tbuckley/cabot-search huggingface dataset:
Abstract 554: Detection and separation of live circulating tumor cells using lipid dye
Authors: Ranjana Mitra, Oscar Goodman Jr, Thuc Timothy Le
Journal: Cancer Research (2015)

Abstract Purpose: Separation of live circulating tumor cells (CTC) for culturing and monitoring treatment response is highly desirable. We have shown previously that CTC could be distinguished from peripheral blood mononuclear cells (PBMC) based on the intracellular lipid content. This study utilizes intracellular lipid as a biomarker to separate live CTC from PBMC for culturing and assessing treatment response. Methods: We used Bodipy dye, a fluorescent fatty acid analog that undergoes native transport and metabolism in living cells, to label lipid-rich CTC. LNCaP cells incubated with 50% plasma for 16 hours were used as mock CTC. Test samples contained PBMC (106 cells) spiked with mock CTC (500 cells), which were stained with Bodipy and antibodies against CD45, a biomarker for leukocytes (PBMC). Bodipy+/CD45- CTC were detected and then sorted using a flow cytometer. The sorted Bodipy+/CD45- cells were evaluated for cell viability and their suitability for culturing with trypan blue staining. Results: The Bodipy/CD45 staining permitted detection and sorting of 375 mock CTC from total 500 spiked LNCAPs (75% efficiency). These cells remained live as confirmed by trypan blue staining indicating suitability for culturing. All sorted cells were further confirmed to be epithelial LNCaP cells with pan-cytokeratin (CK) staining, a biomarker for epithelial cells. The recovery efficiency for live CTC sorting using Bodipy/CD45 staining is comparable with existing methods for isolation of fixed (non-live) CTC using CK/CD45 staining (85%). Conclusion: Bodipy-positive stain together with CD45 negative stain provided an inexpensive and reliable means to isolate live CTC. Citation Format: Ranjana Mitra, Oscar Goodman Jr, Thuc Timothy Le. Detection and separation of live circulating tumor cells using lipid dye. [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 554. doi:10.1158/1538-7445.AM2015-554
Big Renin and Biosynthetic Defect of Aldosterone in Diabetes Mellitus
Authors: Alberto deLeiva, A. Richard Christlieb, James C. Melby, Charles A. Graham, R.P. Day, John A. Luetscher, P.G. Zager
Journal: New England Journal of Medicine (1976)

To determine the cause of selective aldosterone deficiency in two patients with diabetes mellitus, studies of renin and of aldosterone-precursor metabolites were performed under conditions of sodium depletion and ACTH stimulation. Plasma renin concentration was elevated in both patients, and stimulated plasma renin activity was low in one and normal in the other. Fractionation of plasma extracts demonstrated the presence of "big renin," a relatively inactive precursor of renin. Metabolites of aldosterone precursors were increased, suggesting deficient 18-hydroxylase in one patient and dehydrogenase in the other. The results suggest that hypoaldosteronism in diabetic patients may result from combined defects in both renin and aldosterone biosynthesis. (N Engl J Med 295:639–643, 1976)
Initial Chemotherapeutic Doses and Long-Term Survival in Limited Small-Cell Lung Cancer
Authors: Rodrigo Arriagada, Jean-Pierre Pignon, Thierry Le Chevalier
Journal: New England Journal of Medicine (2001)

To the Editor: We previously reported that in a multicenter, randomized trial that involved 105 patients with limited small-cell lung cancer, higher initial doses of cyclophosphamide and cisplatin improved overall survival.1 The study was stopped early at the recommendation of an independent data-monitoring committee, and the median duration of follow-up at the time of publication was 33 months.2 To evaluate whether these findings persisted over the long term, we reevaluated the patients after a median follow-up period of 11 years. The updated overall survival rates for patients who received higher initial doses of cisplatin (100 mg per square meter of . . .
Evaluation of the prostate-specific antigen/solvent interaction analysis (PSA/SIA) assay for prostate cancer (CaP) diagnosis
Authors: S. Vourganti, M. Stovsky, L. Ponsky, M. Siroky, V. Kipnis, O. Fedotoff, L. Mikheeva, B. Zaslavsky, A. Chait, J. S. Jones
Journal: Journal of Clinical Oncology (2009)

