tbuckley/cabot-search huggingface dataset:
P3-18-05: Triple-Negative Breast Cancer: Stem Cells, Cancer and New Treatment Strategy.
Authors: S Yin, L Xu, KB Reddy
Journal: Cancer Research (2011)

Abstract Background: Women with triple negative breast cancer (TNBC) have a worse prognosis compared with other breast cancer subtypes. Hormonal or Herceptin-based therapies were found to be ineffective because of the loss of target receptors such as ER, PR and HER-2 amplification. TNBC has increased recurrence and poor survival, despite initial response to neoadjuvant chemotherapy. The aim of this study was to determine whether current drug treatment(s) eliminates bulk of tumor cells, but it has a minimal effect on cancer stem cells (CSCs) leading to tumor recurrence. Materials and Methods: Cancer stem cells were identified by ALDH-positive population by fluorescence-activated cell sorting. CSCs ability to form mammospheres, are generated in nonadherent and nondifferentiated conditions. Apoptosis was assessed using the Cell Death Detection ELISAPLUS kit. Xenograft tumor formation was evaluated using Nod/Scid mice. Cancer stem cell levels in human TNBC and ER+, PR+ and HER2− tumors were obtained by CD44+/ CD24low/− immunohistochemistry. Results: TNBC tumors express relatively higher levels of cancer stem cells compared to ER-positive, PR-positive and HER2−negative breast tumors. We studied the effects of PARP inhibitors (AZD2281 and BSI-201), paclitaxel, docetaxel, cisplatin and cisplatin plus TRAIL on CSCs derived from CRL-2335 and MDA-MB-468 TNBC cells in vitro. The in vitro data indicates that cisplatin plus TRIAL treatment was most effective in eliminating CSCs compared to PARP inhibitors, cisplatin, paclitaxel and docetaxel. Treatment with cisplatin plus TRAIL also inhibits Wnt-1 signaling and its downstream target, β-catenin, phospho β-catenin, cyclin D1, increased apoptosis, reduced proliferation and mammosphere formation. Inhibition of Wnt-1 by siRNA significantly reduced the ability of CSCs to form mammospheres compared to control. However, maximum effect was seen in cisplatin plus TRAIL treated cells. The combination of cisplatin/TRAIL also inhibited the growth of CRL-2335 Xenografts. Discussion: We demonstrate for the first time that cisplatin plus TRAIL is highly effective in reducing CSCs compared to PARP inhibitors, docetaxel or paclitaxel in TNBC cells in vitro. Inhibition of Wnt-1 signaling pathways by siRNA or cisplatin plus TRAIL reduces cell proliferation and increases apoptosis in CSCs. Taken together the data suggests that cisplatin plus TRAIL treatment has the potential of providing a new strategy for improving the therapeutic outcome in TNBC patients. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-18-05.
FRI0530 Efficacy and Tolerability of Pamidronate in Chronic Recurrent Multifocal Osteomyelitis
Authors: C. Galeotti, S. Loschi, C. Adamsbaum, I. Koné-Paut
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease in children. First-line treatments used are nonsteroidal anti-inflammatory drugs (NSAIDS). Secondary treatments after NSAIDS in case of refractory CRMO are not standardized and have been few evaluated. Biphosphonates, in particular pamidronate, have been used off label in a limited number of patients<sup>1</sup>. <h3>Objectives</h3> A retrospective survey and chart review to evaluate the reasons for use, the efficacy and the tolerability of IV pamidronate in 13 patients with difficult CRMO. <h3>Methods</h3> Thirteen of the 30 patients followed in the pediatric rheumatology unit at Bicêtre hospital, were analyzed retrospectively. Pamidronate treatment was documented as follows: reasons for its use, administration scheme, clinical efficacy (pain was evaluated by visual analog scale (VAS) and tolerability. Radiological changes were evaluated where available. <h3>Results</h3> Thirteen patients (4M, 9F) were treated by pamidronate from November, 2004. The median age at treatment was 10 years (6-14 years). Pamidronate was administered, on demand, intravenously by cycles of 3 consecutive days (0.5 mg/kg at J1, then 1 mg/kg at J2 and J3), following the protocol for osteogenesis imperfecta. Eleven patients received from a single cycle, 1 patient received 4 cycles and 1 patient 6 cycles. Pain resistant to oral and IV NSAIDS was the main reason for all the patients. VAS was 6/10 before pamidronate, and 0/10 36 hours after pamidronate infusion for 11/13 patients. Pain persisted for 1 patient and disappeared after 3 weeks for another one. The clavicle swelling disappeared in 1/5 patients and clearly decreased in 4/5 patients. The median duration of symptom-free intervals between 2 crises was 10 months (1-21.6). Five patients had a MRI after pamidronate treatment, which showed a decrease of the number of the lesions for 4 of them. The main side effects of pamidronate infusions were mild and transient: fever (n=9) with 5 flu-like symptoms, hypocalcaemia (&gt;2mM, n=6; 2 mM, n=5, and 2 were symptomatic). <h3>Conclusions</h3> Our observations show that about 1/3 of patients with CRMO may present difficult to treat acute attacks of bone pain. In these cases, pamidronate appears to be the best pain relieving treatment with a rapid time of response and with limited side effects. <h3>References</h3> Miettunen PM, Wei X, Kaura D, Reslan WA, Aguirre AN, Kellner JD. Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO). Ped Rheum J. 2009 Jan 12;7:2. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5698
1026 PROGRESSION RATE PROFILE AND RELATIONSHIP WITH SURVIVAL IN PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED WITH SORAFENIB BEYOND FIRST PROGRESSION
Authors: M. Reig, J. Rimola, A. Forner, A. Darnell, C. Rodriguez-Lope, N. Llarch, C. Ayuso, J. Bruix
Journal: Journal of Hepatology (2012)
Isolated Severe Right Atrial Dilatation Demonstrated on Planar TI-201 Myocardial Imaging
Authors: MITHILESH KUMAR, HUSSEIN M. ABDEL-DAYEM
Journal: Clinical Nuclear Medicine (1999)

