tbuckley/cabot-search huggingface dataset:
Evaluation of the insulin-like growth factor receptor I and Pyk2 kinase in urothelial carcinomas and effect on motility and invasion of urothelial carcinoma-derived cells.
Authors: A. Morrione, M. Genua, R. V. Iozzo, L. G. Gomella
Journal: Journal of Clinical Oncology (2011)

254 Background: We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial-carcinoma-derived cells without affecting cell proliferation, suggesting that the IGF-IR may play a more prominent role in promoting the transition to the invasive phenotype in bladder cancer. Methods: IGF-IR levels in cancer and normal bladder tissues were analyzed by immunohistochemistry. IGF-IR and Pyk2 signaling pathways were studied in several urothelial carcinoma-derived cancer cells using biochemical assays and siRNA approaches. Pyk2 expression in a bladder tissue array was analyzed by immunofluorescence and by AQUA (Automated Quantitative Analysis). Results: In this studywe demonstrated by immunohistochemical analysis that the IGF-IR expression increased with grade in bladder cancer tissues compared to non-malignant controls. Increased IGF-IR expression in non-tumorigenic T24 urothelial carcinoma cells promoted anchorage independent growth, while IGF-IR targeting in metastatic T24T cells inhibited colony formation in soft-agar. We also discovered that the focal adhesion protein Pyk2 is activated by IGF-I in urothelial carcinoma-derived cells. Using siRNA approaches, we demonstrated that Pyk2 is critical for IGF-IR-dependent motility and invasion and regulates IGF-I-dependent activation of the Akt and MAPK pathways in urothelial cancer cells. Using immunofluorescence and AQUA analysis we also discovered that Pyk2 is overexpressed in bladder cancer tissues compared to normal tissue controls. In urothelial carcinoma-derived tissues there is also increased Pyk2 localization in the nucleus compared to normal tissue controls. Conclusions: Our results provide the first evidence for a role of the IGF-IR and Pyk2 in motility and invasion of bladder cancer cells, and support the hypothesis that the IGF-IR and Pyk2 may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia. The IGF-IR and Pyk2 could also serve as novel tumor biomarkers for diagnosis and possibly prognosis of bladder tumors. No significant financial relationships to disclose.
Fludarabine, Amsacrine, High-Dose Cytarabine and Total Body Irridation Followed by Allogeneic Stem Cell Transplantation for the Treatment of High Risk or Relapsed Acute Lymphoblastic Leukemia.
Authors: Fabian Zohren, Thorsten Graef, Ingmar Bruns, Akos Czibere, Fenk Roland, Haas Rainer, Kobbe Guido
Journal: Blood (2007)
Use of probe-based confocal laser endomicroscopy (pCLE) in the diagnosis of cholangiocarcinoma.
Authors: John D. Wysocki, Celeste Newby, Virendra Joshi
Journal: Journal of Clinical Oncology (2012)

281 Background: Despite technologic advances in endoscopy and new cytologic techniques, cholangiocarcinoma is a challenging diagnosis for the endoscopist and oncologists. Current sampling techniques include cytology brushing, biopsy, and fine needle aspiration but are limited in their sensitivity. Confocal laser endomicroscopy (CLE) is a relatively new modality that offers in-vivo imaging of the gastrointestinal tract with microscopic detail in living cells. Methods: This was an observational study of 10 patients with indeterminate biliary strictures who were evaluated with ERCP, cholangioscopy, and CLE to determine the sensitivity and specificity of tissue biopsy compared to virtual biopsy using this new technology, CLE. All cases were confirmed to be cholangiocarcinoma by histopathology. Fluorescein 10% was used as a contrast agent. Results: The 10 ERCP cases that were reviewed demonstrated biliary strictures that were suspicious for malignancy based on history and clinical presentation. Nearly all initial brushings and traditional biopsies were inconclusive. Subsequent ERCP and cholangioscopy with CLE imaging was performed. The biliary architecture was concerning for malignancy according to the Miami Criteria. Images were reviewed by 2 independent physicians. Every case demonstrated thick bands &gt;20 µm and dark clumps of glands. Bright vessels ( &gt;20 µm) with tortuosity were visualized in seven cases. Other findings include reticular networks of dark bands and small, fine branching bands &lt;20 µm, but these patterns were infrequent. Conclusions: 1.CLE is a novel tool to investigate indeterminate biliary strictures and potentially diagnose cholangiocarcinoma in conjunction with other diagnostic modalities during the initial ERCP and cholangioscopy. 2. Our early experience found sensitivity 90% , specificity of 100% , NPV 90% 3. CLE gives the opportunity to obtain en-vivo targeted biopsies during cholangioscopy as well as reduce repeat procedures and cost.
Magnetic Nanoparticle of Fe3O4 Loaded with Daunorubicin Reverse Leukemia Multidrug Resistance in Vivo
Authors: Bao-An Chen, Bin-bin Lai, Jian Cheng, Feng Gao, Wen-lin Xu, Hui-lin Shen, Jia-hua Ding, Chong Gao, Yun-yu Sun, Jun Wang, Gang Zhao, Hui-hui Song, Wen Bao, Xin-chen Sun, Hong-yan Cheng, Yu-xia Deng, Guo-hong Li, Li-jie Liu, Wen-ji Chen, Ze-ye Shao, Guo-hua Xia, Jue-qiong Wang, Peng Yuan, Xiao-ping Pei, Ning-na Chen, Qin-ning Li, Xue-mei Wang
Journal: Blood (2008)
Microarray-based gene expression profiles to predict ELISA-derived uPA and PAI-1 levels in breast cancer biopsies: A comparison between fresh frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) samples.
Authors: C. Matuschek, H. B. Prisack, E. Boelke, W. Budach, W. Janni, M. Rezai, H. Bojar
Journal: Journal of Clinical Oncology (2011)

