tbuckley/cabot-search huggingface dataset:
Three-dimensional tumor spheroid formation in lyophilized alginate sponge scaffolding
Authors: Richard Fike, Chao Liu, Menachem Tobias, Ferenc Boldog, Kenneth Low, Soverin Karmiol, Sandra Kuligowski, Paul Price, Ilan Eliassi, Ari Gargir, Barry Hudson, Smadar Cohen
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3048 

This study assessed alginate sponge scaffolding for use in tumor spheroid formation, co-cultivation and high throughput screening. Numerous published studies have shown that three-dimensional (3D) cell culture generally yield more in vivo -relevant data than similar studies done with cells growing on plastic in two-dimensions (2D). This is true for both normal as well as for cancer tissues and cell lines. In vitro 3D cell culture promotes cell-to-cell morphological relationships resulting in physical and chemical cues considered to be important in vivo . 3D cell culture also readily permits co-cultivation of cells of different lineages (such as cancer cells with stem cells). Multicellular Tumor Spheroid 3D assays have been shown to be reliable systems to model cancer biology for antitumor drug screening and studying tumor metastasis. Several types of 3D cell culture systems have been used in cancer research to form tumor spheroids. However none of these has been entirely successful for a variety of reasons relating to the complexity of use, non-standardization of materials, or the limited number of samples that can be tested at one time. We report the use of alginate scaffolds for formation of tumor spheroids. These scaffolds are sponges of defined non-animal origin. Culture of C6 glioma cells resulted in the growth of distinct tumor colonies in 5 days, with a rapid increase in tumor number seen in cells grown with 10% FBS compared to cells in media without FBS. We are currently assessing the expression and activation of MMPs in the 3D compared to 2D environment. HepG2 C3A hepatocarcinoma cells were also directly inoculated into the scaffolding, resulting in spheroids which formed in cell culture over several days and expanded for several weeks, increasing in size and morphological complexity. In 96-well plate format, scaffold uniformity is consistent with high throughput screening (HTS) of 3D cell cultures. A 2-fold increase per cell of CYP 1A2 induction of C3A cells was observed in 3D spheroids compared to 2D (plastic) cultures. Co-culture of HepG2 C3A cells with human mesenchymal stem cells (MSC) resulted in what appeared to be growth of a morphologically distinct cell type. In conclusion, the alginate sponge in 96-well plate format appears to be suitable for cancer research applications allowing for both microscopic observations and HTS assays in 3D cell culture format.
Abstract #5136: Characterization of the differential sensitivity to rhTRAIL and to Lexatumumab in human colon carcinoma cell lines (cc).
Authors: Angshuman Sarkar, . Houghton J. DeVecchio , T.S. Jani , R. Humphreys
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Colorectal cancer remains one of the predominant causes of cancer-related deaths in the USA. Although advancement in chemotherapy has enabled the survival rate to increase to 22 months, resistance to chemotherapy remains a major issue. Employment of death receptor ligands in treatment of various cancers is currently being analyzed as a promising target for cancer therapy. We have demonstrated that in cc, the primary target of TRAIL (the native ligand that targets the death receptors DR4 and DR5) and Lexatumumab (a cytolytic antibody that targets TRAIL-R2 (DR5) is DR5. Our data demonstrate that in HCT8 cells, lexatumumab shows greater cytotoxic activity than rhTRAIL whereas VRC5/c1 cells are more sensitive to rhTRAIL than to lexatumumab. DR5 is known to exist as two alternatively spliced isoforms: DR5short (DR5S) and DR5long (DR5L). Since DR5 is an important target in cc for both rhTRAIL and lexatumumab, the basal expression of the two DR5 isoforms was examined in our panel of cc and ratios of DR5S: DR5L were established. Our work has demonstrated that both agents induce the recruitment of more DR5S than DR5L to the receptor complex, which is modulated upon treatment with rhTRAIL or lexatumumab. Western blot analysis of HCT8 cells shows increased induction of DR5 in response to lexatumumab whereas induction of DR5 was significantly higher in rhTRAIL-treated VRC5/c1 cells. It has been reported that NF-kB transcriptionally regulates DR5 expression. EMSA analysis demonstrated significant NF-kB activation in HCT8 cells following lexatumumab treatment whereas in VRC5/c1 cells, TRAIL treatment caused greater NF-kB activation. Furthermore, the differences seen in HCT8 and VRC5/c1 correlated with the differences at the level of the receptor complex. Data demonstrated a differential recruitment of the pro-apoptotic proteins to the DISC in HCT8 and VRC5/c1 cells in response to lexatumumab and TRAIL treatment respectively. Lexatumumab treatment in HCT8 cells and rhTRAIL treatment in VRC5/c1 cells showed increased recruitment of DR5, FADD, caspase-8 and cleaved RIP and reduced levels of full length RIP, c-FLIPL and c-FLIPS in the receptor complex. The potential involvement of TRAF2 and c-IAP2, also recruited to the receptor complexes, in the differential sensitivities to rhTRAIL or to lexatumumab in HCT8 and VRC5/c1 cells is currently under investigation. Supported by NCI awards CA 32613 and CA 108929.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5136.
A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): an Alliance trial
Authors: A. Jatoi, P.D. Steen, P.J. Atherton, D.F. Moore, K.M. Rowland, N.A. Le-Lindqwister, C.S. Adonizio, A.J. Jaslowski, J. Sloan, C. Loprinzi
Journal: Annals of Oncology (2017)
lncRNA HOXD-AS1 Regulates Proliferation and Chemo-Resistance of Castration-Resistant Prostate Cancer via Recruiting WDR5
Authors: Peng Gu, Xu Chen, Ruihui Xie, Jinli Han, Weibin Xie, Bo Wang, Wen Dong, Changhao Chen, Meihua Yang, Junyi Jiang, Ziyue Chen, Jian Huang, Tianxin Lin
Journal: Molecular Therapy (2017)