Isolated enlargement of the right chambers of the heart is uncommon in adults. It usually occurs secondary to subacute bacterial endocarditis involving the tricuspid or pulmonic valves (or both) and often is seen in drug addicts. The authors present an uncommon case involving a patient with AIDS and tricuspid endocarditis associated with isolated severe right atrial dilatation. Planar adenosine stress TI-201 myocardial perfusion imaging showed a large photopenic defect in the lower right chest in the region of the right atrium. First-pass and gated blood pool studies showed right atrial enlargement. TI-201 myocardial imaging confirmed the severe dilatation of the right atrium, which appeared as a photopenic area. The study also revealed a prolonged pulmonary transit time of 12 seconds.
Markers of bone metabolism predict survival in hormone refractory prostate cancer (HRPC): Results from a randomized California Cancer Consortium &amp; University of Chicago trial
Authors: P. N. Lara, J. Longmate, W. Stadler, M. van Loan, J. Wexler, D. I. Quinn, P. Twardowski, E. E. Vokes, D. R. Gandara
Journal: Journal of Clinical Oncology (2005)

4569 Background: Bone metabolism is characterized by bone formation (osteoblasts) and resorption (osteoclasts). Bone mass is dependent on the balance of these activities. In metastatic PC, osteoblasts predominate, leading to sclerotic bone mets. Although biochemical markers of bone metabolism have been evaluated in metastatic PC, they have not been established as prognostic or predictive variables. As part of a randomized phase II trial of 2 doses of the matrix metalloproteinase inhibitor BMS-275291 (Arm A: 1200 vs. Arm B: 2400 mg) in HRPC patients (pts) with bone mets, markers of bone turnover were prospectively assessed and correlated with pt outcome. Methods: Markers of bone formation (osteocalcin [OCN], procollagen N-terminal propeptides: PINP & PIIINP) and resorption (N-telopeptide [NTX], pyridinoline [PYD], deoxypyridinoline [DPD]) in plasma were assayed using commercial enzyme immunoassays. Marker values were dichotomized at the median and correlated with overall (OS) and progression-free survival (PFS) by log-rank. Results: 80 pts were randomized. 4-month (mo) PFS favored Arm A (24% vs. 10%, p=0.009). OS was similar in both arms. 69 pts had evaluable baseline plasma specimens. Due to early progression, only 34 had serial plasma obtained. All markers reported are baseline values. NTX ≤ 14.4 nM had better OS [median survival (MS) not reached vs. 10.7 mos, p<0.0001] & 4-mo PFS (10% vs 22%, p=0.04). OCN > 0.89 ng/mL had better 4-mo PFS (12% vs 20%, p=0.01). PINP and PIIINP < the medians (86.5 & 5.6 ng/mL, respectively) had better OS (MS not reached vs. 12 mos; p<0.0001 and 0.005, respectively) and 4-mo PFS (9% vs. 22%, p=0.02 and p=0.01, respectively). DPD < 57 nmol/dL had better OS (MS not reached vs. 12 months, p=0.0002) and 4-mo PFS (9% vs 25%, p=0.04). Log of PIIINP & PINP predicted survival in a multivariate Cox model (p<0.00002 for the 2-variable model). Bisphosphonate use (23 pts) did not interact with assay results in predicting survival. Conclusion: Baseline levels of bone metabolism markers have prognostic value in HRPC pts with bone mets. Prospective validation in the phase III setting is planned. (NOI CM17101, CM17102; VANCHCS & ACS-CRTG to PNL). No significant financial relationships to disclose.
The Use of Diamox, a Carbonic Anhydrase Inhibitor, as an Oral Diuretic in Patients with Congestive Heart Failure
Authors: Charles K. Friedberg, Robert Taymor, James B. Minor, Mark Halpern
Journal: New England Journal of Medicine (1953)

