tbuckley/cabot-search huggingface dataset:
Abstract 4809: Elucidating acquired drug resistance in multiple myeloma using expression proteomics and phosphorylation profiling
Authors: Bin Fang, Yun Xiang, Sayeef Mirza, Elizabeth Remily-Wood, Linda Mathews, William Dalton, Kenneth Shain, John M. Koomen
Journal: Cancer Research (2012)

Abstract Introduction: Multiple myeloma (MM) is an incurable malignancy of the plasma cell. While patients may initially respond to treatment, the development of acquired drug resistance (ADR) is a consistent feature of the disease. In order to understand the processes involved in ADR, proteomics is used to examine multiple phenotypic outcomes associated with drug resistance in cell line models. Both protein expression and phosphorylation data will be mined for biological mechanisms and candidate biomarkers for detection of ADR in MM patients. Experimental Procedures: Using cell line models of melphalan and doxorubicin resistance, protein expression is compared using spectral counts and extracted ion chromatograms from GeLC-MS/MS data. In addition, phosphorylation profiles are created using SCX peptide fractionation with IMAC phosphopeptide enrichment prior to LC-MS/MS cataloging. Additional hypothesis-driven experiments are conducted using liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) for targeted quantification. In addition to steady state comparisons between naïve and drug resistant cells, initial responses to therapy are also evaluated. Assays developed for interrogation of cell line models can be translated to patient specimens. Data Summary: GeLC-MS/MS expression measurements typically produce semi-quantitative data for &amp;gt; 2,000 proteins (2+ peptides per protein). Phosphorylation analysis has produced a catalog of &amp;gt; 1,000 sites across the entire group of cell lines. Data are manually evaluated for proteins relevant to MM and mapped to pathways using Metacore GeneGO. Because both melphalan and doxorubicin produce DNA damage, common processes include DNA damage repair, cell cycle regulation, and apoptosis. Each drug also produces unique phenotypes. For example, doxorubicin resistance is mediated in large part by multidrug resistance proteins; melphalan resistance is marked by increases in redox proteins. LC-MRM of heat shock proteins and Bcl-2 family apoptosis regulators supplements existing data. LC-MRM is also used to examine the response in the expression of proteins involved in ADR at the onset of treatment in naïve MM cells. Conclusions: Proteomics can further elucidate the biological processes involved with ADR in MM to generate candidate biomarkers. LC-MRM is used in cell line models to develop a platform for assessing panels of proteins related to ADR, which can ultimately be translated to assist in clinical decisions for tailoring therapy to the individual patient. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4809. doi:1538-7445.AM2012-4809
Vitamin D has a greater impact on cancer mortality rates than on cancer incidence rates
Authors: W. B. Grant, C. F. Garland
Journal: BMJ (2014)

Chowdhury and colleagues’ meta-analysis of cancer specific incidence and mortality rates with respect to bottom versus top third of baseline 25-hydroxyvitamin D levels found higher relative risks for those with cancer at time of enrolment than those without.1 The implication of this finding is that vitamin D has a much stronger impact on survival after developing cancer than on reducing the …
Supplemental oxygen for relief of dyspnea in hospice patients.
Authors: L. A. Joque, J. S. Kaur, R. A. Vierkant
Journal: Journal of Clinical Oncology (2010)

