tbuckley/cabot-search huggingface dataset:
Abstract 200: Effects of H. pylori infection in regulation of miRNAs-associated with DNA mismatch repair
Authors: Juliana C. Santos, Mitsue Brianti, Victor de Almeida, Ander Matheu, Marcelo L. Ribeiro
Journal: Cancer Research (2015)

Abstract It is well known that genetic and epigenetic inactivation of DNA mismatch repair (MMR) genes might leads to mutations in cancer-related genes and to cancer development. In gastric carcinogenesis, it has been shown that the infection by H. pylori, the major causative agent of gastric cancer, induces DNA damage and mutation and/or inhibits MMR DNA repair. Recently, it has been reported that miRNAs (miRs) have an important role in regulating genomic stability and MMR DNA repair. Thus, the aim of this work was to identify miRs regulating MMR pathway in H. pylori-associated gastric carcinogenesis To evaluate the effects of H. pylori on miRs releated with MMR, AGS gastric carcinoma cell line and the H. pylori strains 26695, and P12 were used in co-culture experiments for 4, 8 and 12 h. As an initial screening, the AGS cells were co-cultured with H. pylori strain 26695 and subjected to Cancer PathwayFinder miRNA PCR Array (Qiagen) to determine the expression profile of 84 miRs. The expression levels of EXO1, MLH1, MSH2, MSH3, MSH6, POLD3, PMS1, and PMS2 were assessed by real-time PCR. Computational prediction of putative interaction of selected miRs to 3′UTR of MMR mRNAs were obtained from TargetScan, mirDB and MetaCore. The target validation was evaluated using mimics/inhibitors and luciferase gene reporter assays. The results from the Cancer PathwayFinder PCR miRNA Array showded that H. pylori infection (strain 26695) modulates the expression of 23% (19/84) of the miRs after 4 and 12 h of infection, of which 89% were up-regulated and 11% down-regulated. Our data show that H. pylori infection significantly down-regulates the expression of all selected genes. The data generated from computational miR target prediction enriched with the gene expression fold induction indicated that 4 miRs (miR-150-5p, miR-155-5p, miR-3163, and miR-4775) modulated by H. pylori has at least one MMR target gene. Regarding the target validation, our results indicated that MLH1 and MSH2, are regulated by miR-150-5p. The miR-155-5p is involved in down-regulation of MLH1, MSH2, MSH3 and POLD3 expression. MSH3 is regulated by both miR-3163 and miR-4775. Briefly, this study shows that H. pylori impairs MMR DNA repair pathway thought a modulation of miR expression. Citation Format: Juliana C. Santos, Mitsue Brianti, Victor de Almeida, Ander Matheu, Marcelo L. Ribeiro. Effects of H. pylori infection in regulation of miRNAs-associated with DNA mismatch repair. [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 200. doi:10.1158/1538-7445.AM2015-200
Abstract 1555: An automated cage-based method of randomized group distribution in pre-clinical <i>in vivo</i> studies
Authors: Eric M. Ibsen, Jeffrey L. Kumer
Journal: Cancer Research (2015)

Abstract To more closely emulate clinical research methodology, researchers are increasingly utilizing clinically-similar group randomization and distribution methods for oncology studies in animals. It has been common practice to re-house animals into new cages with new cagemates following randomized group distribution. In male animals in particular, this frequently results in high levels of stress, injury and sometimes death due to fighting to re-establish social dominance hierarchies. Since some animals suffer more and others less, based on their relative position within the newly-established hierarchy, the levels of stress vary across the study subject population. The full impact of such stress on anticancer agent efficacy is not known but is widely believed to significantly diminish study integrity. For this reason, many researchers do not re-house male animals, choosing instead to co-house animals from various groups. It is believed that the exposure of cagemates to test agents in excreta and saliva during grooming as well as significantly increasing the risk of accidental mis-dosing can likewise negatively impact study integrity. The commonly-used manual and spreadsheet-based randomization methods do not enable cage-based randomized distribution based on qualitative or quantitative parameters. Commercially available pre-clinical trial applications now offer a solution to the above-mentioned problems.Randomization or distribution of animals based on the mean tumor volume or other parameters within the same cage allow for distribution to groups based on cage means. The variety of cage-based randomization methods available include: pure randomization, stratified sampling randomization and block randomization across multiple numeric parameters. Also, deterministic and matched-pair distribution methods can be used as well.Subjects in cages may be excluded initially based on recorded qualitative observations, and then by acceptable value ranges for numeric parameters. ANOVA results of group means are displayed instantly to ensure similarity between groups. Using software to perform standardized cage-based randomization and distribution is more clinically relevant, mitigating the negative impacts associated with post-randomization re-housing of animals. This significantly decreases the negative impact on study integrity relative to spreadsheet-based methods. Note: This abstract was not presented at the meeting. Citation Format: Eric M. Ibsen, Jeffrey L. Kumer. An automated cage-based method of randomized group distribution in pre-clinical in vivo studies. [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 1555. doi:10.1158/1538-7445.AM2015-1555
Whole Exome Sequencing of CLL Before Second-Line Treatment with Fludarabine and Cyclophosphamide with or without Rituximab (REACH trial).
Authors: Nikola P Konstandin, Annika Dufour, Philipp A Greif, Bianka Ksienzyk, Alexander Graf, Stefan Krebs, Helmut Blum, Stephanie Schneider, Karsten Spiekermann, Wolfgang Hiddemann, Kerstin Trunzer, Martin Weisser, Stefan K Bohlander
Journal: Blood (2012)
EPID-12PSYCHIATRIC SYMPTOMS IN CHILDREN WITH CRANIOPHARYNGIOMA
Authors: Tabitha Cooney, Sonia Partap, Michelle Monje, Cynthia Campen
Journal: Neuro-Oncology (2015)