IT would be highly desirable to obtain a diuretic agent that could be given orally and yet act as effectively as parenterally administered mercurial diuretics, without producing significant toxic mani-festations. The xanthine diuretics,1 , 2 chemically related uracil derivatives3 , 4 and other preparations of mercurials5 , 6 have been ineffective, inconstant in effect or associated with unpleasant side actions or toxicity. Recently, additional mercurial diuretics for oral administration have been tested in patients with heart failure.7 8 9 Another approach to the development of a satis-factory oral diuretic is based on the observation that inhibition of carbonic anhydrase activity in renal-tubule cells not only impairs the tubular . . .
Abstract 2235: Immunohistochemical analysis of RUNX2 in human colon cancer
Authors: Tomohiko Sase, Takashi Suzuki, Kou Miura, Yoshiaki Onodera, Ryuichirou Sato, Hideaki Karasawa, Akihiro Yamamura, Syunichi Kimura, Shinichi Egawa, Chikashi Shibata, Iwao Sasaki, Hironobu Sasano
Journal: Cancer Research (2010)

Abstract [Background] Runt-related transcription factor (RUNX) family comes to attract attention in a field of differentiation and carcinogenesis. However, the RUNX2 expression in human colon cancer has not been fully analyzed. Therefore, we immunohistochemically analyzed the RUNX2 expression in human colon cancer. [Method] Primary colon cancer specimens were obtained from 158 colon cancer patients. All patients had undergone operations at Tohoku University Hospital, from 1994 to 2000. The formalin-fixed paraffin-embedded tissue sections were used for immunohistochemical analysis. [Result] RUNX2 was detected exclusively in nuclear of cancer cells, and 66.5% of cancer tissues were positive for RUNX2 (105/158 cases). Statistical analysis demonstrated that positive RUNX2 status was significantly associated with poor survival (Log-lank test: P=0.0178). In addition, RUNX2-positve patients had higher incidence of lymph node and liver metastasis compared to RUNX2-negative patients (P=0.0147 and 0.0038, respectively) [Discussion] RUNX2 may therefore play an important role in metastatic ability of human colon cancer. 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 2235.
LEFT VENTRICULAR HYPERTROPHY IN ELITE ADOLESCENT ATHLETES: GEORGIAN EXPERIENCE OF PRE-PARTICIPATION SCREENING
Authors: L Maskhulia, V Akhalkatsi, K Chelidze, Z Kakhabrishvili, M Matiashvili, N Chabashvili, T Chutkerashvili
Journal: British Journal of Sports Medicine (2014)

