tbuckley/cabot-search huggingface dataset:
Identification of proteins promoting development of metastatic breast tumors
Authors: E. Seeley, R. E. Ellsworth, D. Ellsworth, M. Sanders, J. A. Hooke, R. Caprioli, C. D. Shriver
Journal: Journal of Clinical Oncology (2007)

1041 Background: Primary breast tumors are constantly shedding tumor cells into the circulatory and lymphatic systems. Although detection of occult tumor cells is a risk factor for recurrence and progression, tumor cells remain detectable years after initial diagnosis in patients without clinical or histological detection of metastasis. Thus the question remains as to why some women with circulating tumor cells develop metastatic breast cancer while others do not. Methods: Negative lymph nodes from women with node negative (n=22) and node positive disease (n=36) were obtained from patients enrolled in the Clinical Breast Care Project. Negative lymph node status was confirmed by IHC analysis. Frozen tissues were sectioned and mounted on gold coated MALDI target plates for protein expression profiling. Hematoxylin and eosin (H&amp;E) stained slides were prepared from serial sections for histological characterization. MALDI matrix was deposited as individual spots on the tissue sections in a histology directed manner to assay specific areas and tissue types of interest. Mass spectral data were then acquired from multiple sites across each tissue section. Results: 131 features were observed in negative nodes from patients without metastatic disease and 129 in negative nodes from patients with lymph node metastases. While the majority of features detected were similar between the two groups, 8.5% were differentially expressed. Two of the features which were expressed at significantly higher levels in nodes from patients with metastatic disease have been putatively identified as thymosin β4 and thymosin β10. Conclusions: Thymosin β4 and 10 have been associated with disease progression and metastatic capacity in a number of tumor types. The overexpression of these proteins in tumor-negative nodes from patients with metastatic disease in other regional nodes suggests lymph nodes do not play a passive role in metastasis, rather, expression of a specific subset of proteins creates an hospitable environment to facilitate colonization. These markers of metastasis may permit molecular discrimination of those patients with indolent disease from those at risk for metastasis and will thus allow for the design of customized treatment regimens to more effectively treat, or prevent, metastatic spread. No significant financial relationships to disclose.
Assessment of personhood indicators for instrument development for persons with primary brain tumors.
Authors: L. Anderson-Shaw, J. L. Villano
Journal: Journal of Clinical Oncology (2010)

e12550 Background: Cancers of the brain, both from a primary or metastatic source, can cause alterations in personal neuro-cognitive ability, and in some patients may even challenge their concept of self. No tool is currently available to measure the concept of personhood in patients with brain tumors (Anderson-Shaw, L. et al. 2010). Although there are several tools in the literature that measure related issues such as quality of life (QOL), no tool measures the concepts of personhood as both patient and loved ones perceive. Our belief is that having the personhood evaluation tool will allow clinicians to detect changes in patients with neurological disorders, including brain tumors, that are clinically meaningful, which may not be identified with current neuro-cognitive or QOL instruments. Methods: Initial data gathering was done through focus group meetings to obtain descriptive data. There were two separate groups, volunteer brain tumor patients recruited from brain tumor patient population at UIC Medical Center and a second group of volunteers who have family members/loved ones with brain tumor. These sessions were moderated and voice recorded. The moderator used several definitions of personhood from the literature to prompt the discussion and asked questions related to these definitions so participants could describe their experience as related to brain tumor and/or treatment. Results: Enrollment included approximately 5 patients with primary brain tumor and 15 family members/loved ones. We found that the general concept discussion prompts given by Feinberg (1992) found meaning with our discussion participants. Through our discussions with patients and loved ones, we have been able to identify important issues that are vital to a working definition of personhood for this patient population. Conclusions: Analysis of the discussion from the focus group is consistent with the concepts related to personhood as a relevant and possible useful clinical tool to assess neurologic deficits in brain tumor patients. No significant financial relationships to disclose.
COPD circle of care: Patient centred education and counselling tool for COPD self-management
Authors: Charles Chan
Journal: European Respiratory Journal (2011)

