tbuckley/cabot-search huggingface dataset:
Abstract 3729: Tumor-specific antibody labeling of pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model using a fluorescent humanized anti-CEA antibody
Authors: Thinzar Lwin, Takashi Murakami, Robert M. Hoffman, Paul J. Yazaki, Michael Bouvet
Journal: Cancer Research (2017)

Abstract Introduction: Delineation of tumor margins is critical in oncologic surgery, particularly in resection of pancreatic cancer. Surgeons are limited in visualization with bright light surgery. Fluorescence guided surgery (FGS) can help surgeons better visualize all potential cancer cells during the operation. In the present study, we show that the use of an anti-CEA antibody conjugated to an 800nm NIR fluorescent dye can selectively label pancreatic cancer in both pancreatic cancer cell lines and patient derived xenograft mouse models (PDOX). Materials/Methods: BxPC3-GFP cells or pancreatic cancer tissue specimens were grafted into flanks of nude mice. Both types of tumors were allowed to grow until 1 cm. Fragments tumors (2 mm3) were grafted onto the pancreatic tail of recipient mice to create PDOX models. After tumors reached 7-10mm in size, 75 ug of Anti-CEA-800 dye was injected into the tail-vein (LI-COR 800 CW IRDye®, Lincoln, NE). Mice were imaged via the Maestro CRI imaging system (Perkin Elmer, Waltham, MA) 24 hours after injection. Results: Images obtained after fluorescent antibody injection showed that anti-CEA-800 specifically labeled both the cell-line-derived tumors and patient-derived tumors with an adequate tumor to background contrast at 24 hours. The dye co-localized with GFP in tagged tumor cells lines. GFP fluorescence had poor penetration if covered by overlying tissue, which was not an issue with the anti-CEA-800 dye. The dye allowed clear identification of the tumor and tumor margin. In the BxPC-3 based tumor, the dye allowed identification of a small 1mm satellite lesion in the spleen that would otherwise have been missed. Conclusions: Fluorescent humanized anti-CEA-800 antibody specifically labeled orthotopically implanted pancreatic cancer xenografts from cell lines and patient derived tissue. Tumor-specific fluorescence imaging clearly identified the primary tumor and satellite lesion. The 800nm wavelength allowed deeper tissue penetration, particularly in areas of tumor covered by normal pancreatic parenchyma. Humanized anti-CEA antibodies conjugated to a radio-labeling agent and LI-COR 800 dye is already in Phase I/II trials. Humanized anti-CEA conjugated with the IR-800 dye is a promising agent for future clinical FGS applications. Citation Format: Thinzar Lwin, Takashi Murakami, Robert M. Hoffman, Paul J. Yazaki, Michael Bouvet. Tumor-specific antibody labeling of pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model using a fluorescent humanized anti-CEA antibody [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 3729. doi:10.1158/1538-7445.AM2017-3729
Abstract 451: Germ free mice accelerate cachexia-associated cancer
Authors: Rodrigo Xavier das Neves, Soumen Roy, Amiran Dzutsev, April Huang, Loretta Smith, Simone Difilippantonio, Hawes Misty, Marília Seelaender, Giorgio Trinchieri
Journal: Cancer Research (2017)