194 Background: The urokinase plasminogen-activator (uPA) and its inhibitor (PAI-1) predict the benefit of node-negative breast cancer patients from chemotherapy. The determination of uPA and PAI-1 need(s) large amounts of tumor tissue. In contrast, microarray-based gene expression profiling (MGEP) requires only small quantities of FF tissue and is applicable to FFPE archival tissue. Identification of MPEG-derived surrogate markers for ELISA-based uPA/PAI-1 may facilitate their analysis together with MPEG-based predictive genes and metagenes. Methods: Three groups of breast cancer biopsies were analysed. Group A: 136 FF tissues from 2008-2009, group B: 85 FF tissues from 2010, group C: 20 independent FFPE tissues. Gene expression was assessed by Agilent 4x44K microarrays. Results: For group A a significant correlation between protein expression of uPA and uPA gene (PLAU) expression (r = 0.627 p &lt; 0.001) and PAI-1 and PAI-1 genes (SERPINE1)(r = 0.281 p = 0.001) was found. Top sets of genes correlated with uPA/PAI-1 protein expression were extracted. For group B additional sets of top correlated genes were identified. The correlation of individual genes with uPA/PAI-1 protein expression was highest for their genes themselves (PLAU: r = 0.694 p &lt; 0.001; SERPINE1 (r = 0.469 p &lt; 0.001). Subsequently consensus gene sets were identified with a good performance for both biopsy sets. Only genes which were significantly correlated with their counterparts in group C were selected, resulting in a final 11-gene model (uPA metagene) and a 6-gene model (PAI-1 metagene). They significantly correlated with uPA/PAI-1 protein expression in all groups of biopsies (uPA: group A: r = 0.621, p &lt; 0.001; group B: r = 0.771, p &lt; 0.001; group C: r = 0.665, p = 0.005; for PAI-1: group A: r = 0.569, p &lt; 0.001; group B: r = 0.687, p &lt; 0.001; group C: r = 0.683, p = 0.008). Conclusions: Reliable MPEG-derived metagenes as surrogate markers for ELISA-based uPA/PAI-1 expression were identified.
Swollen Hand Joints With Asymptomatic Nodules on the Skin
Authors: Hui Qu, Ping Tu, Jin Yu
Journal: JAMA Dermatology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Efficacy of gemcitabine as second-line therapy after S-1 therapy failure in advanced pancreatic carcinoma.
Authors: Masaru Fukahori
Journal: Journal of Clinical Oncology (2012)