Background:  Current gaps exist between heathcare professionals and COPD patients in effective communication & counselling on patient self management.   Aim and objective:  To develop a patient centred counselling tool, based on Canadian Clinical Practice Guidelines, for COPD self management that will meet the needs of family physicians, nurses, respiratory therapists, COPD educators & pharmacists responsible for COPD patient education.   Methods:  7 national stakeholder organizations and 14 healthcare professionals from across Canada collaborated in the development of a patient centred COPD education/counselling tool. A core development board (3 COPD nurse educators, 1 pharmacist, 1 family physicians and 1 respirologist) developed the core materials. Input and direction was then provided by 3 regional committees (each comprised of 2-3 healthcare practitioners) to ensure regional nuances and national application of the tool. The national stakeholder organizations ensured that the tool meet the requirements of the respective organizations. The tool was tested with COPD patients to ensure usability and validity.   Results:  A tool with universal graphics and language in a paper format will be presented at the ERS. The tool contains self management strategies for preventing acute exacerbations, breathlessness, signs of worsening COPD and action plan.   Conclusion:  An effective patient education/counselling tool is required for successful communication between healthcare professionals and patients on COPD patient self-management. The utility and clinical impact of the tool will require HCP education and training.
Trastuzumab-related cardiotoxicity in setting outside clinical trials: A mono-institutional experience
Authors: P. Papaldo, M. Russillo, G. Ferretti, D. Giannarelli, P. Carlini, G. Metro, A. Felici, G. Toglia, V. Graziano, F. Cognetti
Journal: Journal of Clinical Oncology (2008)

22116 Background: Since cardiac failure may occur in ordinary clinical practice at higher rate than in controlled clinical trials with strict entry criteria, we assessed the spectrum of cardiotoxicity during routine trastuzumab (T) treatment for breast cancer patients (pts) of our division. Methods: Data of 72 pts treated with trastuzumab-based therapy for at least 8 months were collected, unless they developed cardiotoxicity (median cumulative time 14: range 8–78 months). Pts characteristics were: potential cardiac risk factors in 15/72 pts, median FE 63% (range 50–80), prior anthracycline-based(A) therapy in 57 pts (79.2%), prior taxane-conteining (Tax) therapy in 37 pts (51.4%) (both 48.6%). Cardiac events (CEs) were defined as a decrease of LVEF to < 50% and/or of ≥ 20% from baseline; or symptoms of CHF according to NYHA class II-IV. LVEF at baseline was normal, performed every 3 months according to the local clinical practice and evaluated at 12 month. Results: CEs developed after a median of 10 months of T. Twenty-one pts (29.2%) experienced CEs. Thirteen of these (18.0%) (9 pretreated with A) developed CHF, NYHA class II-III (6 pts, 8.3%, class III). Two out of the 21 CEs pts had an asymptomatic reduction of < 50% LVEF. Sixteen out of the 72 pts (22.2%) had a ≥ 10% LVEF reduction from baseline (6/16 pts LVEF ≥ 20%). CEs occurred in 33.3% of the pts with a potential risk factor vs 28,1% of those without risk. There were no cardiac deaths. Among the 57 pts pretreated with A, 3 (8,6%) of those who also received Tax experienced cardiotoxicity class II-IV vs. 6 (27.3%) who did not (p=0.05). No pts treated with both A and Tax had a reduction of LVEF ≥ 20% vs. 22.7% of those pretreated with only A (p=0.01). CHF developed in7 cases in the first year, 4 in the second, and 1 in the third. Conclusion: According to our experience, cardiotoxicity of T based therapy is acceptable, but worse than that reported in the controlled clinical trials. No significant financial relationships to disclose.
Analysis of the VEGF family and their receptors in serum/plasma of patients with pre-invasive and invasive cervical cancer
Authors: S. Landt, A. Thomas, A. Fueger, S. Jeschke, S. Korlach, H. Adam, K. Ulm, P. Schmid, J. Blohmer, W. Lichtenegger, S. Kuemmel
Journal: Journal of Clinical Oncology (2006)

