tbuckley/cabot-search huggingface dataset:
CyberKnife high-dose fractionated stereotactic radiosurgery with tumor tracking: An effective non-surgical treatment alternative for single small peripheral lung tumors
Authors: S. M. Malik, K. Erickson, S. Collins, C. Reichner, C. Jamis-Dow, F. Banovac, E. D. Anderson, F. P. Smith, J. Hwang, B. T. Collins
Journal: Journal of Clinical Oncology (2007)

18125 Background: We report preliminary outcomes using CyberKnife radiosurgery with tumor tracking to treat small (&lt;4 cm) peripheral inoperable stage I lung cancers and single pulmonary metastases. Methods: Enrollment of eligible pts began in July 2004. Prior conventional thoracic irradiation and the incorporation of systemic therapy were permitted. Fiducials (3–5) were placed near tumors under CT guidance. Pts received 45–60 Gy in 3 equal 1–2 hour fractions delivered over a 5–9 day period. Results: The median follow-up period of survivors was 12 months (range = 3–24 months). A total of 24 lesions were treated, 15 clinical stage I lung cancers and 9 single lung metastases. Four patients had prior conventional thoracic radiation (17%) and 6 patients received systemic therapy in conjunction with radiosurgery (25%). Two received systemic doses of platinum based doublet chemotherapy, 3 received gefitinib and 1 received sunitinib. Pneumothorax was a complication of fiducial placement in 7 pts, requiring tube thoracostomy in 4. All pts completed treatment with few acute side effects. No unexpected additional toxicities were noted with systemic therapy except for one pt who developed Grade III radiation pneumonitis while receiving gefitinib. A second pt with Grade III radiation pneumonitis had prior extensive conventional thoracic radiation. All tumors responded to treatment at 3 months as seen by a decrease in gross tumor volume. At 12 months 14 CT scans were evaluable. Four lesions responded completely (33%), 2 exhibited a partial response and the remaining 8 were obscured by radiation fibrosis corresponding to the high-dose irradiated volume (57%). Local progression was seen in only 2 single lung metastases at 10 and 12 months. There have been no regional lymph node failures. Four patients have died, 1 of progressive metastatic disease and 3 of comorbid illnesses. Conclusion: CyberKnife high-dose fractionated stereotactic radiosurgery with tumor tracking is an effective well-tolerated treatment option for small peripheral lung tumors, both primary and metastatic. The integration of systemic therapy appears feasible but needs to be further evaluated in clinical trials. No significant financial relationships to disclose.
Abstract 3246: Important differences between exosome biosignatures from prostate cancer patient plasma samples and prostate cancer cell lines
Authors: Teresa Tinder, Traci Pawlowski, David Spetzler, Amber Conrad, Phil Ellis, Patrick Kennedy, Annemarie Tyrell, Unnati Jariwala, Christine Kuslich
Journal: Cancer Research (2010)

