tbuckley/cabot-search huggingface dataset:
Abstract 326: Nucleostemin Induced by Pim-1 Kinase Antagonizes Senescence of Cardiac Progenitor Cells
Authors: Nirmala Hariharan, Anya Y Joyo, Daniele Avitabile, Kaitlen M Samse, Brandi Bailey, Pearl Quijada, Michael McGregor, Sadia Mohsin, Sailay Siddiqi, Mark A Sussman
Journal: Circulation Research (2013)

Decline in stem cell functionality and regenerative capability is a crucial contributor to aging, upon which the c-kit+ cardiac progenitor cell (CPC) pool with enhanced regenerative potential decreases and CPCs with limited proliferative and differentiation potential progressively accumulate. With cardiac stem cells currently being used in the clinic, especially in the elderly population, there is a dire need to understand the phenotypic, molecular and functional characteristics of senescent stem cells to effectively manipulate them for therapy. Nucleostemin (NS), a nucleolar stress sensor protein associated with stem cell pluripotency and regeneration declines upon cardiac aging. We hypothesize that NS is a critical antagonizer of senescence in CPCs. NS expression decreases significantly (-59%, p&lt;0.05), while the % of senescent cells increases in CPCs isolated from old mice (13 month, OCPC) relative to CPCs isolated from young mice (3 month, YCPC). OCPCs are morphologically different, characterized by flat, round cells (p&lt;0.05) with increased bi- &amp; poly-nucleation (p&lt;0.05), slower proliferation (-80%, p&lt;0.01) and altered cell cycle profiles, relative to YCPCs. Decreased NS level is causal for the phenotype observed in OCPCs, as silencing NS in YCPCs induces flattening of cells, increases bi- &amp; poly-nucleation, decreases expression of stem cell marker c-Kit (-55%, p&lt;0.05), upregulates cell cycle inhibitors p53 and p16 (4.2, 3.8 fold, p&lt;0.01) and decreases proliferation (p&lt;0.05). NS-mediated regulation of CPC senescence is p53 dependent, as silencing p53 rescues the phenotype induced by NS-silencing. Interestingly, NS is induced by Pim-1 kinase-mediated stabilization of transcription factor c-Myc, as NS protein expression decreases in CPCs upon knockdown of Pim-1 (p&lt;0.05) or c-Myc (p&lt;0.01); and in the absence of c-Myc, Pim-1 does not upregulate NS. Engineering OCPCs with NS is an effective strategy to antagonize senescence, as observed by decreased % senescent cells, increased proliferation and restored morphology. In conclusion, NS which is induced downstream of Pim-1 kinase, maintains multipotency and inhibits senescence in CPCs, consistent with cumulative evidence that Pim-1 induced cardiac regeneration is mediated in part by NS.
Elevated pretreatment serum concentration of YKL-40—An independent prognostic biomarker for poor survival in patients with metastatic non-small cell lung cancer
Authors: I. Thoem, J. S. Johansen, B. Andritzky, G. Schuch, I. Burkholder, L. Edler, C. Bokemeyer, U. Schumacher, E. Laack
Journal: Journal of Clinical Oncology (2008)

19044 Background: YKL-40 is produced by cancer cells and tumor-associated macrophages and may play a role in cancer cell proliferation, differentiation, survival, invasiveness, metastasis and angiogenesis. A high serum YKL-40 level has been associated with poor prognosis in patients (pts) with several cancer types, but has not been studied in pts with non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate YKL-40 in pretreatment serum samples from patients with metastatic NSCLC. Methods: Pretreatment serum levels (sls) of YKL-40, VEGF, and MMP-9 were analyzed in 189 pts with ELISA. 23 pts (12%) had stage IIIB disease with malignant pleural effusion and 166 pts (88%) stage IV disease. 143 male/46 female, median age 62 years [range 40–75], median Karnofsky PS 90%. 98 pts received gemcitabine and vinorelbine, and 91 pts gemcitabine, vinorelbine, and cisplatin as first line chemotherapy. Results: Pts with metastatic NSCLC had significantly higher YKL-40 sls (median sl 209μg/l, range 19 - 2153) than healthy controls (n=276, median sl 43μg/l, range 20 - 184) (p<0.001). The median overall survival of all 189 pts was 36.9 weeks. No significant difference in overall survival was observed between the chemotherapy regimens, tumor stage, sex, histologic types, and between high and low MMP-9 sls. Whereas pts with a pretreatment YKL-40 sl > 209μg/l (= median sl) had a significantly shorter survival than patients with lower serum YKL-40 (median survival 31.6 vs. 41.4 weeks; p=0.007). Patients with high VEGF sls (i.e. > 1099,5pg/ml (= median sl)) had also a shorter survival compared to patients with lower serum VEGF (34.4 vs. 38.0 weeks; p=0.04). In univariate Cox regression analysis the pretreatment YKL-40 sl, the pretreatment VEGF sl, the Karnofsky PS, and the presence of bone metastases had prognostic significance. In multivariate analysis only the pretreatment sl of YKL-40 and the presence of bone metastases were identified as independent prognostic factors. Conclusion: The pretreatment serum YKL-40 level was identified as an independent prognostic biomarker in metastatic NSCLC and may help to determine the individual prognosis of these patients. No significant financial relationships to disclose.
Prognosis prediction of stage II colon cancer by gene expression profiling
Authors: A. Barrier, D. Brault, S. Houry, S. Dudoit, A. Lemoine, A. Flahault, P. Boelle
Journal: Journal of Clinical Oncology (2006)