BACKGROUND: Craniopharyngiomas occur in the suprasellar region of the brain, an area associated with psychiatric disease. In addition, cranial irradiation may damage the hippocampus and white matter tracts of the developing frontal lobe, areas involved in development and behavior. We hypothesize that children with craniopharyngioma will have a high risk of psychiatric disorders. METHODS: Patients were identified from the Lucile Packard Children's Hospital (LPCH) Pediatric Brain Tumor Database and were included if they were aged birth to 30 years at the time of diagnosis between 1/1/1997 - 6/1/2013. Demographic, treatment, and psychiatric information was abstracted from eligible patients' charts. Descriptive statistics were performed using 2-tailed student's t-test and Fisher's exact test where appropriate. RESULTS: Craniopharyngioma cases were identified in 28 patients, seven of whom had psychiatric symptoms (25%), including psychosis (1) and mood/anxiety disorders (6). Median time to psychiatric symptoms was 4.2 years. There was not a significant difference in age at diagnosis, gender, use of radiation therapy, or use of an Ommaya reservoir between cases and controls. Compared with data reported previously on patients with germ cell tumor (GCT), children with craniopharyngioma were younger at diagnosis (p = 0.03). Although the rate of psychosis appeared less in children with craniopharyngioma (3.6%) compared with GCT (14.3%), the difference was not statistically significant (p = 0.35). There was no difference in time to develop psychiatric symptoms. CONCLUSIONS: Psychiatric sequelae of pediatric brain tumors are under-recognized and poorly understood. We note that pediatric patients with craniopharyngiomas have a high risk for late psychiatric symptoms, particularly mood disorders, although we have not yet elucidated risk factors. Similar rates of psychosis and mood disorders within pediatric patients with craniopharyngioma and GCT suggest psychiatric illness relates to tumor location, and subsequent possible disruption of neural circuitry involving the basal ganglia, hypothalamus, and frontal lobes.
Denosumab versus zoledronic acid in patients with bone metastases from solid tumors other than breast and prostate cancers or multiple myeloma: A number needed to treat (NNT) analysis.
Authors: G. E. Richardson, T. E. Ciuleanu, L. Costa, S. J. M. Gans, J. Á. Garcia Saenz, V. Hirsh, V. Hungria, M. Krzakowski, C. Manegold, H. Nahi, S. Novello, A. L. Petzer, M. E. Rader, P. Solal-Celigny, S. Vadhan-Raj, J. F. Vansteenkiste, P. J. Woll, C. Ke, K. Chung, H. Yeh
Journal: Journal of Clinical Oncology (2011)

9115
PTH-082 Development and delivery of a low-cost regional sphincter of Oddi manometry service
Authors: C W Wells, R Charnley, M Nayar, F McArdle, K Oppong
Journal: Gut (2010)