Castration-resistant prostate cancer (CRPC) that occurs after the failure of androgen deprivation therapy is the leading cause of deaths in prostate cancer patients. Thus, there is an obvious and urgent need to fully understand the mechanism of CRPC and discover novel therapeutic targets. Long noncoding RNAs (lncRNAs) are crucial regulators in many human cancers, yet their potential roles and molecular mechanisms in CRPC are poorly understood. In this study, we discovered that an lncRNA HOXD-AS1 is highly expressed in CRPC cells and correlated closely with Gleason score, T stage, lymph nodes metastasis, and progression-free survival. Knockdown of HOXD-AS1 inhibited the proliferation and chemo-resistance of CRPC cells in vitro and in vivo. Furthermore, we identified several cell cycle, chemo-resistance, and castration-resistance-related genes, including PLK1, AURKA, CDC25C, FOXM1, and UBE2C, that were activated transcriptionally by HOXD-AS1. Further investigation revealed that HOXD-AS1 recruited WDR5 to directly regulate the expression of target genes by mediating histone H3 lysine 4 tri-methylation (H3K4me3). In conclusion, our findings indicate that HOXD-AS1 promotes proliferation, castration resistance, and chemo-resistance in prostate cancer by recruiting WDR5. This sheds a new insight into the regulation of CRPC by lncRNA and provides a potential approach for the treatment of CRPC.
HLA-G 14BP insertion-deletion polymorphism influences response to methotrexate in inflammatory bowel disease.
Authors: B Baburajan, N Prescott, K Herrlinger, F Cummings, M Arenas, M Smith, M Tremelling, A Ansari, M Parkes, D Jewell, C Mathew, A Marinaki, J Sanderson
Journal: Gut (2007)
Targeting c-Met overexpression for overcoming acquired resistance to EGFR TKIs in NSCLC.
Authors: Lanying Gou, Yi-Long Wu, Jinji Yang, Xuchao Zhang
Journal: Journal of Clinical Oncology (2015)