5053 Background: We describe the clinical performance of a novel protein structural assay for prostate cancer (CaP) diagnosis. The assay uses Solvent Interaction Analysis (SIA) to accurately detect changes in PSA isoform composition that differentiate benign and malignant disease, independent of total serum PSA (tPSA). Methods: From January 2007 to September 2008, men already undergoing biopsy for accepted clinical criteria at 3 sites [University Hospitals Case Medical Center (Cleveland); Cleveland Clinic (Cleveland); and Veterans Administration Hospital (Boston)] were enrolled in an IRB approved study. Prior to standard transrectal ultrasound (TRUS) guided biopsy, patients received a digital rectal examination with systematic prostate massage followed by collection of voided urine for use in PSA/SIA. The assay determined the relative distribution of the entire heterogeneous PSA isoform population between two coexisting aqueous phases for diagnostic purposes. Results: 222 men were enrolled in the trial. Biopsy results were classified as case (malignant, n = 100) or control (benign, n = 122). Receiver operating characteristic performance results demonstrated AUC of = 0.88 for PSA/SIA and 0.58 for tPSA. At a cut-off value of the composite structural index K = 1.73, PSA/SIA displayed sensitivity = 100%, specificity = 80%, PPV = 83%, and NPV = 100%. For the same patients at tPSA cut-off level of 4 ng/ml, the sensitivity = 82%, specificity = 27%, PPV = 54%, and NPV = 87%. Conclusions: PSA/SIA uniquely exploits the inherent structural heterogeneity in PSA resulting in superior diagnostic performance over conventional biopsy selection criteria. We hypothesize that the high specificity of PSA/SIA is actually underestimated by standard prostate biopsy sampling error. Future trials will assess the utility of the assay in the surveillance of CaP patients after definitive local therapy and other applications in the diagnosis and management of CaP. [Table: see text]
Construction and Molecular Characterization Of a T-Cell Receptor-Like Antibody and CAR-T Cells Specific For Minor Histocompatibility Antigen HA-1H
Authors: Yoko Inaguma, Yasushi Akahori, Yoshiki Akatsuka, Yuko Murayama, Keiko Shiraishi, Sachiko Tsuzuki-Iba, Akemi Endoh, Juri Tsujikawa, Ayako Demachi-Okamura, Kaho Hiramatsu, Hiroh Saji, Yukiya Yamamoto, Naoki Yamamoto, Nishimura Yasuharu, Toshitada Takahashi, Kiyotaka Kuzushima, Nobuhiko Emi
Journal: Blood (2013)
HIV-Associated Nephropathy
Authors: S Y Tan, P J O'Donnell
Journal: New England Journal of Medicine (1997)

Figure 1. A previously healthy bisexual man presented with the nephrotic syndrome and acute renal failure. The serum creatinine concentration was 7.8 mg per deciliter (693 μmol per liter), the albumin concentration was 15 g per liter, and the 24-hour urinary protein excretion was 12.4 g. Renal ultrasonography demonstrated normal-sized but extremely echogenic kidneys (Panel A), as has been reported in nephropathy associated with human immunodeficiency virus (HIV) infection. The liver is normally more echogenic than the kidney, as illustrated in the ultrasonogram from a healthy subject (Panel B). This ratio was strikingly reversed in our patient (Panel A). The . . .
Anti-TNFα agents curb platelet activation in patients with rheumatoid arthritis
Authors: Angelo A Manfredi, Mattia Baldini, Marina Camera, Elena Baldissera, Marta Brambilla, Giuseppe Peretti, Attilio Maseri, Patrizia Rovere-Querini, Elena Tremoli, Maria Grazia Sabbadini, Norma Maugeri
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Cardiovascular disease is important in rheumatoid arthritis (RA). Tissue factor (TF) is expressed upon platelet activation and initiates coagulation. Anti-tumour necrosis factor-α (TNFα) agents seem to decrease RA-associated cardiovascular events. We investigated whether (1) TNFα activates human platelets and (2) TNFα pharmacological blockade modulates the platelet-leucocyte reciprocal activation in RA. <h3>Design</h3> The expression of platelet TNFα receptors has been assessed by flow cytometry and immunogold electron microscopy. Platelet and leucocyte activation has been assessed also in the presence of antibodies against the TNFα receptors 1 and 2 and of infliximab. TF expression, binding to fibrinogen and phosphatidylserine exposure, has been assessed by flow cytometry, TF activity by coagulation time and by endogenous thrombin generation. Markers of platelet and leucocyte activation have been assessed in 161 subjects: 42 patients with RA, 12 with osteoarthritis, 37 age-matched and sex-matched patients with chronic stable angina and 70 age-matched and sex-matched healthy subjects. <h3>Results</h3> TNFα elicited the platelet activation and the expression of TF, which in turn prompted thrombin generation and clot formation. Inhibition of the TNFα-induced activation restricted platelet ability to activate leucocytes and to induce leucocyte TF. TNFα inhibition did not influence platelet activation induced by collagen, ADP or thrombin receptor activating peptide-6. Platelets of patients with RA were more activated than those of controls. Activation was reduced in patients treated with TNFα inhibitors. <h3>Conclusions</h3> TNFα-dependent pathways control platelet activation and TF expression in RA. Further studies will verify whether the protective effect of TNFα inhibitors on cardiovascular events involves their ability to modulate platelet function.
Analysis of five-year survival rate in patients with proximal femoral tumours after total hip replacement
Authors: S. A. Saravanan, V. Sokolovski, V. Voloshin, M. Aliev, V. Zybikov, D. Nisichenko
Journal: Journal of Clinical Oncology (2006)

