tbuckley/cabot-search huggingface dataset:
Phase I study of ispinesib in combination with carboplatin in patients with advanced solid tumors
Authors: S. F. Jones, E. R. Plummer, H. A. Burris, A. R. Razak, A. A. Meluch, C. J. Bowen, D. H. Williams, J. P. Hodge, M. M. Dar, A. H. Calvert
Journal: Journal of Clinical Oncology (2006)

2027 Background: Kinesin spindle protein (KSP) is required for establishment of mitotic spindle bipolarity and cell cycle progression. Ispinesib (SB-715992), a KSP inhibitor, blocks assembly of a functional mitotic spindle leading to G 2 /M arrest. Carboplatin is a platinum compound that produces predominantly interstrand DNA cross-links. In vivo combination of a platinum-containing agent (cisplatin) and ispinesib resulted in synergistic activity and an increase in maximum tolerated dose (MTD) of ispinesib. In a phase I study of single agent ispinesib on a once every 21-day schedule, the MTD was 18 mg/m 2 with prolonged gr 4 neutropenia and febrile neutropenia as DLTs. Methods: Patients (pts) with advanced solid tumors, PS ≤ 1, and ≤ 3 prior chemotherapy regimens were eligible for this study. Escalating doses of carboplatin (AUC 4-6) were administered over 30 minutes followed by a 1-hour infusion of escalating doses of ispinesib (9– 21 mg/m 2 ) on a 21-day schedule. At least 3 pts were treated at each dose level. The primary objectives of this study included characterizing safety and tolerability and defining the optimally tolerated regimen (OTR). Limited pharmacokinetic (PK) samples were obtained. Clinical response assessments per RECIST criteria were performed every 2 cycles. Results: 24 pts [15 M/9 F; median age 63yrs, ECOG PS 1], were treated at 6 dose levels. The most common tumor types were prostate (7) and breast (4). A median of 3 cycles were administered (range 1–7; total 75 cycles). In 17 pts, the most common toxicities were (# pts, [grade]): nausea (10, Gr 1–2), vomiting (8, Gr 1–3), fatigue (8, Gr 1–2), neutropenia (8, Gr 2–4), anemia (7, Gr 1–3), and thrombocytopenia (7, Gr 1–4). Gr 4 thrombocytopenia was the observed DLT in 2 pts [ispinesib (mg/m 2 )/carboplatin (mg/ml·min) (# pts): 15/6 (1); 18/6 (1). PK assessment of ispinesib and carboplatin will be completed when the OTR has been defined. Unconfirmed minor responses have been observed in 3 pts (breast, prostate, NSCLC) starting at doses of 18/6. Conclusions: Determination of an OTR is ongoing. Ispinesib doses ≥ single agent MTD when combined with carboplatin AUC 6 have an acceptable tolerability profile and demonstrate preliminary evidence of anti-tumor activity. [Table: see text]
Induction of Lung Tumors by Radioactive Isotopes Implanted in the Rat Lung&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H B Kal, C Zurcher, D W van Bekkum
Journal: JNCI Journal of the National Cancer Institute (1986)

Squamous cell carcinomas were induced in the lungs of male WAG/Rij inbred rats by radiation emitted from the isotopes iridium-192 or iodine-125. These isotopes were implanted by a surgical procedure in the lungs of young rats. Forty rats received implants of 192Ir wires and 20 animals, of 125I seeds. In a 14-month observation period, 30 of the 40 animals with implants of 192Ir wires developed tumors. Malignant hemangioendotheliomas occurred with the highest frequency (50%). From the lungs of 12 rats, squamous cell carcinomas were found. In the observation period of 17 months, 3 rats with implants of 125I seeds developed tumors, among which 1 squamous cell carcinoma could be identified. Tumor fragments were transplanted in syngeneic hosts for propagation of the tumors. Histologic appearances of tumors remained constant in subsequent passages. Responses of transplanted tumors growing in the flanks of syngeneic hosts to doses of radiation, methotrexate, or vinblastine were determined. Although the histologic appearances of the 5 squamous cell carcinomas were similar, tumor-doubling times and responses to irradiation and chemotherapeutic drugs were different. Small cell or large cell carcinomas were not observed.
In Vivo Distinction Between a Target Cell for Friend Virus (FVI) and Murine Hematopoietic Stem Cells2
Authors: Anthony G. Nasrallah, Michael P. McGarry
Journal: JNCI Journal of the National Cancer Institute (1976)