<h3>Introduction</h3> Sphincter of Oddi (SO) dysfunction (SOD) is a functional disorder that can cause severe morbidity. SO manometry (SOM) measures SO pressure (SOP) and is the definitive test for SOD.1 SOD can be treated with sphincterotomy.1 ERCP in patients with SOD increases risk of complications.23 Sphincterotomy can cause long-term complications.4 As such patient selection and pre-procedure counselling is paramount.5 SOM is not widely available (in UK) and commercial SOM equipment is expensive. <h3>Methods</h3> We retrospectively evaluated the first 18 months of a new SOM service. Patients were referred from Northern region clinicians. After careful selection those with type II SOD were offered SOM. An in-house manometric system was developed using a water-perfused system constructed from existing invasive BP measuring equipment and a standard SOM catheter. Before use it was evaluated and produced reliable and valid pressure measurements comparable with commercial systems. <h3>Results</h3> Between 1/2008 and 7/2009, 29 patients (25F:4M) underwent SOM (36 procedures), following MRCP in 26, endoscopic ultrasound in 24 and SO Botox injection in 11. SO hypertension (SOH) was diagnosed in 16 and 18 patients underwent sphincterotomy (16-SOH, 1-choledocholithiasis, 1-dilated CBD at MRCP). There were five episodes of pancreatitis (14%) and one episode of cholangitis (after 36 SOM procedures). Discharge was within 24 h of the procedure in 21 patients, within 1 week in 9 and after 1 week in 6, in 4 of whom the pain was felt to be functional, (range 0–36 days, mean 4, median 1). One patient needed HDU care and one NJ feeding. In 13 of the 36 procedures a prophylactic pancreatic duct (PD) stent was placed. Of 16/29 patients who were contactable by phone for long-term follow-up (average 280 days, SD 142 days), 9 (82%) out of 11 who had sphincterotomy described a sustained symptomatic improvement. Only 2 (40%) out of 5 with no sphincterotomy reported an improvement. <h3>Conclusion</h3> Over half (56%) of patients having SOM had SOD indicating appropriate patient selection. The pancreatitis rate for SOM was 10 times that of all other ERCP in our unit but in keeping with published series.23 The in-house equipment was effective and allowed the service to be delivered without commercial costs. Sphincterotomy provided long-term benefit to over 80% of patients. The service will be further developed in light of these findings, with earlier discharge of patients with functional post-procedure pain and an increase in PD stent placement rate.
Menopausal symptoms may be confused with side effects of tamoxifen
Authors: Jacqui Wise
Journal: BMJ (2016)

Women taking tamoxifen to prevent breast cancer may mistake common menopausal symptoms for side effects of the drug and be prompted to stop treatment, research shows.1

Researchers from the University of Leeds and Queen Mary University London, UK, said that doctors should support women, particularly in the first 12 months of treatment, to help reduce the high drop-out rate seen with tamoxifen.

Results from the International Breast Cancer Intervention Study (IBIS-1), which is investigating whether tamoxifen can reduce the risk of breast cancer developing …
Endothelial progenitor marker CD133 mRNA expression in peripheral blood mononuclear cells predicts outcome of cancer patients
Authors: N. Mehra, M. Penning, J. Maas, N. Van Daal, E. Voest
Journal: Journal of Clinical Oncology (2006)