19508 Background: To analyse the five-year survival rate in patients with proximal femoral tumours after total hip replacement. Methods: Between the period of 1994–2003, 50 patients were operated (Total Hip Replacement) for proximal femoral tumours at the Department of General Oncology (Bone &amp; Soft tissue tuomurs), N. N. Blokhin Cancer Research Institute &amp; Moscow Regional Clinical Research Institute, Moscow, Russian Federation. The histological diagnoses included 14 - metastases, 10 - osteosarcoma, 8 - chondrosarcoma, 4 - Ewing’s sarcoma, 4 - Giant cell tumor, 3 - malignant fibrous histiocytoma, 2 paraosteal and 2 periosteal osteosarcoma, and 1 each from primary neuroectodermal tumor, myeloid disease, and aneurysmal bone cyst. The follow-up ranged from 1–9 years (mean follow-up 5 years). 21 patients (45.7%) had pathological fracture. The cause of the pathological fracture was metastasis in 12 patients (26%). 28 patients (60.8%), had soft tissue invasion. All the survival analyses were done using Kaplan-Meier survivorship analysis method. Functional outcome was estimated using Enneking’s evaluation criteria. Results: The overall survival rate of patients was 66.7% at 5 years. 2 patients had local recurrence.12 patients had metastases after surgery. In that 11 patients were died. There was no evidence of disease in 32 patients. In 3 patients, we performed disarticulation of the hip joint because of the local recurrence. The overall survival rate of limb was 92.7% at 5 years. The overall survival rate of prostheses was 84.2% at 5 years. At the latest follow up, functional outcome was excellent in 15 (30%) patients, good in 27 (54%) patients, fair in 5 (10%) patients, poor in 3 (6%) patients. Conclusions: Though the extent of the muscle and bone resection is large, there is no doubt that endoprosthetic replacement of the proximal femur provides a good functional and oncological outcome when compared with the various other reconstructive surgeries. No significant financial relationships to disclose.
The Usefulness of Chest Radiographs in First Asthma Attacks
Authors: Jeffrey C. Gershel, Harold S. Goldman, Ruth E. K. Stein, Steven P. Shelov, Micha Ziprkowski
Journal: New England Journal of Medicine (1983)

To assess the value of routine chest radiography during acute first attacks of asthma, we studied 371 consecutive children over one year of age who presented with an initial episode of wheezing. Three hundred fifty children (94.3 per cent) had radiographic findings that were compatible with uncomplicated asthma and were considered negative. Twenty-one (5.7 per cent) had positive findings: atelectasis and pneumonia were noted in seven, segmental atelectasis in six, pneumonia in five, multiple areas of subsegmental atelectasis in two, and pneumomediastinum in one. The patients with positive films were more likely to have a respiratory rate above 60 or a pulse rate above 160 (P less than 0.001), localized rales or localized decreased breath sounds before treatment (P less than 0.01), and localized rales (P less than 0.005) and localized wheezing (P less than 0.02) after treatment; also, these patients were admitted to the hospital more often (P less than 0.001). Ninety-five per cent (20 of 21) of the children with positive films could be identified before treatment on the basis of a combination of tachypnea, tachycardia, fever, and localized rales or localized decreased breath sounds. Most first-time wheezers will not have positive radiographs; careful clinical evaluation should reveal which patients will have abnormal radiographs and will therefore benefit from the procedure.
Measuring the value of quality of life in cancer: An index based on EORTC QLQC-30
Authors: P. Kind
Journal: Journal of Clinical Oncology (2005)

