tbuckley/cabot-search huggingface dataset:
Phase II study of sagopilone (ZK-EPO) plus prednisone as first-line chemotherapy in patients with metastatic androgen-independent prostate cancer (AIPC)
Authors: J. Graff, D. C. Smith, L. Neerukonda, M. Alonso, G. R. Jones, T. M. Beer
Journal: Journal of Clinical Oncology (2008)

5141 Background: The microtubule stabilizer docetaxel, in combination with prednisone, prolongs life in patients with metastatic AIPC. Epothilones are a new class of microtubule stabilizers. The activity and safety of the fully synthetic epothilone B analogue sagopilone (ZK-EPO) was evaluated in chemotherapy-naïve AIPC patients. Methods: Patients with metastatic AIPC received sagopilone, 16 mg/m2 IV over 3 hours every 21 days and prednisone 5 mg PO BID continuously. Treatment was repeated every 21 days for up to 6 cycles. Extended treatment was allowed for patients felt to benefit from treatment at the end of 6 cycles. Among the first 13 patients, 3 responders (consensus PSA criteria) were required for enrollment to continue to a total goal of 46. Results: 29 patients were enrolled between August 2006 and October 2007 and accrual continues. All patients are evaluable for safety and 24 of 29 patients are evaluable for response. Patients who were not evaluable for response include 4 on treatment and 1 who was ineligible. The median number of cycles therapy was 4 (range 1 to 11). Toxicity ≥Grade 3 included: neuropathy 24%, fatigue 8%, diarrhea 4%, dizziness 4%. Of the 24 patients evaluable for response, 5 (21%; 95%CI: 7–42%) met the criteria for PSA response (confirmed ≥50% reduction in PSA) and 14 (58%; 95%CI: 37–78%) had a 30% reduction in PSA within 3 months of enrollment, a measure recently shown to most strongly correlate with subsequent survival in studies of docetaxel. Of 12 patients with radiographic measurable disease, 1 had a confirmed complete response and 1 a confirmed partial response (PR) by RECIST criteria. An additional 4 patients had an unconfirmed PR. Conclusions: Sagopilone is active in AIPC. Further follow-up is required to verify the level of activity and tolerability and to set this in the context of other agents, such as docetaxel combined with prednisone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Oncology Bayer HealthCare Pharmaceuticals Bayer HealthCare
Studies on Acute Leukemia and Infectious Mononucleosis of Childhood. III. Incidence of Spontaneous Lymphoblastoid Transformation in Bone Marrow Cultures<xref ref-type="fn" rid="FN2">2</xref>
Authors: Matilda Benyesh-Melnick, Donald J. Fern-Bach, Sylvia Dessy, Raymond T. Lewis
Journal: JNCI Journal of the National Cancer Institute (1968)

During a 5-year period, 757 fibroblastic bone marrow cultures from 373 children (482 cultures from 114 children with acute leukemia, 49 cultures from 48 children with infectious mononucleosis, 210 cultures from 195 children with various other diseases, and 16 cultures from 16 normal children) were studied to determine the frequency of occurrence and pattern of distribution of a spontaneous conversion to mixed cultures containing lymphoblastoid and fibroblastic cells—a phenomenon termed “spontaneous lymphoblastoid transformation of fibroblastic bone marrow cultures.” Lymphoblastoid transformation occurred in 59 of the 757 cultures studied. Of these, 19 were from 11 of the 114 (10%) children with leukemia—4 children yielding altered cultures more than once. The incidence was similar in cultures derived during relapse or remission. The incidence of lymphoblastoid transformation was much higher in cultures of children with infectious mononucleosis; 27 of the 48 children studied (56%) yielded altered cultures. In addition, the same changes were found in cultures of 13 of the 195 children (7%) with other disease entities, several diagnosed as presumptive infectious mononucleosis. None of the 16 normal children studied yielded transformed cultures. The close association of lymphoblastoid transformation with infectious mononucleosis, the absence of random distribution among the 482 cultures from the patients with leukemia, and the repeated occurrence in serial bone marrow cultures from only certain leukemia patients indicate that the phenomenon was characteristic for the individual bone marrow aspirate cultured and not due to random sampling of the population studied. Cytological examination did not reveal detectable differences in the altered cultures, regardless of the clinical diagnosis of the children from whom the cultures were derived.
A phase I trial of continuous hyperthermic peritoneal perfusion using cisplatin in pediatric patients with carcinomatosis.
Authors: A. A. Hayes-Jordan, H. L. Green, P. M. Anderson, L. Xiao, K. Hunt, P. F. Mansfield
Journal: Journal of Clinical Oncology (2010)