10087 Background: We examined whether expression of CD133, a surface molecule expressed on progenitors of hematopoietic and endothelial lineages, is increased in the peripheral blood mononuclear cells (PBMC’s) of cancer patients. Furthermore we correlated CD133 mRNA expression with tumor prognostication factors and overall survival. Methods: PBMC’s were isolated from the blood of 130 advanced cancer patients (43 renal cell carcinoma, 27 colorectal cancer, 34 prostate cancer, 27 head and neck cancer). Clinicopathological parameters were obtained. Median follow-up time was 16 months after inclusion (range 3–33 months). For the quantification of CD133 mRNA we used a real-time detection and quantification method based on nucleic acid sequence-based amplification (NASBA). Also U1A DNA was quantified as internal control for input and isolation. CD133 mRNA copy numbers were expressed as copies per 10.000 cells, as determined by U1A DNA. Results: Patients with metastasized disease have a significant increase in CD133 mRNA as compared to patients without metastasis. This increase is strongest in patients with bone metastasis. Subgroup analysis in patients with bone involvement show that CD133 mRNA also correlates with PSA (n=34)and inversely with hemoglobin (n=50). CD133 mRNA expression is an independent predictor for overall survival in Cox’s multivariate analysis (variables in the model included age, hemoglobin, metastasis, previous treatment and CD133 as categorical variable). A CD133 mRNA cut-off value was established by Receiver Operating Characteristic analysis of CD133 expression in relationship to survival (sensitivity 64% and specificity 71%). Cancer patients with more than 200 copies of CD133 mRNA, demonstrate a decreased survival compared to patients with lower CD133 expression (median survival 8 and 15.4 months, respectively). In patients with bone metastasis the median survival of high and low expressers is 6.3 months and 21.9 months, respectively. Conclusions: mRNA expression of stem-cell marker CD133 is increased in cancer patients with metastasized disease and an independent prognostic factor for overall survival. Increased CD133 mRNA expression may reflect an activated angiogenic state in these cancer patients. [Table: see text]
Cancer/Testis Antigen CT45 Is Frequently Expressed in Hodgkin’s Lymphoma and Associated with Nodular Sclerosis Subtype and Advanced Disease.
Authors: Alexander Claviez, Christine Mauz-Körholz, Hans-Jürgen Heidebrecht, Günther Schellong, Dieter Körholz, Wolfgang Dörffel, Reza Parwaresch, Markus Tiemann
Journal: Blood (2006)
Long Term Outcome of Patients with Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid, Arsenic Trioxide with or without Gemtuzumab Ozogamicin
Authors: Farhad Ravandi, Jorge E. Cortes, Guillermo Garcia-Manero, Elihu Estey, Gautam Borthakur, Elias J Jabbour, Stefan Faderl, Susan O'Brien, William Wierda, Sherry Pierce, Mark Brandt, Steven M. Kornblau, Tapan Kadia, Naval Daver, Courtney DiNardo, Srdan Verstovsek, Alessandra Ferrajoli, Michael Andreeff, Marina Konopleva, Zeev Estrov, Maria Foudray, Hagop M. Kantarjian
Journal: Blood (2015)
The Earliest Stages of Loss of Stem Cell Self-Renewal in-Vivo Is Linked to Upregulated Biosynthesis of “Quiet” Mitochondria and Is Influenced by CXCR4 Activation and STAT3 Gene Deletion.
Authors: Charlie Mantel, Steven Messina-Graham, Akira Moh, Xin-Yuan Fu, Hal E. Broxmeyer
Journal: Blood (2009)
A phase I, single-institution, open-label, dose escalation trial with an expansion cohort evaluating the safety and tolerability of AZD6244 and IMC-A12 in subjects with advanced solid malignancies.
Authors: Shabina Roohi Ahmed, Douglas Wilmot Ball, David Cosgrove, Angela Scardina, Emily Petito, Melinda Downs, Barry Nelkin, Helen X. Chen, Laurence A Doyle, Ross C. Donehower, Michael Anthony Carducci, Nilofer Saba Azad
Journal: Journal of Clinical Oncology (2012)

3020 Background: Significant crosstalk exists between the PI3K and Raf/MEK/ERK pathways and treatment of select cell lines with a MEK inhibitor and an IGF1-R inhibitor has been shown to cause greater inhibition of growth than either agent alone. IMC-A12 (I) is a recombinant human monoclonal antibody directed IGFI-R; it blocks interaction between IGF-1R and its ligands, IGF-I and -II. AZD6244 (A) is a highly selective, non-competitive MEK ½ inhibitor. Methods: The study is a phase I, dose-escalation with a standard 3+3 design. Eligible patients had advanced solid tumor, good end organ function and performance status with exclusion for poorly controlled diabetes or growth hormone abnormalities. Part 1: open label, dose escalation. Pts were treated with A at 50 mg BID, then 75 mg BID; I at 12mg/kg q2wk held constant. DLTs were defined as grade (G) 3 or 4 toxicities during cycle 1. Part 2: expansion cohort of 15 pts for correlative endpoints and PK studies; serial tumor biopsies will be evaluated for changes in signaling in the IGF pathway, including p-ERK, p-Akt and RAS. Mutational analysis of RAS and RAF will be done to correlate with PD endpoints and disease response. Results: Part 1: 16 patients accrued with 6 treated at DL1 and 10 treated at DL2. Multiple tumor types were represented, including 4 colon, 2 thyroid, 2 pancreatic, and 1 breast. At 75 mg of A, there was 1 DLT of visual changes. G3 AEs included nausea/vomiting (n=2, 12%), visual changes/retinopathy (n=2, 12%), MRSA skin infection (n=1, 6%), (n=1, 6%), hyperglycemia (n=1, 6%), and stroke (n=1, 6%). Other common AEs included acneform rash (n=10, 63%), nausea/vomiting (n=6, 37%), anorexia (n=4, 25%), and diarrhea (n=3, 19%). Of 10 evaluable patients in Part 1, 1 had a partial response and 4 patients had stable disease (40%). Sustained responses of 10 and 14 months were seen in the DTC patients. 3 patients are currently enrolled in the expansion cohort. The RP2D is 50 mg of A, due to the visual changes seen with 75 mg, and 12mg/kg of I. Conclusions: A at 50 mg QD combines safely with I 12mg/kg. An expansion cohort is underway to determine if this combination warrants further investigation.
Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.
Authors: Roland Fenk, Peter Schneider, Martin Kropff, Ali-Nuri Huenerlituerkoglu, Ulrich Steidl, Carlo Aul, Axel Heyll, Rainer Haas, Guido Kobbe
Journal: Blood (2004)
Cat-Scratch Disease
Authors: Julien Dubreuil, Arthur Dony, Gilles Salles, Alexandra Traverse-Glehen, Francesco Giammarile, Andrea Skanjeti
Journal: Clinical Nuclear Medicine (2016)

