tbuckley/cabot-search huggingface dataset:
Abstract 4396: MicroRNA MIR551B amplified at 3q26.2 locus activate c-KIT expression and causes resistance to anoikis of ovarian cancer cells
Authors: Pradeep Chaluvally-Raghavan, Fan Zhang, Wenbin Liu, Moss Tyler, Shuangxing Yu, Sunila Pradeep, Prahlad Ram, Yiling Lu, Anil Sood, Gordon Mills
Journal: Cancer Research (2014)

Abstract Background and Hypothesis The 3q26.2 loci amplification is present in at least 35% of high grade serous ovarian cancer (HGSEOC). Recently we identified a microRNA, MIR551B located in the 3q26 amplicon. However, the potential role of microRNAs amplified at 3q26 amplicon and their functions in ovarian tumorigenesis has not been studied previously. Thus, our studies have the potential to provide novel mechanism underlying MIR551B oncogenesis in ovarian cancer. Results The 3q26.2 locus is large and structurally complex suggesting that multiple coding genes located in the amplicon could contribute to tumor initiation and progression alone or through cooperative activity. High-resolution SNP-based copy number analysis of 533 high-grade serous ovarian cancer samples demonstrated that MIR551B is highly amplified as a consequence of the 3q26.2 amplicon. Expression analysis in the Cancer Genome Atlas (TCGA) data sets showed that amplification of MIR551B is associated with increased expression of maturedmicroRNA miR551b in the recently defined proliferative subtype of ovarian cancer. Reverse phase protein array (RPPA) demonstrated that enforced expression of miR551b-5p increased the expression c-KIT oncogene and activated the ERK signaling pathway. Our target search analysis identified a potential novel mechanism whereby miR551b-5p could bind to a target site in the promoter of c-KIT oncogene and increase the transcription of c-Kit mRNA. Strikingly, enforced expression of miR551b-5p induced the survival and proliferation of ovarian surface epithelial cells detached from extracellular matrix. Of note, miR551b-5p expression in recurrent ovarian tumors are higher than the primary ovarian cancers. Summary Our results show that copy number alterations (CNAs) of MIR551B are associated with increased levels of mature microRNA, miR551b. Mechanistic studies revealed a novel role of microRNA miR-551b-5p to induce transcriptional activation by interacting with the promoter of the c-Kit oncogene, which in turn renders cells resistant to anokis a critical component of the survival and spread of ovarian cancer in the peritoneal cavity. Our results propose the c-KIT transcriptional activation induced by miR551b-5p is a key mechanism of survival of ovarian cancer cells in the ascitic fluid in the peritoneal cavity. Citation Format: Pradeep Chaluvally-Raghavan, Fan Zhang, Wenbin Liu, Moss Tyler, Shuangxing Yu, Sunila Pradeep, Prahlad Ram, Yiling Lu, Anil Sood, Gordon Mills. MicroRNA MIR551B amplified at 3q26.2 locus activate c-KIT expression and causes resistance to anoikis of ovarian cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4396. doi:10.1158/1538-7445.AM2014-4396
The Metabolism of Drugs by Hepatic Tumors
Authors: Richard H. Adamson, James R. Fouts
Journal: Cancer Research (1961)

Transformation from normal hepatic cell to tumor cell may be accompanied by a loss of ability to metabolize certain drugs by enzymes in the microsomal fraction. This change did not occur to any measurable extent during the “precancerous” stage; nor was it present in hepatic cells adjacent to the DAB-induced tumor. Only the neoplastic cell has lost this function—even severely damaged hepatic cells retained normal levels of metabolism of the drugs used in our experiments.

The loss of enzyme activity in DAB-induced tumors was probably caused by an actual deficit of enzyme protein and not by a cofactor deficiency or by the presence of inhibitors in such tumors.

Animals bearing hepatic tumors may be more “sensitive” than normal animals to some drugs. We have shown some tumor-bearing animals sleep longer after hexobarbital administration.

