tbuckley/cabot-search huggingface dataset:
Carcinogenesis Assay of Subtractions of Cigarette Smoke Condensate Prepared by Solvent-Solvent Separation of the Neutral Fraction&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Fred G. Bock, A. P. Swain, R. L. Stedman
Journal: JNCI Journal of the National Cancer Institute (1972)

Carcinogenesis assay was conducted on subfractions of the neutral fraction (NF) of cigarette smoke condensate, subfractions that were prepared by solvent partition. Of the 2 major subfractions, the “methanolinsoluble” neutrals (MIN) were much more active than the “methanolsolubles” neutrals (MSN). Distribution of MSN between nitromethane and carbon disulfide yielded 2 active fractions. Poor dose-response effects suggest that extraneous materials may reduce the activity of MSN. Analysis of the recovery of MSN is difficult, but apparently there were significant losses during separation. On countercurrent distribution (CCD), MIN yielded 3 active and 2 inactive subfractions. Recovery of the activity of MIN in the subfractions was excellent in comparison with an earlier separation with silicic acid chromatography. Recoveries might be improved if CCD is applied to the NF before the more rigorous chromatographic separations.
Decreased variability of expired CO2 yield in infants with bronchopulmonary dysplasia
Authors: Sotirios Fouzas, Christoph Häcki, Edgar Delgado-Eckert, Elena Proietti, Philipp Latzin, Roland Neumann, Sven Schulzke, Urs Frey
Journal: European Respiratory Journal (2013)

Background: Bronchopulmonary dysplasia (BPD) is characterized by alterations in ventilation-to-perfusion (V/Q) matching and gas exchange capacity. The aim of this study was to examine the breath-by-breath variability in the expired CO2 volume (VCO2) and to assess its value in describing disturbances of gas exchange in BPD.  Methods: Lung function parameters from 181 healthy infants (128 term, 53 preterm) and 87 infants with BPD (46 mild, 55 moderate, 32 severe) were compared. Expiratory capnograms were obtained by mainstream capnography over 100 consecutive tidal breaths. The ratio of VCO2 to expiratory volume (Ve) was used as measure of the expired CO2 yield per breath. The tho-dimensional (2D) domain area of the VCO2/Ve embedding plot (1-breath lag) and the domain area of the VCO2-Ve scatter plot (both calculated by an ellipse-fiting method) were used as indicators of the variability in CO2 yield.  Results: BPD infants had smaller 2D VCO2/Ve domains (median [IQR]: 7.8 [4.9-11.6] vs. 10.6 [7.1-15.3]; P  Conclusions: Infants with BPD presented significantly lower breath-by-breath variability in CO2 yield, a finding that may reflect disease-related disturbances in V/Q matching and gas exchange capacity.
Allogeneic blood cell transplantation without posttransplant colony-stimulating factors in patients with hematopoietic neoplasm: a phase II study.
Authors: C Rosenfeld, R Collins, L Piñeiro, E Agura, J Nemunaitis
Journal: Journal of Clinical Oncology (1996)

PURPOSE There is limited experience with allogeneic blood cell transplantation (BCT). In an earlier pilot study, the combination of bone marrow and blood did not produce severe acute graft-versus-host disease (GVHD). We now report the results of a phase II study using blood stem cells alone in 19 patients. PATIENTS AND METHODS The median age was 40 years. All patients had hematopoietic malignancies and received transplants from HLA-identical sibling donors. GVHD prophylaxis consisted of cyclosporine plus prednisone. Posttransplant colony-stimulating factors were not administered. Donors were mobilized with subcutaneous granulocyte colony-stimulating factor (G-CSF; 16 microg/kg/d) for 5 days. Apheresis was performed on 2 consecutive days. RESULTS The median cell content of the two apheresis was 11.9 x 10(8) WBC/kg, 3.2 x 10(8) CD3/kg, and 8.3 x 10(6) CD34/kg. The median time to achieve an absolute neutrophil count (ANC) &gt; or = 500/microL was 13 days, and 14 days to a platelet count &gt; or = 50,000/microL. All patients engrafted. Platelet recovery was faster in marrow historic control groups. Blood cells in all tested cases contained more than 95% donor cells on day 30. The actuarial incidence of acute GVHD was 37%, and 13% for grade II-IV GVHD. Limited, corticosteroid responsive, chronic GVHD developed in 33% of assessable patients. At a median follow-up of 192 days, actuarial survival was 75%. CONCLUSION Transplantation of a high number of stem cells may lead to rapid engraftment without the use of posttransplant colony-stimulating factors. GVHD does not appear to be more severe than in similarly treated patients undergoing bone marrow transplantation. For allogeneic transplantation, mobilized blood cell collections are an alternative to bone marrow collections.
Preliminary results from a phase II study of lenalidomide oral monotherapy in relapsed/refractory aggressive non-Hodgkin lymphoma
Authors: P. H. Wiernik, I. S. Lossos, J. Tuscano, G. Justice, J. M. Vose, D. Pietronigro, K. Takeshita, A. Ervin-Haynes, J. Zeldis, T. Habermann
Journal: Journal of Clinical Oncology (2007)