Busulphan (BU) treatment of DBA/2 mice with hypertransfusion (HT)-induced polycythemia resulted in an ablation of detectable hematopoietic stem cells (CFUS) in pooled marrow from the long bones. Daily injections of erythropoietin (EP) stimulated an EP-responsive population of cells in the absence of detectable CFUS. Mice treated with BU and EP and having HT-induced polycythemia were inoculated with the polycythemia-inducing strain of Friend virus (FVP) and determinations were made for the presence of tumor colony-forming units (tCFU). No change in CFUS/10(6) bone marrow cells was detected as a result of EP treatment. However, tCFU were increased more than 100-fold in HT-BU-EP-treated mice compared with saline-treated controls. The demonstration of tCFU in mice in which CFUS were not detectable indicated that this leukemogenic effect of FVP could occur in the absence of the pluripotent stem cell. Furthermore, the increased numbers of this FVP target cell in the EP-stimulated, BU-treated mice with HT-induced polycythemia supported the model licating the target for this effect in the EP-responsive cell population.
Tumor laterality influences the prognostic impact of Bcl-2 expression in curatively resected NSCLC patients
Authors: Lars Henning Schmidt, Tilmann Spieker, Martin Schuler, Alessandro Marra, Karsten Wiebe, Wolfgang Berdel, Carsten Mueller-Tidow, Wiewrodt Rainer
Journal: European Respiratory Journal (2013)

Introduction: Overexpression of anti-apoptotic proteins shows impact on prognosis in in non-small-cell lung cancer (NSCLC). To investigate the effects in NSCLC, we focused on several apoptotic factors such as Bcl-2, Bcl-xl, Mcl-1, and pp32/PHAPI and included the aspect of tumor laterality, since lung tumor laterality also influences surgical procedures and mortality. Material and Methods: Using tissue microarray Immunohistochemistry, the prognostic impact of the expression profiles of Bcl-2, Bcl-xl, Mcl-1 and pp32/PHAPI was investigated in 436 NSCLC tissue samples (median age: 65 years; 77% male) with correlation analysis, Log rank tests and Cox proportional hazard models. Results: For Bcl-2, positive expression was found in 97 cases (23%), for Bcl-xl in 151 cases (37%), for Mcl-1 in 230 cases (57%) and for in 279 cases (66%). Both univariate and multivariate analysis identified the expression of Bcl-2 as the best prognostic marker. In stage I non-squamous cell tumors, a synergistic positive prognostic effect of Bcl-2 and Bcl-xl co-expression was found. Moreover, Bcl-2 expression of tumors located on the right side showed best prognostic impact (p=0.001). Conclusion: We identified Bcl-2 to be a strong independent factor for an improved outcome in resected NSCLC patients, at first glance contradictory to the findings in lymphomas and other solid tumors. However, we hypothesize this effect to directly derive from a better accessibility and resectability of invisibly affected distant lymph nodes in right sided surgical procedures in Bcl2 positive tumors. Future concepts in surgical oncology should owe respect to laterality.
Relationship between type 1 diabetes and atopic diseases in a twin population
Authors: S. F. Thomsen, D. L. Duffy, K. O. Kyvik, A. Skytthe, V. Backer
Journal: Allergy (2010)