Abstract Exosomes are endosome-derived vesicles secreted by many cell types, including tumor cells. The vesicles are formed intracellularly by invagination followed by fusion with the multivesicular body (MVB). The MVB ultimately merges with the plasma membrane, leading to exocytosis of the exosomes, which consequently have a similar membrane protein composition as their cell of origin; this provides the exosomes with unique biosignatures. Furthermore, these circulating exosomes participate in cellular communication by transporting mRNAs, microRNAs and proteins to target cells where they can elicit biological responses. This study compared the biosignatures identified from prostate cancer (PCa) cell line-derived exosomes to those found in exosomes isolated from the plasma of PCa patient samples. To develop an exosome-specific protein and RNA signature for PCa, we studied RNA and surface membrane protein profiles by flow cytometry (FACS) of exosomes derived from four prostate cancer cell lines, VCaP, 22Rv1, LNCaP and DU145. The exosome biosignatures identified from the cell lines were then measured in plasma exosomes isolated from PCa patients. We found that there was variability between the four cell line exosome-specific mRNA expression levels and exosome surface protein content. The mRNA exosome biosignatures identified in the four cell lines were not found in the exosomes from plasma samples of patients with PCa. Using a combination of antibodies for B7H3, PSMA and CD63 by FACS, we identified a protein signature from all prostate cancer cell line exosome populations that defined a specific subpopulation of exosomes containing all 3 proteins on their surface. Interestingly, this same exosome subpopulation was not found in exosomes derived from patients with PCa. Additionally, exosome-specific mRNA expression of two mRNA transcripts often found to be overexpressed in PCa, STEAP1 and SPINK1, were consistently identified in exosomes derived from prostate cancer cell lines VCaP and 22Rv1, but were only found in the plasma derived exosomes from one out of eight patients with PCa. Our results show that prostate cancer cell lines are not appropriate models for the development of exosome-specific disease profiles in prostate cancer; this will be investigated in additional cell lines. We find that patient samples are essential to identify disease-specific exosome biosignatures. These findings support the development of a versatile diagnostic platform based on exosome-specific biosignatures found in the plasma of patient samples for prostate and other cancers. 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 3246.
Abstract 1985: Omega-3 polyunsaturated fatty acids induce cell cytotoxicity through apoptosis and autophgy in brain cancer in vitro and in vivo
Authors: Hye-rim Oh, Kaipeng Jing, Soyeon Shin, Nayeong Kim, Soyeon Jeong, Eun-ah Cho, Jun-Young Heo, Ji-Hoon Park, Kang-Sik Seo, Jeong-su Han, Jong-Il Park, Gi-Ryang Kweon, Seung-Kiel Park, Wan-Hee Yoon, Byung-Doo Hwang, Kyu Lim
Journal: Cancer Research (2012)

Abstract One of the most common and biologically aggressive of malignant astrocytic gliomas is glioblastoma (GBM). Studies have revealed a significant role of phosphatidylinositol-3-OH kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling activation during GBM development. Omega-3 polyunsaturated fatty acids (≥3-PUFAs) have been shown to inhibit several cancer cells growth such as breast cancer cells. Here, we examined the anticancer effect of α3-PUFAs in D54 malignant glioma (D54MG) cells. We show that docosahexaenoic acid (DHA), a α3-PUFA, induced apoptosis in D54MG cells, as confirmed by the formation of cleaved PARP, TUNEL assay and cytofluorometric analysis. DHA-treated D54MG cells also showed a significant increase in autophagic activity as revealed by LC3-II elevation, autophagic vesicles formation and autophagy flux assays, suggeting that both apoptosis and autophagy contribute to the DHA-induced tumor cell death. The DHA-induced cell death in D54MG cells was accompained by the activation of AMPK and decrease in the Akt phosphorylation. DHA also decreased the activity of mTOR and the level of its downstream molecule 4EBP as analyzed by the Western blot assay. DHA-induced apoptosis and autophagy were partially blocked by transient overexpression of Akt, supporting the inhibition of Akt being beneficial to the death of GBM cells. In in vivo studies, the growth of implanted murine GBM cells in Fat-1 transgenic mice, that can produce high levels of α3-PUFA, was significantly inhibited, and the apoptotic index was higher compared with wild type mice. Together, these results suggest that α3-FUFAs induce cell cytotoxicity through apoptosis and autophgy in brain cancer. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology(2011-0006232).] 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 1985. doi:1538-7445.AM2012-1985
P530 FACTORS ASSOCIATED WITH ADIPONECTIN SERUM LEVELS IN PATIENTS WITH LIVER CIRRHOSIS
Authors: T.E. Silva, M.C. Silva, M.L.A. Alencar, M.S. Coelho, L.M. Wildner, M.L. Bazzo, D.A. Chica, E.B. Dantas-Correa, J.L. Narciso-Schiavon, L.L. Schiavon
Journal: Journal of Hepatology (2014)
Abstract PD02-08: Development of DNA Aptamers That Inhibit Invasion, Migration, and Growth of Breast Cancer Cells
Authors: RL Kopco, J Iida, JR Lehman, S Somiari, R Somiari, RJ Mural, CD. Shriver
Journal: Cancer Research (2010)