Possible therapeutic implications are mentioned.
Cannabidiol-induced apoptosis in human leukemia cells: A novel role of cannabidiol in the regulation of p22phox and Nox4 expression
Authors: Robert J. McKallip, Wentao Jia, Jerome Schlomer, Prakash S. Nagarkatti, Mitzi Nagarkatti
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4617 

In the current study, we examined the effect of the non-psychoactive cannabinoid, cannabidiol, on the induction of apoptosis in leukemia cells. Exposure of EL-4, Jurkat or Molt-4 cells to cannabidiol in vitro led to a significant reduction in cell viability and the induction of apoptosis. Furthermore, in vivo cannabidiol treatment of EL-4-bearing mice led to a significant decrease in tumor burden and an increase in apoptotic tumors. Cannabidiol-induced apoptosis was inhibited by the CB2-selective antagonist and not by CB1-selective or VR1-selective antagonists. Exposure to cannabidiol led to the activation of a number of caspases, including caspase-8, caspase-9, and caspase-3, and to cleavage of PARP. In addition, the level of full-length Bid was decreased following exposure to cannabidiol, suggesting possible cross-talk between the intrinsic and extrinsic apoptotic pathways. The role of the mitochondria was further suggested as exposure to cannabidiol led to loss of mitochondrial membrane potential and release of cytochrome C. Interestingly, cannabidiol exposure led to an increase in ROS production and cannabidiol-induced apoptosis could be blocked by treatment with the ROS scavenger, α-tocopherol and the NADPH oxidase inhibitor, DPI. Examination of the expression of NADPH oxidases revealed that cannabidiol exposure led to the upregulation of p22 phox and NOX4. In addition, cannabidiol exposure led to a decrease in the levels of p-ERK, p-JNK and p-p38 MAPK, which could be blocked by treatment with a CB2-selective antagonist or α-tocopherol. Together, the results from this study demonstrate that cannabidiol is a potent inducer of apoptosis in leukemia and that this mechanism may be related to the regulation of NAPDH oxidases and the production of reactive oxygen species.
Molecular Diagnostics in Cancer Therapeutic Development: Maximizing Opportunities for Individualized Treatment
Authors: George Adrian Calin
Journal: Clinical Cancer Research (2006)

PL-34   Alterations in miRNA genes play a critical role in the pathophysiology of many, perhaps all, human cancer: cancer initiation and progression can involve microRNAs (miRNAs) - small non-coding RNAs that can regulate gene expression. At the present time, the main mechanism of microRNoma (defined as the full complement of microRNAs present in a genome) alteration in cancer cells seems to be represented by aberrant gene expression, characterized by abnormal levels of expression for mature and/or precursor miRNA sequences in comparison with the corresponding normal tissues. Loss or amplification of miRNA genes has been reported in a variety of cancers and altered patterns of miRNA expression may affect cell cycle and survival programs. Germline and somatic mutations in miRNAs or polymorphisms in the mRNAs targeted by miRNAs may also contribute to cancer predisposition and progression. The causes of the widespread differential expression of miRNA genes between malignant and normal cells can be explained by the genomic location of these genes in cancer-associated genomic regions, by epigenetic mechanisms as well as by alterations of members of the processing machinery. MicroRNAs expression profiling has been exploited to identify miRNAs that are potentially involved in the pathogenesis of human cancers. MicroRNAs profiling achieved by various methods has allowed the identification of signatures associated with diagnosis, staging, progression, prognosis and response to treatment of human tumors.
Abstract 3827: Predictions for recurrence of non-muscle invasive bladder cancers by circulating miRNAs
Authors: Shu-Hong Lin, Jie Lian, Yuanqing Ye, Colin P. Dinney, Xifeng Wu
Journal: Cancer Research (2014)

