tbuckley/cabot-search huggingface dataset:
Abstract P3-10-08: A new in vitro method of growing and studying inflammatory breast cancer emboli
Authors: HL Lehman, EJ Daasner, PB Vermeulen, LY Dirix, S Van Laere, KL van Golen
Journal: Cancer Research (2012)

Abstract Inflammatory breast cancer (IBC) is the deadliest form of breast cancer, presenting as intralymphatic emboli. Emboli within the dermal lymphatic vessels are thought to contribute to rapid metastasis. The lack of appropriate in vitro models has made it difficult to accurately study how IBC emboli metastasize. To date, attempts at creating IBC tumor emboli in vitro have used 3-dimensional culture on a solid layer of MatrigelTM, which does not resemble the physical properties of the lymphatic system. Dermal lymphatic fluid produces oscillatory fluid shear forces and is 1.5–1.7-fold more viscous than water with a pH range of 7.5–7.7. We have established a method for forming tumor emboli by culturing the IBC cell lines in suspension with either polyethylene glycol- or hyaluronic acid-containing medium and oscillatory fluid shear forces. Non-IBC cells do not form emboli under identical conditions. In vitro IBC emboli were analyzed for expression of markers associated with patient emboli and their ability to undergo amoeboid movement. In a direct comparison, the in vitro IBC emboli closely resemble IBC patient emboli with respect to size, composition and E-cadherin expression. Further, cells from the emboli are able to invade in clusters via RhoC GTPase-dependent amoeboid movement. Invasion by clusters of IBC cells is disrupted by exposure to TGFβ. This study provides a biologically relevant in vitro model to accurately grow and study inflammatory breast cancer biology and metastasis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-10-08.
Abstract 4541: The design, synthesis and evaluation of selective FR α and β substrates with potent GARFTase inhibitory activity as antitumor agents
Authors: Xilin Zhou, Xin Zhang, Aleem Gang, Christina Cherian, Zhanjun Hou, Larry H. Matherly, Roy L. Kisliuk
Journal: Cancer Research (2010)