5016 Background: The vascular endothelial growth factor (VEGF) family and their receptors are essential regulators of angiogenesis and lymphangiogenesis. This study examined the significance of circulating VEGF, VEGF-C, VEGF-D and their receptors VEGFR-1 and VEGFR-2 in patients with preinvasive and invasive cancer in relation to conventional prognostic parameters. Methods: Blood samples were obtained from 125 women before initial treatment (CIN I-III n = 50; FIGO stage I-IV n = 51; relapse n = 24). Plasma (p) and serum(s) levels of pVEGF, sVEGF-D, sVEGFR-1, sVEGFR-2 (R&amp;D Systems, USA) and sVEGF-C (IBL, Japan) were determined by using a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Results: The highest level of pVEGF (p = 0.007) and sVEGFR-2 (p = 0.014) were detected in patients with recurrent disease, whereas the highest level of sVEGF-D (p = 0.046) were measured in patients with preinvasive lesions (CIN I-III). Furthermore, significantly elevated levels of sVEGF-C (p = 0.021) were detected in early stages (FIGO I-II) in comparison with advanced stages (FIGO III-IV) of cervical cancer. No significant difference in concentration was observed between the various grades of cervical intraepithelial neoplasia (CIN I-III). Correlations between conventional prognostic markers such as lymph node status (N0/N1), lymphangioinvasion (L0/L1), angioinvasion (V0/V1) and grading (G1/G2/G3) were investigated. Increased plasma levels of VEGF (p = 0.036) correlate with the dissemination of tumor cells to regional lymph nodes (N1),whereas serum VEGF-D levels were significantly decreased in women with lymph-node involvement (N1) (p = 0.045) and vascular invasion (L1) (p = 0.019). None of these members of the VEGF family were found to correlate significantly with histological subtype (squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma) or grading of the tumor cells (G1/G2/G3). Conclusions: These results show that circulating concentrations of VEGF are associated with the stage of disease. In an early stage of cervical cancer a switch to a lymphangiogenic phenotype (VEGF-D, VEGF-C) might be possible. No significant financial relationships to disclose.
Abstract 9754: Low Diastolic Arterial Pressure During Pre-Explant Off-Pump Trials can Induce Misleading Overestimation of Left Ventricular Function with Potential Risk for Early Recurrence of Heart Failure after Left Ventricular Assist Device Removal
Authors: Michael Dandel, Evgenij Potapov, Juliane Vierecke, Alexander Stepanenko, Thomas Krabatsch, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2012)