3565 Background: The aims of the present study were: 1) to identify a prognosis signature (PS), based on microarray gene expression measures, in stage II colon cancer patients and to assess its accuracy with resampling techniques ; 2) to assess the accuracy, also with resampling techniques, of a previously proposed 23-gene PS. Methods: Colon tumor mRNA samples from 50 patients were profiled using the Affymetrix HGU133A GeneChip (22283 sequences). In a first part, the 50 patients were randomly divided into 2 groups (G1 and G2) of equal size that were considered alternately as training and validation sets. In a second part, the 50 patients were randomly divided into 1600 training (size=n) and validation (size=50-n) sets. Informative genes were selected on the training set by taking the 30 most differentially expressed genes between patients who recurred and those who remained disease-free; the accuracy of this PS was assessed by comparing the predicted prognosis (using a diagonal linear discriminant analysis (DLDA)) and the actual evolution for all the validation set patients. Using the same random splits, the accuracy of the 23-gene PS was assessed with a DLDA that used learning set patients as reference samples. Results: The 30-gene PS that was identified from G1 (G2) patients yielded a 80% (84%) prognosis prediction accuracy when applied on G2 (G1) patients. With resampling techniques, the prediction accuracy regularly increased with the learning set (LS) size: 65.5% (range=52.5–75%) with LS of size 10, and 82.7% (range=60–100%) with LS of size 40. Comparisons of compositions of the 100 PS for a given value of n suggested a high instability of informative genes; with LS of size 10, 7 genes were part of at least 10% of signatures; with LS of size 40, 7 genes were part of all the 100 signatures. The accuracy of the previously proposed 23-gene PS also increased with the learning set size. Conclusion: Microarray gene expression profiling represents a promising technique to predict the prognosis of stage II colon cancer patients. The present study also outlines the high instability of informative gene selection and suggests the usefulness of resampling techniques to obtain an honest assessment of prognosis prediction accuracy. No significant financial relationships to disclose.
Predictive factors of adjuvant therapy-related amenorrhea for patients with breast cancer.
Authors: N. Tamura, T. Kato, C. Shimizu, T. Kinoshita, Y. Fujiwara
Journal: Journal of Clinical Oncology (2011)