Abstract Glycinamide ribonucleotide formyl transferase (GARFTase) catalyzes the first of two formyl transfer steps in the de novo purine biosynthetic pathway. Potent inhibitors of GARFTase and de novo purine biosynthesis have shown promise as antitumor drugs. However, a lack of selectivity and toxicity has been a major hurdle for GARFTase inhibitors as cancer chemotherapeutic agents. We recently reported a series of thieno[2,3-d]pyrimidine classical antifolates that are specifically taken up by the folate receptor (FR) and inhibit FR expressing tumor cells at nanomolar IC50 values (IC50= 4.9 nM in human KB tumor cells, IC50= 5.9 nM in human IGROV1 tumor cells,). GARFTase was confirmed as the target. Notably, the thieno[2,3-d]pyrimidine antifolates are unique and distinct from all other classical antifolates evaluated, including pemetrexed (PMX), raltitrexed (RTX), and methotrexate (MTX) in that they are neither substrates for reduced folate carrier (RFC) nor for the proton-coupled folate transporter (PCFT). This characteristic results in selective targeting of FR-expressing cells, without toxicity to normal cells that express RFC. To further investigate the structural requirements of antifolates with respect to FR substrate activity, a series of four 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines with different aryl side chains were synthesized. This afforded potent antitumor agents with increased inhibitory activity against FRα expressing tumor cells (IC50= 2 nM in human KB tumor cells) 2.5- fold more potent than the lead benzoyl compound. In addition, these thieno[2,3-d]pyrimidines were specific for FRα and were not transported by RFC or PCFT and indicated that the nature of the bicyclic scaffold is an important structural determinant for transport specificity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4541.
AB0475 Vitamin d status analysis in behçet syndrome patients. a case-control study
Authors: M. Kechida, O. Harzallah, I. Hellara, R. Klii, F. Najjar, S. Mahjoub
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Vitamin D has newly well-proven immunomodulatory effects (1, 2). This vitamin inhibits TH<sub>1</sub> proliferation and cytokine’s production and activates TH<sub>2</sub> functions. It also regulates toll like receptors expression on blood monocytes surface (3). Behçet’s syndrome (BS) is a chronic multisystem inflammatory disease which would be due, in genetically predisposed patients, to an abnormal T cell (TH<sub>1</sub>) activation in response to environmental and/or endogenous stimuli of the innate immune system via TLR. Few studies focused on vitamin D role in BS. <h3>Objectives</h3> The aim of our work was to analyze vitamin D status in BS patients. <h3>Methods</h3> Vitamin D status was analyzed in 40 BS patients (mean age: 37.5 years, sex ratio: 1.85) in comparison to age and sex matched 40 healthy controls. Patients under steroids and/or calcium and vitamin D were excluded. Vitamin D deficiency was defined by a 25(OH)D<sub>3</sub> level below 10 ng/ml. A level above 30ng/ml was considered as normal. 25(0H)D3 level was measured by electrochemiluminescence. <h3>Results</h3> 25 (0H)D<sub>3</sub> mean level was at 14,64 ng/ml (3 – 44,29ng/ml). A vitamin D deficiency was attested in 14/40 cases (35%). 25 (0H)D<sub>3</sub> level was normal in only 2 patients. However, there wasn’t any difference between 25(0H)D<sub>3</sub> levels in BS patients and healthy controls. Comparison between main demographic and biological characteristics of the two groups is summarized in table 1. <h3>Conclusions</h3> Nearly 1/3 of BS patients have a vitamin D deficiency. However there wasn’t any difference between 25(0H)D<sub>3</sub> levels in patients and controls. Few studies (4, 5) focused on vitamin D status in BS and their results are controversial. Other studies with larger samples are required. <h3>References</h3> Holick MF. Vitamin D: Extraskeletal Health. Rheum Dis Clin N Am 2012; (38) : 141– 60 Hewison M. Vitamin D and theImmune System: New Perspectives on an Old Theme. Rheum Dis Clin N Am. 2012 (38): 125– 39 Sadeghi K, Wessner B, Laggner U et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular pattern. Eur J Immunol 2006; 36:361–70 Do JE, Kwon SY, Park S et al. Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behçet’s disease. Rheumatology 2008; 47: 840–48 Karatay S, Yildirim K, Karakuzu A. Vitamin D status in patients with Behcet’s Disease. CLINICS 2011; 66(5):721- 3 <h3>Disclosure of Interest</h3> None Declared
Analyse d'une cohorte de 297 patients consécutifs avec au moins une néoplasie colorectale de classe 4 ou 5 de la classification de Vienne à la coloscopie
Authors: R Desgrippes, S Henno, G Bouguen, M Pagenault, PN d'Halluin, S Manfredi, L Siproudhis, JF Bretagne
Journal: Endoscopy (2011)

Introduction: La pratique de la coloscopie diffère selon les centres, et ses résultats selon les indications. Aussi, le but du travail a été d'étudier dans une population hospitalière la prévalence et les caractéristiques des patients avec néoplasie de classe 4 (dysplasie de haut grade, cancer in situ ou intra-muqueux) ou classe 5 (cancer infiltrant au moins la sous-muqueuse) de la classification de Vienne, ainsi que leurs modalités thérapeutiques.
Reversal of Cushing's Syndrome by Vandetanib in Medullary Thyroid Carcinoma
Authors: Camille Baudry, Anne-Cécile Paepegaey, Lionel Groussin
Journal: New England Journal of Medicine (2013)

A patient with refractory Cushing's syndrome due to corticotropin production by a medullary thyroid cancer had a quick response to vandetanib even before tumor shrinkage was evident.
National Trends in Nonoperative Management of Rectal Adenocarcinoma
Authors: Clayton Tyler Ellis, Cleo A. Samuel, Karyn B. Stitzenberg
Journal: Journal of Clinical Oncology (2016)

