tbuckley/cabot-search huggingface dataset:
Abstract 368: Phage display derived antibodies for the detection of mesenchymal CTCs in TNBC
Authors: Stephen Kalscheuer, Jayanth Panyam
Journal: Cancer Research (2015)

Abstract Enumeration of circulating tumor cells (CTCs) in peripheral blood of patients allows clinicians to obtain immediate evidence of metastatic dissemination. CELLSEARCH® is the only method currently approved for CTC detection (1). The critical assumption of the CELLSEARCH® platform is that CTCs will express EpCAM, based on the fact that the cell of origin in carcinoma is epithelial. However, the key cellular event that gives rise to CTCs is epithelial-to-mesenchymal transition (EMT) and the acquisition of the mesenchymal phenotype within the primary tumor. Recent studies have demonstrated EMT marker gene expression in CTCs, especially during disease progression. (2, 3). Thus, the full complement of CTCs may not be effectively captured with existing CTC technologies that rely solely on epithelial marker expression. We have developed a competition based cell panning procedure which employs a commercially available single chain Fv (scFv) phage display library to identify antibodies with selective affinity to EMT phenotypic cells. HMLE cells as well as a sub-clone stably expressing Twist1 (HMLE-Twist1; a transcription factor known to induce EMT) were used for the panning. A two-color fluorescent scheme was employed to selectively sort the target cells from mixed populations containing the control cells, in the presence of phage library, via fluorescence activated cell sorting. Repeated iterations of this procedure yielded a scFv (‘clone 6′) with selective affinity to HMLE-Twist1cells. We then engineered a full length human IgG1 antibody in which the variable region sequences were derived from clone 6 scFv. The clone 6 IgG showed high affinity for metastatic cell lines (MDA-MB-231-LM2, LCC6, and HS578T). The antibody was also able to detect the presence of CTCs in an orthotopic MDA-MB-231-LM2 mouse tumor model. Intra-sample comparison showed distinct cell populations captured with anti-EpCAM antibody and Clone 6 IgG. Unlike those captured by anti-EpCAM antibody, the cells captured by Clone 6 were negative for EpCAM expression and were mesenchymal in phenotype. Future studies will examine the usefulness of clone 6 IgG in recognizing CTCs in patient samples. References 1. M. Cristofanilli et al., New Engl J Med 351, 781 (2004). 2. B. Aktas et al., Breast Cancer Res : BCR 11, R46 (2009). 3. G. Kallergi et al., Breast Cancer Research : BCR 13, R59 (2011). Citation Format: Stephen Kalscheuer, Jayanth Panyam. Phage display derived antibodies for the detection of mesenchymal CTCs in TNBC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 368. doi:10.1158/1538-7445.AM2015-368
Abstract 391: Feasibility and Image Quality of a New Sub-mSv Coronary CT Angiography Protocol Using Prospectively ECG-Triggered High-Pitch Spiral Acquisition
Authors: Stephan Achenbach, Mohamed Marwan, Tiziano Schepis, Dieter Ropers, Tobias Pflederer, Werner G Daniel, Axel Kuettner, Katharina Anders, Michael Uder, Michael Lell
Journal: Circulation (2009)

Introduction : Coronary CT angiography (CTA) provides clinically useful information in selected patients, but high radiation exposure has been a limitation. We evaluated the feasibility and image quality of a new scan mode, prospectively ECG-gated high-pitch spiral imaging, for coronary CTA with an effective dose below 1 mSv.   Methods:  60 consecutive patients referred for ruling out coronary stenoses were studied. Selection criteria were absence of previously known coronary disease, body weight ≤ 100 kg, and sinus rhythm    Results:  Out of 81 patients screened for inclusion, 21 were excluded: 11 because heart rate remained > 60/min even after beta blockade, and 10 for a body weight > 100 kg. In all 60 included patients, imaging was successfully performed. Mean heart rate before and during coronary CTA was 70±11 and 52±4 beats/min. Mean scan length was 117±9 mm, mean duration of data acquisition was 258±20 ms. Mean dose-length product was 62±5 mGy*cm, the resultant mean effective dose was 0.87±0.08 mSv (range: 0.78 – 0.99 mSv). Of 896 coronary artery segments, 847 (95%) had an image quality score of 1, 36 segments (4.6%) a score of 2, 8 segments (1.0%) a score of 3, and 4 segments (0.4%) were “uninterpretable”.   Conclusion:  In non-obese patients with a low and stable heart rate, coronary CTA using prospectively ECG-triggered high-pitch spiral acquisition can be performed with high image quality and a consistent radiation dose below 1.0 mSv.
News of Tropical Diseases
Authors: B BARBER
Journal: BMJ (1963)