8091 Background: c-Met amplification and T790M are both recognized as the common molecular mechanisms of acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in advanced NSCLC. Methods: Advanced NSCLC patients with AR to EGFR TKIs were detected for c-Met overexpression by immunohistochemistry ≥ 50% tumor cells with moderate to high intensity staining were defined as c-Met positive. The statuses of EGFR, ALK, KRAS and ROS1 were tested. c-Met, p-Met, EGFR, p-EGFR, ERBB3, p-ERBB3, AKT, p-AKT, MAPK, p-MAPK, which were important markers in MET and EGFR signal pathway ,were tested by IHC. Results: From January 2013 to January 2015, 126 advanced NSCLC patients with AR to gefitinib or erlotinib were enrolled prospectively. The frequency of c-Met overexpression was 28.6% (36/126), c-Met overexpression+T790M 13.5% (17/126), T790M 24.6% (31/126), SCLC or squamous cell transformation 1.6% (2/126), KRAS mutation 0.8% (1/126), ROS1 fusion 0.8% (1/126) ,ALK fusion 0.8%(1/126) and unknown mechanism 29.3% (37/126), respectively. Eleven c-Met overexpressed patients received gefitinib plus c-Met inhibitors crizotinib. Response rate (RR) by RECEIST was 45.5% (5/11), Disease control rate (DCR) was 54.5% (6/11), Progression disease (PD) was 45.5% (5/11). For patients with c-Met overexpression and without T790M DCR was 100% (5/5). Among these patients 40% (2/5) cases were ongoing at data cut-off. The longest duration of response to date is > 6 months. For patients with both c-Met/T790M positive no RR was found. We detected the protein expression of c-Met, p-Met, EGFR, p-EGFR, ERBB3, p-RBB3, AKT, p-AKT, MAPK, p-MAPK in tumor of 9 cases with c-Met/T790M by IHC. The results showed that all of the markers were positive in ≥ 50% cases (each marker was positive in at least 5 cases, respectively). Conclusions: c-Met overexpression could be as a biomarker for AR. Combination of EGFR TKIs and c-Met inhibitor is a good strategy to overcome AR for c-Met overexpressed patients, but not effective in c-Met/T790M-coexisting cases. One of the possible mechanism of resistance could contribute to both MET and EGFR signal pathway active.
Androgen Deprivation Therapy and Subsequent Dementia—Reply
Authors: Kevin T. Nead, Samuel Swisher-McClure, Nigam H. Shah
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
Lenalidomide Plus R-CHOP (R2CHOP) in Patients with Follicular Lymphoma: Data from a Phase 1/2 Study
Authors: Ayed O. Ayed, Levi Pederson, William R. Macon, Betsy R. Laplant, Craig B. Reeder, James M. Foran, Garth Nelson, Candido E. Rivera, Thomas M. Habermann, Thomas E. Witzig, Grzegorz S. Nowakowski
Journal: Blood (2016)
Discussions regarding reproductive and sexual health among young adult survivors of cancer.
Authors: Ying Wang, Leo Chen, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2013)

9588 Background: Infertility and sexual dysfunction can result from many cancer treatments and may become a source of significant distress for young adult cancer survivors. Our aims were to 1) characterize the frequency in which reproductive and sexual health discussions occur in a population-based cohort of young cancer patients and 2) identify clinical factors associated with such discussions. Methods: Patients aged 20 to 39 years who were diagnosed with solid tumors from 2006 to 2008, evaluated at any 1 of 5 regional cancer centers in British Columbia, Canada and alive at 2 or more years after their initial diagnosis were included. Demographics, tumor and treatment characteristics, and information on patient-physician conversations were analyzed. Using regression models, we explored the relationships between clinical factors and whether or not discussions had occurred. Results: A total of 397 patients were identified: median age was 35 years (IQR 31-38), 28% were men, 88% had ECOG 0, and 73% reported being in a relationship. Tumor sites included breast (50%), testicular (27%), gynecological (17%), and colorectal (6%). A significant proportion of patients received chemotherapy and radiation that posed the potential risk of infertility or sexual dysfunction. However, only 224 (56%) and 24 (6%) of individuals had a discussion about reproductive and sexual health, respectively, within the first month of their diagnosis. At 6 months, an additional 25 (6%) and 16 (4%) patients had discussed these concerns with their physicians. Age, gender, ECOG, relationship status, and type of chemotherapy and radiation were not correlated with whether or not discussions had occurred (all p&gt;0.05). In regression models, tumor site was associated with differences in reproductive and sexual health discussions between patients and physicians (Table). Conclusions: Among young adult survivors of cancer, fertility and particularly sexual function are inadequately addressed during discussions near the time of initial cancer diagnosis. [Table: see text]
Optimizing Next-Generation AML Therapy: Activity of Mutant IDH2 Inhibitor AG-221 in Preclinical Models
Authors: Daniel Thomas, Ravindra Majeti
Journal: Cancer Discovery (2017)