Abstract Triple negative (TN) breast cancers are defined by a lack of expression of estrogen, progesterone, and her-2/neu receptors. It is widely recognized that TN breast cancers have a poorer prognosis than other subtypes of breast caner. Given the lack of effective targeted therapies for TN breast cancer patients, understanding of the mechanisms of growth and invasion of these tumors will provide insight into developing novel approaches to lower the mortality from TN breast cancer. We utilized three TN breast cancer cell lines (HCC38, HCC1806, HCC1937) as model systems to characterize mechanisms of growth, migration, and invasion. FACS analyses demonstrated that these TN cell lines showed a phenotype of CD44+CD24-/lowepithelial specific antigen (ESA)+. An inhibitory antibody against exon v10 of CD44 significantly inhibited three-dimensional (3D) growth of tumor cells. Importantly, this antibody also inhibited alpha2beta1/alpha3beta1 integrins-mediated migration and invasion into matrigel. These results suggest that CD44 harboring exon 10 facilitates progression and metastasis of TN breast cancer cells in vivo by enhancing growth, migration, and invasion. We also demonstrated that this exon interacts with a cell surface tyrosine kinase, EphA2. Thus, we hypothesize that CD44 would form a molecular complex with EphA2 through exon v10 on TN breast cancer cells that plays a key role in facilitating invasion and metastasis. In order to develop novel reagents to inhibit TN breast cancer invasion and metastasis, we have utilized SELEX (systematic evolution of ligands by exponential enrichment) to isolate DNA aptamers that specifically recognize exon v10 of CD44. DNA aptamers are functional molecules with the appropriate sequence and structure to form a complex with a target molecule. Typically, dissociation constants for these aptamer-target complexes are in the high pico-molar to low nano-molar range, which is comparable to antibodies. Given the fact of the ease of chemical synthesis and modifications of oligonucleotides, DNA aptamers that recognize cancer cells will be easier to develop and have a great impact for the next generation of strategies for cancer detection, diagnosis, and therapy. We describe the development of “function-blocking” DNA aptamers specific for exon v10 of CD44 that inhibits TN breast cancer invasion and metastasis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD02-08.
Abstract 1285: Smad4 loss leads to reduced DNA repair and skin cancer.
Authors: Doyel Mitra, Pamela Fernandez, Bian Li, Ningjing Song, Gangwen Han, Xiao-Jing Wang
Journal: Cancer Research (2013)

Abstract Solar ultraviolet (UV) radiation is the primary cause of skin cancer. Non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of skin cancer and accounts for 2-3 million worldwide cases of cancer each year. The transcription factor Smad4 is a central mediator in the transforming growth factor β (TGFβ), activin, and bone morphogenetic protein (BMP) signaling pathways. Smad4 loss occurs frequently in human skin squamous cell carcinoma (SCC), but it is unknown if this event is causal to ultraviolet-induced (UV) carcinogenesis, a major etiological factor in human skin cancer. In the present study, we exposed mice with keratinocyte-specific Smad4 deletion (K14.Smad4−/−) and wildtype (WT) mice to chronic UV irradiation. Compared to WT littermates, K14.Smad4−/− mice exhibited increased susceptibility to UV-induced skin cancer. Histological examination revealed that UV-induced Smad4−/− tumors were all SCCs. Moreover K14.Smad4−/− skin shows increased DNA damage due to reduced expression of DNA repair genes compared to WT skin. We have identified a novel mechanism by which Smad4 suppresses skin cancer by promoting repair of UV-induced DNA lesions. Citation Format: Doyel Mitra, Pamela Fernandez, Bian Li, Ningjing Song, Gangwen Han, Xiao-Jing Wang. Smad4 loss leads to reduced DNA repair and skin cancer. [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 1285. doi:10.1158/1538-7445.AM2013-1285
NC-14 * SPEECH MAPS GENERATED BY nTMS AND CORRELATION WITH DIRECT INTRAOPERATIVE ELECTRICAL STIMULATION
Authors: R. Rotta, S. Tummala, S. Guillory, S. Prabhu, G. Rao, N. Levine, D. Suki, F. Lang, J. Weinberg, R. Sawaya
Journal: Neuro-Oncology (2014)