9163 Background: Dyspnea is an uncomfortable sensation of breathing that is common in hospice patients regardless of terminal diagnosis. Oxygen is frequently used to treat this symptom, but few studies assess efficacy in the hospice population. Widespread use of oxygen may preclude use of more effective therapies and has financial implications for hospice agencies. Further study is needed to define the optimal use of supplemental oxygen in hospice patients. Methods: Retrospective chart review of oxygen use in all patients admitted to our hospice program from January 1, 2009 through June 30, 2009. Results: A total of 92 patients were admitted with a mean age of 77 years (SD 13.5). Cancer was the most common diagnosis (n=46, 50%). Twelve patients (13%) had decline in clinical status, 5 (5.4%) had chronic obstructive pulmonary disease, 5 (5.4%) had congestive heart failure, 3 (3.3%) had coronary artery disease and 5 (5.4%) had leukemia. The remaining were other single diagnoses. Sixty-eight (79%) of the patients were prescribed oxygen. The mean number of days on oxygen was 68 (SD 31.2). Twenty-four (26.1%) patients were on oxygen prior to admit. It was ordered the day of admission in 25 (27.2%) and after in 19 (20.6%). Of those patients prescribed oxygen on or after admission, 29 (65.9%) used it, 6 (13.7%) did not, and use was unknown in 10 (22.7%). For 61 (66%) patients documentation of dyspnea included various clinical descriptors. For 28 (30.4%) patients, a dyspnea score (1-10 scale) was recorded. Following oxygen administration, 23 (33.8%) patients reported improvement, 14 (20.5%) no change, and 3 (4.4%) felt worse. For 22 (32.4%) patients no response was recorded. The total cost of oxygen for all patients during the study period was $25,384 with a mean of $276 (SD $344). Conclusions: Oxygen was often prescribed for patients admitted to our hospice with variable documentation of its effectiveness in relieving dyspnea. A subset of patients was prescribed this therapy but it was not utilized. This therapy is expensive and further study is needed to identify the best method of assessing dyspnea in hospice patients and how supplemental oxygen should be utilized to optimize patient outcomes and minimize cost. No significant financial relationships to disclose.
P163 Accuracy Of Inflammatory Markers To Distinguish Between Pneumonia And Pulmonary Embolism In Acute Settings
Authors: L. Chishimba, F. Iqbal, A. Kasule, A. Joynson, J. Williams, S. Argawal, I. Hussain
Journal: Thorax (2014)

<h3>Backgroud</h3> In emergency settings, the presence of significant rise in inflammatory markers in patients with acute respiratory symptoms suggest an alternative diagnosis rather than pulmonary embolism (PE), hence reduces the clinical probability of PE and the need for CTPA/VQ. However, it is increasingly recognised that PE is associated with abnormal concentrations of many proteins involved in inflammation and vascular injury, yet there is inadequate data describing the difference in these proteins from infective processes. <h3>Aims</h3> We aimed to determine whether there is a difference in inflammatory markers between acute PE and community acquired pneumonia (CAP) or acute lower respiratory infection (LRTI). <h3>Methods</h3> A random sample of emergency departments (ED) and patients evaluated for acute PE at our institution (January 2013–December 2013) were retrospectively evaluated for D-dimer, C-reactive protein (CRP) and serum white cell (WCC) levels. PE was diagnosed by a positive CTPA in all cases. Inflammatory markers in confirmed PE cases were compared and matched with those of community acquired pneumonia (CAP) and acute lower respiratory infection (LRTI). We excluded all cases with incidental, chronic or previous PE. <h3>Results</h3> A total of 295 patients were included (mean age 67.7 ± 18.45 yrs; 159 males), of which 167 (56.6%) had PE, 58 (19.7%) had CAP, 63 (21.4%) LRTI and seven (2.4%) had other respiratory conditions (Table 1). The mean WCC (g/l) was similar between PE (10.9 ± 4.8), pneumonia (11.9 ± 5.2) and acute LRTI (12.2 ± 5.9) (p = 0.2). Similarly, there were no significant differences among disease groups for median CRP levels (mg/l); PE (67.3 (4–412); CAP (88.9 (12–417) and acute LRTI (median 68.9 (9–284), (p = 0.322). In contrast, levels of D-dimer were significantly higher in PE than CAP or ARTI) (p = 0.000). <h3>Conclusions</h3> In patients suspected of acute PE, unlike D-dimer, levels of WCC or CRP do not reliably distinguish between PE, pneumonia or acute LRTI. These may not be relied upon to determine the clinical probability of PE.
Abstract 5355: HPV-16 infection alters cellular microRNA expression in squamous cell carcinoma of the head and neck (SCCHN)
Authors: Abigail I. Wald, Susanne I. Wells, Robert L. Ferris, Saleem A. Khan
Journal: Cancer Research (2010)