Smith describe the pathology, clinical features, and response to treatment of primary lymphoma of the testis (p.891).Monocular Blindness: Serial photographs suggest that transient monocular blindness in a man with ipsilateral internal carotid artery thrombosis was due to platelet micro-emboli (p.894).Aspirin and the Stomach: Dr. D. N. Croft offers cytological and biochemical evidence that both soluble and pure calcium aspirin cause exfoliation of gastric epithelium (p.897).Lupus Erythematosus: Intradermal autogenous leucocyte test fails to differentiate systemic from discoid forms (p.901).Renal Cortical Necrosis: Recovery, but with residual diffuse renal calcification (p.903).Plasma Infusions: Montreal workers report on plasma changes and incidence of side-effects after plasma infusion.No reactions occurred after autologous infusions.Neither predniso- lone nor chlorpheniramine reduced reactions to non-autologous plasma (p.904).Tube Feeds: Design of tube feeds for surgical patients (p.909)." Ilosone ": Hepatic dysfunction reported after ilosone (erythromycin estolate) (p.913).Pre-mixed Gases: Separation of gases on cool- ing (p.915).Use in midwifery (p.886).Urethral Diverticulum with 101 stones (p.917).
Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis
Authors: P C Simmonds
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To determine the benefits and harms of palliative chemotherapy in patients with locally advanced or metastatic colorectal cancer and to compare the outcomes for elderly and younger patients. <b>Design:</b> Meta-analysis of individual patient data and published summary statistics from trials for which individual patient data could not be obtained from the investigators. <b>Studies:</b> All randomised controlled trials comparing palliative chemotherapy with supportive care in patients with advanced colorectal cancer that were identified by computerised and hand searches of the literature, scanning references, and contacting investigators. <b>Main outcome measures:</b> Survival, disease progression, quality of life, and toxicity. <b>Results:</b> 13 randomised controlled trials including a total of 1365 patients met the inclusion criteria. Meta-analysis of seven trials that provided individual patient data (866 patients) showed that palliative chemotherapy was associated with a 35% reduction in the risk of death (95% confidence interval 24% to 44%). This translates into an absolute improvement in survival of 16% at both six and 12 months and an improvement in median survival of 3.7 months. No age related differences were found in the effectiveness of chemotherapy, but elderly patients were under represented in trials. The overall quality of evidence relating to treatment toxicity, symptom control, and quality of life was poor. <b>Conclusions:</b> Chemotherapy is effective in prolonging time to disease progression and survival in patients with advanced colorectal cancer. The survival benefit may be underestimated in this analysis as some patients in the control arms received chemotherapy.
Toxicity associated with neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC).
Authors: M. S. Beg, O. O. Olowokure, S. Ali, S. A. Ahmad
Journal: Journal of Clinical Oncology (2010)

e14670 Background: Patients with BRPC are offered neoadjuvant therapy in an attempt to improve margin negative (R0) resection rates. We reviewed our experience with BRPC in an effort to identify the toxicity profile for this subset of patients. Methods: We performed a retrospective review of BRPC cases over a 5-year period. Individual charts were reviewed for baseline characteristics, reason for borderline resectability, treatment given and significant toxicity i.e grade II or more (CTCAE Version 3). Results: Twenty-eight cases met the selection criteria for our study and toxicity details were available for 20 cases. Most common cause for borderline resectability was >180 ° encasement of superior mesenteric (SM) vein/portal vein in 15 cases and <180° involvement of SM artery in 5 cases. Chemoradiation (CRT) was administered in 11 cases. Significant toxicity occurred in 15/20 cases (75%), most common being anemia (45%), neutropenia (35%), thrombocytopenia (30%). Admission to the hospital was required by 5 (25%) patients, there were no grade IV toxicities and no deaths. Patients undergoing chemotherapy alone (CT) had an increased incidence of toxicity compared to CRT. Of those undergoing surgery (n=12), 10 patients received CT alone and 2 received CRT. R0 resection was achieved in 8 patients and 9 proceeded to receive adjuvant therapy. Conclusions: A subset of patients with BRPC can be successfully downstaged with neoadjuvant therapy. Although therapy is associated with significant grade II-III toxicity in most patients, a majority of patients are able to complete therapy. In our experience CT, which was associated with greater toxicity, was more likely to be associated with surgical downstaging compared to CRT. Toxicity n=20 (%) No toxicity 1 2 3 4 Neutropenia 10 (50) 3 (15) 3 (15) 4 (20) 0 Anemia 9 (45) 2 (10) 9 (45) 0 0 Thrombocytopenia 11 (55) 3 (15) 1 (5) 5 (25) 0 LFT abnormalities 19 (95) 0 0 1 (5) 0 Nausea/vomiting 12 (75) 4 (20) 2 (10) 2 (10) 0 Diarrhea 18 (90) 1 (5) 1 (5) 0 0 Renal failure 18 (90) 2 (10) 0 0 0 Rash 14 (70) 3 (15) 2 (10) 1 (5) 0 Fatigue 14 (70) 3 (15) 2 (10) 1 (5) 0 No significant financial relationships to disclose.
The association between sterilizing activity and drug distribution into tuberculosis lesions
Authors: Brendan Prideaux, Laura E Via, Matthew D Zimmerman, Seokyong Eum, Jansy Sarathy, Paul O'Brien, Chao Chen, Firat Kaya, Danielle M Weiner, Pei-Yu Chen, Taeksun Song, Myungsun Lee, Tae Sun Shim, Jeong Su Cho, Wooshik Kim, Sang Nae Cho, Kenneth N Olivier, Clifton E Barry, Véronique Dartois
Journal: Nature Medicine (2015)
Abstract #4420: PLX4032, a selective B-RafV600E inhibitor demonstrates potent antitumor activity in preclinical melanoma models
Authors: Fei Su, Hong Yang, Brian Higgins, Kenneth Kolinsky, Richard Lee, Kathryn Packman, Kathleen Schostack, David Heimbrook, Gideon Bollag
Journal: Cancer Research (2009)