248 Background: Gemcitabine (GEM) and GEM-containing combination chemotherapy have been established as standard first-line therapies for advanced pancreatic carcinoma (APC). In the GEST study, a phase III clinical trial that compared the results for GEM, S-1, and GEM+S-1 therapies, there was no significant difference between overall survival (OS) for GEM and GEM+S-1; S-1 and GEM had similar efficacies as first-line treatment for APC. Therefore, S-1 is expected to be used as first-line therapy. In our study, we have evaluated the efficacy and outcomes of second-line GEM therapy after S-1 therapy failure in APC. Methods: We retrospectively examined the data for 27 patients (pts) with APC refractory to first-line S-1 therapy. All the pts had undergone second-line GEM therapy during October 2000–February 2009 at National Cancer Center Hospital after first-line S-1 therapy. Tumor responses were analyzed using Response Evaluation Criteria in Solid Tumors. The Kaplan-Meier method was used to evaluate tumor progression and survival. Results: The Eastern Cooperative Oncology Group Performance Status was 0 or 1. The male:female ratio was 16:11 and median age was 62 years (range, 42–75 years). Four pts (14%) exhibited a partial response to second-line GEM therapy, 11 (40%) showed stable disease, and 12 (44%) showed progressive disease. Grade 3 adverse events for second-line GEM therapy were neutropenia in 2 pts and upper gastrointestinal hemorrhage in 1 pt. Grade 4 adverse events were not observed. The median progression-free survival was 77 days (95% confidence interval, 33–121 days) and the median OS after second-line GEM therapy was 240 days (95% confidence interval, 156–324 days). Conclusions: Although this study had a small sample population and retrospective design, the results indicate that GEM has good antitumor activity with tolerable toxicity. Second-line GEM therapy was found to be effective after first-line S-1 therapy failure in APC.
Effect of neoadjuvant docetaxel treatment for locally advanced prostate cancer on miRNA expression: A pilot study.
Authors: Sara Moscovita Falzarano, Ming Zhou, Paula Carver, Eric A. Klein, Robert Dreicer, Cristina Magi-Galluzzi
Journal: Journal of Clinical Oncology (2012)

139 Background: Taxanes are microtubule-stabilizing drugs used investigationally in adjuvant and neoadjuvant settings of prostate cancer (PCA) treatment in an attempt to improve systemic control of high risk disease. Understanding mechanism of response to taxanes is an essential step in developing novel combination therapies to improve PCA response rates. MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression by binding target messenger RNAs and inhibiting their stability and/or translation. In cancer miRNAs can act as oncogenes and/or tumor suppressor genes. The objective of our study was to identify miRNAs that are affected by neoadjuvant docetaxel in high-risk PCA. Methods: Whole cell RNA was extracted from formalin-fixed paraffin-embedded (FFPE) radical prostatectomy specimens from 8 patients with high grade PCA treated with neoadjuvant docetaxel, 8 high grade untreated PCA and their corresponding untreated non-neoplastic tissue. Tumors were matched by Gleason score, patient age and year of surgery. The expression of 88 cancer-associated miRNAs was then quantified using a PCR-based miRNA microarray assay. Results: Thirty-eight (43%) of the 88 analyzed miRNAs (including miR-205, miR-222, and miR-1) were sgnificantly downregulated in untreated PCA compared with untreated non-neoplastic tissue, and one (miR-183) was upregulated. Twenty (23%) miRNAs (including miR-218, miR-124, and let-7b) were significantly upregulated in treated compared to untreated PCA. The expression levels of 16 of these miRNAs (including miR-9, miR-133b, and miR-27b) were reverted to values similar to untreated non-neoplastic prostatic tissue, as a result of docetaxel treatment. Conclusions: Our results indicate a potential role of miRNAs in PCA response to taxanes. A subset of miRNAs are downregulated in untreated tumors but upregulated in treated PCA to the levels compared to untreated non-neoplastic tissue, suggesting a miRNA modulation towards a non-neoplastic expression profile with neoadjuvant docetaxel treatment. Further studies are underway to evaluate the miRNA-mediated effects of taxanes in PCA.
Emerging therapies for inherited retinal degeneration
Authors: Hendrik P. N. Scholl, Rupert W. Strauss, Mandeep S. Singh, Deniz Dalkara, Botond Roska, Serge Picaud, José-Alain Sahel
Journal: Science Translational Medicine (2016)

This Review discusses current and emerging therapies for treating inherited retinal degeneration.
Cost of care for prostate cancer patients: An observational cohort study comparing clinical trials to standard care.
Authors: B. Jones, R. Syme, M. Eliasziw, B. J. Eigl
Journal: Journal of Clinical Oncology (2011)