Abstract Up to 30% of squamous cell carcinoma of the head and neck (SCCHN) contain human papillomavirus (HPV) type 16 DNA. The presence of HPV DNA in these cancers is associated with a better disease outcome, and an understanding of the differences between HPV-positive and HPV-negative SCCHN has significant clinical importance. MicroRNAs (miRNAs) are approximately 22 nucleotides long, single-stranded RNAs that regulate gene expression at a posttranscriptional level. We hypothesize that HPV infection alters cellular miRNA expression which leads to changes in the expression of their target genes. We investigated the expression of cellular miRNAs using microarrays and quantitative Real Time RT-PCR. We found that 3 miRNAs were upregulated and 8 miRNAs were downregulated in HPV-positive SCCHN cell lines compared to HPV-negative SCCHN cell lines. MiR-363, miR-497, and miR-33 were upregulated, while miR-155, miR-181a, miR-181b, miR-29a, miR-218, miR-222, miR-221, and miR-142-5p were downregulated. We also analyzed miRNA expression in HPV-positive and HPV-negative SCCHN tumors and normal oral tissues. There were 17 up- and 1 downregulated miRNAs in SCCHN tumors compared to normal oral mucosa. These included several miRNAs that are known to be altered in many cancers, such as miR-21, miR-17-5p, and miR-145. MiR-363, the most upregulated miRNA in the HPV-positive cell lines, was also upregulated in HPV-positive tumors compared to HPV-negative tumors. Preliminary data using cell lines expressing HPV-16 E6 and/or E7 oncogene has shown that miR-363 expression increases with the expression of E6. These results suggest a possible role of HPV in altering the expression of specific cellular miRNAs, including miR-363. Studies are currently in progress to identify miR-363 gene targets by utilizing gene expression data and spectral counting proteomics. MiRNAs altered by the presence of HPV may identify specific pathways targeted by the virus, and may provide novel therapeutic targets for HPV-associated SCCHN. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5355.
Stat Bite: Survival Rates for Cancer of the Corpus Uteri
Authors: L. C. Harlan, L. A. G. Ries
Journal: JNCI Journal of the National Cancer Institute (1992)

Stat BiteSurvival Rates for Cancer of the Corpus Uteri Linda C. Harlan, Ph.D., Linda C. Harlan, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn A. Gloeckler Ries Lynn A. Gloeckler Ries Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 2, 15 January 1992, Page 77, https://doi.org/10.1093/jnci/84.2.77 Published: 15 January 1992
Discover It Today, Tax It Tomorrow: Basic Biomedical Research Spawns Biotech Industry
Authors: R. M. Hadsell
Journal: JNCI Journal of the National Cancer Institute (1989)

Discover It Today, Tax It Tomorrow: Basic Biomedical Research Spawns Biotech Industry Get access Robert M. Hadsell, Ph.D. Robert M. Hadsell, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 5, 1 March 1989, Pages 322–326, https://doi.org/10.1093/jnci/81.5.322 Published: 01 March 1989
Abstract 4138: Fluorescence laparoscopy with an LED light source enables fluorescence-guided resection of pancreatic cancer, labeled with fluorophore-conjugated antibodies, in mouse models.
Authors: Cristina A. Metildi, Sharmeela Kaushal, George A. Luiken, Mark A. Talamini, Robert M. Hoffman, Michael Bouvet
Journal: Cancer Research (2013)

