tbuckley/cabot-search huggingface dataset:
M-Trap: Exosome-Based Capture of Tumor Cells as a New Technology in Peritoneal Metastasis
Authors: Alexandre de la Fuente, Lorena Alonso-Alconada, Clotilde Costa, Juan Cueva, Tomas Garcia-Caballero, Rafael Lopez-Lopez, Miguel Abal
Journal: JNCI Journal of the National Cancer Institute (2015)

Remodeling targeted tissues for reception of tumor cells metastasizing from primary lesions is a consequence of communication between the tumor and the environment that governs metastasis. This study describes a novel approach that aims to disrupt the process of metastasis by interfering with this intense dialogue. Proteomics and adhesion assays identified exosomes purified from the ascitic fluid of ovarian cancer patients (n = 9) as intermediaries of tumor cell attachment. A novel tumor cell capture device was fabricated by embedding exosomes onto a 3D scaffold (metastatic trap [M-Trap]). Murine models of ovarian metastasis (n = 3 to 34 mice per group) were used to demonstrate the efficacy of M-Trap to capture metastatic cells disseminating in the peritoneal cavity. Kaplan-Meier survival curves were used to estimate cumulative survival probabilities. All statistical tests were two-sided. The exosome-based M-Trap device promoted tumor cell adhesion with a nonpharmacological mode of action. M-Trap served as a preferential site for metastasis formation and completely remodeled the pattern of peritoneal metastasis in clinically relevant models of ovarian cancer. Most importantly, M-Trap demonstrated a statistically significant benefit in survival outcomes, with mean survival increasing from 117.5 to 198.8 days in the presence of M-Trap; removal of the device upon tumor cell capture further improved survival to a mean of 309.4 days (P < .001). A potent artificial premetastatic niche based on exosomes is an effective approach to impair the crosstalk between metastatic cells and their environment. In the clinical setting, the capacity to modulate the pattern of dissemination represents an opportunity to control the process of metastasis. In summary, M-Trap transforms a systemic, fatal disease into a focalized disease where proven therapeutic approaches such as surgery can extend survival.
Comment on Inzucchi et al. Management of Hyperglycemia in Type 2 Diabetes, 2015: A Patient-Centered Approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38:140–149
Authors: Chiara Mazzucchelli, Caterina Bordone, Davide Maggi, Renzo Cordera
Journal: Diabetes Care (2015)

Inzucchi et al. (1) suggested that the newer class of hypoglycemic drugs should be preferred to sulfonylureas because of a safer profile with a superimposable hypoglycemic effect. In particular, they state that sulfonylureas are not indicated in chronic kidney disease because of an increased risk of hypoglycemia and potentially cardiovascular death. We challenge this conclusion, in main part, because sulfonylureas have been considered as a class, without taking into account specific properties of each drug—particularly gliclazide, which can be safely prescribed to patients with chronic kidney disease (2). Sulfonylureas have been prescribed to subjects with type 2 diabetes …
A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes
Authors: Anja Löffler, Peter Kufer, Ralf Lutterbüse, Florian Zettl, Peter T. Daniel, Jan M. Schwenkenbecher, Gert Riethmüller, Bernd Dörken, Ralf C. Bargou
Journal: Blood (2000)
Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study.
Authors: W P McGuire, J A Blessing, D Moore, S S Lentz, G Photopulos
Journal: Journal of Clinical Oncology (1996)