The Ras-Raf-MEK-ERK signaling pathway plays a critical role in many aspects of human tumorigenesis. B-Raf mutations have been found in over 7% of all human cancers (melanoma 50-70%, papillary thyroid 35-70%, ovarian 35% and colorectal 12-30%). The majority of the B-Raf mutations involve a single amino acid substitution, V600E, resulting in constitutive activation of the MEK-ERK signaling pathway. PLX4032 is a first-in-class small molecule, selective B-Raf V600E   small molecule inhibitor. We report here that PLX4032 specifically inhibits melanoma cell proliferation and MEK phosphorylation only in melanoma cell lines bearing B-Raf V600E  but not in cells harboring wild type B-Raf or non-V600E B-Raf mutations. The ability to inhibit MEK and ERK phosphorylation by PLX4032 correlates with inhibition of cellular proliferation in melanoma cell lines. In nude mice implanted with human melanoma xenografts bearing B-Raf V600E , complete tumor regression was observed with PLX4032 monotherapy, and antitumor and survival effects are significantly better than temozolomide monotherapy. When PLX4032 was combined with temozolomide, DTIC and 17-AAG  in vitro , either synergistic or additive effects were observed in melanoma cell lines. However, in vivo combination of PLX4032 and temozolomide did not increase either antitumor activity or survival over that provided by monotherapy of PLX4032.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4420.
Abstract P291: Similar Over-Reporting of Physical Activity among African Immigrant Men and Women: The Africans in America Study
Authors: Paola Aldana, Caroline Thoreson, Michelle Duong, Madia Ricks, Amber Courville, Lilian Mabundo, Anne Sumner, Stephanie Chung
Journal: Circulation (2015)

Levels of physical activity (PA), an important risk factor for cardiometabolic disease, may decline in Africans after immigration and it is unknown whether PA type differs by sex. To determine PA profile and perceived activity in African immigrants, we examined PA type and intensity using the self-report Multi-Ethnic Study of Atherosclerosis (MESA) Typical Week Physical Activity Survey (TWPAS). Physical activity levels were defined as time spent in total and moderate-vigorous PA in 80 African immigrants living in the DC metro area, who self-identified as healthy (66% male; age 39.1±9.4y (mean±SD), range 22-58y; BMI 28.2±4.4 kg/m 2 , range 19.7-41.2). Total and moderate-vigorous PA were 1952.1±1759.6 and 717.6±840.3 min•wk -1 , respectively and did not vary by sex, P=0.9 (Fig 1). Men and women reported spending equal amounts of time in each moderate-vigorous PA category (household, occupational, childcare, intentional and volunteer, P=0.7). Ninety-five percent of Africans reported meeting moderate-vigorous PA guidelines &gt; 150 min•wk -1 (Fig 1A). However, 10% of Africans reported more total PA than there are minutes in a week (Fig 1B) and 1/3 reported excessive weekly moderate-vigorous PA (total &gt;5hr•dy -1 and intentional &gt; 2 hr•dy -1 ). In the 26 Africans with &gt;5 hr•dy -1 of total moderate-vigorous PA, those with an annual income of ≥$30,000 reported greater levels of moderate-vigorous PA than those with an income &lt;$30,000, 4866.8±1646.3 vs. 3558.7±769.9, respectively (P=0.01). Moderate-vigorous PA levels did not vary in this group by African birth region, education, years in the US or percent weight gain since immigration (P&gt;0.3). Self-reported PA profiles were similar among African immigrant men and women, but were over-reported by at least 10% of respondents. Over-reporting may be more common in Africans of higher socioeconomic status. The MESA TWPAS questionnaire provides insight into PA profiles in African immigrants, but is suboptimal for quantitative examination of PA levels.
Abstract 1409: Molecular Imaging of Post-Infarction Cardiac Remodeling and Effects of Anti-Angiotensin Therapy
Authors: Susanne W Van Den Borne, Satoshi Isobe, Johan Verjans, Artiom Petrov, Dagfinn Lovhaug, Peng Li, Matthijs Blankesteijn, Mat Daemen, Bertram Pitt, Leonard Hofstra, Jagat Narula
Journal: Circulation (2007)