9544 Background: The delivery of regional hyperthermic chemotherapy using continuous hyperthermic peritoneal perfusion (CHPP) has been well established in adults with carcinomatosis. This approach has not previously been used in children. Here we report a phase I trial of CHPP using cisplatin after extensive cytoreductive surgery for pediatric patients with extensive abdominal metastasis from sarcomatosis or mesothelioma. Methods: This phase I study includes 10 enrollments in patients age 3 to 18 years who received dose escalation of cisplatin after cytoreductive surgery followed by CHPP at a single institution. A standard 3 by 3 dose escalation format was used starting at 100 mg/m2. Patients diagnosed with desmoplastic small round cell tumor (DSRCT), rhabdomyosarcoma (RMS), liposarcoma and mesothelioma who had refractory and extensive abdominal disease were included. Patients with liver metastasis were included. However, patients with disease outside of the abdominal cavity were excluded. A summary of morbidities and toxicities including dose limiting toxicity (DLT) and maximum tolerated dose (MTD) are reported. Results: All subjects enrolled completed the study and there were no on study mortalities. DLT was renal insufficiency manifest as elevation in creatinine without the need for dialysis. MTD was 150 mg/m2 given for 90 minutes at 40.5 degrees Celsius. There were 2 grade 3 renal toxicities, 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities and one grade 3 ileus. There was one grade 3 cardiomyopathy, asymptomatic and resolved with Beta blockers and one grade 4 wound complication. Number of tumor implants removed prior to hyperthermic perfusion with cisplatin ranged from 5 to 402 including splenectomy, partial diaphragm resection, bowel resection, cholecystectomy and partial peritonectomy. Hospital stay ranged from 5 to 13 days. Forty percent of patients had progressive disease (PD) and 60% had a complete response (CR) for at least 6 months. Conclusions: CHPP using cisplatin is safe in children at a dose of 100 mg/m2 at 40.5 degrees Celsius for 90 minutes. Renal insufficiency is likely at doses at, or greater than150 mg/m2. No significant financial relationships to disclose.
Disease activity is longitudinally related to sacroiliac inflammation on MRI in male patients with axial spondyloarthritis: 2-years of the DESIR cohort
Authors: Victoria Navarro-Compán, Sofia Ramiro, Robert Landewé, Maxime Dougados, Corinne Miceli-Richard, Pascal Richette, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> To investigate the longitudinal relationship between inflammatory lesions in sacroiliac joints on MRI (MRI-SI) and clinical disease activity measures (DA) in patients with axial spondyloarthritis (axSpA). <h3>Methods</h3> Two-year follow-up data from 167 patients (50% males, mean (SD) age 33 (9) years) fulfilling the Assessment of SpondyloArthritis international Society axSpA criteria in the DEvenir des Spondylarthopathies Indifférenciées Récentes cohort with MRI-SI at baseline, 1 year and 2 years were analysed. The relationship between MRI-SI (as dependent variable) and DA (Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), patient9s global DA, night pain, C reactive protein and erythrocyte sedimentation rate, as independent variables) was investigated using two types of generalised estimating equations (GEE) models: model of absolute scores and model of change scores. <h3>Results</h3> In the model of absolute scores, the relationship between DA and MRI-SI was different for males and females: in males, but not in females, a statistically significant relationship with MRI-SI was found for all DA except BASDAI. In the model of changes, only ASDAS (beta (95% CI): 2.79 (0.85 to 4.73) and pain at night (0.97 (0.04 to 1.90)) were significantly associated in males while again in females no significant relationship was found. ASDAS fitted the data best. <h3>Conclusions</h3> In male patients, but not in female patients, with axSpA, clinical DA, especially if measured by ASDAS, is longitudinally associated with MRI-SI inflammatory lesions.
Phase I trial of murine monoclonal antibody L6 in breast, colon, ovarian, and lung cancer.
Authors: G E Goodman, I Hellström, L Brodzinsky, C Nicaise, B Kulander, D Hummel, K E Hellström
Journal: Journal of Clinical Oncology (1990)

