity of CTC identification was confirmed by detection of the expression of the Epstein-Barr virus encoded small RNA (EBER) in the CTCs. This method also allowed the simultaneous analysis of the expression of multiple protein markers including CD45, cytokeratin and ERCC1. It is expected that the development of noninvasive methodologies for tumor marker studies will facilitate their clinical application for improved patient care and monitoring in the future.
Note: This abstract was not presented at the meeting.
Citation Format: Edwin P. Hui, Brigette BY Ma, KC Allen Chan, Charles ML Chan, SC Cesar Wong, Ka Fai To, Herbert HF Loong, Frankie KF Mo, Roger KC Ngan, Anthony TC Chan. Examination of ERCC1 status in circulating tumor cells as a prognostic tool for patients with nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3776. doi:10.1158/1538-7445.AM2017-3776
Abstract 3811: Defining the relevant genome in solid tumors
Authors: Hamidi Habib R. , Bandla Santoshi , Khazanov Nick , William Paul , Bonevich Nikki , Zurenko Chris , Anstead Sarah , Taylor Chris , Richmonds Reuban , Galimberti David , Kopp Ken , Cyanam Dinesh , Hogan Michael , Mittal Vinay , Sadis Seth 
Published: July 2017

Abstract
Decades of cancer research including comprehensive molecular profiling combined with the development of a broad array of targeted therapies have created the opportunity to transform cancer care by implementing precision oncology based approaches. An important element of this system is the widespread availability of robust and cost-effective multi-variate profiling methods to characterize relevant cancer associated molecular alterations in the future. Current commercially available multi-variate profiling methods vary dramatically with regard to the number of cancer genes that are interrogated. Given that many large scale and detailed molecular profiling studies have been completed, the landscape of somatic alterations in solid tumors is reasonably well-known. Furthermore, the specific gene variants that are relevant to application of targeted therapies are also a matter of record. Therefore, we set out to define the number of relevant cancer genes for precision oncology research based on the currently available empirical evidence. To define recurrent somatic alterations in solid tumors, we created a compendium of variant calls from &gt; 15,000 exomes, defined focal amplifications and deletions from &gt; 30,000 arrays, and defined recurrent fusions from several thousand RNAseq profiles. Statistical approaches were implemented to define genes containing recurrent missense mutations (i.e., hotspots), enriched in truncating mutations or subject to recurrent copy number gain/loss or translocation. This gene set was then used to comprehensively search approved cancer drug labels, clinical practice guidelines, and clinical trials to identify records containing published evidence that specific recurrent somatic gene variants were used as part of the indication statement of an approved targeted therapy, were recommended for testing as part of clinical practice for therapeutic decisions, or were used as enrollment criteria in clinical trials. The relevant cancer genome thus defined consists of &lt; 100 genes. These results suggest that targeted multi-variate profiling approaches may be sufficient to support precision oncology goals in the future.
Citation Format: Habib R. Hamidi, Santoshi Bandla, Nick Khazanov, Paul William, Nikki Bonevich, Chris Zurenko, Sarah Anstead, Chris Taylor, Reuban Richmonds, David Galimberti, Ken Kopp, Dinesh Cyanam, Michael Hogan, Vinay Mittal, Seth Sadis. Defining the relevant genome in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3811. doi:10.1158/1538-7445.AM2017-3811
Abstract 3813: MPF as a monitoring biomarker for a mesothelin-targeted therapy against malignant mesothelioma and other cancer
Authors: Yu Yunkai , Hassan Raffit , Zhang Jingli , Onda Masanori , Pastan Ira , Cao Liang 
Published: July 2017

