tbuckley/cabot-search huggingface dataset:
Using an interactive CD-ROM to gain informed consent for chemotherapy: Attempting to improve patient anxiety and depression during treatment
Authors: I. N. Olver, H. S. Whitford
Journal: Journal of Clinical Oncology (2007)

17071 Background: In a previous study, we found that an interactive CD-ROM did not adequately improve patients’ recall of chemotherapy treatment information compared to standard written information enough to warrant changes to the consent procedure. However, we further investigated whether this alternative mode of information delivery helped improve patients’ anxiety and depression over the treatment phase. Methods: Ninety-eight new patients about to commence chemotherapy were randomized to receive written information or an interactive CD-ROM containing treatment information before giving informed consent. Patients’ anxiety and depression were assessed pre- treatment using the Hospital Anxiety and Depression Scale (HADS) and once again at their second chemotherapy session along with their recall of treatment related information. Seventy patients completed all assessments. Results: Results indicated that anxiety and depression levels of the current sample were greater than those of normative groups including general population and cancer samples. Between/within subjects ANOVAs revealed that anxiety did decrease over the first phase of patients’ treatment (p = .001), but that written and CD-ROM groups did not differ in that increase (p = .99). Alternatively, depression scores increased during treatment but not significantly (p = .58) and once again, scores did not differ between the two information groups (p = .64). Conclusions: Given the results of some additional correlational analyses it appears that anxiety and depression scores are negatively associated with patients’ ability to recall and essentially understand aspects of treatment information given to them prior to chemotherapy. However, changing the mode of treatment information delivery does not appear to affect these psychological problems, and in turn, how they affect informed consent. No significant financial relationships to disclose.
Geogenic dust impacts cell viability and inflammatory cytokines in human airway epithelial cells
Authors: Holly D. Clifford, Anthony Kicic, Kara Perks, Luke J. Berry, Kak-Ming Ling, Erika N. Sutanto, Alexander N. Larcombe, Graeme R. Zosky
Journal: European Respiratory Journal (2014)

Background Environmental particulate matter (PM) exposure has been linked epidemiologically to exacerbations of lung disease. We have previously shown using in vivo animal models that geogenic (earth-derived) PM can exacerbate the response to respiratory infection. However, the specific impact of geogenic PM on human airway cells is not known.

Aim To determine the effects of community-sampled geogenic dust PM10 (PM <10µm diameter) in human airway epithelial cells (AEC).

Methods Geogenic dust was sampled from four towns in Western Australia (Kalgoorlie, Karratha, Tom Price and Port Hedland), and the PM10 fraction was extracted. Two immortalized human AEC models (NuLi-1, healthy; CuFi-1, cystic fibrosis) were exposed in vitro to geogenic PM10 (10µg/mL in PBS). After 24h incubation, cell viability and inflammatory cytokine production (IL-6, IL-8, RANTES) were assessed.

Results Cell viability was significantly decreased in the CuFi-1 AECs, when exposed to geogenic PM10 from Kalgoorlie (18.5% ±7.8; p=0.008), Karratha (18.9% ±3.6; p=0.007), Tom Price (20.7% ±6.0; p=0.003) and Port Hedland (19.2% ±5.7; p=0.006), compared with control. No loss of viability was observed in the NuLi-1 cells. In CuFi-1 AECs, IL-6 levels were significantly higher compared with control when exposed to geogenic PM10 (all p<0.001), as were IL-8 levels in the NuLi-1 cells (all p<0.001).

Conclusion Geogenic dust particles impact on human AECs, affecting viability and inflammatory cytokine production. This has important implications for respiratory health in individuals living in arid environments who are exposed to high particulate loads of geogenic origin, particularly those with pre-existing respiratory conditions.
Back-up bone marrow is frequently ineffective in patients with poor peripheral-blood stem-cell mobilization.
Authors: M J Watts, A M Sullivan, D Leverett, A J Peniket, A R Perry, C D Williams, S Devereux, A H Goldstone, D C Linch
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess hematologic recovery and procedure-related mortality in patients who received high-dose therapy with stem-cell support, in whom the peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells &lt; 1 x 10(6)/kg). The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC) measurements and the value of bone marrow obtained after PBSC collection failure was assessed. PATIENTS AND METHODS The study group comprised 324 consecutive patients mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and G-CSF alone (14 patients). Between one and four aphereses were performed. RESULTS In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+ cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but platelet independence was delayed (&gt; 28 days) in eight patients. Of 28 patients with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC alone and five had delayed engraftment. Twelve patients with less than 1 x 10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected after PBSC collection failure. Eleven patients were assessable for engraftment; four patients had slow (&gt; 21 days) or delayed (&gt; 28 days) neutrophil recovery and eight patients had delayed platelet recovery. In the group of patients who received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths. CONCLUSION This study shows that delayed hematologic recovery is frequent if less than 1 x 10(6)/kg CD34+ cells are infused after high-dose therapy, particularly with GM-CFC less than 1 x 10(5)/kg. The procedure-related mortality in this latter group is high. In most patients whose PBSC collection contains less than 1 x 10(5)/kg GM-CFC, the use of bone marrow cells does not improve engraftment, which suggests that poor PBSC mobilization usually indicates poor marrow function.
Primary mediastinal small cell melanoma achieved by EBUS-TBNA
Authors: Sebastian Fernandez-Bussy, Gonzalo Labarca, Alex Castro, Ivan Caviedes
Journal: Thorax (2015)