Murine monoclonal antibody (MAb) L6 binds to an antigen expressed on the surface of breast, colon, ovary, and nonsmall-cell lung cancer. This antibody effects antibody-dependent cellular cytotoxicity (ADCC) with human mononuclear cells and complement-dependent cytotoxicity (CDC) with human complement. Because of these activities, we conducted a phase I trial of MAb L6 in patients with advanced cancer. Nineteen patients whose tumors highly expressed antigen were selected for this trial. Eighteen were evaluable. MAb L6 was administered at dose levels ranging from 5 mg/m2/d to 400 mg/m2/d for 7 days and was well tolerated. The only side effects detected were fever and headaches at the highest dose levels. The serum half-life of L6 was directly related to dose and ranged from a mean of 7.7 hours at 5 mg/m2/d to 29.1 hours at 400 mg/m2/d. Peak serum concentrations ranged from 0.22 micrograms/mL to 362 micrograms/mL. Biopsies at the end of treatment showed L6 to localize well to tumor cells with apparent in vivo saturation occurring at dose levels above 100 mg/m2/d. Thirteen patients formed human antimouse antibodies (HAMA), some as early as day 13. One patient with recurrent breast cancer on the chest wall achieved a complete remission. The response was first noted at 5 weeks and a pathologic complete remission occurred at 14 weeks. Because of its favorable binding properties and the encouraging clinical effect observed, future evaluation of this MAb appears warranted.
Costs and outcomes associated with febrile neutropenia-related hospitalizations across patients with varying cancer types: A retrospective analysis
Authors: M. B. Schilling, C. Parks, R. G. Deeter
Journal: Journal of Clinical Oncology (2009)

e20560 Background: Neutropenia, the major dose-limiting toxicity of chemotherapy, is a frequent, often serious, and sometimes fatal complication of myelosuppressive chemotherapy. Its economic and clinical impact is often under-appreciated, and thus this study evaluates the contribution of febrile neutropenia (FN) by tumor type as related to healthcare cost and mortality. Methods: FN patients in this study were identified as having cancer (ICD-9-CM: 140.xx - 208.xx), neutropenia (288.0x) and either opportunistic infections (110 total codes) or fever of unknown origin (780.6) who were hospitalized between 1/05 and 6/08 in a retrospective cohort study from the Aspen US healthcare database (∼11 million pts, &gt;342 inpatient facilities, and &gt;300 million charge-detail records). Unadjusted mean healthcare cost of hospitalization, length of hospital stay (LOS), and mortality rates were calculated, stratifying by cancer type (breast, metastatic breast, and lung cancers, non-Hodgkin lymphoma (NHL), or other hematologic tumors). Results: Among 598 hospitalized patients (mean age 63 years; 53% female) with cancer experiencing FN, the mean cost of hospitalization, LOS and mortality varied significantly by tumor type ( Table ). Conclusions: FN hospitalizations are costly and may be associated with significant mortality. Considerable variations exist across cancer types for hospitalization costs, LOS and mortality. The tumor type is important in assessing the economic and clinical impact of FN hospitalizations. [Table: see text] [Table: see text]
Abstract P070: The Relationship Between Weight and Fruit and Vegetable Consumption, Assessed by Serum Carotenoids and Self-Report: Results from the PREMIER Trial
Authors: Jessie L Parker, Liwei Chen, Diane C Mitchell, Hsin-Chieh Yeh, Cheryl Anderson, Lawrence J Appel
Journal: Circulation (2012)

Background: Increased intake of fruits and vegetables (F/V) may protect against adiposity, but effects on weight have been inconsistent. Our objective was to examine the relationship between fruit and vegetable intake and weight, using direct and indirect measures of dietary intake: self-reported 24-hour recall and serum carotenoid levels. Methods: Participants from the PREMIER lifestyle intervention trial were included in this analysis (n=554). Dietary measures included 24-hour dietary recalls and serum carotenoid levels, from a fasting blood sample. The outcome was weight in pounds. Nested linear mixed models were used to examine the association between F/V and weight. Results: Mean F/V increased from 4.6 (SD 2.4) to 5.6 (SD 3.2) (p=&lt;.01), mean serum carotenoids increased from 53.2 (SD 31.9) to 68.1 (SD 42.5) (p=&lt;.01). At 18 months, participants in the lowest quintile of fruit and vegetable change reported an average intake of 4.42.8 servings of fruits and vegetables, and those in the highest quintile of change reported an average intake of 7.73.2 servings. In a multivariate model adjusting for age, race, gender, intervention, energy, study site, and time, lower body weight was associated with higher F/V intake measured by dietary recall (−0.63 lbs, 95% CI −0.83 to −0.42, per 1 serving increase in F/V) and serum carotenoids (−0.13 lbs, 95% CI −0.15 to −0.11, per 1 ug/dl increase in carotenoids). Results were somewhat attenuated but consistent after additional adjustments for working heart rate, exercise, calories from sugar-sweetened beverages, marital and employment status, and alcohol use . Conclusions: Greater fruit and vegetable consumption was associated with decreased body weight. Results were consistent for both objective and self-reported measures of fruit and vegetable intake.
Advance care planning (ACP) prior to hematopoeitic stem cell transplantation (HSCT) in patients with cancer is associated with improved survival
Authors: F. R. Loberiza, A. K. Ganti, J. O. Armitage, P. J. Bierman, R. G. Bociek, M. P. Devetten, L. J. Maness, J. M. Vose, S. Lee
Journal: Journal of Clinical Oncology (2007)