PURPOSE Taxol (paclitaxel; Bristol-Myers Squibb, Princeton, NJ) is a new antineoplastic drug with broad-spectrum activity in solid tumors, including epithelial ovarian cancer, head and neck cancer, esophageal cancer, breast cancer, bladder cancer, and lung cancer. Its unique mechanism of action, polymerization of tubulin monomers, has stimulated both clinical and preclinical research on this agent. As limited drug supplies became more plentiful, a phase II trial of Taxol was initiated in patients with advanced squamous cervix cancer who had received no prior chemotherapy. PATIENTS AND METHODS In this trial, 30 assessable patients were initially entered onto the study and four partial responses were seen. Further accrual of 22 assessable patients was then accomplished to define better the response rate with smaller confidence intervals. The starting dose of Taxol was 170 mg/m2 (135 mg/m2 for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalations to 200 mg/m2 and deescalations to 110 mg/m2 were allowed based on adverse effects. RESULTS The final response rate was 17% (two complete responses and seven partial responses). The primary and dose-limiting toxicity was neutropenia. CONCLUSION The response rate makes Taxol a drug with sufficient activity to explore it in combination with other agents with similar activity.
OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.
Authors: Robert Hans Ingemar Andtbacka, Frances A. Collichio, Thomas Amatruda, Neil N. Senzer, Jason Chesney, Keith A. Delman, Lynn E. Spitler, Igor Puzanov, Susan Doleman, Yining Ye, Ari M. Vanderwalde, Robert Coffin, Howard Kaufman
Journal: Journal of Clinical Oncology (2013)

LBA9008 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Treatment of lymphoblastic lymphoma in adults.
Authors: C N Coleman, V J Picozzi, R S Cox, K McWhirter, L M Weiss, J R Cohen, K P Yu, S A Rosenberg
Journal: Journal of Clinical Oncology (1986)

Forty-four adult patients with lymphoblastic lymphoma (LBL) were treated according to one of two protocols. Both included (1) induction with cyclophosphamide, doxorubicin, vincristine, prednisone, and L-asparaginase; (2) CNS prophylaxis; and (3) maintenance therapy with methotrexate (MTX) and 6-mercaptopurine. In the second protocol, CNS prophylaxis began earlier than in the first protocol and included cranial irradiation and intrathecal (IT) MTX rather than simultaneous high-dose systemic and IT MTX. The overall response rate was 100% (95% complete). With a 26-month median follow-up, the 1-and 3-year actuarial freedom from relapse (FFR) for the composite patient group was 70% and 56%, respectively. The incidence of CNS relapse was reduced from 31% in the first protocol to 3% in the second protocol (P = .04, Gehan). Patients can be assigned retrospectively to low (n = 19) and high (n = 25) risk prognostic groups, as indicated by a multivariate analysis of pretreatment prognostic factors. High-risk is defined by Ann Arbor stage IV disease with bone marrow or CNS involvement or initial serum lactate dehydrogenase (LDH) concentration of greater than 300 IU/L (normal, less than 200). FFR of low- and high-risk groups at 5 years are 94% and 19%, respectively (P = .0006). Low-risk patients are highly curable using this approach to adult LBL. More intensive treatment for high-risk patients is warranted.
A Prospective Evaluation of Endogenous Sex Hormone Levels and Colorectal Cancer Risk in Postmenopausal Women
Authors: Neil Murphy, Howard D. Strickler, Frank Z. Stanczyk, Xiaonan Xue, Sylvia Wassertheil-Smoller, Thomas E. Rohan, Gloria Y. F. Ho, Garnet L. Anderson, John D. Potter, Marc J. Gunter
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Postmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain.
Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus
Authors: K. Malmberg
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. <b>Design:</b> Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). <b>Subjects:</b> 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. <b>Main outcome measure:</b> Long term all cause mortality. <b>Results:</b> The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P=0.011).The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P=0.004). <b>Conclusion:</b> Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. <h3>Key messages</h3> Diabetes mellitus is common among patients with acute myocardial infarction Diabetic patients with myocardial infarction have a poor short and long term prognosis Poor metabolic control is common among diabetic patients with myocardial infarction Improved metabolic control by means of acute insulin-glucose infusion followed by long term intensive insulin treatment improves long term prognosis among these patients
Systemic Tolerance Mediated by Melanoma Brain Tumors Is Reversible by Radiotherapy and Vaccination
Authors: Christopher M. Jackson, Christina M. Kochel, Christopher J. Nirschl, Nicholas M. Durham, Jacob Ruzevick, Angela Alme, Brian J. Francica, Jimmy Elias, Andrew Daniels, Thomas W. Dubensky, Peter Lauer, Dirk G. Brockstedt, Emily G. Baxi, Peter A. Calabresi, Janis M. Taube, Carlos A. Pardo, Henry Brem, Drew M. Pardoll, Michael Lim, Charles G. Drake
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for the efficacy of tumor-targeted immunotherapies is largely unknown. Experimental Design: The B16 murine melanoma model was used to compare cytotoxic responses against established tumors in the CNS and in the periphery. Cytokine analysis of tissues from brain tumor–bearing mice detected elevated TGFβ secretion from microglia and in the serum and TGFβ signaling blockade reversed tolerance of tumor antigen-directed CD8 T cells. In addition, a treatment regimen using focal radiation therapy and recombinant Listeria monocytogenes was evaluated for immunologic activity and efficacy in this model. Results: CNS melanomas were more tolerogenic than equivalently progressed tumors outside the CNS as antigen-specific CD8 T cells were deleted and exhibited impaired cytotoxicity. Tumor-bearing mice had elevated serum levels of TGFβ; however, blocking TGFβ signaling with a small-molecule inhibitor or a monoclonal antibody did not improve survival. Conversely, tumor antigen–specific vaccination in combination with focal radiation therapy reversed tolerance and improved survival. This treatment regimen was associated with increased polyfunctionality of CD8 T cells, elevated T effector to T regulatory cell ratios, and decreased TGFβ secretion from microglia. Conclusions: These data suggest that CNS tumors may impair systemic antitumor immunity and consequently accelerate cancer progression locally as well as outside the CNS, whereas antitumor immunity may be restored by combining vaccination with radiation therapy. These findings are hypothesis-generating and warrant further study in contemporary melanoma models as well as human trials. Clin Cancer Res; 22(5); 1161–72. ©2015 AACR.
Emerging Agents and New Mutations in EGFR-Mutant Lung Cancer
Authors: Deborah Ayeni, Katerina Politi, Sarah B. Goldberg
Journal: Clinical Cancer Research (2015)