8052 Background: Lenalidomide (Revlimid), an immunomodulatory drug of the IMiDs class, is approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. This study was designed to assess the safety and efficacy of lenalidomide in patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed/refractory aggressive NHL with measurable disease after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Results: As of enrollment cut-off, 50 patients were enrolled and 49 received drug. Forty-one patients were evaluable for response. The median age was 65 (46–84) and 18 were female. Histology was diffuse large B-cell lymphoma [DLBCL] (n=21), follicular center lymphoma grade 3 [FL] (n=3), mantle cell lymphoma [MCL] (n=14) and transformed [TSF] (n=3). Median time from diagnosis to lenalidomide was 3.2 (0.4–32) years and median number of prior treatment regimens was 3 (1–7). Fourteen patients (34%) exhibited an objective response (5 complete responses unconfirmed (CRu) and 9 partial responses (PR)), 12 had stable disease (SD) for a tumor control rate (TCR) of 63% and 15 progressive disease (PD). Responses were seen in each of the aggressive histologic subtypes studied: DLBCL (5/21), MCL (6/14), FL (2/3), and TSF (1/3). Five of 11 patients (45%) with a prior stem cell transplant responded. Progression free survival although ongoing is currently &gt; 239 (&gt;191 - &gt;373) days in patients experiencing CRu and &gt; 160 (&gt;54 - &gt;251) days in patients with PR. Most common Grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%) while most common Grade 3 adverse events were neutropenia (22%), leukopenia (14%) and thrombocytopenia (12%). Conclusion: Lenalidomide oral monotherapy is active with manageable side effects in relapsed/refractory aggressive NHL. No significant financial relationships to disclose.
KL-6 is a useful serum biomarker for early detection of interstitial lung disease
Authors: Nobuoki Kohno, Nobuhisa Ishikawa, Naoko Deguchi, Hiroshi Iwamoto, Shinichiro Ohshimo, Kazunori Fujitaka, Yoshinori Haruta, Hiroshi Murai, Noboru Hattori
Journal: European Respiratory Journal (2012)

Background:  We previously generated a murine IgG1 monoclonal antibody that recognizes a sialylated sugar chain designated KL-6. KL-6 is a high-molecular-weight glycoprotein classified as human MUC1; it has been reported as a sensitive biomarker for various types of interstitial lung diseases (ILDs). However, the clinical significance of KL-6 for early detection of ILDs has not been well evaluated.   Aims:  We aimed to determine whether serum levels of KL-6 are of any diagnostic value in the case of patients with early stages of ILDs.   Methods:  We retrospectively collected the data of 69 patients with ILD who underwent surgical lung biopsy (28 patients with chronic hypersensitivity pneumonitis, 27 with idiopathic interstitial pneumonitis, and 14 with collagen vascular disease-associated interstitial pneumonia). Serum and bronchoalveolar lavage fluid (BALF) concentrations of KL-6 were assayed using a sandwich-type electrochemiluminescence immunoassay. In addition, KL-6 expression in diseased lung specimens obtained from surgical lung biopsy was analyzed using immunohistochemistry and digital image analysis.   Results:  The proportion of serum KL-6-positive cases (KL-6, ≥500 U/ml) was 94.2% (65 of the 69 patients with ILDs). Furthermore, even when the analysis was restricted to ILD patients with normal lung function (%VC, ≥80%), the proportion of serum KL-6-positive cases was 92.6% (25 of 27 patients examined). KL-6 was prominently expressed in regenerating type II pneumocytes, and its serum and BALF levels were correlated to its expression levels in the diseased lungs.   Conclusion:  KL-6 may be a useful biomarker for ILDs even in early stages of ILDs and may greatly improve the current diagnostic methods.
The evolving role of the endocannabinoid system in gynaecological cancer
Authors: Thangesweran Ayakannu, Anthony H. Taylor, Jonathan M. Willets, Justin C. Konje
Journal: Human Reproduction Update (2015)