9026 Background: HSCT carries an increased risk of mortality. Thus, patients are encouraged to have ACP. However, discussions about ACP is not a casual process since it may elicit undue anxiety to the patients and their families. Anecdotally, pts fear that discussion of the possibility of death is inconsistent with hoping for the best outcome. We therefore compared the outcomes of pts with or without ACP who received HSCT for cancer. Methods: ACP was defined as having living will, power of attorney for health care, or life-support instructions conducted prior to transplant. ACP were reviewed in pts who were at least 19 yo and received first allogeneic or autologous HSCT for cancer between 2001 and 2003. Pts were classified into: 1) No ACP, 2) ACP prior to cancer dx, 3) ACP after cancer dx but prior to HSCT. Multivariate analysis (MVA) was done to evaluate the relative risk of mortality at 1 year according to ACP while adjusting for other prognostic factors. Results: 343 pts were included in the study: 172 (50%) did not have ACP, while 171 (50%) pts had ACP. Of those with ACP, 127 pts (74%) were available for review. Characteristics were similar between pts with and without reviewable ACP. 28 pts had ACP prior to cancer dx, 87 had ACP prior to HSCT, while 12 had ACP after HSCT. 64% of pts with ACP had both power of attorney and a living will, 16% had a living will alone and 19% had power of attorney alone. Older pts (p &lt;0.001) and Caucasians (p = 0.04) were more likely to have ACP. MVA were confined to the 172 pts with no ACP and 115 who had ACP before HSCT and showed that pts with ACP prior to HSCT had a significantly lower risk of mortality (see table ). Conclusions: Despite a diagnosis of cancer and hospitalization for HSCT, only 50% of patients had engaged in ACP. ACP at any time before HSCT was associated with higher one-year survival. Engagement in ACP is not necessarily inconsistent with hoping for the best outcome in HSCT. Further study is warranted to explore the reasons for engaging or not in ACP. No significant financial relationships to disclose. [Table: see text]
Sarcoma Induced in Rats by Extracts of Plants and by Fractionated Extracts of Krameria ixina2
Authors: Roger W. O'Gara, Cecil W. Lee, Julia F. Morton, Govind J. Kapadia, Lucia J. Dunham
Journal: JNCI Journal of the National Cancer Institute (1974)

Plant substances are suspected as among the causes of cancer in the esophagus. Extracts of 8 plants commonly used internally by natives of the island of Curacao, West Indies, where esophageal cancer is frequent, were assayed in NIH Black rats for the production of sarcoma by subcutaneous injection. Our aim was to develop a preliminary screening test for suspected plants. Extract of Acacia villosa root was highly toxic, and the size of the dose was reduced; sarcomas developed after short latent periods in 100% of the rats that survived the toxic effects. Root of Melochia tomentosa also produced sarcomas in 100% of treated rats; Heliotropium angiospermum (without root) produced sarcomas in 75% of the rats. Sarcomas did not develop in rats treated with plant materials from Annona glabra, Cajanus indic us, Capraria biflora, Mangifera indica, and Mentzelia aspera. A preliminary study was made of 3 fractions of whole Krameria ixina (without root), which produced sarcomas in 100% of rats in a previous experiment. Sarcomas did not develop after injections of a fraction in the aqueous extract after removal of tannins by precipitation with caffeine.
SHFJV (super imposed high frequency jet ventilation), ETCO2 correlation to PaCO2 in diagnostic and therapeutic rigid bronchosscopy
Authors: Gabriela Koller-Halmer, Ingrid Schindler, Hubert Koller
Journal: European Respiratory Journal (2011)

We report the findings on 42 patients who underwent diagnostic and therapeutic interventional rigid bronchoscopy under SHFJV.