Abstract Third-generation mutant-specific EGFR tyrosine kinase inhibitors are showing robust clinical activity, particularly in lung cancers harboring the EGFRT790M mutation, yet acquired resistance to these agents emerges. Additional mutations in EGFR can confer resistance that, depending on their genomic context, could determine new drug sensitivities of the cancer cells. Clin Cancer Res; 21(17); 3818–20. ©2015 AACR. See related articles by Ercan et al., p. 3913 and Niederst et al., p. 3924
Management of postchemotherapy residual mass in patients with advanced seminoma: Indiana University experience.
Authors: S M Schultz, L H Einhorn, D J Conces, S D Williams, P J Loehrer
Journal: Journal of Clinical Oncology (1989)

Thirty-six patients with advanced seminoma treated with cisplatin combination chemotherapy were evaluated to assess the significance of postchemotherapy residual radiographic mass. All patients had a minimum follow-up of 2 years. Of the 36 patients 21 had an evaluable residual radiographic mass after completion of chemotherapy. Twelve of these patients had a less than 3 cm maximal transverse diameter residual mass, and nine had a greater than 3 cm persistent mass postchemotherapy. Only three of these 21 patients underwent postchemotherapy retroperitoneal lymph node dissection, and the histopathology revealed only necrotic fibrous tissue. The remaining patients were followed by close observation including repeat abdominal computed tomography (CT) every 3 months the first year and every 6 months the second year (or until normal); further therapeutic intervention was given only on evidence of progressive disease. Nineteen of these 21 patients have no evidence of disease, including eight of nine with greater than 3 cm persistent radiographic abnormality. The optimal management for advanced seminoma patients with a persistent radiographic mass postchemotherapy remains unresolved. However, based on this small series, we feel that observation is a viable option, reserving radiotherapy or chemotherapy for those patients who subsequently develop progressive disease.
Human immunodeficiency virus and other sexually transmitted diseases in Cuban women
Authors: M.E. Rodríguez, A. Llop, V. Capó, V. Kourí, S. Resik, L. Rojas, Y. Soto, M. Muné, I. Rodríguez, U.R. Hengge
Journal: Clinical Microbiology and Infection (2005)
Intercultural consultations
Authors: S. Patel
Journal: BMJ (1995)