184 Background: Monetary support of clinical trials is a fundamental necessity for improving treatment and prevention methods; however, current economic data pertaining to the per-patient costs of treating prostate cancer are limited. A concurrent lack of certainty regarding the cost requirements of standard care patients makes it difficult for healthcare professionals and policy makers to generate informed decisions regarding budgets and funding needs. Prostate cancer clinical trials are facing a national funding crisis due to the perception that patients enrolled in clinical trials consume more resources than patients receiving standard care. Methods: A retrospective observational cohort study was conducted to examine the costs incurred by prostate cancer patients at the Tom Baker Cancer Center over one year. Costs for 36 patients enrolled in one of nine cancer trials were compared with costs for 36 matched control subjects who received standard care. Resource utilization was tracked using medical charts and quantified by prices listed in the TBCC's 2009 Clinical Trials Budget template. Results: No evidence was found to support a difference in overall resource utilization between clinical trial patients and standard of care patients (Paired two-tailed t- test, N= 36, p =0.90). There was, however, variability in the types of resources used by each patient population, indicating that, while trial patients may take up significantly more clinic time (p =0.04), undergo more tests and procedures (p &lt; 0.001) and require more diagnostic imaging (p = 0.01), standard care patients are more likely to receive costly interventions such as radiation therapy (p =0.06). Pharmaceutical costs have not yet been included in the analysis and could drastically alter the final results. Conclusions: This study revealed differences in the cost distribution of clinical trials patients versus standard of care patients, which could be used by administrators to improve budgeting and time allocation. The lack of difference in overall cost may be helpful to research advocates attempting to encourage centers to take on more trials. Further analysis is required before definitive conclusions can be drawn. No significant financial relationships to disclose.
Abstract 4399: Utilizing cobalt coordination chemistry as a traceless prodrug strategy in targeted drug delivery
Authors: Robby A. Petros, Duong T. Nguyen, Ronaldo J. Cavazos, Clifford S. Morrison, Jana B. Lampe, Alesha N. Harris, Brian K. McFarlin
Journal: Cancer Research (2015)

Abstract We recently reported the synthesis of albumin nanoparticles using cobalt as a traceless, reductively labile crosslinker. Here, we report in vitro characterization of particle uptake for fluorescently labeled cobalt crosslinked albumin nanoparticles (Co-Alb-FITC NPs) via image-based flow cytometry as well as preliminary toxicity data. Uptake of Co-Alb-FITC NPs by gastric carcinoma cells (SNU-5) was rapid, but could be dramatically reduced through the addition of an inhibitor of macropinocytosis. High levels of non-specific uptake of other particle types were also observed suggesting SNU-5 cells possess high macropinocytic activity. Cancers harboring mutated Ras (&amp;gt;20% of all cancers) are known to take up protein via macropinocytosis to satisfy metabolic demands. Because SNU-5 cells are not known harbor mutated Ras, our findings may indicate that other cancers rely on this mechanism as well, which would have important implications for observing selectivity in active nanoparticle targeting strategies. The Co-Alb NPs themselves were found to exhibit no inherent toxicity. Based on these initial findings, Co-Alb NPs were loaded with the active metabolite of camptothecin, SN-38, to explore their potential as a delivery vector for hydrophobic drugs. An albumin-topotecan prodrug conjugate was also synthesized by crosslinking the amine group in topotecan with lysine residues in the protein, which should be applicable to other amine-containing therapeutics. Characterization of drug loading and release will be discussed along with preliminary in vitro characterization. Citation Format: Robby A. Petros, Duong T. Nguyen, Ronaldo J. Cavazos, Clifford S. Morrison, Jana B. Lampe, Alesha N. Harris, Brian K. McFarlin. Utilizing cobalt coordination chemistry as a traceless prodrug strategy in targeted drug delivery. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4399. doi:10.1158/1538-7445.AM2015-4399
Is conscious content available only to the skeletal muscle system?
Authors: Andreas Keller
Journal: Behavioral and Brain Sciences (2016)

I applaud Morsella et al.'s approach to investigate consciousness in terms of behavioral control. After all, the function of the brain is to control behavior, and consciousness contributes to the function of the brain. However, I question whether conscious content is available only to the skeletal muscle system, as the principle of parallel responses into skeletal muscle (PRISM) (Morsella 2005) proposes.
Prolonged red cell storage before transfusion increases extravascular hemolysis
Authors: Francesca Rapido, Gary M. Brittenham, Sheila Bandyopadhyay, Francesca La Carpia, Camilla L’Acqua, Donald J. McMahon, Abdelhadi Rebbaa, Boguslaw S. Wojczyk, Jane Netterwald, Hangli Wang, Joseph Schwartz, Andrew Eisenberger, Mark Soffing, Randy Yeh, Chaitanya Divgi, Yelena Z. Ginzburg, Beth H. Shaz, Sujit Sheth, Richard O. Francis, Steven L. Spitalnik, Eldad A. Hod
Journal: Journal of Clinical Investigation (2016)