Background Athlete's heart should be differentiated from the hypertrophic cardiomyopathy (HCM)-leading cause of exercise related sudden cardiac death in young athletes. Some genetic variations of HCM are characterized by a benign clinical course and a delayed onset of the disease. Therefore, substantial increase of left ventricular wall thickness (LVWT) in adolescent athletes needs relevant strategies in pre-participation screening (PPS). Objective To identify adolescent athletes with left ventricular hypertrophy (LVH) and differentiate physiological LVH from HCM. Design Observational follow-up study. Setting: Sports Medicine Clinical Centre. Participants 978 asymptomatic and normotensive highly trained (≥12 h/week) adolescent athletes (92.9% males) aged 12–18 years, representatives of national teams of 14 sporting disciplines. Interventions Cardiovascular evaluation with medical history, physical examination, 12-lead resting and stress electrocardiography, and echocardiography. LV structure and function were measured in 2002–2006. Main outcome measurements The participants were followed prospectively until 2008 with respect to LVH, and until 2012 with respect to HCM. Results 12 (1.2%) athletes, all males had LVWT ≥12 mm (12–15) and normal ECG pattern: 10 of them had normal diastolic indices and LV end diastolic diameter (LVEDD) 52.6±4.8mm (46–61); other 2 athletes had LVEDD&lt;45mm. One of them had normal diastolic function and peak oxygen uptake (VO2max) of 58.8 mL/kg/min. An other athlete (15 yrs) with LVWT 15 mm, LVEDD 43 mm, and decreased VO2max of 41.5 mL/kg/min,Tissue Doppler Imaging (TDI) revealed mildly reduced É-9cm/s and heightened E/É-8.8. Three months of detraining slightly decreased LVWT but did not improve LVEDD and TDI indices. The athlete was advised against competitive sports and referred for further cardiovascular evaluation. Follow-up over a longer period revealed advanced changes in LVWT and diastolic indices, and confirmed HCM. Conclusions Substantial LVH in Georgian elite adolescent athletes is rare. PPS with systematical approach can be a valuable tool in differentiation between physiological LVH and mild expression of HCM.
P5-13-21: Japanese Patients with Discordance in Estrogen Receptor between Primary Breast Cancer and Recurrent Tumor Have a Poorer Outcome.
Authors: K Tanaka, H Kawaguchi, S Kuba, C Koga, S Nishimura, T Yoshiyama, M Ishida, Y Nakamura, S Ohno
Journal: Cancer Research (2011)

Abstract Background Decisions of systemic treatment for recurrent breast cancer are usually based on the estrogen receptor (ER), progesterone receptor (PR), and HER2 receptor status of the primary tumor. Recently, discordance in receptor status between primary and recurrent tumors has been reported. The objective of this study was to compare receptor status between the primary and recurrent tumor, and to evaluate overall survival (OS) after the diagnosis of recurrence between patients with discordant and concordant receptor status. Material and Methods Patients with recurrent breast cancer treated at National Kyushu Cancer Center between January 2004 and May 2011 were reviewed retrospectively. Primary and recurrent lesions were analyzed for ER and PR by immunohistochemistry (IHC) and HER2 by IHC or fluorescence in situ hybridization (FISH). OS in discordant and concordant groups for each receptor was estimated by Kaplan-Meier method and compared by log-rank test. Results Among 283 recurrent breast cancer patients both primary and recurrent tumor information for ER, PR, and HER2 was available in 69. Among these, recurrent biopsy specimens were obtained from locoregional recurrence in 72.5% and from distant metastases in 27.5%. Discordant rate in receptor status between the primary and recurrent tumor was 36.2%. Discordant rate in ER, PR, and HER2 was 14.4%, 23.1%, and 4.3%, respectively. Two-year OS after the diagnosis of recurrence in discordant and concordant ER group was 66.7% and 84.7%, respectively. The discordant ER group had significantly worse OS than the concordant ER group (P = 0.040). There was no significant difference in OS between the discordant and concordant PR group (P = 0.950). Conclusions Because discordance of receptor status between primary and recurrent tumors may exist, tissue confirmation of receptor status of recurrent tumor should be considered. Japanese patients with discordant ER between primary and recurrent tumor had a poorer outcome. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-21.
Development of Neurologic Manifestations of Pernicious Anemia during Multivitamin Therapy
Authors: C. Lockard Conley, Julius R. Krevans
Journal: New England Journal of Medicine (1951)