Abstract Orthotopic mouse models of human pancreatic cancer were established with the BxPC-3 RFP pancreatic cancer cell line. Two weeks after implantation, mice were randomized to undergo bright light laparoscopic resection (BLR) (n=19) or fluorescence-guided laparoscopic resection (FLR) (n=19). Fluorescence laparoscopy was performed with a 495-nm emission filter and a Stryker L9000 LED light source 24 hours after tail vein injection of anti-CEA-Alexa 488 antibodies. Bright light laparoscopy was performed with a Stryker X8000 xenon light source. Pre- and postoperative images were taken with the Olympus OV-100 Small Animal Imaging System to assess completeness of resection. Postoperatively, whole body images were obtained to assess for recurrence and follow tumor progression. Intravital and ex vivo images were obtained at termination to evaluate tumor burden. FLS enabled real-time identification and localization of brightly-fluorescent BxPC-3 RFP tumor labeled with anti-CEA-Alexa 488. Furthermore, there was adequate background illumination for surgical navigation permitting improved resection. At termination at 12 weeks, mice in the FLS group had a smaller pancreatic tumor burden compared to mice from the BLS group (5.75 mm2 vs 28.43 mm2; p=0.012). Mice in the FLS group also experienced decreased local recurrence (47.4% vs 78.9%, p=0.046) and distant recurrence (68.4% vs 94.7%, p=0.045) compared to mice in the BLS group. Fluorescence-guided surgery has significant potential to improve laparoscopic approaches in the treatment of pancreatic cancer. Citation Format: Cristina A. Metildi, Sharmeela Kaushal, George A. Luiken, Mark A. Talamini, Robert M. Hoffman, Michael Bouvet. Fluorescence laparoscopy with an LED light source enables fluorescence-guided resection of pancreatic cancer, labeled with fluorophore-conjugated antibodies, in mouse models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4138. doi:10.1158/1538-7445.AM2013-4138
New England Journal of Medicine and Reuters Near Agreement on Embargo
Authors: Cori Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article New England Journal of Medicine and Reuters Near Agreement on Embargo Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 8, 19 April 1989, Pages 562–563, https://doi.org/10.1093/jnci/81.8.562 Published: 03 January 1990
Cyclic Administration of Pamidronate in Children with Severe Osteogenesis Imperfecta
Authors: Francis H. Glorieux, Nicholas J. Bishop, Horacio Plotkin, Gilles Chabot, Ginette Lanoue, Rose Travers
Journal: New England Journal of Medicine (1998)

Severe osteogenesis imperfecta is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain. There is no effective therapy for the disorder. We assessed the effects of treatment with a bisphosphonate on bone resorption.
Intrauterine Infection with Varicella-Zoster Virus after Maternal Varicella
Authors: Sharon G. Paryani, Ann M. Arvin
Journal: New England Journal of Medicine (1986)

We investigated the consequences of maternal infection with varicella-zoster virus in a prospective study of 43 pregnancies complicated by varicella and 14 pregnancies complicated by herpes zoster. Nine of 43 pregnant women with varicella had associated morbidity--pneumonia (4 women), death (1), premature labor (4 of 42), premature delivery (2 of 42), and herpes zoster (1). Intrauterine varicella infection was identified on the basis of clinical evidence (anomalies characteristic of the congenital varicella syndrome, acute varicella at birth, or herpes zoster in infancy) or immunologic evidence (IgM antibody to varicella-zoster in the neonatal period, persistent IgG antibody to varicella-zoster at one to two years of age, or in vitro lymphocyte proliferation in response to varicella-zoster virus antigen). The congenital varicella syndrome occurred in 1 of 11 infants of women with first-trimester varicella. Immunologic evidence of intrauterine varicella infection was present in 7 of 33 infants tested; 4 of these infants were asymptomatic. According to clinical or immunologic criteria, 8 of 33 infants had evidence of intrauterine varicella infection. These observations show that varicella during pregnancy was associated with maternal morbidity and evidence of fetal infection, but that herpes zoster was not.
Abstract P5-03-09: Receptor Activator of Nuclear Factor Kappa B (RANK) as a potential therapeutic target in triple-negative breast cancer
Authors: ME Reyes, H Masuda, D Zhang, JM Reuben, W Woodward, BG Darnay, GN Hortobagyi, NT Ueno
Journal: Cancer Research (2012)