Abstract Summary: AG-221 or enasidenib is a first-in-class selective inhibitor of mutated isocitrate dehydrogenase 2 (IDH2) with early demonstrated clinical efficacy in acute myeloid leukemia as a single agent, yet with persistence of mutant IDH2 clones. Two articles in this issue of Cancer Discovery provide further insight into the biological activity of AG-221 in promoting differentiation of IDH2-mutant cells and reversing aberrant DNA methylation over time, and demonstrating preclinical activity in combination with a targeted FLT3 kinase inhibitor to eliminate IDH2-mutant clones. Cancer Discov; 7(5); 459–61. ©2017 AACR. See related article by Yen et al., p. 478. See related article by Shih et al., p. 494.
IL-17-triggered downregulation of miR-497 results in high HIF-1α expression and consequent IL-1β and IL-6 production by astrocytes in EAE mice
Authors: Kai Shan, Rongrong Pang, Chenhui Zhao, Xiaomei Liu, Wenxing Gao, Jing Zhang, Dan Zhao, Yingwei Wang, Wen Qiu
Journal: Cellular and Molecular Immunology (2017)
DIAGNOSTIC AND CLINICAL SIGNIFICANCE OF ANTI-RO52 ANTIBODIES IN 609 CASES WITH PRIMARY BILIARY CIRRHOSIS FROM UK, SPAIN AND GREECE
Authors: Maria G. Mytilinaiou, Albert Pares, Elias S. Spyrou, Eirini I. Rigopoulou, George N. Dalekos, Diego Vergani, Dimitrios P. Bogdanos
Journal: Hepatology (2009)
Appropriate endpoints for evaluation of new antibiotic therapies for severe infections: a perspective from COMBACTE’s STAT-Net
Authors: Jean-François Timsit, Marlieke E. A. de Kraker, Harriet Sommer, Emmanuel Weiss, Esther Bettiol, Martin Wolkewitz, Stavros Nikolakopoulos, David Wilson, Stephan Harbarth
Journal: Intensive Care Medicine (2017)

In this era of rising antimicrobial resistance, slowly refilling antibiotic development pipelines, and an aging population, we need to ensure that randomized clinical trials (RCTs) determine the added benefit of new antibiotic agents effectively and in a valid way, especially for severely ill patients. Unfortunately, universally accepted endpoints for the evaluation of new drugs in severe infections are lacking. We review and discuss the current practices and challenges regarding endpoints in RCTs in this field and propose novel approaches. Usual endpoints actually recommended for drug development suffer from important flaws. Mortality requires large sample size and only partly related to the infectious process. Clinical cure rate is highly subjective in critically ill patients where symptoms may be related to other intercurrent events. Currently, composite endpoints, hierarchical nested designs, and competing risks analysis seem to be the most promising new tools for designing and analyzing clinical trials in this area, although they require further validation. Regulatory authorities, pharmaceutical companies, and clinicians need to agree on the most appropriate clinical endpoints for severe infections to ensure efficient approval of new, effective antibiotic agents.
Mast cells mediate neutrophil recruitment and vascular leakage through the NLRP3 inflammasome in histamine-independent urticaria
Authors: Yuumi Nakamura, Naotomo Kambe, Megumu Saito, Ryuta Nishikomori, Yun-Gi Kim, Makoto Murakami, Gabriel Núñez, Hiroyuki Matsue
Journal: The Journal of Experimental Medicine (2009)
Traumatic Spondylolisthesis of the Axis
Authors: Anis Khelifi, Faycel Saadaoui
Journal: New England Journal of Medicine (2017)