Abstract Background: Circulating microRNAs (miRNAs) have been extensively associated with disease conditions, and shown to be involved in tumorigenesis. In the current study, we aimed to identify miRNAs which are present specifically in the serum of non-muscle invasive bladder cancer (NMIBC) patients and correlate these miRNAs with clinical outcomes. Method: A pilot study was first conducted to profile the expression of 754 miRNAs using the Taqman® microRNA Array and identified 89 miRNAs that can be detected at high levels in more than 30% of samples. In this study, we applied a two-stage design with discovery phase of 280 cases followed by the validation phase of 276 cases using the Fluidigm BioMark™ System to assess whether these 89 miRNAs were associated with bladder cancer clinical outcomes. Results: Among 280 cases in the discovery phase, 134 recurrence events were observed. Further stratification by treatment showed that 147 patients received Bacillus Calmette-Guerin (BCG) treatment and 78 patients received transurethethral resection only (TUR). COX regression on dichotomized expression of miRNAs revealed that 2 and 6 miRNAs were associated with recurrence in the BCG group and the TUR group with p-values &amp;lt;0.05, respectively. The most significant observed association with recurrence had p-values of 0.008(BCG) and 0.005 (TUR). We constructed risk scores for recurrence using previous miRNAs identified by COX regression. Patients with high risk scores had significantly shorter recurrence-free survival in BCG group (p=0.006, mean survival time 9.04 and undefined for high risk and low risk scores) but not in TUR group possibly due to small sample size (p=0.114, mean survival time 4.60 and 14.04). We are in the progress of further verifying associations between candidate miRNAs and clinical outcomes in an additional 276 NIMBC samples. Conclusion: Our preliminary results demonstrate the potential of miRNAs as predictive markers for NMIBC recurrence. Citation Format: Shu-Hong Lin, Jie Lian, Yuanqing Ye, Colin P. Dinney, Xifeng Wu. Predictions for recurrence of non-muscle invasive bladder cancers by circulating miRNAs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3827. doi:10.1158/1538-7445.AM2014-3827
Abstract P177: Higher Frequency of Fast Food Consumption is Associated with Lower Likelihood of Meeting Dietary Reference Intakes (DRIs): Findings from the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: ARPITA BASU, Christina M Shay, Laura Colangelo, David R Jacobs, Linda Van Horn
Journal: Circulation (2014)

Background: Dietary Reference Intakes (DRIs) are reference values established by the Food and Nutrition Board of the Institute of Medicine and are intended for purposes of planning and assessing diets for healthy populations. As consumption of fast food has continued to increase, the question of nutrient adequacy is of growing concern. Purpose: The purpose of this investigation is to quantify the association between frequency of fast food consumption and likelihood of meeting DRIs in a middle age adult population. Methods: Coronary Artery Risk Development in Young Adults (CARDIA) is a multi-center longitudinal study among black and white men and women who, at year 20 of follow up, were ages 38-50 years (n=3,089). Dietary intake was assessed by trained, certified interviewers using the validated CARDIA Diet History questionnaire. Fast food frequency was quantified based on responses to a dietary behavior questionnaire and categorized according to 0, &gt;0-&lt;1, 1-&lt;3, and 3+ times/wk. Logistic regression was used to quantify associations between fast food frequency and the likelihood of meeting DRIs accounting for age, sex, race, study center, education, smoking status, and energy intake. Results: More frequent consumption of fast food was associated with lower likelihood of meeting recommended levels of several essential nutrients and greater likelihood of exceeding recommended intakes of sodium and sugar (Table1). Conclusions: These findings raise awareness of the need for targeting public health messages aimed at improving diets of fast food consumers, for example, by improving foods served at fast food restaurants to help meet nutrient needs in the US diet.
284. Oncolytic Adenovirus E1B-19kD Deletion and E3B Retention Results in Both Enhanced Potency and Tumor Necrosis Factor - Mediated Selectivity
Authors: Bertie H. C. G. M. de Leeuw, Maarten ter Horst, Mark Rodijk, Michael Brenner, Rob C. Hoeben, Peter A. E. Sillevis Smitt
Journal: Molecular Therapy (2004)

In order to improve the efficacy of first generation adenoviral vectors for glioma treatment, we designed conditionally replicating viruses in which the E1A gene is under the control of the promoter (gfa2) of the glia specific intermediate filament Glial Fibrillary Acidic Protein (GFAP) and similar constructs containing additional glial specific enhancers.
Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia
Authors: M S Khodadoust, B Luo, B C Medeiros, R C Johnson, M D Ewalt, A S Schalkwyk, C D Bangs, A M Cherry, S Arai, D A Arber, J L Zehnder, J Gotlib
Journal: Leukemia (2015)
Effect of pregnancy in asthma on health care use and perinatal outcomes
Authors: Sujeong Kim, Jinhee Kim, So Young Park, Hye-Yeon Um, Kyoungjoo Kim, Yuri Kim, Yunjin Park, Seunghee Baek, Sun-Young Yoon, Hyouk-Soo Kwon, You Sook Cho, Hee-Bom Moon, Tae-Bum Kim
Journal: Journal of Allergy and Clinical Immunology (2015)
Cord blood IgE. II. Prediction of atopic disease
Authors: L. G. Hansen, A. Høst, S. Halken, A. Holmskov, S. Husby, L. B. Lassen, K. Storm, O. Østerballe
Journal: Allergy (1992)

Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1‐year birth cohorts (1983‐1984 and 1985–1986) in Denmark ( n = 1189 + 1625). For follow‐up we chose all infants with cord blood IgE ≥ 0.5 kU/1 and a randomly chosen group of the same size with cord blood IgE &lt; 0.5 kU/1. A total of 762 infants were clinically evaluated at 18 months of age. A diagnosis of definite atopy, probable atopy or no atopy, including both IgE and non‐IgE mediated disease was established. Applying different cord blood IgE cut‐off values (0.3, 0.5, 0.8, 1.1) we did not find an excess of atopic infants among those with elevated cord blood IgE irrespective of the chosen cut‐off value. Atopic predisposition or family history of atopic disease was defined as at least one parent or older siblitig with atopic disease. Significantly more infants with a family history developed atopy at 18 months. In the 2 series the positive predictive values of cord blood IgE≥0.5 were 43% and 46% and the sensitivities were 17% and 15%. The predictive values of having a family history were 48% and 44% and the sensitivities were 55% and 58%. Clinical aspects Cord blood IgE analysed by Phadebas IgE PRIST was a poor predictor of infants developing atopic disease before the age of 18 months.
Researchers Probe Depression in Children
Authors: Rebecca Voelker
Journal: JAMA (2003)

FOR MORE THAN TWO DECADES, childhood depression has presented researchers and clinicians with some of the most fascinating and anxiety-provoking questions in the fields of psychiatric and psychological research. Some, like whether prepubertal youth are even capable of being depressed and successfully treated, have been answered with a resounding “yes.” Others, like the impact of long-term antidepressant use on the developing brain, remain for the future frontiers of research. According to epidemiological studies, about 2.5% of prepubertal children and up to 8.3% of adolescents in the United States have depression (J Am Acad Child Adolesc Psychiatry. 1996; 35:1427-1439). But surprisingly, it wasn’t until the late 1970s, through pioneering studies of researchers such as the late Joachim Puig-Antich, MD, of the Western Psychiatric Institute and Clinic in Pittsburgh, Pa, that groundbreaking findings demonstrated that children do, indeed, possess a strong enough concept of “self” to experience such feelings as guilt, which is a central component of depression. Puig-Antich developed a medical model for assessing depression in children that involved direct interviews with the children themselves rather than observing how they play. “Children were asked about symptoms, whether they feel sad, if they cry, and if they feel guilty—it was revolutionary when the kids were interviewed directly,” explains Barbara Geller, MD, professor of psychiatry at Washington University in St Louis, Mo. “With that came the recognition that children, even the very young, can have serious, major depression the same as adults.” Since then, researchers have attempted to determine whether depression in children really is the same disorder as in adolescents and adults, or if there are important differences. What they are finding is a mixed picture. Although the basic underpinnings—the fact that both environmental and biological factors play a role—are the same, some notable differences (including dif-
Is Resistance (N)ever Futile? A Response to “Futility in Chronic Anorexia Nervosa: A Concept Whose Time Has Not Yet Come” by Cynthia Geppert
Authors: Cushla McKinney
Journal: The American Journal of Bioethics (2015)

As a former chronic, treatment-resistant anorexic, I would like to preface this commentary by saying that that I am incredibly grateful that mine was not considered a futile case despite meeting th...
Ramstedt's Operation in District Hospitals — Is it Safe?
Authors: P J McDonald
Journal: Journal of the Royal Society of Medicine (1986)

Over a 10-year period, 47 infants with congenital hypertrophic stenosis underwent Ramstedt's pyloromyotomy in a district general hospital. The operations were carried out by 10 surgeons-6 consultants and 4 registrars. There were 3 major wound infections and 3 incisional hernias. One infant was referred to a specialist centre for reoperation.
Autogenous Immunity to Endogenous RNA Tumor Virus: Chronic Humoral Immune Response to Virus Envelope Antigens in B6C3F 1 Mice 2
Authors: Barry L. Batzing, M. Yurconic, M. G. Hanna
Journal: JNCI Journal of the National Cancer Institute (1974)

(C57BL/6♀ × C3H/Anf ♂) F1 (B6C3F1) mice were evaluated for immunologic reaction to endogenous murine leukemia virus (MuLV). By immunoelectron microscopy (IEM) it was demonstrated that throughout life these mice possess significant levels of free serum antibody specific for MuLV envelope antigen(s). Immunoglobulin and endogenous MuLV antigen(s), presumably in the form of immune complexes, became localized within kidney glomeruli with age; this deposition correlated well with the chronic development of glomerulonephritis. Immunoglobulin eluted from kidneys of aged animals also was shown by IEM to be specific for virus envelope antigen(s). Although the function of antibody in B6C3F1 mice cannot be positively defined from these studies, it may be 1 critical component in the systemic regulation of levels of infectious endogenous leukemia virus.
Paediatric transplantation comes of age
Authors: D. Kelly, A. Mayer
Journal: BMJ (1998)