217 Background: Reproductive age breast cancer patients often experience therapy-related amenorrhea so preserving fertility after treatment is a major concern. Anti-mullerian hormone (AMH) values have been reported useful in predicting menopause for infertility treatment patients, but published information is limited regarding breast cancer patients. If amenorrhea can be predicted before treatment, breast cancer patients hoping to have children in the future can consider this information in choosing treatment. Our aim was to predict patient fertility using AMH values. Methods: Forty breast cancer patients, 25-45 years of age (median, 35.5), who received adjuvant chemotherapy (CT) or endocrine therapy (ET), had AMH values retrospectively assayed from frozen serum before and after treatment. AMH values were then analyzed in relation to clinicopathological factors using logistic analysis. Of 19 adjuvant CT patients whose AMH values could be assayed, Cox’s proportional hazard model indicated a correlation in terms of amenorrhea and time to menses resumption between clinicolpathological factors and AMH values. Results: The mean pretreatment AMH value for all 40 patients was 21.4pM (range, 3-78) and a correlation was demonstrated with patient age, but not breast cancer intrinsic subtype or stage. AMH values decreased to the lower limit after treatment for all CT patients regardless of age, but there was a difference in degree depending on patient age for ET patients. Of the 19 CT patients, the mean AMH value was 25.6pM (3-78). These patients all underwent a regimen of anthracycline with 11 (58%) also receiving a regimen of taxiane. After starting CT, 17 patients (89%) experienced amenorrhea, but 11 (59%) resumed menstruation within one year of finishing CT and 15 (78%) resumed within two years. There were no significant differences among CT patients in age, pretreatment AMH value, intrinsic subtype or stage, but patients receiving taxiane demonstrated a noteworthy trend. Conclusions: Although we were unable to predict menopause directly using AMH values given the small number of patients in this study, we could estimate the risk of menopause as being either low or high for CT patients based on age and type of regimen.
Annals On Being a Doctor Story Slam - Red Mittens
Authors: Michael A. LaCombe
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 January 2016Annals On Being a Doctor Story Slam - Red MittensFREEMichael A. LaCombe, MDMichael A. LaCombe, MDFrom Maine General Medical Center, Augusta, Maine.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/V15-0012 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals On Being a Doctor Story Slam - Red Mittens This story, "Red Mittens," by Dr. Michael A. LaCombe, is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation. (Duration 5:23)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals On Being a Doctor Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Maine General Medical Center, Augusta, Maine.Note: This story is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation.Corresponding Author: Michael A. LaCombe, MD, 12 Eighth Maine Avenue, Peaks Island, ME 04108; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 January 2016Volume 164, Issue 2Page: SS1 ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Erectile function following unilateral cavernosal nerve graft
Authors: J. M. Corman, L. S. Borden, G. R. Hanson
Journal: Journal of Clinical Oncology (2007)

15642 Background: Over the past 20 years, radical prostatectomy has been a mainstay in the treatment of localized prostate cancer. With the adoption of nerve-sparing procedures, select patients may avoid the consequence of erectile dysfunction.Certain patients who are not candidates for nerve-sparing procedures may be eligible for nerve interposition grafts. While bilateral cavernosal nerve grafting after radical prostatectomy has shown efficacy, the effect of unilateral nerve grafting remains unclear. To further ascertain this outcome, we evaluated a large group of patients who underwent a unilateral cavernosal nerve replacement. Methods: Forty patients underwent unilateral nerve sparing surgery with concomitant contralateral cavernosal nerve replacement by a single surgeon from 2002 to 2006. Patient were selected based upon pre-op nomogram risk assessment, endorectal MRI evidence of extra capsular disease or intraop histology demonstrating margin positivity. Age, demographic data, Gleason score, clinical and pathologic stage and pre and post op IIEF data was collected and prospectively analyzed. An additional phone interview was conducted to assess outcomes and morbidity. Results: Full demographic and interview data was available for 28 of 40 patients (70%). Median follow-up was 19 months. The median age at RRP was 53 with a median pre-operative PSA of 6.5. Median pre- and post-op IIEF scores were 25 and 15 respectively. Median change in IIEF scores was 7.5. 22 of 28 patients (79%) men report being able to penetrate after surgery. 17 of those 22 (77%) continue to require PDE-5 inhibitors to facilitate penetration. 3 of the 6 patients (50%) who were unable to have intercourse following nerve replacement received adjuvant hormonal or radiation therapy. 27 patients (96%) reported numbness at the graft harvest site with three (10.7%) describing this as bothersome. One patient experienced a graft site infection and two of 28 (7.1%) patients reported pain at the harvest site. Conclusion: Unilateral sural nerve grafting is a feasible and well-tolerated approach for patients who must undergo wide resection of a neurovascular bundle. While men do show a sizable decrease in their IIEF score, 79% were able to achieve penetration following surgery. The majority of men require PDE-5 inhibitors to facilitate intercourse. No significant financial relationships to disclose.
Neoadjuvant chemotherapy for stage III and IV epithelial ovarian cancer: A comparative study
Authors: V. Loizzi, G. Cormio, G. Di Vagno, L. Resta, A. Cazzolla, A. Di Gilio, A. Cuccovillo, L. Selvaggi
Journal: Journal of Clinical Oncology (2004)