INTRODUCTION: IOM of language pathways is the gold standard for the safe resection of gliomas; navigated TMS has been shown to be useful in generating speech maps prior surgery. This study test the clinical utility of nTMS for mapping language and its concordance with intraoperative stimulation. METHODS: We describe 12 patients with gliomas adjacent to language areas. All cases were performed with nTMS, DES for language mapping. We analyzed, positive and negative sites preoperatively and intraoperatively, and correlated them to the extent of resection and a 1-mo follow-up. RESULTS: Navigated TMS positive maps, was achieved in 11 (92%), and 8 (80%) of cases had language errors during DES. 3527 site were stimulated during nTMS mapping, 225 (7%) was positive, 77 (34%) speech arrest, 78 (35%) performance errors and 70 (31%) semantic errors. TP correlation was achieved in 8 (67%) of cases, TN correlation 1 (8%) and FP correlation was achieved in 1 (8%) of cases. In TP cases, GTR was achieved in 6 (75%) of cases and after 1-mo follow-up 1 (14%) case developed new deficit and improvement was seen in 1(14%) case. In the only case of TN correlation, GTR resection was achieved, without deficits after 1-mo follow-up. CONCLUSION: nTMS correlated well with DES in generated language mapping, with a rate of TP according 67% and the only case with negative response in nTMS was TN. We have shown that nTMS has a high rate of concordance with DES; nTMS has 100% sensitivity, and 50% specificity when compared with DES. PPV at 89% and NPV 100%. The majority of positive sites were achieved in Broca's area and Wernicke's area. Additionally, if the nTMS reveal speech arrest distant from surgical exposure, this may be an additional utility for nTMS in explaining apparent negative mapping results in intraoperative stimulation.
The Finding of Chronic Pyelonephritis in Males and Females at Autopsy
Authors: Susan E. T. Kleeman, Lawrence R. Freedman
Journal: New England Journal of Medicine (1960)

THE pathogenesis of histologically proved chronic pyelonephritis is frequently obscure. Although pyelonephritis has been defined as "the pathologic alterations (in the kidney) which occur subsequent to the multiplication of pathogenic bacteria,"1 patients with this diagnosis commonly do not give a history of urinary-tract infection and may have urine cultures that are repeatedly sterile. In addition, since these pathologic alterations may be found in kidneys with other diseases, their mere presence does not demonstrate that bacteria contributed to their development. Thus, it is to be expected that observers would disagree whether a given lesion should be called pyelonephritis since some lesions . . .
Prospective analysis of the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in pancreatic masses, using a 22-gaude or 25-gauge needle
Authors: Choi ERyoung
Journal: Endoscopy (2011)

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is widely performed to diagnose pancreatic masses. Recently 25-gauge needle (25G) is available, which is thinner and more flexible than 22-gauge needle (22G) for EUS-FNA. Smaller needle, like a 25G might provide less bloody component, less complications and more safe and easier to maneuver than using larger needle. The aim of this study was to compare efficacy of 25G with 22G in EUS-FNA for pancreatic tumor.
Preoperative Tc-99m-Pertechnetate Scan Visualization of Gross Neck Metastases From Microcarcinoma Papillare and Another Papillary Carcinoma of Tall Cell Variant Scintigraphically Presented Like Small Warm Nodule in Graves Disease Patient
Authors: Vinko Marković, Davor Eterović, Ante Punda, Valdi Pešutić-Pisac, Tihomir Kuna
Journal: Clinical Nuclear Medicine (2010)