support junior medical staff in their initial management ofpatients with acute stroke.As Dennis and Langhorne highlight, patients with stroke in acute facilities compete for nursing time with patients who are seen to have more urgent need.They also compete for medical, physiotherapy, and occupational therapy time.Rehabilitation of patients with stroke is time consuming and should include education and emotional and psychological support for the patients and their carers.For these reasons the use of resources by patients with acute stroke in most acute facilities is inadequate, and improvements in stroke care can realistically be achieved only by correcting deficiencies and targeting resources at the patients and their carers.We believe that high quality care of patients with acute stroke and their carers can be achieved only by establishing acute and rehabilitation stroke units.Deficiencies in resources should be addressed to allow these units to function optimally.
Assessment of tumor size and movement trajectories using CT scans with different pitch settings
Authors: Paul Martin Putora, Marciana Nona Duma, Florent Baty, Michal Devecka, Martin Brutsche, Ludwig Plasswilm
Journal: European Respiratory Journal (2012)

Introduction:  Pitch Settings of CT scanners have an influence on the way moving lesions are reconstructed. These images have an impact on target definition in radiotherapy planning, therefore the Planning-CT settings are of central importance for correct tumor irradiation and normal tissue sparing.   Method:  A water filled 40mm table tennis ball serving as a tumor phantom was moved along an elipsoid trajectory by a custom-assembled Lego(c) based device with a cycle duration of 4.2 seconds. The pitch/slice settings tested were termed  (2.5mm, standard pitch),  (2.5mm, half pitch), and  (0.625mm, half pitch).   Results:  The volume of the ball was overestimated with the volume of the tumor-phantom growing from 82% for the fast CT, 171% for the intermediate CT and 300% for the slow CT. The phantom trajectory could best be reconstructed in the slow CT. The different sizes can be seen here:   Conclusion:  The custom lung phantom proved to work well for the specified task. The effect of CT settings during planning-CT acquisition on the resulting volumes was significant. Acquisition of slow-CT images for radiotherapy planning enables a better targeting of the moving tumor and sparing of normal lung tissue specifically when respiratory gating is not available.
Characteristics of the ventilatory response to incremental exercise in asthma
Authors: Worawan Sirichana, Ymi N. Ton, Christopher B. Cooper
Journal: European Respiratory Journal (2014)

Introduction 

Asthma patients can have exercise limitation due to expiratory flow limitation, ventilatory limitation, decreased ventilatory efficiency from gas exchange abnormalities or exercise induced bronchoconstriction. We examined the ventilatory response characteristics during maximal incremental exercise testing in a large cohort of asthma patients.

Methods 

We collated data from clinical exercise tests performed from 2008-2012 using a symptom-limited incremental exercise protocol on a cycle ergometer. Physiological measurements analyzed included maximum oxygen uptake (VO2max), metabolic threshold when lactate began to accumulate (VO2θ), ventilatory efficiency (VE/VCO2), the ventilatory threshold (VCO2θ), ventilatory reserve and cardiac reserve.