Purpose Neoadjuvant chemoradiation for stage II/III rectal cancer results in up to 49% of patients with a clinical complete response. As a result, many have questioned whether surgery can be omitted for this group of patients. Currently, there is insufficient evidence for chemoradiation only, or nonoperative management (NOM), to support its adoption. Despite this, anecdotal evidence suggests there is a trend toward increased use of NOM. Our objective was to examine the use of NOM for rectal cancer over time, as well as the patient- and facility-level factors associated with its use. Methods We included all incident cases of invasive, nonmetastatic rectal adenocarcinoma reported to the National Cancer Database from 1998 to 2010. We performed univariate and multivariate analyses to assess for NOM use over time, as well as associated patient- and facility-level factors. Results A total of 146,135 patients met the inclusion criteria: 5,741 had NOM and 140,394 had surgery with or without additional therapy. From 1998 to 2010, NOM doubled, from 2.4% to 5% of all cases annually. Patients who were black (adjusted odds ratio [AOR], 1.71; 95% CI, 1.57 to 1.86), uninsured (AOR, 2.35; 95% CI, 2.08 to 2.65) or enrolled in Medicaid (AOR, 2.10; 95% CI, 1.90 to 2.33), or treated at low-volume facilities (AOR, 1.53; 95% CI, 1.42 to 1.64) were more likely to receive NOM than were patients who were white, privately insured, and treated at a high-volume facility, respectively. Conclusion NOM demonstrates promise for the treatment of rectal cancer; currently, however, the most appropriate strategy is to pursue this approach with well-informed patients in the context of a clinical trial. We observed evidence of increasing NOM use, with this increase occurring more frequently in black and uninsured/Medicaid patients, raising concern that increased NOM use may actually represent increasing disparities in rectal cancer care rather than innovation. Further studies are needed to assess survival differences by treatment strategy.
Abstract 2390: Growth analysis of M-406 mammary adenocarcinoma in F1 and F2 generations of a cross between resistant and susceptible mice lines
Authors: Juan M. Cáceres, Lucas Pagura, Mariano F. Zacarías-Fluck, O Graciela Scharovsky, Ricardo J. Di Masso, María J. Rico, Viviana R. Rozados
Journal: Cancer Research (2011)

Abstract Breast cancer is a complex, multifactor disease that affects about 10% of women in industrialized countries. Inbred mice models provide an interesting tool for identifying genes that control susceptibility to breast cancer. CBi- mice was artificially selected for body conformation from CBi. The mammary adenocarcinoma M-406 developed spontaneously in CBi female mouse and is maintained in vivo in mice of the same line. When CBi- mice are s.c. challenged with M-406 they show 100% take and 100% regression (resistance). In contrast, the tumor grows exponentially (susceptibility) in CBi mice. The aim of this study was to characterize the tumor behavior in both F1 reciprocal hybrids [(CBi × CBi-) and (CBi- × CBi) n=48], and in the four F2 combinations between them: F2A [(CBi- × CBi) × (CBi- × CBi)]; F2B [(CBi- × CBi) × (CBi × CBi-)]; F2C [(CBi × CBi-) X (CBi- × CBi)] and F2D [(CBi × CBi-) X (CBi × CBi-)] n=185. Adult female and male mice where challenged s.c. with M-406 by trocar, three tumor fragments (∼8 × 105cells). Tumors were measured three times/week and tumor volumes were calculated as follows: V = 0.4 (ab2), where V = volume (mm3), a = largest diameter (mm) and b = smallest diameter (mm). Tumor volume vs time data were fit to an exponential growth model Vt: S*e[k*t]. M-406 grew exponentially in 45/48 F1 mice. Non statistical differences were found in tumor growth rates between sexes on the reciprocal F1s. Significant differences in tumor volume doubling time (TvDT = 0.69/k) were observed between sexes in two of the four F2 combinations: F2A [females: 5.34 ± 0.44; males: 4.27 ± 0.26; t=2.154, P=0.038] and F2D [females: 4.04 ± 0.14; males: 4.85 ± 0.38; t=1.804, P=0.041]. When comparing females TvDT, F2D had a faster growth rate than F2A (P=0.0097), while non statistical differences were evident in males (P = 0.102). It is concluded that susceptibility to M-406 in CBi mice is inherited as a dominant trait. Genes involved in susceptibility inheritance would be autosomic, as the tumor behaviour in both F1 reciprocal hybrids is similar. The analysis of F2 alternative combinations allowed the identification of maternal effect as well as sexual dimorphism influencing tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2390. doi:10.1158/1538-7445.AM2011-2390
Abstract 2349: DLC1 interaction with S100A10 mediates inhibition of in vitro cell invasion and tumorigenicity of lung cancer cells
Authors: Xu-Yu Yang, Nicolae C. Popescu, Drazen B. Zimonjic
Journal: Cancer Research (2010)