To cite this article: Thomsen SF, Duffy DL, Kyvik KO, Skytthe A, Backer V. Relationship between type 1 diabetes and atopic diseases in a twin population. Allergy 2011; 66: 645–647. Abstract Aim: To study the association between type 1 diabetes and atopic diseases in a twin population. Methods: We performed record linkage between questionnaire-defined atopic dermatitis, asthma and hay fever, and hospital discharge diagnoses of type 1 diabetes in 54 530 Danish twins, 3–71 years of age. Results: The age- and sex-adjusted risk of atopic dermatitis was decreased in subjects with type 1 diabetes compared with nondiabetic subjects, (2.1%vs 9.9%), odds ratio (OR) = 0.23 (0.07–0.71), P = 0.011, whereas asthma and hay fever were not significantly associated with type 1 diabetes. Within twin pairs discordant for type 1 diabetes, the diabetic twin had a lower risk of atopic dermatitis relative to the nondiabetic co-twin. Genetic factors for atopic dermatitis and type 1 diabetes were negatively correlated (r = −0.30), P = 0.0009. Conclusions: These findings substantiate the Th1 vs Th2 cell dichotomy for type 1 diabetes and atopic dermatitis, and indicate an inverse association between genetic factors for these disorders.
Pulmonary alveolar proteinosis: A case report
Authors: Önder Öztürk, Isa Döngel, Metin Çiris, Alparslan Çelik, Hasan Ekrem Çamas, Seher Karakus, Oguz Çelik
Journal: European Respiratory Journal (2013)

A 30 age male patient, working as a welder and a driver, applied to our hospital with dyspnea that began 4 months ago. Despite of various antibiotics and bronchodilators therapy for asthma and pneumonia, his complaints worsened. There were bilateral diffuse infiltrations on his postero-anterior chest graphy and PO2:53 mmHg, SaO2:%88 was found at arterial blood gas measurements. There were interstitial septal thickening, bilateral interstitial and alveolar densities, increased densities combined with each others in the style of ground glass areas on thorax tomography. The view of bronchoalveoler lavage (BAL) fluid was milky. The staining of the fluid with PAS (periodic acid-Schiff) was pozitif and proteinaceous materials containing d-PAS resistant globules were seen. Asido resistant bacillus and the other pathogens were not cultured negative in sputum, in post bronchoscopic sputum and BAL material. Wedge resection was made by video-assisted thoracoscopic surgery. Histopathology report of biopsy material revealed “Pulmonary alveolar proteinosis (PAP)”. Although massive lung lavage was planned for the patient, it was not applied to him because of clinical and radiological improvements, having shunt fraction   As a conclusion, the acute and chronic effects of welding fumes to lungs may caue PAP and the physicians should consider PAP as a rare disease in the differential diagnosis of patients with dypsnea symptoms and having bilateral diffuse infiltrations on chest graphy.
Use of Young Nude Mice for Selection of Subpopulations of Cells With Increased Metastatic Potential From Nonsyngeneic Neoplasms&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: Vincent A. Pollack, Isaiah J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1982)

The purpose of these studies was to investigate whether young (3-wk-old) nude mice, which lack functional T-lymphocytes and demonstrate low natural killer cell activity, could serve as in vivo models for the selection of metastatic subpopulations of cells from heterogeneous allogeneic melanomas. Three-week-old BALB/cAnN or N:NIH(S) nude mice received iv injections of single cells harvested from either the B16 or K-1735 melanoma. Individual pulmonary metastases were harvested 4 weeks later and implanted sc into nude mice to expand the population. Cells from each of these metastases colonized in the lungs of 3-week-old nude mice and 6-week-old normal syngeneic mice with significantly higher efficiency than did cells from the parent tumors. It was concluded that, in addition to being a useful in vivo model for ascertaining the metastatic potential of neoplasms, the healthy young nude mouse could be used for selecting and maintaining tumor cell variants of high metastatic potential room heterogeneous allogeneic tumors.
CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma.
Authors: J Lundin, A Osterborg, G Brittinger, D Crowther, H Dombret, A Engert, A Epenetos, C Gisselbrecht, D Huhn, U Jaeger, J Thomas, R Marcus, N Nissen, C Poynton, E Rankin, R Stahel, M Uppenkamp, R Willemze, H Mellstedt
Journal: Journal of Clinical Oncology (1998)

PURPOSE CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (&lt; 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.
Abstract 4269: Randomized Comparison of Additive Cilostazol and High Maintenance-Dose Clopidogrel in Patients with Poor Response to Clopidogrel
Authors: Young-Hoon Jeong, Bong-Ryong Choi, In-Suk Kim, Choong Hwan Kwak, Jin-Yong Hwang, Seung-Whan Lee, Seong-Wook Park
Journal: Circulation (2008)

Background - The aim of the study was to compare platelet inhibition by additive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) and high maintenance-dose (MD) clopidogrel 150...
Rate of Disease Progression in Breast Cancer: A Clinical Estimate of Prognosis Within Nodal and Anatomic Stages&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M E Charlson, A R Feinstein
Journal: JNCI Journal of the National Cancer Institute (1984)