Abstract The syndrome of cancer cachexia is currently defined as a state of ill health, malnutrition and physical wasting with marked white adipose tissue (WAT) and skeletal muscle mass wasting, representing the clinical consequence of a chronic and systemic inflammatory response. Over the last decade, WAT has been recognized as an important endocrine organ, and earning a lot of attention during cancer cachexia development. We investigated the role of microbiota along the cachexia associated cancer. We performed experiments with conventional and Germ Free mice (GF) (n=6 in each group) of 8-10 weeks old C57B/6, which were subcutaneously injected with LLC cells [4x106 cells in 0.2 mL; Tumor-bearing, (TB) or PBS control (C)]. We performed Immunohistochemistry, RT- qPCR, and Western Blot. We observed that GF Tumor-bearing mice have increased several symptoms of the cachexia compared to conventional TB mice. The WAT mass was decreased 50% in GF Tumor-bearing mice compared to all groups, which indicates a pathway related to lipolysis, as we found increased level of phosphorylated enzymes in GF Tumor-bearing mice. We also observed that GF Tumor bearing mice decreased skeletal muscle mass and gene expression that are related with atrophy were increased in GF Tumor bearing mice. Our data suggested that homeostasis of microbiota may impair the development of the cachexia syndrome. Citation Format: Rodrigo Xavier das Neves, Soumen Roy, Amiran Dzutsev, April Huang, Loretta Smith, Simone Difilippantonio, Hawes Misty, Marília Seelaender, Giorgio Trinchieri. Germ free mice accelerate cachexia-associated 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 451. doi:10.1158/1538-7445.AM2017-451
Angiotensin II for the Treatment of Vasodilatory Shock — Promise and Caution
Authors: R. Phillip Dellinger, Stephen Trzeciak
Journal: New England Journal of Medicine (2017)

Shock is one of the most common reasons for admission of patients to an intensive care unit. Low blood pressure is a hallmark of shock, and raising blood pressure is one of the foremost therapeutic goals in this setting. In patients with vasodilatory (i.e., "distributive") shock, who represent approximately two thirds of all patients with shock,1 the usual method of raising blood pressure after fluid resuscitation is intravenous infusion of a vasopressor agent. The agents most commonly used to raise blood pressure in patients with vasodilatory shock are the adrenergic agents norepinephrine (recommended first-line therapy) and epinephrine — both of . . .
Abstract 262: Analysis of demographics, survival and patterns of care of pediatric glioblastoma using National Cancer Database
Authors: Jigisha Thakkar, Meng Liu, Emily Van Meter Dressler, John L. Villano
Journal: Cancer Research (2017)

Abstract Background We analyzed the largest clinical database in the United States, the National Cancer Database (NCDB), comprising over 70% of cases diagnosed and/or treated at commission on Cancer approved institutions. We analyzed current hospital-based epidemiologic frequency, survival and patterns of care of pediatric glioblastoma (GBM). Methods Cases included patients 0-19 years between 1998-2011. Inclusion criteria for histology codes included for GBM 9440, 9441 and 9442 (9440 (GBM), 9441(Giant Cell) and 9442 (Sarcomatas component) and tumor sites (C70.0-C72.9, C75.1-C75.3) related to the brain: brain stem, cerebellum, cerebrum, ventricle and brain not otherwise specified (NOS). Kaplan-Meier survival estimates were calculated for each demographic criteria and treatment plan and Cox proportional hazards models were employed to assess the risk of mortality. Demographic variables analyzed were age, gender, race, Hispanic origin, income, education, region and insurance status. Comparisons were made among histologic subtypes and primary site. Results 1173 patients with GBM from age 0 to 19 years were identified from 1998 to 2011 in the United States, of which 21.5%, 24.5% and 54.0% were in age group 0-5, 6-10 and 11-19 years old. The largest group (48%) received advanced care including a combination of radiation (XRT), chemotherapy and surgery. On the other hand, the no treatment group was the smallest comprising of 4% cases. 14% received surgery only, 8% received a combination of XRT and surgery and 9% received a combination of XRT and chemotherapy. Patients that received combination of XRT, chemotherapy and surgery had significantly improved survival when compared to those without any treatment (p = 0.0048). Patients that received surgery or chemotherapy had significantly improved survival as compared to patients that did not receive the above treatments (p = 0.0027). Conclusion We report an extensive demographic and survival analysis of pediatric GBM. Observed difference likely reflect biology across age, gender, race and origin groups. Our analysis demonstrates concern in the delivery of optimal care to a large percentage of pediatric patients. These treatments include surgery and chemotherapy that have demonstrated survival benefits. Adverse effects of chemotherapy and XRT can limit the appropriate administration of treatment. Citation Format: Jigisha Thakkar, Meng Liu, Emily Van Meter Dressler, John L. Villano. Analysis of demographics, survival and patterns of care of pediatric glioblastoma using National Cancer Database [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 262. doi:10.1158/1538-7445.AM2017-262
Abstract 1833: Imaging-guided brain tumor surgery strategy based on a triple-modality MRI-PET-fluorescence imaging probe and imaging analysis
Authors: Hui Meng, Yushen Jin, Shaowei Zhang, Shuai Zhang, Xibo Ma, Jie Tian
Journal: Cancer Research (2017)