The successful development of solid organ transplantation has revolutionised the outlook for many infants and children dying of liver, kidney, or cardiac failure. Over the past two decades rapid advances in both medical knowledge and surgical technique have not only extended the range of indications for transplantation but have also led to improved survival and good quality of life.

End stage renal disease affects about 150 children a year in Britain. Many of these children are kept alive by renal dialysis but at considerable physical, psychological, and financial cost. Half the children requiring renal replacement are aged under 12, but until 10 years ago the results of transplantation in small children were discouraging because of graft loss due to technical complications. A combination of technical advances and clinical experience has now made transplantation the preferred option for children with renal failure.

The high rate of vascular thrombosis has been reduced …
The Strength of Association Between Surrogate End Points and Survival in Oncology
Authors: Vinay Prasad, Chul Kim, Mauricio Burotto, Andrae Vandross
Journal: JAMA Internal Medicine (2015)

The strength of association between surrogate end points and survival in oncology is important to understand because surrogate end points are frequently used in oncology clinical trials, supporting US Food and Drug Administration approvals and National Comprehensive Cancer Network guideline recommendations.To identify and evaluate trial-level meta-analyses of randomized clinical trials quantifying the association between a surrogate end point and overall survival in medical oncology. Trial-level correlations test whether treatments that improve the surrogate end point also improve the final end point and are widely considered the strongest evidence to validate a surrogate end point.Our literature search was built on earlier reported data sets and updated with Google Scholar and MEDLINE searches conducted on December 26, 2014. For MEDLINE, search terms included ("regression" or "correlation") and "surrogate" and "end point [or endpoint]" and ("oncology" or "cancer"). For Google scholar, search terms included ("regression" or "correlation") and "surrogate end point [or endpoint]" and "overall survival" and "trial level." A total of 108 abstracts were retrieved, and 62 articles were read in full in addition to articles identified through prior reviews.We found 36 articles in which 65 specific correlations between a surrogate end point and survival were identified. Surrogate end points were studied in the neoadjuvant, adjuvant, locally advanced, and metastatic settings. The most common sources for trials included in the 36 articles were systematic reviews of the published literature (10 of 36; 28%), and published literature and meeting abstracts (14 of 36; 39%). Four meta-analyses (11%) used a convenience sample, and only 5 studies (14%) attempted to include unpublished trials by surveying clinical trial registries. Among these 5 studies, only 352 of 684 eligible trials (51.1%) were included in the analyses. More than half of reported correlations (34 of 65; 52%) were of low strength (r ≤ 0.7). Approximately a quarter (16 of 65; 25%) were of medium strength (r > 0.7 to r < 0.85), and 15 of 65 (23%) were highly correlated (r ≥ 0.85) with survival.Most trial-level validation studies of surrogate end points in oncology find low correlations with survival. All validation studies use only a subset of available trials. The evidence supporting the use of surrogate end points in oncology is limited.
Chromosome Banding Patterns in Ehrlich and Yoshida Ascites Tumors2
Authors: Motomichi Sasaki, Michiko Mori, Mitsuo Oshimura
Journal: JNCI Journal of the National Cancer Institute (1974)

Chromosomal banding patterns of the hyperdiploid Ehrlich mouse carcinoma (EC) and the Yoshida rat sarcoma (YS) were studied by the quinacrine fluorescence and Giemsa banding methods. The banded karyotypes of both tumors deviated greatly from those of normal somatic cells of host animals. Although most EC cells possessed 43 chromosomes including 1 A, 2 B, and 3 m markers, the banded profile of the karyotype was highly variable. There were usually 26 abnormal elements in which the origin was untraceable even with banding analysis. Of the remaining 17 elements, 14 exhibited apparently normal morphology with normal banding patterns, whereas 3 showed partially normal patterns. The stem line cells of YS had 40 chromosomes, 12–13 apparently normal and 27–28 structurally altered elements. Among the abnormal elements, 9 were traceable either totally or partially. The cell population of YS was more homogeneous compared to that of EC.