BACKGROUND. Some countries have limited the maximum allowable storage duration for red cells to 5 weeks before transfusion. In the US, red blood cells can be stored for up to 6 weeks, but randomized trials have not assessed the effects of this final week of storage on clinical outcomes.
Outcomes by breast cancer subtype in patients treated with accelerated partial breast irradiation.
Authors: J. B. Wilkinson, C. Shah, M. Amin, S. F. Shaitelman, L. Nadeau, P. Chen, M. Wallace, C. Mitchell, I. S. Grills, A. A. Martinez, F. A. Vicini
Journal: Journal of Clinical Oncology (2011)

83 Background: To determine clinical outcomes for patients treated with accelerated partial breast irradiation (APBI) based on breast cancer subtype. Methods: We evaluated 516 consecutive patients who received APBI with a minimum follow-up of 6 months. Methods of APBI delivery included interstitial brachytherapy (n=221), balloon-based brachytherapy (n=201), and 3D-CRT (n=106). Women were assigned a breast cancer subtype (BCST) based on results of testing for estrogen (ER), progesterone (PR), and human epidermal growth factor (HER2/neu) receptors. Those without test results for all three receptors were excluded. 278 patients were eligible and submitted for analysis. Receptor subtypes were approximated as follows: ER+, PR+/–, and HER-2 negative [luminal A (LA), 164 pts.]; ER+, PR+/–, and HER-2 positive [luminal B (LB), 81 pts.]; ER/PR–, HER-2+ [HER-2 (H2), 5 pts.], and ER/PR/HER-2 negative [basal (B), 28 pts.]. An analysis was then performed to estimate IBTR, RNF, DM, DFS, CSS, and OS. Results: Mean age was 66 years, median follow-up was 4.9 yrs. Basal and H2 subtype patients had higher histologic grades (Gr. 3 = 75% vs. 10% LA/LB, p&lt;0.001), larger tumors (13.0mm vs. 10.7mm LA/LB, p=0.05), and were more likely to receive chemotherapy (68% vs. 15% LA/LB, p&lt;0.001). Basal subtype patients were also more likely to be African American (18% vs. 4% LA/LB, p=0.002). Margin and nodal status were similar between all BCSTs. At five years, IBTR rates were 2.9%, 3.2%, 0%, and 4.8% for LA, LB, H2, and B subtypes, respectively (p=0.75). The IBTR within the B subtype group was due to a single elsewhere failure, the rate of which was not statistically different than that for the LA subtype (2.9%, p=0.30). DM was only seen in LA (2.5%) and LB (1.4%) (p=0.87). Disease-free survival (95-100%), CSS (97%-100%), and OS (80-100%) (Table) were also not statistically different (p=0.98, 0.85, 0.24, respectively) between BCST categories. Conclusions: Five-year local control rates after treatment with APBI are excellent for luminal, HER2, and triple-negative phenotypes of early-stage breast cancer. Further study of BCST is important and may be useful when counseling patients on adjuvant treatment options following breast-conserving surgery.
Constitutive Expression of the ‘Lymphoid Enhancer Factor 1‘ (Lef-1) Perturbs Early Hematopoietic Development and Induces a Lethal Myeloproliferative Syndrome in a Subset of Transplanted Mice.
Authors: Konstantin Petropoulos, Farid Ahmed, Christina Schessl, Natalia Arseni, Aniruddha Deshpande, Wolfgang Hiddemann, Rudolf Grosschedl, Michaela Feuring-Buske, Christian Buske
Journal: Blood (2005)
Kinetics of Engraftment and Graft Versus Host Disease After Cotransplantation of Ex Vivo Expanded and Unexpanded Cord Blood Units In Immunodeficient Mice.
Authors: Li Ming Ong, Xiubo Fan, Pak Yan Chu, Florence Gay, Justina Ang, Zhihong Li, Jianzhu Chen, SaiKiang Lim, Ralph Bunte, William Hwang
Journal: Blood (2010)