Abstract Deleted in liver cancer 1 (DLC1) is a multidomain Rho-GTPase-activating protein (RhoGAP) and a tumor suppressor in several human common cancers. DLC1's structure predicts its interaction with a number of other proteins with various cellular functions. Previously we have shown that S100A10 (also known as p11), a key plasminogen receptor on the surface of cell membrane, colocalizes and binds with DLC1 in cell cytoplasm. The binding sites were mapped to the central domain of the DLC1 and at the end of C-terminus of S100A10. The same terminus is also a binding site for Annexin A2, which is believed to regulate availability of extracellular S100A10 and, therefore, dynamics of plasmin formation. Now we demonstrate that DLC1 competes with Annexin A2 for interaction with S100A10. DLC1 binding to S100A10 did not affect DLC1's RhoGAP activity but did reduce availability of S100A10 for binding by Annexin A2. Furthermore, the expression of DLC1 also affected S100A10 expression in a dose dependent manner, and increased S100A10 ubiquitin-dependent degradation. All of the above interactions attenuated plasminogen activation and resulted in inhibition of in vitro cell migration, invasion, colony formation and anchorage independent growth of aggressive and tumorigenic lung tumor cells. Transduction of DLC1-negative breast tumor cells significantly reduced the ability of tumor cells to form pulmonary metastases as well as inhibited distant dissemination of liver tumor cells in athymic mice. Current observations provide a plausible mechanism for DLC1 antimetastatic function by negatively affecting plasminogen activation, which in turn lead to a significant reduction in invasiveness of tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2349.
Thoracic Actinomycosis Imaging With Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography
Authors: C. J. HOEKSTRA, O. S. HOEKSTRA, J. P. TEENGS, P. E. POSTMUS, E. F. SMIT
Journal: Clinical Nuclear Medicine (1999)

A 55-year-old man presented with progressive pain on the left hemithorax. A mass in the left upper lobe was seen on the chest radiograph. CT showed mediastinal lymphadenopathy and a mass in the left upper lobe with invasion of the chest wall. The results of all cytologic and microbiologic examinations were normal. The clinical diagnosis was bronchial carcinoma. A PET scan showed enhanced uptake within the left chest wall without mediastinal lymphadenopathy. At that stage, the left hemithorax had become indurated. Microbiologic examination of pus, which dripped out of the mass after incision, showed gram-positive anaerobic organisms. A clinical diagnosis of actinomycosis was made.
Rare Cerebral and Pulmonary Metastases From Low-Grade Basal Cell Adenocarcinoma of the Parotid Gland
Authors: Ruixue Cui, Xin Cheng, Fang Li, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2011)

Basal cell adenocarcinoma of the parotid gland is a low-grade malignancy that rarely metastasizes. We described a 32-year-old man with history of a right total parotidectomy for basal cell adenocarcinoma of the parotid gland 5 years ago, presenting with severe headache. A brain MRI revealed enhancing brain lesions that were confirmed as metastases from the parotid gland malignancy. A body FDG PET/CT demonstrated 2 mildly hypermetabolic lesions in the lungs, with pathology showing metastatic basal cell adenocarcinoma of the parotid gland.
Correlation of epigenetic silencing of <i>SOCS3</i> with a subset of prostate cancer with aggressive behavior.
Authors: F. Pierconti, M. Martini, T. Cenci, F. Pinto, P. Bassi, L. Larocca
Journal: Journal of Clinical Oncology (2010)