Abstract Precise brain tumor resection is valuable for increasing the 5-year survival rate. However, the delineation of tumor margin is a major challenge. Transferrin modified nanoprobes had the property of passing the blood-brain barrier (BBB). Here, we endeavored to use transferrin to fabricate a triple-modality magnetic resonance imaging-PET-fluorescence imaging molecule agent (MPF) which could improve diagnostic sensitivity and specificity of the brain tumors in the imaging acquisition and analysis. The localization of the tumor were determined by the MRI before surgery. Glucose metabolism was derived from PET imaging which would be an important influence factor for surgery strategy. Tumor margin was delineated using the quick segmentation methods according to the fluorescence imaging after craniotomy which could reduce residual tumor after resection. Finally, tissues were sliced and stained with hematoxylin and eosin every 5 mm. The histology results were processed into a whole image which can be used to evaluate the accuracy of intraoperative tumor margin. This three modality imaging-guided surgery strategy is a promising method which will probably achieve its application in clinical trials in near future. Citation Format: Hui Meng, Yushen Jin, Shaowei Zhang, Shuai Zhang, Xibo Ma, Jie Tian. Imaging-guided brain tumor surgery strategy based on a triple-modality MRI-PET-fluorescence imaging probe and imaging analysis [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 1833. doi:10.1158/1538-7445.AM2017-1833
Water pressure method for duodenal endoscopic submucosal dissection
Authors: Naohisa Yahagi, Toshihiro Nishizawa, Motoki Sasaki, Yasutoshi Ochiai, Toshio Uraoka
Journal: Endoscopy (2017)

Duodenal endoscopic submucosal dissection (ESD) is difficult due to insufficient mucosal elevation, because of the coarse submucosal layer [1]. We report on the "water pressure method" for duodenal ESD.
Abstract 3862: <i>In vivo</i> chemopreventive of pseudosemiglabrin via inhibition of tumor angiogenesis and manipulation of hormones in estrogen-responsive breast cancer
Authors: Loiy E. Ahmed Hassan
Journal: Cancer Research (2017)