IN SOME patients with pernicious anemia neurologic manifestations occur before significant anemia develops. Such cases have been uncommon in the past. At the Johns Hopkins Hospital in the five-year period prior to 1950, the diagnosis of pernicious anemia was established in 58 patients in whom the disease had not previously been recognized. In 8 of these patients blood values were essentially normal at the time the diagnosis was made. However, in 7 of these 8 cases anemia was known to have been present prior to admission, and there was a definite history of treatment with folic acid, liver extracts or . . .
Abstract 2446: Real-time molecular imaging of targeted therapies in patient-derived tumor cells by quantitative immunofluorescence microscopy
Authors: Stephen M. Rothenberg, Jennifer Wargo, Dejan Juric, Ryan B. Corcoran, Daniel Winokur, Keith T. Flaherty, Jose Baselga, Shyamala Maheswaran, Jeffrey A. Engelman, Daniel A. Haber
Journal: Cancer Research (2012)

Abstract Serial radiographic imaging is the primary means for determining the efficacy of cancer treatments. However, a long time interval is required before changes are appreciated, and the direct effects of therapy on tumor cells cannot be measured. We have utilized highly multiplexed, quantitative immunofluorescence microscopy to monitor multiple signaling proteins simultaneously in direct tumor biopsies and circulating tumor cells obtained serially from patients with BRAF- and PIK3CA-mutant solid cancers undergoing treatment with agents that target these mutated oncogenes. Changes in signaling that accurately predict subsequent clinical response can be determined from small numbers (∼100) of tumor cells and are apparent within days of the first dose of therapy, and weeks before radiographic determination of response. Preliminary results suggest that therapeutic efficacy (or lack thereof) is correlated with both the degree and rapidity of downregulation of tumor cell signaling. The ability to measure the effects of therapy directly in patient-derived tumor cells may permit real time information about efficacy (or lack thereof) to be rapidly incorporated into the decision to continue an ongoing therapy or to switch to a new one, or in the identification of patient populations most likely to respond to a novel class of agents. 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 2446. doi:1538-7445.AM2012-2446
CHARACTERISTICS AND SPECIFIC ECG FINDINGS IN 200 PATIENTS WITH STRESS-INDUCED “TAKOTSUBO” CARDIOMYOPATHY COMPARISON BETWEEN TYPICAL AND ATYPICAL FORMS
Authors: Slayman Nabih Obeid, Antonio H. Frangieh, Jelena R. Ghadri, Thomas F. Lüscher, Christian Templin
Journal: Journal of the American College of Cardiology (2015)
Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo
Authors: Suzanne Eldridge, Giovanna Nalesso, Habib Ismail, Karin Vicente-Greco, Panos Kabouridis, Manoj Ramachandran, Andreas Niemeier, Joachim Herz, Costantino Pitzalis, Mauro Perretti, Francesco Dell'Accio
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Osteoarthritis (OA) is a leading cause of disability for which there is no cure. The identification of molecules supporting cartilage homeostasis and regeneration is therefore a major pursuit in musculoskeletal medicine. Agrin is a heparan sulfate proteoglycan which, through binding to low-density lipoprotein receptor-related protein 4 (LRP4), is required for neuromuscular synapse formation. In other tissues, it connects the cytoskeleton to the basement membrane through binding to α-dystroglycan. Prompted by an unexpected expression pattern, we investigated the role and receptor usage of agrin in cartilage. Methods Agrin expression pattern was investigated in human osteoarthritic cartilage and following destabilisation of the medial meniscus in mice. Extracellular matrix (ECM) formation and chondrocyte differentiation was studied in gain and loss of function experiments in vitro in three-dimensional cultures and gain of function in vivo, using an ectopic cartilage formation assay in nude mice. Receptor usage was investigated by disrupting LRP4 and α-dystroglycan by siRNA and blocking antibodies respectively. Results Agrin was detected in normal cartilage but was progressively lost in OA. In vitro, agrin knockdown resulted in reduced glycosaminoglycan content, downregulation of the cartilage transcription factor SOX9 and other cartilage-specific ECM molecules. Conversely, exogenous agrin supported cartilage differentiation in vitro and ectopic cartilage formation in vivo. In the context of cartilage differentiation, agrin used an unusual receptor repertoire requiring both LRP4 and α-dystroglycan. Conclusions We have discovered that agrin strongly promotes chondrocyte differentiation and cartilage formation in vivo. Our results identify agrin as a novel potent anabolic growth factor with strong therapeutic potential in cartilage regeneration.