4646 Background: Chronic inflammation and the subsequent tissutal alterations may play a key role in prostate carcinogenesis. In this way, molecular alterations of the suppressor of cytokine signaling (SOCS) 3, one of the most important inhibitory molecule of the inflammatory signal transduction circuitries, could contribute to explain the pleiotropic role of interleukin (IL)-6 in this type of cancer. Methods: We analyzed the methylation status and mRNA expression of SOCS3 in 20 benign prostate hyperplasias (BPH) and in 51 prostate cancer specimens. After DNA modification with bisulphite, we analyzed the SOCS3 methylation status using Methylation-Specific PCR (MSP-PCR). Hypermethylation was confirmed by sequencing after subcloning. In addition, epigenetic silencing of this gene was also confirmed by real-time PCR. We statistically analyzed the correlation between our results and clinical data. Results: We found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer. On the contrary, all BPH and normal controls had an unmethylated pattern. Real-time analysis showed that in methylated cases mRNA expression for SOCS3 was reduced by 3 and 4 folds as compared to BPH and unmethylated prostate cancer, respectively. Interestingly, SOCS3 mRNA was more expressed in unmethylated prostate cancer than in BPH. Moreover, methylation of SOCS3 promoter significantly associated with intermediate-high grade Gleason score (p=0.0007) and with an unfavorable clinical outcome (p=0.0019). In addition, we found a concordant result in the methylation status of SOCS3 both in biopsies and in prostate after surgical resection. Conclusions: Our data suggest that methylation of SOCS3 may be involved in the pathogenesis of prostate cancer and could identify in the bioptic specimen the subset of tumor with an aggressive behavior. In conclusion, SOC3 methylation could be a new prognostic marker and novel target for therapy. No significant financial relationships to disclose.
Reply to Kadayifci and Brugge
Authors: Masayuki Kitano, Ken Kamata, Masatoshi Kudo
Journal: Endoscopy (2014)

We thank Drs. Kadayifci and Brugge for their valuable comments. They discussed the utility of performing endosonography-guided fine-needle aspiration (EUS-FNA) for the differential diagnosis of cystic lesions in the pancreas. We agree that the differential diagnosis of pancreatic cystic lesions can be aided by analyzing fluids for carcinoembryonic antigen and amylase levels, and by performing cytology, GNAS mutation analysis, and confocal endomicroscopy [1] [2] [3]. In our study [4], patients with branch duct intraductal papillary mucinous neoplasms (IPMNs; cystic lesions connected to the pancreatic duct) underwent surgery because they had symptoms, mural nodules, or concomitant pancreatic ductal adenocarcinomas (PDACs). Pathological diagnosis of all of the resected cystic lesions connected to the pancreatic duct showed that they were branch duct IPMNs. During the same study period, some patients who had pancreatic cystic lesions that were not connected to the pancreatic duct underwent surgery; however, in these cases, the cystic lesions consisted of serous cystic neoplasms, mucinous cystic neoplasms, branch duct IPMNs, and other types of cystic lesions. In other words, the differential diagnosis of cystic lesions that are not connected to the pancreatic duct is difficult and sometimes requires interventional diagnostic methods [1] [2] [3], as mentioned by Drs. Kadayifci and Brugge.
Abstract 4105: Signaling network-based analyses of sonic hedgehog pathway components: predictions and possibilities.
Authors: Anshu Malhotra, Chad R. Potts, Africa Fernandez-Lopez, Rachel Rotenberry, Anna M. Kenney
Journal: Cancer Research (2013)

Abstract A subclass of Medulloblastoma shows considerable dependence on the Sonic Hedgehog (Shh) pathway. Since cellular functions are a consequence of coordinated networks involving protein-protein interactions, it is imperative to explore different events cooperating with Shh entities in order to explore novel targets for medulloblastoma therapy. The Yes Associated Protein (YAP), a component of the Hippo pathway, has been previously established as a downstream target of the Shh pathway (Fernandez et al 2011). Several interesting gene targets featured in the networks developed by us using YAP overexpression in CGNPs. A concurrent upregulation of IGF2 and H19, both imprinted genes, was observed. Possible links between the Shh/Hippo pathways and IGF2 signaling also featured in the networks developed in the study. Important links to lipid metabolism, a process highly active in medulloblastomas and essential for the proliferation of CGNPs, were also predicted. The study includes results of signaling interactions between the Shh/Hippo pathways and entities from other relevant pathways that together play a role in medulloblastoma development and proliferation. Citation Format: Anshu Malhotra, Chad R. Potts, Africa Fernandez-Lopez, Rachel Rotenberry, Anna M. Kenney. Signaling network-based analyses of sonic hedgehog pathway components: predictions and possibilities. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4105. doi:10.1158/1538-7445.AM2013-4105