BACKGROUNDThe 'endocannabinoid system' (ECS), comprising endogenous ligands (endocannabinoids) and their regulating enzymes, together with the cannabinoid receptors, has attracted a great deal of attention because it affects not only all facets of human reproduction, from gametogenesis through to parturition and beyond, but also targets key mechanisms affecting some hallmarks of cancer. Recent evidence showing that cannabinoid receptors play a very important role in the development of malignancies outside of the reproductive organs suggests a similar role for the ECS in the establishment or continued development of gynaecological malignancy.
Abstract 18576: Areas of Disease Knowledge as Differential Predictors of Outcomes Among Adolescents and Adults With Congenital Heart Disease
Authors: Jamie L Jackson, Brian Misiti, Curt J Daniels, Kathryn Vannatta
Journal: Circulation (2013)

Introduction: Adolescent and adult survivors of congenital heart disease (CHD) often have difficulty reporting diagnosis and surgical history, as well as reasons for follow-up care and disease heritability. However, aspects of disease knowledge associated with patients’ self-care or their health-related quality of life (HRQoL) are not well understood. The current study aimed to assess multiple dimensions of disease knowledge and their relationships with patient self-management and HRQoL among survivors of CHD. Methods: Individuals with CHD (N = 185) were recruited from adult and pediatric cardiology clinics (93% recruitment rate). Participants were 15 to 39 years of age (M = 24.7 + 6.9) with simple (22%), moderate (44%), or complex (34%) lesions. Participants were asked to recall their diagnosis, surgical history, and current medications (RECALL), identify complications of CHD for which they are at risk and symptoms of those complications (RISK), and answer general questions about CHD, (e.g., duration of care, endocarditis, and heritability) (GENERAL). Disease knowledge was reported in percent accuracy. Measures of self-management included self-reported saturated fat intake (DIET) and frequency x intensity of physical activity (ACTIVITY). HRQoL was measured by the Physical (PCS) and Mental (MCS) Component Scales of the SF-36. Hierarchical regression analyses were conducted with age, lesion severity, RECALL, RISK, and GENERAL knowledge as predictors of self-management and HRQoL. Results: RISK and GENERAL knowledge were the only significant predictors of DIET (β = -0.19, p = 0.038, β = -0.22, p = 0.009) and ACTIVITY (β = 0.20, p = 0.043, β = -0.21, p = 0.017). However, age (β = -0.18, p = 0.037) and RECALL knowledge (β = 0.18, p = 0.022) were the only significant predictors of PCS. None of the variables significantly predicted MCS. Conclusion: This is the first study to report an association between disease knowledge and self-management among survivors of CHD. The findings suggest that understanding one’s future risks and general self-care may be more predictive of health behaviors than knowing personal medical history. Therefore, different aspects of disease knowledge may need targeting for intervention depending on the type of patient outcome.
Time Trends in Survival in Acute Lymphocytic Leukemia&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: C Zippin, S J Cutler, D Lum
Journal: JNCI Journal of the National Cancer Institute (1975)

Comparison of patients under 20 years of age with acute lymphocytic leukemia diagnosed in 1955-64 with those whose disease was diagnosed in 1965-69 revealed a marked improvement in median survival time, from 9.5 to 16.8 months. This improvement occurred among patients with less favorable hematologic and symptomatic characteristics as well as among patients with more favorable ones. However, a shift in patient characteristics was consistent with the concept of diagnosis earlier in the natural history of the disease. In the more recent period, fewer patients were classified as severely disabled, and a somewhat higher proportion were in more favorable categories with respect to platelet count, percent of polymorphonuclear leukocytes, organomegaly, and bleeding or infection. Initial treatment was markedly different during the two time periods; this reflected a shift toward the use of combinations of chemotherapeutic agents and steroids.
Quality of life (QoL) measurement in breast cancer patients who were offered an evaluation at the hereditary cancer unit
Authors: M. D. Diz, I. Snitcovsky, G. F. Almeida, S. Maistro, M. H. Federico
Journal: Journal of Clinical Oncology (2006)