5117 Background: The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy with those treated conventionally with primary debulking surgery. Methods: From February 1994 to October 2003, all consecutive cases of advanced stage epithelial ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Results: Thirty women with advanced stage epithelial ovarian carcinoma were treated with neoadjuvant chemotherapy and were compared to other 30 patients who underwent primary debulking surgery. Patients in the neoadjuvant chemotherapy were significantly older (p=0.03) and had a poorer ECOG performance status (p=0.02) compared to the controls. However, no statistical difference was observed in overall disease-specific survival (p=0.66) and disease-free survival (p=0.25) between the two groups. Conclusions: Despite patients in the neoadjuvant chemotherapy group are significantly older and have a poorer performance status, this treatment modality does not compromise survival. Prospective randomised trials comparing neoadjuvant chemotherapy to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer. No significant financial relationships to disclose.
Aviation Toxicology: An Introduction to the Subject and a Handbook of Data
Journal: JAMA (1953)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Specific Targeting of Chlorambucil to Tumors With the Use of Monoclonal Antibodies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M J Smyth, G A Pietersz, B J Classon, I F McKenzie
Journal: JNCI Journal of the National Cancer Institute (1986)

The concept of attaching cytotoxic drugs, such as the alkylating agent chlorambucil (CBL), to "tumor-specific" antibodies for the treatment of cancer is attractive, inasmuch as the specificity of CBL could be increased and its systemic toxicity reduced. To this end, CBL was activated by N-hydroxysuccinimide to produce an active ester derivative that was covalently coupled to monoclonal antibodies reactive with murine cell surface antigens. Up to 30 molecules of CBL were specifically bound per molecule of antibody, without impairing the alkylating activity of CBL and with minimal loss of antibody activity. The in vitro cytotoxicity of the conjugate was tested by the inhibition in [3H]thymidine incorporation into tumor cells, which demonstrated the conjugate to be specifically cytotoxic toward antibody-reactive cell lines, having more activity than the free drug. In vivo treatment of (C57BL/6 X BALB/c)F1 mice bearing a murine thymoma with CBL-antibody conjugates gave prolonged survival times and greater inhibition of growth of established tumors than was obtained with free antibody or CBL alone. The study is one of the first examples of the greater toxicity of a drug coupled to antibody, inasmuch as most drugs when coupled to antibody lose activity. CBL-monoclonal antibody conjugates may, therefore, provide a means of specifically attacking tumors, which could be therapeutically useful.
DCE-MRI perfusion imaging of head and neck squamous cell carcinoma nodal metastasis: Identifying radioresistance and the distant metastatic phenotyp
Authors: H. Quon, S. Kim, L. A. Loevner, M. A. Rosen, E. Sherman, A. Kilger, H. Poptani
Journal: Journal of Clinical Oncology (2008)

6041 Background: Nodal metastatic HNSCC (NM-HNSCC) represents a unique population of cells that may develop distant metastasis (DM) and increased radioresistance leading to the practice of post-RT neck dissections (ND). We hypothesized that the tumor vasculature may be important for both phenotypes. Methods: Since 2005, 50 subjects with NM-HNSCC (minimum 1 cm) treated with concurrent platinum based chemoradiotherapy were prospectively enrolled and evaluated with DCE-MRI to evalute nodal perfusion. DCE- MRI was performed on a Siemens 1.5 or 3T scanner with a modified fast 3D spoiled gradient-echo sequence. Patient motion movement was corrected for. A single dose of Gd-DTPA (0.1 mM/kg) was injected at 1 mL/s into an antecubital vein, followed by saline flush and scanning for 9 minutes. The signal-intensity time curves for the first 60 seconds from the nodal tumor and the arterial input function was used to compute the normalized integrated area under the curve (NIAUC60). Patients were treated in a uniform fashion utilizing a simultaneous infield boost IMRT prescription technique to 70.4 Gy in 32 fr. Descriptive statistics were used to summarize the data. Nonparametric statistical analysis was applied for comparative analyses. Results: 45 studies are available for analysis. Follow-up ranged from 1–21 months (mean 9 months). Analysis demonstrates a significant association between low nodal perfusion and radioresistance as defined by a positive ND (p=0.012). A significant association was seen between low nodal perfusion and the risk of DM (p=0.048). A scattterplot of nodal perfusion vs. nodal volume demonstrated an inverse relationship fitting a logarithmic model (R2=0.412, p<0.01). At the NIAUC60 cutoff of 0.4 which separated patients with or without residual neck disease, the logarithmic model predicted a corresponding nodal volume of 228 cc which reflects a nodal size of ∼6x6x6 cm. Conclusions: These observations lead to speculations that poor pre-treatment tumor perfusion may be a common mechanism associated with radioresistance and development of the distant metastatic phenotype. The prediction of a clinically prognostic nodal size offers internal validity for the clinical significance of nodal perfusion. No significant financial relationships to disclose.