Abstract
Introduction: Tumor antigen mesothelin had been shown to be elevated in mesothelioma, ovarian, pancreatic, and lung cancer. The mesothelin gene encodes a precursor protein of 69 kDa, which is cleaved into a 31 kDa soluble megakaryocyte potential factor (MPF), and a cell membrane-bound 40 kDa mesothelin. There is a high degree of interest in targeting mesothelin for mesothelioma and other cancers with various antibody-based agents, and some successes in early stage clinical trials with some of the agents. For the development of these targeted therapeutics, specific biomarkers would be needed for monitoring treatment responses, and detecting and evaluating tumor progression. The current test that detects mesothelin is not suitable due to the antigen-binding from the therapeutic antibodies. There is an urgent need to develop and validate an alternative test to support these clinical trials and for disease management.
Methods: Using ECLIA technology and proprietary antibody reagents, we developed a new test for the cleaved MPF polypeptide. We further conducted comprehensive analytical and clinical validation of the test according to the guidelines for tumor antigen tests. Using samples from a retrospective clinical trial with an anti-mesothelin immunotoxin and the standard 1st line chemotherapeutic agents for newly diagnosed malignant mesothelioma patients, we examined the effectiveness of the test for treatment monitoring of the investigational therapy.
Results: Our data gives a strong validation for the analytical and clinical performances of MPF test. While no other current test has been proven to be able to monitor response of mesothelioma to systemic therapies, our data provides the proof of clinical effectiveness for MPF test. In the patients with the elevated tumor antigen, there is a specific and highly significant reduction of MPF at the end of each treatment cycle for a total of 6 cycles in the patients with objective response. Later, about half of these patients with objective response and MPF reduction regained the levels of MPF at the time of disease progression.
Conclusion: The study indicates that MPF test is effective in monitoring the treatment response to systemic therapies for mesothelioma patients with elevated MPF. It may also provide pivotal information on the expression of target mesothelin protein when tumors progress.
Citation Format: Yunkai Yu, Raffit Hassan, Jingli Zhang, Masanori Onda, Ira Pastan, Liang Cao. MPF as a monitoring biomarker for a mesothelin-targeted therapy against malignant mesothelioma and other cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3813. doi:10.1158/1538-7445.AM2017-3813
Abstract 3819: Identification and quantification of isoforms of eukaryotic initiation factor 4E as biomarker in Mnk inhibitor-treated mouse model by capillary-based immunoassay platform
Authors: Ke Zhiyuan , Wang Sifang , Manoharan Vithya , Vuddagiri Susmitha , Ong Esther , Lim Sharon , Ong Sin Tiong , Sangthongpitag Kanda , Kassoum Nacro , Hill Jeffrey , Lee May Ann 
Published: July 2017

Abstract
Elevated levels of the phosphorylated m7G cap binding protein, eukaryotic initiation factor 4E (eIF4E) are associated with neoplasia. An observed oncogenic signaling effect upon activation of Erk1/2 or p38 MAPKs in cells is the phosphorylation of eIF4E specifically at Serine 209 by downstream kinase MAP kinase-interacting kinase 1 and 2 (Mnks). Therefore, inhibiting Mnks could be a potential therapeutic approach that selectively targets cancer cells without introducing toxicity to normal cells. To measure the target engagement and efficacy of Mnk inhibitors, we have established a sensitive method to quantitatively detect phospho-eIF4E and non-phospho-eIF4E. Here, we report using NanoPro 100 system, an automated capillary-based immunoassay platform that could separate the phosphorylated and non-phosphorylated eIF4E isoforms based on different isoelectric points. Primary antibodies against both non-phospho eIF4E and Serine 209 phosphorylated eIF4E were used for identification and verification of eIF4E isoforms in protein samples obtained from cell lysate, blood samples and tumor samples. Two major isoforms of eIF4E with isoelectric point at 5.38 for phospho-eIF4E and 5.88 for non-phospho-eIF4E were identified in eIF4E-overexpressing K562 cells. siRNA knockdown of eIF4E expression reduced both isoforms, while treatment with Mnk inhibitor only reduced phospho-eIF4E level. The measurement and quantification of the relative changes of phosphorylated eIF4E by this method can potentially be used in monitoring the efficacy of Mnk inhibitors in xenograft and future clinical trials.
Citation Format: Zhiyuan Ke, Sifang Wang, Vithya Manoharan, Susmitha Vuddagiri, Esther Ong, Sharon Lim, Sin Tiong Ong, Kanda Sangthongpitag, Nacro Kassoum, Jeffrey Hill, May Ann Lee. Identification and quantification of isoforms of eukaryotic initiation factor 4E as biomarker in Mnk inhibitor-treated mouse model by capillary-based immunoassay platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3819. doi:10.1158/1538-7445.AM2017-3819