18532 Background: An Hereditary Cancer Unity was recently established in our service and we aimed to determine how many of our pts with a history of breast cancer would fulfill the criteria for undergoing BRCA1/2 genetic counseling. In addition, we asked whether or not a routine referral for a consultation in this population should impact on QoL. Methods: From September to November 2005, 180 women being followed-up at our service with a history of breast cancer, not in chemotherapy, were invited to schedule a appointment for genetic counseling. 130 pts answered the invitation and were asked to complete QoL questionnaires EORTC QL30 and BR23 (QLQ) validated into Brazilian Portuguese, before and after genetic counseling. Data were analyzed by Wilcoxon test or regression analysis, whatever appropriate, p≤0.05 considered significant. Results: All 130 pts were evaluated and BRCA1/2 mutation risk assessed based on previously published criteria (Frank et al, JCO 20:1480,2002). We evaluated that, as a whole, 25 pts harbor at least 10% probability and 3 were identified that present at least 20% probability. Three additional pts had bilateral cancer. None of these pts had been previously referred to genetic counseling. Regarding EORTC QLQ pre- and post genetic counseling, we found no differences regarding global QoL (75 vs 66), functional scales physical (80 vs 86), role (100 vs 100), cognitive (83 vs 83, social (100 vs 100), sexual function (83 vs 83), sexual pleasure (50 vs 66) or future perspective (33 vs 66) (p &gt; 0.05). Concerning the emotional scale, we found an improvement after counseling (58 vs 75, p = 0.034) which seems to be clinically meaningful. Emotional status and global QoL were positively correlated (p &lt; 0.000, r = 0.473, Pearson correlation). Conclusions: Our impression is that genetic counseling benefit breast cancer pts in terms of QoL, perhaps decreasing emotional distress. Apart from that, we need to define which risk threshold should be adopted in our service. Acknowledgment: to Marcelo Lopes technical assistance. No significant financial relationships to disclose.
Chromogranin A Is Preferentially Cleaved into Proangiogenic Peptides in the Bone Marrow of Multiple Myeloma Patients
Authors: Mimma Bianco, Anna Maria Gasparri, Barbara Colombo, Flavio Curnis, Stefania Girlanda, Maurilio Ponzoni, Maria Teresa Sabrina Bertilaccio, Arianna Calcinotto, Angelina Sacchi, Elisabetta Ferrero, Marina Ferrarini, Marta Chesi, P. Leif Bergsagel, Matteo Bellone, Giovanni Tonon, Fabio Ciceri, Magda Marcatti, Federico Caligaris-Cappio, Angelo Corti
Journal: Cancer Research (2016)

Angiogenesis has been postulated to be critical for the pathogenesis of multiple myeloma, a neoplastic disease characterized by abnormal proliferation of malignant plasma cells in the bone marrow (BM). Cleavage of the N- and C-terminal regions of circulating chromogranin A (CgA, CHGA), classically an antiangiogenic protein, can activate latent antiangiogenic and proangiogenic sites, respectively. In this study, we investigated the distribution of CgA-derived polypeptides in multiple myeloma patients and the subsequent implications for disease progression. We show that the ratio of pro/antiangiogenic forms of CgA is altered in multiple myeloma patients compared with healthy subjects and that this ratio is higher in BM plasma compared with peripheral plasma, suggesting enhanced local cleavage of the CgA C-terminal region. Enhanced cleavage correlated with increased VEGF and FGF2 BM plasma levels and BM microvascular density. Using the Vk*MYC mouse model of multiple myeloma, we further demonstrate that exogenously administered CgA was cleaved in favor of the proangiogenic form and was associated with increased microvessel density. Mechanistic studies revealed that multiple myeloma and proliferating endothelial cells can promote CgA C-terminal cleavage by activating the plasminogen activator/plasmin system. Moreover, cleaved and full-length forms could also counter balance the pro/antiangiogenic activity of each other in in vitro angiogenesis assays. These findings suggest that the CgA-angiogenic switch is activated in the BM of multiple myeloma patients and prompt further investigation of this CgA imbalance as a prognostic or therapeutic target. Cancer Res; 76(7); 1781-91. ©2016 AACR.
The Psychopathology of Suicide: A Clinical Model Approach
Authors: Jerome A. Motto
Journal: American Journal of Psychiatry (1979)