Monitoring of the patients included ECG, blood pressure, SaO2, EtCO2, arterial blood gas analysis, FIO2 jet, FIO2 aw.

SHFJV is defined as weight-based innovative mechanical ventilation combined with superposition of two jet-streams in an open system.

The high-frequency jet-stream is responsible for the oxygenation; the normo-frequency jet-stream regulates the CO2.

Basic patient characteristics (mean±SD):

– Age 59.7±13.8

– FEV1 (liter) 2.79±0.58

– PaCO2 (mmHg) 35.52±6

Findings after 10 minutes SHFJV:

– PaCO2 (mmHg) 35.13±11.78*

– ETCO2 (mmHg) 27.48±4.81

– FIO2 (%) 64.76±12.95

*p=0,001

General characteristics of SHFJV:

– No CO2 increase

– No risk of barotrauma (open system conditions)

– No air trapping (open system conditions)

– Best ventilation in open system

– Integrated gas analysis

– Electronically controlled

– Laser application without fire risk (laser safe mode)

Summary: SHFJV in diagnostic and therapeutic rigid bronchoscopy is a safe and effective method of ventilation to achieve sufficient oxygenation without any increase of PaCO2.
Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus
Authors: Sarah A Jones, Andrew E J Toh, Dragana Odobasic, Marie-Anne Virginie Oudin, Qiang Cheng, Jacinta P W Lee, Stefan J White, Brendan E Russ, Simona Infantino, Amanda Light, David M Tarlinton, James Harris, Eric F Morand
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease, mediated by disrupted B cell quiescence and typically treated with glucocorticoids. We studied whether B cells in SLE are regulated by the glucocorticoid-induced leucine zipper (GILZ) protein, an endogenous mediator of anti-inflammatory effects of glucocorticoids. Methods We conducted a study of GILZ expression in blood mononuclear cells of patients with SLE, performed in vitro analyses of GILZ function in mouse and human B cells, assessed the contributions of GILZ to autoimmunity in mice, and used the nitrophenol coupled to keyhole limpet haemocyanin model of immunisation in mice. Results Reduced B cell GILZ was observed in patients with SLE and lupus-prone mice, and impaired induction of GILZ in patients with SLE receiving glucocorticoids was associated with increased disease activity. GILZ was downregulated in naïve B cells upon stimulation in vitro and in germinal centre B cells, which contained less enrichment of H3K4me3 at the GILZ promoter compared with naïve and memory B cells. Mice lacking GILZ spontaneously developed lupus-like autoimmunity, and GILZ deficiency resulted in excessive B cell responses to T-dependent stimulation. Accordingly, loss of GILZ in naïve B cells allowed upregulation of multiple genes that promote the germinal centre B cell phenotype, including lupus susceptibility genes and genes involved in cell survival and proliferation. Finally, treatment of human B cells with a cell-permeable GILZ fusion protein potently suppressed their responsiveness to T-dependent stimuli. Conclusions Our findings demonstrated that GILZ is a non-redundant regulator of B cell activity, with important potential clinical implications in SLE.
Clinical and pathological features of posttransplant lymphoproliferative disorders: Influence on survival and response to treatment
Authors: R. Hauke, B. Smir, T. Greiner, P. Bierman, S. Tarantolo, J. Anderson, B. Shaw, J. Armitage
Journal: Annals of Oncology (2001)

To review the clinical and pathological characteristics of patients with posttransplant lymphoproliferative disorders (PTLD) occurring after solid organ transplantation and determine the influence of these characteristics on response to treatment and survival.Retrospective review of 32 patients.Overall five-year survival was 59%. Forty-five percent of patients diagnosed within the first year after transplant had advanced disease. Characteristics that were associated with poorer survival were diagnosis within the first year posttransplant, monoclonal tumors and presentation with an infectious mononucleosis-like syndrome. Six of eight patients treated with surgery are alive and disease-free.Patients with PTLD can achieve long-term survival. Surgery can play an important role in selected patients. Characteristics that may be associated with poorer survival are diagnosis within the first year after transplant, presence of a monoclonal tumor or an infectious mononucleosis-like presentation.