From data obtained in the patient's history, the clinical rate of progression of disease in breast cancer patients can be estimated as slow, intermediate, or rapid. The strata defined by these rates had previously been shown to create prognostic gradients within groups of patients similar in anatomic stage or nodal status. In a second, validating cohort of 465 women with primary breast cancer, the strata delineating rate of disease progression were shown to have a cogent prognostic impact when the proportional hazards model was used to control simultaneously for nodal and anatomic status. In addition, the distinctions persisted when different types of treatment were taken into account. These findings from a multivariate analysis employing the Cox method confirmed the importance of clinical rate of disease progression in estimating prognosis of breast cancer.
Motility and Adhesiveness in Human Neutrophils
Authors: C. Wayne Smith, James C. Hollers, Richard A. Patrick, Clare Hassett
Journal: Journal of Clinical Investigation (1979)

Human peripheral blood neutrophils (PMN) obtained from healthy adults were examined in vitro with techniques adapted to assess the effects of chemotactic factors (CF) on cellular configuration and adhesiveness. The results were compared with those that use certain conventional techniques for assessing chemotaxis and chemokinesis. Exposure of PMN to N-formyl-l-methionyl-l-phenylalanine (f-Met-Phe), zymosan-activated serum, bacterial chemotactic factor, or a low molecular weight chemotactic factor from activated serum (C5a) in the absence of a gradient resulted in a change in cellular shape from a spherical to a polarized configuration in a high percentage of cells. This occurred rapidly in suspension, under conditions designed to exclude a role for cell adhesiveness, and was reversible upon removal of the CF. Restimulation of cells with the CF resulted in reappearance of the polarized configuration to the same extent as on initial stimulation with one exception: f-Met-Phe pretreated cells failed to respond to f-Met-Phe, though they responded fully to the other CF. Each CF caused a significant increase in PMN attachment to protein-coated glass. This enhanced adhesiveness was not reversible upon removal of the CF when the cells were treated under conditions shown to produce chemotactic deactivation. Cells treated under these conditions also exhibited significantly reduced motility on glass and in micropore filters in the absence of a gradient of CF. Bacterial chemotactic factor, even at high concentrations, failed to produce deactivation and did not cause a sustained enhancement of adhesiveness.
The deja vu experience: remembrance of things past?
Authors: H N Sno, D H Linszen
Journal: American Journal of Psychiatry (1990)

The déjà vu experience is a common phenomenon, occurring in pathological as well as nonpathological conditions. It has been defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. The authors discuss the epidemiologic data, clinical features, and etiology of the phenomenon of déjà vu. They also review the different hypotheses on the psychopathogenesis of the déjà vu experience and introduce an explanation based on the hologram as a mnestic model.
Evaluation of race as a prognostic factor in multiple myeloma. An ancillary of Southwest Oncology Group Study 8229.
Authors: M R Modiano, P Villar-Werstler, J Crowley, S E Salmon
Journal: Journal of Clinical Oncology (1996)

PURPOSE The objective of this investigation was to assess the impact of race (black v white) on the survival of patients with multiple myeloma treated within the context of a large clinical trial. PATIENTS AND METHODS A cohort of patients randomized to receive one of two treatment regimens and monitored for at least 10 years was studied to assess the impact of race as a prognostic factor, after adjusting for other known factors such as stage of disease. Patients were recruited from the referral network of the Southwest Oncology Group (SWOG), a national multiinstitutional consortium that includes both academic and community treatment centers. Patients had a diagnosis of multiple myeloma and had not previously been treated for this disease. They were carefully characterized as to demographic and clinical features, and were randomized to receive one of two treatment regimens, which proved to have virtually identical outcomes. The outcome measure was survival, measured from the date of randomization to the date of last contact. Patients still alive at last contact date were treated as censored observation. RESULTS Survival for black myeloma patients was similar to that for white patients, both overall and adjusted for prognostic factors such as stage. CONCLUSION Observed differences in mortality between blacks and whites cannot be attributed to differences in survival after diagnosis, given comparable treatment.
Pulmonary vasoreactivity in spontaneously hypertensive rats :Effects of leptin and endothelin-1
Authors: Samantha Gomart, Cécile Damoiseaux, Pascale Jespers, Nathalie Labranche, Stéphanie Pochet, Robert Naeije, Kathleen Mc Entee, Laurence Dewachter
Journal: European Respiratory Journal (2013)