A 25-year-old man presented with neck pain after a high-speed motor vehicle collision. A radiograph and a computed tomographic scan showed fractures of the right and left pedicles of the C2 vertebra, sometimes called a hangman’s fracture.
Integrative Analysis Identifies a Novel AXL–PI3 Kinase–PD-L1 Signaling Axis Associated with Radiation Resistance in Head and Neck Cancer
Authors: Heath D. Skinner, Uma Giri, Liang P. Yang, Manish Kumar, Ying Liu, Michael D. Story, Curtis R. Pickering, Lauren A. Byers, Michelle D. Williams, Jing Wang, Li Shen, Suk Y. Yoo, You Hong Fan, David P. Molkentine, Beth M. Beadle, Raymond E. Meyn, Jeffrey N. Myers, John V. Heymach
Journal: Clinical Cancer Research (2017)

Abstract Purpose: The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach. Experimental Design: We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (n = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis. Results: RR cell lines exhibited upregulation of several proteins compared with controls, including increased activation of Axl and PI3 kinase signaling as well as increased expression of PD-L1. Additionally, inhibition of either Axl or PI3 kinase led to decreased PD-L1 expression. When clinical samples were subjected to RPPA and mRNA expression analysis, PD-L1 was correlated with both Axl and PI3K signaling as well as dramatically associated with local failure following radiotherapy. This finding was confirmed examining a third cohort using immunohistochemistry. Indeed, tumors with high expression of PD-L1 had failure rates following radiotherapy of 60%, 70%, and 50% compared with 20%, 25%, and 20% in the PD-L1–low expression group (P = 0.01, 1.9 × 10−3, and 9 × 10−4, respectively). This finding remained significant on multivariate analysis in all groups. Additionally, patients with PD-L1 low/CD8+ tumor-infiltrating lymphocytes high had no local failure or death due to disease (P = 5 × 10−4 and P = 4 × 10−4, respectively). Conclusions: Taken together, our data point to a targetable Axl–PI3 kinase–PD-L1 axis that is highly associated with radiation resistance. Clin Cancer Res; 23(11); 2713–22. ©2017 AACR.
Expression of CDCA3 Is a Prognostic Biomarker and Potential Therapeutic Target in Non–Small Cell Lung Cancer
Authors: Mark N. Adams, Joshua T. Burgess, Yaowu He, Kathy Gately, Cameron Snell, Shu-Dong Zhang, John D. Hooper, Derek J. Richard, Kenneth J. O’Byrne
Journal: Journal of Thoracic Oncology (2017)
Plasmacytoid and conventional dendritic cells cooperate in crosspriming AAV capsid-specific CD8+ T cells
Authors: Geoffrey L. Rogers, Jamie L. Shirley, Irene Zolotukhin, Sandeep R. P. Kumar, Alexandra Sherman, George Q. Perrin, Brad E. Hoffman, Arun Srivastava, Etiena Basner-Tschakarjan, Mark A. Wallet, Cox Terhorst, Moanaro Biswas, Roland W. Herzog
Journal: Blood (2017)
American Society of Clinical Oncology Strategic Plan for Increasing Racial and Ethnic Diversity in the Oncology Workforce
Authors: Karen M. Winkfield, Christopher R. Flowers, Jyoti D. Patel, Gladys Rodriguez, Patricia Robinson, Amit Agarwal, Lori Pierce, Otis W. Brawley, Edith P. Mitchell, Kimberly T. Head-Smith, Dana S. Wollins, Daniel F. Hayes
Journal: Journal of Clinical Oncology (2017)

In December 2016, the American Society of Clinical Oncology (ASCO) Board of Directors approved the ASCO Strategic Plan to Increase Racial and Ethnic Diversity in the Oncology Workforce. Developed through a multistakeholder effort led by the ASCO Health Disparities Committee, the purpose of the plan is to guide the formal efforts of ASCO in this area over the next three years (2017 to 2020). There are three primary goals: (1) to establish a longitudinal pathway for increasing workforce diversity, (2) to enhance ASCO leadership diversity, and (3) to integrate a focus on diversity across ASCO programs and policies. Improving quality cancer care in the United States requires the recruitment of oncology professionals from diverse backgrounds. The ASCO Strategic Plan to Increase Racial and Ethnic Diversity in the Oncology Workforce is designed to enhance existing programs and create new opportunities that will move us closer to the vision of achieving an oncology workforce that reflects the demographics of the US population it serves.