The author hypothesizes that certan types of persons at high risk for suicide constitute definable clinical models, that the process of arriving at a suicidal outcome involves elements unique to each model, and that these elements can be considered manifestations of psychopathology. This approach is investigated using two models: "Males Under Forty" and "Stable with Forced Change." The results indicate statistically reliable differences between the models in the distributions of estimated risks for persons who subsequently committed suicide compared with those who did not. The implications of the associated highrisk variables as reflections of psychopathologic processes are considered.
T790M mutation and c-MET amplification might be correlated to TTP of EGFR-TKI in NSCLC
Authors: Y. Wu, T. S. Mok, H. Chen, X. Zhang, A. Guo, P. A. Jänne
Journal: Journal of Clinical Oncology (2008)

8107 Background: In current knowledge about 50% of non-small cell lung cancer resistance to TKI is due to the occurrence of a secondary mutation in exon 20 of EGFR (T790M) and 20% to c-MET amplification. The relationship between time to progression and mutation or amplification is still unknown. This study was to investigate the difference between T790M mutation and C-MET amplification in gefitinib or erlotinib resistant NSCLC. Methods: 14 EGFR-TKI resistant NSCLC tissue samples and 23 samples without treatment of EGFR-TKI were collected. T790M mutation was detected by direct sequencing. C-MET was quantified by SYBR Green real time qPCR in cancer tissues selected by laser microdissection. Results: T790M mutation was detected in 21.4% (3/14). C-MET was highly amplificated in 15.4% (2/13). Both coexisting of T790M mutation and C-MET amplification in one sample was not detected. The median TTP in 14 cases resistant to EGFR-TKI was 210 days and overall survival 449 days. The median TTP in patients with highly amplificated C-MET was 40 days and OS 68 days. The TTP in cases with T790M mutation was 398 days and OS 680. The remaining cases with neither T790M nor C-MET were 192 and 477 days. Theses suggested that there were some relationship between TTP of TKI and resistant mutation or c-MET amplification. 100% (5/5) patients with T790M or highly amplificated c-MET were resistant to subsequent treatments (chemotherapy or irradiation) following EGFR-TKI, but 44.4% (4/9) cases achieved disease control when negative T790M or C-MET. Conclusions: T790M mutation and c-MET amplification might predict the resistance to EGFR TKI. The study implies that T790M mutation or highly amplificated C-MET is correlated to TTP of EGFR-TKI treatment in NSCLC. And the presence of T790M or highly amplificated C-MET might predict poor response to further treatment failure to EGFR-TKI. No significant financial relationships to disclose.
Effect of Asparagine and Glutamine Deficiency on Normal and Leukemic Cells 2
Authors: Robert Schrek, John S. Holcenberq, Karam V. Batra, Joseph Roberts, William C. Dolowy
Journal: JNCI Journal of the National Cancer Institute (1973)

Normal and leukemic human blood cells and cells from mouse lymphoma 6C3HED were incubated in media that lacked L-asparagine or L-glutamine or both. Viable cell counts and the incorporation of radioactive L-leucine into cell proteins were measured before and after incubation. The absence of either L-asparagine or L-glutamine from the media produced a delayed cytocidal effect on 6C3HED cells and caused a decreased uptake of L-leuclne, Cells from patients with acute leukemia also required L-asparagine and Lglutamine for survival at 37° C for 2–5 days, but seemed less sensitive than the 6C3HED cells. L-Glutamine but not L-asparagine deficiency killed lymphocytes from 5 of 6 patients with chronic leukemia and inhibited the uptake of LL-leucine. L-Asparagine deficiency had no effect, and L-glutamine deficiency only minimal effect, on normal lymphocytes as measured by percent survival or L-leucine uptake. Transformation of normal lymphocytes by pokeweed mitogen was, however, completely inhibited by a deficiency of L-glutamine but not by a deficiency of L-asparagine.