Background A major goal after left ventricular assist device (LVAD) implantation is the detection of myocardial recovery which allows LVAD removal. After normalization of LV size, the pre-explant off-pump LVEF is paramount for selection of patients with the potential to remain stable after LVAD removal. However, patients with similar off-pump LVEF but different systemic arterial pressure during off-pump trials often show differences in post-explant cardiac stability. We assessed the importance of diastolic pressure for weaning decisions. Methods Among the 82 patients weaned from LVADs since 1995, we selected for evaluation a more homogenous patient cohort which included only those with idiopathic dilated cardiomyopathy before LVAD insertion and pre-explant off-pump LVEF ≥ 45%. We analyzed the relationship between post-weaning stability and pre-explant LV size, geometry and function (end-diastolic diameter, relative wall thickness and short/long axis ratio, systolic wall motion velocity and LVEF), considering also the arterial pressure during off-pump trials. Results Pre-explant LVEF in the evaluated patients was 49 ±3.9%. There were no significant differences in pre-explant LVEF between patients with and without heart failure (HF) recurrence during the first 5 post-weaning years (48.5 ±2% vs. 49.2 ±4.3%), but patients with HF recurrence had lower diastolic arterial pressure during the final pre-explant off-pump trial in comparison with post-weaning stable patients. (47.9 ±3.6mmHg vs. 66.9 ±7.8mmHg, p&lt;0.001). Pre-explant off-pump LVEF &lt; 55% with low diastolic arterial pressure of ≤ 50mmHg showed 87.5% predictive value for post-weaning HF recurrence. After maximum unloading promoted cardiac improvement, patients with off-pump arterial diastolic pressure ≤ 50mmHg showed higher pre-explant alterations for all off-pump parameters related to LV size, geometry and function than patients who had off-pump arterial diastolic pressure &gt; 50mmHg (p &lt; 0.05). Conclusion Reduced LV afterload in patients with low off-pump diastolic arterial pressure can induce misleading overestimation of LV function. In patients with pre-explant LVEF ≥ 45%, off-pump diastolic arterial pressure ≤ 50mmHg is a relevant risk factor for post-weaning HF recurrence.
Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive-dose chemotherapy.
Authors: H M Kantarjian, M Talpaz, J Hester, E Feldman, M Korbling, J Liang, M B Rios, T L Smith, L Calvert, A B Deisseroth
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate whether intensive chemotherapy followed by peripheral stem-cell (PSC) collections during early hematopoietic recovery results in a higher percentage of diploid cell collections in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). PATIENTS AND METHODS Fifty-five adults with Ph-positive CML received intensive chemotherapy with daunorubicin and high-dose cytarabine (ara-C) (DAUNO-HDAC; 26 patients) or fludarabine, high-dose ara-C, and mitoxantrone (FAM; 29 patients). Collections of the peripheral mononuclear cells were initiated when the WBC count was &gt; or = 0.8 x 10(3)/microL. Simultaneous peripheral and marrow samples were subjected to cytogenetic studies. RESULTS Thirty-eight of 55 patients (69%) were able to undergo the PSC collections. The rate of collection was higher in chronic phase (26 of 30 patients; 87%) than in accelerated (11 of 17; 65%) and blastic phases (1 of 8; 12%). Among the 30 patients in chronic phase, cytogenetic analyses of PSC showed cytogenetic responses (Ph-positive &lt; 95%) in 60%, which were major (Ph &lt; 35%) in 43% and complete (Ph = 0%) in 27%. Seven of 19 patients with simultaneous studies (37%; 23% of total) had a significantly lower percentage of Ph-positive cells in the peripheral collection compared with the marrow collection; one had the reverse phenomenon (5%; 3% of total). Cytogenetic responses were modest in both peripheral and marrow collections in CML accelerated and blastic phases. Myelosuppression-associated complications were frequent, resulting in febrile episodes in 76% of patients. CONCLUSION PSC collection during early hematopoietic recovery from intensive chemotherapy allowed the collection of diploid-rich stem cells, mostly in chronic-phase CML. The approach could be used for in vivo purging before autologous stem-cell transplantation (ASCT).
Sequential FDG-PET scanning in the assessment of response to neoadjuvant chemotherapy in operable esophageal cancer
Authors: L. Melcher, W. Wong, B. Sanghera, S. M. Bentzen, M. Hall, J. Chambers, E. Townsend, W. Fountain, M. Harrison
Journal: Journal of Clinical Oncology (2004)

4056 Background: Neoadjuvant chemotherapy using two cycles of cisplatin and 5FU is standard practice in the UK in patients with potentially operable cancer of the esophagus. The role of FDG-PET scanning in predicting response to this chemotherapy was assessed. Method: Twenty-three patients with potentially operable disease at presentation underwent two cycles of chemotherapy as in the OEO2 trial protocol. FDG-PET scanning was performed before chemotherapy, and again after the second cycle of chemotherapy in seventeen patients. Two independent assessors, who were unaware of the histopathological results, assessed the percentage change in tumour SUV max, mean and tumour to liver ratio. Histopathological regression was graded according to the Mandard score 1 to 5 (where 1 represents a complete response, and 5 represents no regression). Association between histopathological and FDG-PET response was quantified by Spearman's rank correlation coefficient, rS. Results: No significant correlation was found between change in SUV max (rS=-0.188, 95% CI –0.613,0.322) mean (rS=-0.118, 95% CI –0.118,0.384) or tumour:liver ratio (for max values rS=0.098, 95% CI –0.402,0.553, for mean values, rS=0.127, 95% CI –0.377, 0.573;) and histopathological response. Conclusion: There is a universal lack of agreement when assessing FDG-PET scans as to which parameters should be reported; in this study, all the frequently used parameters were analysed – yet no correlation with histological response was found. Changes in FDG-PET scans post neoadjuvant chemotherapy in patients with potentially operable esophageal cancer should be interpreted with caution, since this study has sufficient statistical power to rule out any clinically useful positive correlation with histopathological response to chemotherapy. No significant financial relationships to disclose.
Dietary Effects of Menhaden Oil on the Growth and Membrane Lipid Composition of Rat Mammary Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: J J Jurkowski, W T Cave
Journal: JNCI Journal of the National Cancer Institute (1985)