Systemic hypertension may be associated with increased pulmonary vascular resistance in absence of demonstrable increased left ventricular filling pressures ( Olivari et al. Circulation. 1978; 57: 1185-90 ). There has been report of enhanced pulmonary vasoreactivity to hypoxia in patients with systemic hypertension ( Guazzi et al. Circulation. 1987; 75: 156-62 ). Chronic hyperleptinemia has been shown to contribute to systemic hypertension associated to obesity. We investigated pulmonary vascular reactivity to endothelin(ET)-1 and leptin in normotensive Wistar (WKY) and spontaneously hypertensive rats (SHR). Pulmonary (PA) and thoracic artery (TA) rings were sampled in SHR and WKY rats. Vascular reactivity to phenylephrine (PHE), ET-1 and leptin was evaluated in endothelium-intact and -denuded rings mounted in organ baths. In controls, ET-1 induced a higher level of contraction in PA than in TA. After PHE precontraction, leptin relaxed intact PA and TA, while no response was observed in denuded arteries. After ET-1 precontraction, leptin induced a greater time-dependent relaxation in intact TA than PA. In SHR, PHE- and ET-1-induced contraction was enhanced in intact PA. Contraction to PHE and ET-1 was respectively 51% and 32% higher in denuded than intact control PA, while this was respectively reduced to 16% and abolished in SHR. After PHE precontraction, leptin induced a similar endothelium-dependent relaxation in SHR and controls. After ET-1 precontraction, endothelium-dependent relaxation to leptin was abolished in SHR PA. In SHR, pulmonary vascular reactivity is altered with a loss of endothelial blunting effect to vasoconstrictors and of leptin-induced vasodilation.
First isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. Swiss Group for Clinical Cancer Research.
Authors: M Borner, M Bacchi, A Goldhirsch, R Greiner, F Harder, M Castiglione, W F Jungi, B Thürlimann, F Cavalli, J P Obrecht
Journal: Journal of Clinical Oncology (1994)

PURPOSE We performed a randomized phase III multicenter study to compare systemic treatment versus no treatment after complete excision and radiotherapy for isolated first locoregional recurrence in patients with breast cancer. PATIENTS AND METHODS One hundred sixty-seven good-risk patients with an estrogen receptor (ER+) positive recurrence or, in case of unknown receptor status, a disease-free interval (DFI) of greater than 12 months and &lt; or = three recurrent tumor nodules each &lt; or = 3 cm in diameter were entered onto the study. They were randomized to observation subsequent to local treatment or to receive tamoxifen (TAM) until disease progression. Seventy-nine percent of the patients were postmenopausal. RESULTS The median observation period for the entire study population was 6.3 years. The median disease-free survival (DFS) duration was 26 months for observation and 82 months for TAM patients (P = .007). This was mainly due to the reduction of further local recurrences, whereas the occurrence of early distant metastases was delayed. A multivariate analysis identified DFI and treatment with TAM as significant prognostic factors for DFS. The 5-year overall survival (OS) rates were 76% and 74%, respectively (P = .77). DFI was also a prognostic factor for OS. CONCLUSION Systemic therapy with TAM after isolated locoregional recurrence of breast cancer significantly increased 5-year DFS rates from 36% to 59% compared with observation alone and prolonged median DFS by more than 4.5 years in patients with ER+ tumors or in the case of unknown ER status with a DFI of greater than 12 months and minimal tumor burden. Treatment with TAM currently has no significant impact on OS, but the median survival duration of the study population has not yet been reached.
Carriage of encapsulated bacteria in Gabonese children with sickle cell anaemia
Authors: F. Schaumburg, B. Biallas, E. Ngoune Feugap, A.S. Alabi, B. Mordmüller, P.G. Kremsner, M.P. Grobusch, B. Lell, M. van der Linden, G. Peters, A.A. Adegnika
Journal: Clinical Microbiology and Infection (2012)