Background. Collagen deposition and interstitial fibrosis contribute to development of cardiac remodeling and heart failure (HF) after myocardial infarction (MI). We used Tc-99m-labeled Cy5.5-RGD imaging peptide (CRIP), for molecular imaging of the extent of collagen deposition. Methods. Of 46 Swiss-Webster mice, (MI) was induced in 41 by left coronary artery occlusion and 5 mice were imaged unmanipulated. Of these, 6, 6, and 5 mice, received intravenous CRIP for micro-SPECT/micro-CT imaging in vivo after 2, 4, and 12 weeks of MI. Eight mice received captopril or captopril with losartan for 4 weeks following MI before CRIP imaging for the assessment of effect of anti-angiotensin therapy on collagen deposition. To evaluate the specificity of the probe, 6 animals received scrambled peptide 4 weeks after MI. The remaining 10/46 mice, received CRIP without a radiolabel after 2 weeks of MI for histological characterization of tracer uptake by two-photon microscopy. Results. Distinct myocardial CRIP uptake was observed in the infarct area and border zone. The quantitative uptake in the infarct area, expressed as percent injected dose per gram (%ID/g), was highest in mice at 2 weeks (2.75±0.46%), followed by 4 (2.26±0.09%), and 12 weeks (1.74±0.24%) after MI as compared to uptake in sham-operated mice (0.59±0.19%). In the peri-infarct and remote areas, the uptake was higher at 12 weeks. The histologic characterization revealed specificity of the probe for replacement, interstitial and perivascular fibrosis. Captopril (1.78±0.31%) and combination of captopril and losartan (1.13±0.28%) significantly decreased radiotracer uptake in the infarct. The uptake of scrambled peptide (0.74 ±0.17%) was similar to CRIP uptake in normal myocardium. Conclusions. Radiolabeled CRIP allows for noninvasive visualization of interstitial alterations during cardiac remodeling. The CRIP uptake is significantly reduced with captopril and losartan treatment. If proven clinically feasible, such a strategy would help identify and prevent evolution of heart failure in post-MI patients.
Endogenous Candida Endophthalmitis
Authors: Roy D. Brod, Harry W. Flynn, John G. Clarkson, Stephen C. Pflugfelder, William W. Culbertson, Darlene Miller
Journal: Ophthalmology (1990)

Eight consecutive cases of culture-proven endogenous Candida endophthalmitis (ECE) were managed between 1980 and 1988. All patients were treated with vitrectomy and injection of intravitreal amphotericin B. Blood cultures were negative in all patients, although Candida albicans was cultured from a foot ulcer in one patient. No systemic therapy was used in three patients, three patients received oral ketoconazole, and two patients received oral flucytosine postoperatively. Intravenous amphotericin B was not used because of lack of evidence of disseminated candidiasis and the systemic toxicity associated with its use. The ECE responded favorably to treatment in all cases. Final vision was better in patients with a shorter interval between onset of symptoms and initiation of antifungal therapy. Posttreatment visual acuities were: four eyes ≥ 20/50, two eyes at 20/80 to 20/200, and two eyes < 5/200. This series showed that ECE without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B.
The British Society of Gastroenterology
Authors: J J Bernier, M Seligmann, R Worms, J P Ferrier, J C Rambaud
Journal: Gut (1969)