Results 

We identified 71 patients (41 women) with asthma, aged 45.0 ± 18.3 years. Mean ± SD pre-exercise FEV1 was 94.4 ± 22.1%, FEV1/FVC was 80.5 ± 10.6% and maximum voluntary ventilation (MVV) was 118 ± 42 L·min-1 (94.1 ± 27.9%). VO2max and VO2θ were respectively 2.06 ± 0.80 L·min-1 and 1.11 ± 0.37 L·min-1 (61.6 ± 14.7% of predicted VO2max). VE/VCO2 was 29.2 ± 4.5 and VCO2θ was 1.81 ± 0.70 L·min-1. Eight of 71 cases had VO2max < 80% predicted and a low metabolic threshold. Four of 13 (30.8%) cases with FEV1 < 80% predicted, demonstrated low aerobic capacity. Only one case showed ventilatory limitation. More frequent causes of exercise limitation were deconditioning or cardiovascular impairment. Ventilatory efficiency was within normal limits.

Conclusions 

Asthma patients with lower lung function were more likely to have lower aerobic capacity. However, this was usually due to deconditioning rather than gas exchange abnormalities or ventilatory limitation.
Phase II trial of oral altretamine for relapsed ovarian carcinoma: evaluation of defining response by serum CA125.
Authors: G J Rustin, A E Nelstrop, M Crawford, J Ledermann, H E Lambert, R Coleman, J Johnson, H Evans, S Brown, W Oster
Journal: Journal of Clinical Oncology (1997)

PURPOSE A phase II study was performed of oral altretamine in 71 patients with ovarian carcinoma who entered clinical complete remission with CA125 levels less than 35 U/mL after initial or second-line chemotherapy, and relapsed more than 6 months later. Response was compared between standard and CA125-based criteria. PATIENTS AND METHODS Altretamine 260 mg/m2 was given in divided doses daily for 14 days per month. Response was evaluated according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 45 of 66 eligible patients. Response was assessed according to precise CA125 criteria in 51 patients based on either a confirmed &gt; or = 50% or &gt; or = 75% decrease in CA125 levels. RESULTS A combination of domperidone, dexamethasona, and chlorpromazine at night controlled toxicity in most patients, which was mainly nausea (National Cancer Institute criteria grade 2 or 3 in 27), vomiting (grade 2 or 3 in 19, grade 4 in one), and tiredness (grade 2 or 3 in 15). Responses (complete plus partial) were seen in 18 (40%; 95% confidence interval [CI], 25.4% to 54.6%) of those evaluated according to EORTC criteria and in 20 (39%; 95% CI, 25.5% to 52.9%) of those evaluated according to CA125 level. The overall response rate was 26 of 57 (45.6%) and was related to treatment-free interval: 6 to 12 months, 35%; 12 to 24 months, 52%; and greater than 24 months, 67%. The medium duration of response was 8 months. CONCLUSION Oral altretamine is a useful agent in patients-who relapse after previously responsive ovarian cancer. Response evaluation by a strict CA125 definition gave a similar estimate of the efficacy of altretamine as EORTC criteria.
High blood pressure, antihypertensive medication and lung function in a general adult population
Authors: Eva Becker, Stefan Karrasch, Holger Schulz, Sven Gläser, Christa Meisinger, Margit Heier, Annette Peters, H.-Erich Wichmann, Jürgen Behr, Rudolf Maria Huber, Joachim Heinrich
Journal: European Respiratory Journal (2011)

Background: Several studies showed that blood pressure and lung function are associated. Additionally, potential effect of antihypertensive medication, esp. beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, we aimed to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population.

Methods: Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Information on medical history and use of antihypertensive medication was available, too. Multivariate regression models were applied to study the association between blood pressure, antihypertensive medication and lung function.

Results: High blood pressure as well as antihypertensive medication were associated with lower FEV1 (p=0.02 resp. p=0.05; R2: 0.65) and FVC (p=0.01 resp. p=0.05, R2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for FVC (p=0.03; R2: 0.65), while for FEV1 the association was of borderline significance (p=0.07; R2: 0.73).

Conclusion: Our analysis indicates that both high blood pressure and antihypertensive treatment are associated with reduced lung function in a general adult population. Furthermore, we speculate that the negative effect of antihypertensive medication on lung function is mainly attributable to beta-blockers.