Abstract Background: Triple-negative breast cancer (TNBC) has a poorer prognosis in comparison to other breast cancer subtypes because of its high metastatic rate. There is evidence that cancer stem cells (CSCs), known to have an epithelial-to-mesenchymal (EMT) phenotype, may contribute to the metastasis of breast cancer. Denosumab (an anti-RANK ligand antibody) is currently being explored as a treatment for breast cancer in phase II and III clinical trials. RANK is thought to regulate mammary stem cells. Therefore, we hypothesized that RANK promotes tumorigenicity and metastasis of TNBC via the regulation of EMT and enrichment of CSCs. We sought to determine the effects of RANK expression on the tumorigenic and metastatic activities of TNBC cells and whether RANK is a potential therapeutic target in TNBC. Methods: Primary breast tumor specimens from the MD Anderson Cancer Center Tumor Bank were stratified by ER/HER2 status. We analyzed RANK mRNA expression levels, obtained by Affymetrix gene chip array, in ER+/HER2-negative breast tumors (n = 22) and ER−/HER2-negative breast tumors including TNBC tumors (n = 18). To study the effects of RANK suppression in TNBC cells, we generated two stable RANK shRNA MDA-MB-231 TNBC cell lines and a negative shRNA cell line as a control and examined whether knockdown of RANK expression correlated with a decrease in mesenchymal markers, vimentin and snail, and stem cell marker, ALDH1, invasion, migration, and tumorigenicity in TNBC cells. Results: An analysis of RANK mRNA expression levels among human primary breast cancer specimens revealed increased RANK expression in ER−/HER2-negative primary breast tumors including TNBC tumors, compared with ER+/HER2-negative primary breast tumors (p = 0.034). Knocking down RANK in MDA-MB-231 cells significantly inhibited migration (p = 0.0005) and invasion (p = 0.0006) and reduced the stem cell subpopulation, as shown by a decrease in mammospheres (p = 0.0188) and ALDH1 activity. Further, in a three-dimensional (3D) cell culture model, we observed significant inhibition of projections in MDA-MB-231 cells with knockdown of RANK (p &amp;lt; 0.05), which correlated with downregulation of the mesenchymal markers vimentin and snail shown by qRT PCR analysis. Conclusion: Our data demonstrate that RANK may promote the tumorigenesis of TNBC by enriching cancer stem cells. In future studies, we will investigate the effect of RANK inhibition on metastasis in vivo using a TNBC xenograft model. Our long-term goal is to develop RANK-targeted therapy for TNBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-03-09.
PTH-002 A Single Centre Audit Comparing Colonoscopy Completion and Complication Rates in older and Younger Patients: Abstract PTH-002 Table 1
Authors: L Harrison, R Parish, R Shenderey
Journal: Gut (2013)

<h3>Introduction</h3> Colonoscopy is the gold standard test for large bowel assessment. Radiological techniques are available and have a high sensitivity and specificity for diagnosing colorectal cancer.<sup>1</sup> As part of the Joint Advisory Committee (JAG) for endoscopy accreditation, units should achieve a caecal intubation rate of &gt; 90%. We audited our unit’s performance. <h3>Methods</h3> We audited colonoscopies carried out in 2011 at a District General Hospital. Endoscopy reports of 75 patients aged 80 and over and 75 patients under 75 years old were analysed. <h3>Results</h3> 1635 colonoscopies were carried out by the unit in 2011. The pick-up rate for cancer was at least 3.5% and for polyps was 23%. Completion of colonoscopy in under 75 year olds was 97%. Completion in over 80 year olds was 79%. The unit’s overall completion rate in 2011 was 90% (24% terminal ileum, 65% caecum, 1% anastomosis). Colonoscopy was better tolerated in the younger group with discomfort suffered in 7% of patients compared to 11% of elderly patients (see table 1). The overall pick-up rate for cancer in both groups was 3%. <h3>Conclusion</h3> The completion rate in the elderly (79%) was below the standard as set by JAG (&gt; 90%). This was due to more discomfort experienced by the elderly group and more complications. There were six new colorectal cancer diagnoses in the elderly. These cancers could have been diagnosed by radiographic techniques such as CT colonography or CT with faecal tagging. The 2011 NICE guidance on the management of colorectal cancer2 states that CT colonography can be used as a safe and effective alternative to colonoscopy. This audit demonstrates that patient selection for colonoscopy is very important. CT colonography should be considered for the first line investigation in the elderly to reduce unnecessary complications and low overall colonoscopic completion rates. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Pickhardt PJ, Hassan C, Halligan S, Marmo R. Colorectal cancer: CT colonography and colonoscopy for detection--systematic review and meta-analysis. Radiology 2011; 259(2):393–405. National Institute of Health and Clinical Excellence. Colonoscopic surveillance for prevention of colorectal cancer in people with ulcerative colitis, Crohn’s disease or adenomas. London: NICE 2011. http://www.nice.org.uk/nicemedia/live/13415/53641/53641.pdf [Accessed 5/1/13]