crinology Research Unit, Edinburgh) The requirements for a radioimmunoassay for a protein or polypeptide hormone are threefold: (1) a specific antiserum with a high energy of reaction; (2) a radioactive preparation of the hormone; and (3) a method for the separation of antibody-bound radioactive hormone from free radio- active hormone.Crude hog gastrin prepared by the method of Gregory and Tracyl was used for immunizing and antibodies were raised in New Zealand white rabbits using complete Freund's adjuvant.A radioiodinated preparation of pure gastrin with a specific activity of about 100 1Ac/jug (200 mC/,ug) was prepared using the chloramine-T method of Hunter and Greenwood.2The separation of antibodybound gastrin from free gastrin was performed using cellulose acetate electrophoresis.Cross-reaction studies have been performed using synthetic human gastrin and pure hog gastrin, human and hog antral extracts and plasmas, and preparations of secretin and pancreozymin/cholecystokinin.The sensitivity of this assay is 2 ng per ml using pure solutions.It is hoped that in the future it will be possible to make the assay sufficiently sensitive to assay gastrin-like activity in the body fluid of human subjects.
Knockdown of farnesyltransferase (FTase) beta subunit expression inhibits FTase activity and tumor growth in nude mice
Authors: James Hawker, Said M. Sebti
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3799 

Direct evidence that inhibition of the enzyme activity of the housekeeping protein FTase results in suppression of human tumor growth is lacking. To this end, we designed a specific siRNA directed against the beta subunit of the alpha/beta FTase heterodimer and shown that the siRNA represses expression of the FTase beta gene and inhibits the enzymatic activity of FTase but not of the closely related family member geranylgeranyltransferase I. Prenylation of target substrates such as Ras was also decreased by FTβ specific siRNA. FTβ knockdown resulted in morphological reversion of H-Ras transforrmed cells and decreased cell viability. In addition, FTβ siRNA, but not control siRNAs, decreased cell proliferation and increased cell death. FTβ specific siRNA reduced MAPK but not Akt activation. Finally, we observed that tumor growth in a mouse xenograft model of human lung A-549 tumors was impaired by in vivo injection of siRNA specific to FTβ, but not control siRNA. Our findings show that inhibition of FTase expression in human cancer cells impairs tumor growth in vivo.
Treatment of sex offenders with medroxyprogesterone acetate
Authors: P Gagné
Journal: American Journal of Psychiatry (1981)

Forty-eight male patients with long-standing histories of deviant sexual behavior received medroxyprogesterone acetate and milieu therapy for up to 12 months. Forty subjects responded positively, all within 3 weeks, with diminished frequency of sexual fantasies and arousal, decreased desire for deviant sexual behavior, increased control over sexual urges, and improvement in psychosocial functioning. Improvement in deviant sexual behavior and psychosocial functioning was maintained after treatment ended, and there was no evidence of permanent physiological changes. The author suggests that medroxyprogesterone acetate associated with counseling may be the treatment of choice for patients with long-term deviant sexual behavior. He discusses the ethical issues involved.
Surveillance of tularaemia in Kosovo*, 2001 to 2010
Authors: R Grunow, A Kalaveshi, A Kühn, G Mulliqi-Osmani, N Ramadani
Journal: Eurosurveillance (2012)

* This designation is without prejudice to positions on status, and is in line with UNSCR 1244/99 and the ICJ Opinion on the Kosovo declaration of independence.
Similar Levels of Complement Activation in Both Patients with Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome: The Report from the Korean TTP Registry
Authors: Doyeun Oh, Ji Young Huh, So Young Chong, In-Ho Kim, Soo-Mee Bang, Chul-Won Jung, Jong-Wook Lee, Hong Ghi Lee, Sun Min Lee, Yeo-Kyeoung Kim, Yong Park, Seongsoo Jang, Jin-Seok Kim, Deog-Yeon Jo, Dae Young Zang, Hwi-Joong Yoon, Ho-Young Yhim, Sang Kyun Sohn, Junshik Hong, Won-Sik Lee, Ross I Baker
Journal: Blood (2014)
Abstract 15462: Ideal Cardiovascular Health and Cardiovascular and Stroke Risk in Whites, Blacks and Hispanics: the Northern Manhattan Study
Authors: Chuanhui Dong, Tatjana Rundek, Clinton B Wright, Mitchell S Elkind, Sandino Cespedes, Ralph L Sacco
Journal: Circulation (2011)

Background and Objective: To improve the cardiovascular health of all Americans by 20% by 2020, the AHA defined the metrics of ideal, intermediate and poor cardiovascular health for 7 health factor...