6013 Background: EORTC QLQC-30 is a generic measure of health-related quality of life (HrQoL) in cancer. Version #3 consists of 28 items with a 4-category response and 2 further general items coded on a 7-point response category scale. Responses are converted into corresponding numeric scores that are summed to produce a total score. However, QLQC-30 cannot be used in cost-effectiveness analysis because it is not standardized on a value scale where full health = 1 and dead = 0. This paper reports on a method for converting QLQC-30 into a weighted index that overcomes this limitation Methods: Baseline observations from a previously reported study of 177 patients with pancreatic cancer were available for analysis. HrQoL was assessed using both the QLQ-C30 and EQ-5D, a generic measure based on 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) that defines 245 health states which can be converted into an index score (EQ-5Dindex) on a scale where dead = 0 and full health = 1. This index was previously calibrated in a national study of the UK population using Time Trade-Off procedures (n=3,395). Results: 28 QLQC-30 items were recoded as dichotomous values and analysed using an OLS regression model with EQ-5Dindex as the dependent variable. 5 items (short walk, sleeping, physical impact on family life, washing/dressing, concentration) and 1 general item (overall health) formed the best fit with an r2 of 0.490. Mean absolute error was less than 0.01. Correlation between observed EQ-5Dindex and estimated values was high. The index based on these items differentiated between patients classified by the Karnofsky Performance Scale. Conclusions: QLQC-30 items can be used to construct a weighted index that represents HrQoL on a 0–1 scale that has legitimacy for use in economic analysis. This index may also have independent status as a measure of health outcomes in cancer. No significant financial relationships to disclose.
Case 34-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Marc B. Garnick, Frederick C. Koerner
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 32-year-old man was admitted to the hospital because of a question of metastatic testicular cancer.He was well until four months earlier, when he noticed slight pain and swelling of the left testis, accompanied by a nonproductive cough and exertional dyspnea. Three months before admission an x-ray film of the chest (Fig. 1), obtained elsewhere, revealed a diffuse fibronodular pattern in both lungs. Pulmonary-function studies showed mild to moderate restrictive and obstructive defects. A diagnosis of interstitial lung disease was made. One month later there was an increase in long-standing low-back pain.One month before admission . . .
The mid-arm muscle circumference measurement and the prognosis of stage IV non-small cell lung cancer patients.
Authors: R. F. Tartari, C. Abreu Nunes, J. Moreira, F. Bortolon, D. L. Da Silva, A. Armando, O. C. Junior, A. F. Ferreira Filho
Journal: Journal of Clinical Oncology (2010)

e18058 Background: Patients with stage IV non-small cell lung cancer (NSCLC) comprise a very heterogenous population in relation to overall survival (OS). Strong prognostic factors are still needed to improve decisions regarding standard treatment options, to stratify patients for inclusion in innovative therapeutic trials and to identify patients best served by palliative care without systemic chemotherapy. The mid-arm muscle circunference (MAMC) is a bedside anthropometric measurement that estimates somatic protein reserve which is an early indicator of nutritional depletion. The measurement of MAMC is simple, non-invasive, objective, and inexpensive. We evaluated MAMC as a potential prognostic factor in patients with stage IV NSCLC. Methods: A prospective OS analysis of 56 (29 women) non-selected consecutive patients (Karnofsky status range 30-90) with stage IV NSCLC who had their MAMC measured as part of the nutritional evaluation. The MAMC results were expressed as a percentage of the expected reference values, adjusted for sex and age. Patients were categorized as normal (MAMC > = 90%) or depleted (MAMC < 90%). The study was approved by the Ethics Comitte and all patients signed the informed consent form. Results: The mean age of patients was 63 years (range 47-80) and mean MAMC was 89 (range 66–122), with 55% of patients (31) classified as depleted. Median OS of all patients was 6.2 months (95%CI: 5.1–7.3). In the subgroup with normal MAMC, median OS was 10.2 months (95% CI: 9.2–11.1). In patients classified as depleted, the median OS was 5.0 months (95%CI: 4.2–5.8). The OS difference between these two subgroups was highly statistically significant (p < 0.001 by the logrank test, HR = 0.21, 95%CI: 0.09–0.5 for patients with normal MAMC). In a multivariated analysis with the Karnofsky status, age and sex as covariates, the OS difference between MAMC groups remained statistically significant (p < 0.001 by the Cox proportional hazards method). Conclusions: MAMC is a strong independent prognostic factor in stage IV NSCLC patients. In our series, patients with MAMC < 90% of the expected value had poor overall survival. No significant financial relationships to disclose.
PTU-129 Do gastrointestinal cancer patients want to decide where they have tests and surgery? a questionnaire study of provider choice and information needs
Authors: BE Byrne, OD Faiz, A Darzi, CA Vincent
Journal: Gut (2015)