The objective of this study was to evaluate the effect of quantitative differences in dietary menhaden oil, an n-3 polyunsaturated marine oil, on mammary tumor development and to compare these results with those produced by corn oil, an n-6 polyunsaturated vegetable oil. Inbred female BUF rats were treated with the carcinogen N-methyl-N-nitrosourea (CAS: 684-93-5) and maintained on diets containing graded levels of each of the respective oils. Our results indicated that diets containing 20% menhaden oil produced a reduction in tumor incidence and a prolongation of the tumor latent period. This finding contrasted sharply with the enhanced tumor development and shortened latent period observed in the animals fed the equivalent dietary level of corn oil. Fatty acid analyses performed on the lipids extracted from the tumor and hepatic microsomes of the animals on the menhaden oil diets demonstrated that the proportion of eicosapentaenoic acid (No. of C-atoms:No. of double bonds = 20:5) present in these microsomal lipids was related inversely to mammary tumor development.
Abstract 15492: ADAM12 Modifies Severity of Peripheral Arterial Disease; Evidence from Preclinical and Human studies
Authors: Ayotunde O. Dokun, Mitsuharu Okutsu, W. Schuyler Jones, Damian Craig, Svati H. Shah, Douglas A. Marchuk, R. John Lye, Brian H. Annex
Journal: Circulation (2013)

Ayotunde Dokun, 2013 Finalist and Presenting Author
Effects of prednisolone on glomerular signal transduction cascades in experimental glomerulonephritis.
Authors: M Seto, S Kim, H Yoshifusa, Y Nakamura, T Masuda, A Hamaguchi, S Yamanaka, H Iwao
Journal: Journal of the American Society of Nephrology (1998)

In vitro data support that activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) regulate the gene expression of numerous growth factors and cytokines involved in the development of glomerulonephritis (GN). However, the in vivo activation and role of these transcription factors are poorly understood. This study examines whether these transcription factors are activated in antithymocyte serum (ATS)-induced GN in vivo and whether prednisolone suppresses activation of them. As assessed by gel mobility shift assay, glomerular DNA binding activity of AP-1 containing both c-Jun and c-Fos and NF-kappaB composed of P-50 and P-65 subunits was significantly increased after ATS injection. Furthermore, as estimated by in-gel kinase assay, glomerular activity of extracellular signal-regulated kinases (ERK) and c-jun NH2-terminal kinases (JNK), which are mitogen-activated protein kinases (MAPK) known to activate AP-1 and NF-kappaB in vitro, was significantly increased after ATS injection, preceding the increase in AP-1 activity. Prednisolone treatment significantly prevented the increase in urinary protein and albumin excretion and glomerular cell proliferation in ATS-induced GN, indicating the beneficial effects of prednisolone on this GN. Prednisolone significantly suppressed the increased glomerular ERK and JNK activities and AP-1 binding activity, but not glomerular NF-kappa binding activity. This study provides the first evidence of the marked increase in glomerular MAPK activities, and AP-1 and NF-kappa binding activities in ATS-induced GN. The beneficial effect of prednisolone on this GN may be partially mediated by the suppression of MAPK, followed by the suppression of AP-1.
Acute Idiopathic Thrombocytopenic Purpura — Management in Childhood
Authors: George R. Buchanan, Pedro A. de Alarcon, Stephen A. Feig, Gerald S. Gilchrist, John N. Lukens, Christopher L. Moertel, Alan R. Cohen, Joseph D. Dickerman, Edwin N. Forman, Bertil E. Glader, Jeanne M. Lusher
Journal: Blood (1997)