Purpose: Preoperative scintigraphic visualization of metastases from well-differentiated thyroid microcarcinoma in patients with Graves disease is extremely rare, as is the scintigraphic visualization of poorly differentiated thyroid carcinoma as a warm nodule. We present a patient with Graves disease and both of these rare entities. Case Report: A 47-year-old woman complained of a growing left-side neck mass and symptoms of thyrotoxicosis. On clinical examination, the thyroid was palpable without discernible nodularity, while the left side of the neck was occupied by 3 gross, painless nodules. She also had signs of thyrotoxicosis and biochemical parameters of Graves hyperthyroidism. Ultrasound examination showed moderately hypoechogenic thyroid with a small hypoechogenic nodule in the upper pole of the left lobe and 3 gross, almost normoechogenic nodules on the left side of the neck. On Tc-99m-pertechnetate pinhole scintigraphy there was a small, warm nodule in the upper pole of the left lobe and 3 gross metastatic nodules on the left side of the neck. Fine needle aspiration of the neck nodules was consistent with metastases from thyroid papillary carcinoma. After thyrostatic preparation a total thyroidectomy with left modified radical neck dissection was done. Results and Conclusion: Histopathologic examination disclosed 2 carcinomas in the left thyroid lobe. One of them was a tall cell variant of papillary carcinoma in the upper pole of the left lobe that measured 5 mm and corresponded to the small warm nodule, and the second one was a classic form of papillary microcarcinoma that measured 2 mm. Metastases accrued from the classic form of papillary microcarcinoma. Although the patient had 2 thyroid carcinomas, one with metastases and the other of more aggressive form, which is consistent with advanced stage and aggressiveness, she is now disease-free, 4 years after the operation and radioiodine ablation.
MYOCARDIAL WASHOUT OF T1-201 FOLLOWING DIPYRIDAMOLE INFUSION VARIES WITH THE INFUSED DOSE: IMPLICATION THAT ADEQUATE MYOCARDIAL HYPEREMIA MAY NOT BE ACHIEVED BY STANDARD DIPYRIDAMOLE DOSE.
Authors: George T. OʼByrne
Journal: Clinical Nuclear Medicine (1986)

Jamshid Maddahi, Alan Rozanski, Ken Van Train, Alan Waxman, and Daniel S. Berman. Cedars-Sinai Medical Center, Los Angeles, CA.
PMO-125 Neutrophil intracellular toll-like receptor (TLR) 9 expression serves as a biomarker that determines presence and severity of encephalopathy in acute liver failure and cirrhosis
Authors: G K Manakkat Vijay, R D Abeles, S Ramage, A Riva, J M Ryan, N J Taylor, J A Wendon, S Chokshi, Y Ma, D L Shawcross
Journal: Gut (2012)