FDG-PET/CT is a standard of care in staging and response assessment of Hodgkin lymphoma. Hence, it is important to recognize pitfalls owing to the potential therapeutic impact. We report a case of a 29-year-old woman affected by stage III bulky Hodgkin lymphoma. The interim FDG-PET/CT showed a complete metabolic response. After three new cycles of chemotherapy, the patient showed fever and lymphadenopathy at clinic examination, PET/CT revealed several FDG uptakes at lymph nodes in inguinal and iliac region. Pathologic analyses, after biopsy and serologic examinations, led to the diagnosis of cat-scratch disease.
C-Reactive Protein Protects Myeloma Cells from Apoptosis Via Activating ITAM-Containing Fcγ RII.
Authors: Jing Yang, Michele Wezeman, Xiang Zhang, Jianfei Qian, Songyoul Hong, Xiaohong Han, Liang Zhang, Larry W. Kwak, Qing Yi
Journal: Blood (2006)
Abstract 5412: Lysosome disruption rapidly and effectively induces necrosis in aggressive thyroid carcinomas
Authors: Devora Champa, Antonio Di Cristofano
Journal: Cancer Research (2015)

Abstract Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are very aggressive and lethal neoplasms for which there is currently no effective therapy. By activating Kras and deleting p53 in the mouse thyroid we have generated a mouse model of PDTC progressing to ATC. These tumors are characterized by elevated levels of anti-apoptotic members of the Bcl2 family. Tumor cell lines established from this model as well as similarly aggressive human thyroid cancer cell lines undergo cell death upon treatment with Obatoclax, an inhibitor of the anti-apoptotic Bcl2 family members. Even though several studies have suggested that Obatoclax induces apoptosis or necroptosis by binding to its designated targets in a number of different cancer models, our studies show that Obatoclax induces necrosis in both human and mouse thyroid cancer cell lines. By exploiting its autofluorescence, we show that Obatoclax is found in association with lysosomes, but not with mitochondria as it would be expected given the location of its known Bcl2-family targets, and that it causes rapid lysosome disruption. Obatoclax was also able to induce a block in the later stages of autophagy, as shown by an accumulation of autophagosomes upon treatment, likely as a result of lysosome impairment. Furthermore, Bafilomycin A1, an inhibitor of lysosomal acidification, counteracts the effect of Obatoclax and allows for cell survival. These findings suggest a novel mechanism of action for Obatoclax, in which direct lysosome disruption leads to necrosis. Strikingly, human and mouse thyroid cancer cell lines are also sensitive to other lysosome-destabilizing agents. Importantly, transformed human thyroid cell lines are much more sensitive to Obatoclax than non-transformed thyroid cells, suggesting the existence of a useful therapeutic window. Even though Obatoclax has been removed from clinical trials due to low anti-tumor activity and toxic side effects, its efficacy in killing thyroid cancer cells otherwise refractory to treatment, and the alternative mechanism of action involved in this process support a new approach for targeting aggressive thyroid neoplasms. In conclusion, our data show that aggressive thyroid cancer cells are intrinsically sensitive to lysosome destabilization, and this characteristic can be exploited for the development of novel therapeutic approaches. Citation Format: Devora Champa, Antonio Di Cristofano. Lysosome disruption rapidly and effectively induces necrosis in aggressive thyroid carcinomas. [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 5412. doi:10.1158/1538-7445.AM2015-5412
Reduced Intensity (RI) Allogeneic Cord Blood Hematopoietic Cell Transplantation (Allo CBHCT) in Pediatric Patients with Malignant and Non-Malignant Diseases.
Authors: Gustavo Del Toro, M. B. Bradley, P. Satwani, E. Morris, C. van de Ven, Y.-K. Cheung, D. Yamashiro, J. Garvin, M. Bhatia, E. Roman, J. Schwartz, O. Militano, E. Cooney, K. Wolownik, R. Hawks, S. Foley, M. S. Cairo
Journal: Blood (2005)