<h3>Introduction</h3> Choice of provider has been an important strategy among policy makers over recent years, intended, in part, to drive improvements in quality and efficiency of health care. Provider choice has been relatively under-studied among patients with cancer, compared with benign disease. This study examines decision-making experiences, preferences and information needs among patients who have had surgery for gastrointestinal cancer. <h3>Method</h3> This questionnaire study used the single-item Control Preferences Scale to determine patients’ experiences and preferences when being referred for tests, and choosing where to have surgery. Participants used a Likert scale to rate the importance of 23 information items covering a variety of structures, process and outcomes at hospital- and department-level. Participants were recruited by post and online. <h3>Results</h3> 463 responses were included. Where indicated, 334 of 415 (80.5%) respondents had upper gastrointestinal cancer. Postal response rates were higher than online (47.2% vs 23.1%,<i>p &lt; 0</i>.001). Patients reported very low levels of involvement in provider choice, with their doctor deciding where they underwent tests or surgery in 77.0% and 81.8% of cases, respectively. Over two-thirds of participants would have preferred greater involvement in provider choice. Information on how long cancer patients wait for treatment, annual operative volume and postoperative mortality rate, as well as retained foreign bodies and infection rates were considered very important. <h3>Conclusion</h3> There is a substantial unmet desire for greater involvement in provider choice among gastrointestinal cancer patients. Participants in this study attached particular importance to surgery-specific information. Improving involvement and information provision will require a coordinated approach in both primary and secondary care. Greater involvement in decision-making may increase satisfaction and contribute to a greater sense of control among these patients. <h3>Disclosure of interest</h3> None Declared.
Pharmacodynamic properties of the anti-IGF-IR monoclonal antibody CP-751,871 in cancer patients
Authors: M. N. Pollak, M. Q. Lacy, A. Lipton, L. Demers, K. Leitzel, J. S. de Bono, D. Yin, L. Roberts, A. Sharma, A. Gualberto
Journal: Journal of Clinical Oncology (2007)

3587 Background: The Insulin like Growth Factor I receptor (IGF-IR), a tyrosine kinase, is widely expressed in human tissues. IGF- IR and its ligands (IGF-I and IGF-II) are expressed by many human cancers (e.g., breast, prostate, colorectal and non-small cell lung). Binding of the ligands to the IGF-IR activates key cellular signaling pathways important for stimulating cellular proliferation and inhibiting apoptosis. IGF- I and IGF-II are present in the circulation, but also locally expressed in neoplastic tissue. Bioavailability of these ligands is regulated by a family of IGF binding proteins (IGFBPs1–6). CP-751,871, a fully human monoclonal antibody, is a highly specific and potent inhibitor of IGF-IR activation. In vitro experiments show that binding of CP 751,871 to IGF-IR induces receptor internalization and degradation. This antibody has been shown to have antineoplastic activity using both in vivo and in vitro pre-clinical models. Methods: Blood samples were collected for characterization of the pharmacokinetic and pharmacodynamic properties of CP-751,871 in phase 1 trials of this agent given to cancer patients either alone or in combination with chemotherapy. The endpoints assessed included among others: CP-751,871 plasma concentrations, total and free IGF-I, IGFBP-3, soluble IGF-IR and IGF-IR expression on granulocytes and tumor cells. Results: CP 751,871 exposure increased with dose over the 800-fold dose range investigated. Pharmacokinetic profiles were consistent with target-mediated disposition. A dose-dependent downregulation of soluble IGF-IR serum concentration and IGF-IR expression was observed, with sustained inhibition for the entire dosing period (3–4 week cycles) observed at doses ≥ 1.5 mg/kg. As predicted for an agent that interferes with IGF-I action, IGF-I and IGFBP-3 serum levels were up-regulated in a similar dose-dependent manner. Conclusions: The pharmacodynamic endpoints of clinical trials provide evidence that CP-751,871 targets IGF-IR in granulocytes, tumor cells and tissues involved in regulation of the growth hormone -IGF-I axis. These data provide proof of principle for the use of CP-751,871 as a first-in-class therapeutic approach to inhibit the IGF-IR pathway in cancer patients. No significant financial relationships to disclose.