Abstract Breast cancer is the most frequently diagnosed form of malignancy and the second leading cause of death in Western women. Mortality and most of the complications associated with breast cancer are due to metastasis developing in regional lymph nodes and in distant organs, including bone, lung, liver and brain. Chemopreventive is administration of chemical agents to prevent the initiational and promotional events associated with carcinogenesis. Some chemopreventive agents can prevent reaction or attacking molecules by different ways, these agents can suppress growth factors or signaling pathway. On this study we examined (-)-Pseudosemiglabrin (SSG) a natural compound extracted from Tephrosia apollinea on breast cancer cells and tumor vascularization in vitro and in vivo. Hormone sensitive breast cancer cell MCF-7 was found subtitle susceptible to SSG, it showed profound antitumorgeneis via inhibiting breast cancer cell migration, invasion and colony formation in vitro settings. In silico investigation of potential PARP inhibitor, SSG showed high binding affinity comparable to Rucaparib (standard PARP inhibitor). The natural compound significantly inhibited the sprouting of new blood vessels in ex vivo rat aorta ring assay; the antiangiogenic efficacy is perturbed by targeting VEGF expression and VEGFR phosphorylation. SSG completely inhibited the onset of breast cancer in animals pretreated with the compound. Molecular docking study showed that SSG binds to active site of Aromatase (the enzyme responsible for a key step in the biosynthesis of estrogens) with binding affinity better than standard aromatase inhibitor (Arimidex), moreover the compound has inhibitory activity against estrogen receptor in the breast cancer cells comparable to Tamoxifen. Our findings reveal that (-)-Pseudosemiglabrin can potentially be beneficial in preventing breast cancer in high-risk women or it can be adjuvant therapy with standard chemotherapy or even can be used for the treatment of women who have been diagnosed with breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Loiy E. Ahmed Hassan. In vivo chemopreventive of pseudosemiglabrin via inhibition of tumor angiogenesis and manipulation of hormones in estrogen-responsive breast 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 3862. doi:10.1158/1538-7445.AM2017-3862
Abstract 4313: Protein synthesis modulates paraptotic death induced by inhibition of cyclophilins in glioblastoma (GBM) cells
Authors: Lin Wang, Justin Gundelach, Richard Bram
Journal: Cancer Research (2017)

Abstract In this study, we investigated the mechanisms underlying cell death induced by the small molecule cyclophilin inhibitor NIM811. NIM811 effectively killed GBM cells through a non-apoptotic pathway, as there was no nuclear shrinkage or caspase activation. Instead, death was preceded by dramatic cytosolic vacuolization, stemming from enlargement of the endoplasmic reticulum (ER). RNA-seq revealed upregulation of genes pertinent to the unfolded protein response (UPR) and autophagy. Western blotting for UPR and autophagy mediators also supported a transient UPR signaling and compromised autophagy during prolonged NIM811 treatment. By utilizing a bicistronic reporter plasmid, we independently quantitated Cap-dependent and Cap-independent translation. We further assessed the long-term effects mediated by different short-term paraptosis inhibitors via colony formation assay. We find that NIM811 initiates paraptosis in GBM cells, due to an abnormal upregulation of protein translation that caused accumulation of misfolded or unfolded proteins in ER. Transient activation of pro-survival autophagy and UPR signals were shutdown during prolonged treatment with NIM811, thus allowing cell death to occur. Cycloheximide was previously reported by others to suppress paraptosis. In our studies, we find instead that it temporarily delayed vacuole formation, but actually enhanced paraptotic cell death in the long term. The mTOR inhibitors rapamycin or torin-2 rescued cells from NIM811 induced paraptosis by sustaining autophagy and the UPR, and specifically restrained cap-dependent translation. We propose that ER vacuolization could be a protective response generated by cells to isolate defective proteins within the ER in order to prevent misfolded aggregates to interfere with cellular homeostasis. For that reason, simply inhibiting vacuole formation without clearing protein accumulation in the ER was insufficient to prevent cell death. These findings aid our understanding of cellular mechanisms that contribute to non-apopotic death. Moreover, this work underlines the importance of evaluating cellular responses in cell death experiments over multiple time frames to judge the true impact. Citation Format: Lin Wang, Justin Gundelach, Richard Bram. Protein synthesis modulates paraptotic death induced by inhibition of cyclophilins in glioblastoma (GBM) 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 4313. doi:10.1158/1538-7445.AM2017-4313
Abstract 1800: Noninvasive approach to assess metastatic lesion of advanced colorectal cancer by denoised deep target sequencing
Authors: Jun-Kyu Kang, Hwang-Phill Kim, Seul-Ki Cheon, Ye-Lim Park, Yoojoo Lim, Sae-Won Han, Tae-You Kim
Journal: Cancer Research (2017)