<h3>Introduction</h3> There is a marked propensity for patients with acute liver failure (ALF) and cirrhosis to develop sepsis and inflammation which may hasten the development of hepatic encephalopathy (HE) and cerebral oedema. Neutrophil dysfunction is an important biomarker of poor prognosis in liver failure and neutrophil TLR9 expression upregulates with ammonia exposure. There is a paucity of understanding regarding the relationship between neutrophil dysfunction and the development of HE, moreover there is a lack of predictive/prognostic biomarkers that differentiate ALF patients that will go on to develop HE. The aim of this study was to investigate the relationship between neutrophil TLR9 and development of HE. <h3>Methods</h3> In healthy controls (n=12) and patients with ALF (n=12) and cirrhosis (n=50) we investigated neutrophil TLR9 expression using fluorochrome-conjugated monoclonal antibodies [CD16 (PE), CD11b (APC-Cy7) and TLR9 (APC) (after cytofixation/permeabilisation)] by flow cytometry in determining responses to endotoxin and bacterial challenge at baseline, and following 2 h stimulation with lipopolysaccharide (LPS) and ammonia. Pro- and anti-inflammatory cytokines were determined by CBA. <h3>Results</h3> Baseline neutrophil TLR9 expression was significantly higher in patients with HE (ALF: Grade 3/4 vs controls: p&lt;0.02, vs grade 0–2: p&lt;0.03) (Cirrhotics: Grade 3/4 vs controls: p&lt;0.03, vs grade 0–2: p&lt;0.05). Moreover their baseline TLR9 expression was associated with severity of HE and higher IL6 and IL8 levels. CD16 expression was downregulated by a median of 45% (range 25%–85%) in ALF patients with grade 3/4 HE compared to controls and in cirrhotics by a median of 88% (range 5%–90%) (Grade 3/4 vs controls: p&lt;0.05). Baseline CD11b expression did not differ between controls and patients. Exposure to LPS and ammonia upregulated TLR9 and CD11b and downregulated CD16. <h3>Conclusion</h3> Neutrophil TLR9 expression in patients with ALF and cirrhosis serves as a useful biomarker that differentiates those who develop high grade HE from those who do not. High baseline TLR9 expression and low CD16 expression promote a pro-inflammatory cytokine milieu that may help to explain the propensity to develop infection and why inflammation hastens the development of HE. TLR9 antagonists may be of therapeutic value in restoring neutrophil activity. <h3>Competing interests</h3> None declared.
ET-28 * COMBINATION THERAPY WITH MET TYROSINE KINASE INHIBITOR EMD1214063 AND BEVACIZUMAB
Authors: S. Keir, M. Roskoski, D. Gasinski, H. Friedman, D. Bigner
Journal: Neuro-Oncology (2014)

INTRODUCTION: EMD1214063 is a MET tyrosine kinase inhibitor with the potential for antineoplastic activity. Selectively binding to MET tyrosine kinase, EMD1214063 disrupts MET signal transduction pathways which may induce apoptosis in tumor cells overexpressing this kinase. The receptor tyrosine kinase MET is the product of the proto-oncogene c-Met and is overexpressed or mutated in many tumor cell types; this protein plays key roles in tumor cell proliferation, survival, angiogenesis and metastasis. As a part of this study, we looked at the combination of EMD1214063 with Bevacizumab (BEV). METHODS: Subcutaneous (08-0357 and 09-0477) and intracranial (09-0477) brain tumor xenografts were grown in athymic BALB/c mice. These xenograft lines were selected for treatment based on phospho-MET, total MET, HGF mRNA, and MET copy number expression. After tumor size reached 200-500 mm3 subcutaneously or 3 days after intracranial implantation, groups of 8-10 mice were stratified into the following groups: control, EMD1214063 alone, BEV alone, and EMD1214063 + BEV. RESULTS: For 08-0537 the combination of EMD1214063 + BEV produced a 12.06 day delay (P < 0.004), however, the additive effect of BEV alone + EMD1214063 alone was 13.97 days. For 09-0477, using a subcutaneous model, EMD1214063 alone produced a 26.41 day delay (P < 0.001) and the combination with BEV delayed tumor growth by 43.01 days (P < 0.001). The additive effect of single agents was 29.39 days. Intracranially, EMD1214063 alone increased survival by 56% (P < 0.023) and when combined with BEV survival increased to 180% (P < 0.001) The additive effect of single agents was an 88% increase in survival. CONCLUSION: Our studies confirm that EMD1214063 in combination with BEV is active against GBM in both subcutaneous and intracranial models. Furthermore, the data indicates that EMD1214063 is also active as a monotherapy in specific xenograft lines. The driver of single agent activity may be related to HGF expression.