Abstract The cell-free DNA (cfDNA) represents a minimally invasive and alternative source of tumor DNA for molecular profiling. Despite next-generation sequencing (NGS) technique is qualified for genotyping cancer using cfDNA as a noninvasive method, it has caused problems as sequencing error and reproducibility. cfDNA in plasma and gDNA of Peripheral Blood Mononuclear Cells (PBMC) were isolated from each 54 advanced colorectal cancer patients. 39 available tumor tissues were isolated from same patients. Deep target-sequencing was performed with paired-end library enriched exons of 10 genes which are recurrently mutated in colorectal cancer. To reduce sequencing error, we devised ‘Denoising’ and calculated concordance of somatic variants between cfDNA and tumor tissue sequencing data. In addition, correlation of concordance data was analyzed with the clinical information. As a result, we selectively could detect clinically important somatic alteration among low/high variant allele frequency (0.31%~79.42%). For somatic alteration of 10 genes, sensitivity, specificity and accuracy were increased from 84.5%, 74.6% and 76.9% to 87.6%, 92.0% and 91.1% respectively after ‘Denoising’. On the other hand, patients with high cfDNA concentration(&amp;gt;50ng/ml) had higher somatic mutant fragments and larger metastatic lesion in liver than patients who have low cfDNA concentration. Our study showed that denoised deep target-sequencing is a suitable method for cfDNA genotyping and provides insights into strategies for monitoring metastatic lesion of advanced colorectal cancer. Citation Format: Jun-Kyu Kang, Hwang-Phill Kim, Seul-Ki Cheon, Ye-Lim Park, Yoojoo Lim, Sae-Won Han, Tae-You Kim. Noninvasive approach to assess metastatic lesion of advanced colorectal cancer by denoised deep target sequencing [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 1800. doi:10.1158/1538-7445.AM2017-1800
Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study
Authors: Ariela Noy, Sven de Vos, Catherine Thieblemont, Peter Martin, Christopher Flowers, Franck Morschhauser, Graham P. Collins, Shuo Ma, Morton Coleman, Shachar Peles, Stephen Smith, Alina Smith, Brian Munneke, Isaiah Dimery, Darrin Beaupre, Robert W Chen
Journal: Blood (2016)
Abstract 4907: Elucidating the inhibitory role of plant alkaloids in breast cancer metastasis
Authors: Waqas Iqbal, Saleh Alkarim, Jamal S. Sabir, Roop S. Bora, Kulvinder S. Saini
Journal: Cancer Research (2017)

Abstract Despite extremely high morbidity and mortality of &amp;gt;90% from metastasis, it remains one of the most challenging process for targeted therapeutic interventions. Identification and characterization of chemically active and bioavailable compounds from medicinal plants targeting the cell-signaling pathways of Cancer Stem Cells (CSCs), tumor cells and their microenvironment that abet metastasis is of great clinical significance. Hence, MCF-7; a breast cancer cell line, was treated with fractionated alkaloidal extracts from Rhazya stricta with previously documented anti-cancer activity in lung and pancreatic cancer cell lines. RNA-seq. analysis was performed for samples treated with compounds that actively inhibited cell migration in scratch assay to further substantiate their anti-metastatic role at the cellular and molecular level. Genomic data corroborated the presence of anti-metastatic compounds that actively down-regulated genes involved in promoting metastasis (CDC6), cell migration (KIF23, DLGAP5), invasion and CSCs’ expansion (PTTG1). We also found down-regulation of GAS1 expression, an enhancer of Hedgehog signaling pathway. To our knowledge, this study, first of its kind, sets precedence in exploiting the anti-metastatic potential of these compounds. Further proof of concept studies in mouse models of breast cancer to establish precise mechanism-of-action(s), would certainly open up avenues for the development of new chemical entities (NCEs), targeting metastasis regulating gene(s) with precision. Citation Format: Waqas Iqbal, Saleh Alkarim, Jamal S. Sabir, Roop S. Bora, Kulvinder S. Saini. Elucidating the inhibitory role of plant alkaloids in breast cancer metastasis [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 4907. doi:10.1158/1538-7445.AM2017-4907