A 54-year-old woman, heavy smoker (30 packs/year) presented with 1-month of dry cough, in association with intermittent mild haemoptysis. She denied other complaints, has no remarkable medical problems and was not on any medications.

She looked well, and physical examination was normal. Chest X-ray showed a mediastinal mass, and chest CT scan confirmed a heterogeneous pretracheal mass extended from the upper third down to the main carina. PET-CT scan demonstrated increased standardised uptake values, without extra mediastinal involvement (figure 1).



Figure 1 
Chest CT scan showed a heterogeneous mediastinal mass. PET-CT scan …
Targeted proteomics analysis of EGFP expressing metastatic breast cancer cells using mass spectrometry.
Authors: Leasa Greene, Sarah Schwartz, Sarah Dallas, Patricia Veno, Lynda Bonewald
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

605 

Breast cancer metastases to bone or other soft tissues result in complications including treatment difficulty and poor patient prognosis. Identification of tumor markers that are metastasis site specific, such as bone versus soft tissue organs, may enable the design of novel approaches for the diagnosis, monitoring and treatment of breast cancer metastasis. To monitor metastasis for site-specific biomarkers, breast cancer metastastatic tumors were analyzed in their metastatic microenvironment by MALDI TOF MS (matrix assisted laser desorption/ionization time-of-flight mass spectrometry). This approach allows for MS analysis of discrete tumor deposits within intact tissue sections.

MDA-MB-231 breast cancer cells as well as an EGFP-expressing MDA-MB-231 cell line were used in a nude mouse breast cancer metastasis model. Metastases from the EGFP-expressing cell line metastasis were analyzed to evaluate the effectiveness of correlating tumor deposit localization by fluorescence microscopy prior to MALDI TOF MS protein profiling. Healthy control mice and those with metastatic tumors were sacrificed when bone lesions were detected by X-ray. Tumor, muscle, bone, bone marrow, liver and kidney tissues were harvested and immediately frozen on dry ice and stored at -80°C.

Consecutive, frozen 10-12 μm thick tissue sections were cut and mounted on glass microscope slides or chilled MALDI target plates. Tissues on glass slides were stained with either toluidine blue for tissue morphology or DAPI nuclear stain, mounted in 9:1 glycerol: PBS and viewed by bright field or fluorescent microscopy. Tumor cell deposits and other areas of interest were located and targeted for protein profiling. Images taken of each slide documented the morphology of the metastatic target and surrounding tissue regions. Droplets of MALDI matrix were applied to each target area as indicated by the microscopic images and MS protein profiling was performed using an Applied Biosystems Voyager DE-STR MALDI mass spectrometer (Framingham, MA).

MALDI-TOF protein profiling was performed on the specific tissue areas identified by microscopic analysis. Analysis of the metastatic cells demonstrated greater than 20 protein signals with potential differential expression between non-tumor regions as well as between tumor metastases to different tissues, such as bone compared to adrenal gland. The techniques applied here are applicable to a variety of studies including monitoring small molecule localization within tissues and determining protein pattern changes in response to exposure or treatment.
Prevalence of memory problems that limit daily functioning in adult cancer patients: A national representative sample of the U.S. population.
Authors: P. Jean-Pierre, P. Winters, T. Ahles, M. Antoni, D. Armstrong, F. Penedo, S. E. Lipshultz, T. L. Miller, G. R. Morrow, K. Fiscella
Journal: Journal of Clinical Oncology (2010)

9134 Background: Cancer and its treatments can adversely affect important aspects of cognitive functioning, especially memory. Few epidemiological studies, however, have examined the prevalence of memory impairment in cancer patients. This study quantifies the difference in memory problems between cancer and non-cancer populations. Methods: We used a stratified multi-stage probability sample of the civilian non- institutionalized U.S. population drawn from the National Health and Nutrition Examination Survey. Individuals with brain tumors were excluded because their cognitive impairments may have resulted directly from brain pathology or surgery/treatment. Participants were asked about limiting memory impairment that interfered with daily functioning using a self-report measure that was validated with scores on the Digit Span Test (given to a sub-sample). We adjusted our logit model for age, sex, race/ethnicity, education, poverty and general health condition. Analyses were conducted using SAS 9.2 and SAS-callable SUDAAN 10.0 statistical software packages. Results: The sample included 9,819 individuals (4,862 males; 4,957 females) age 40 years and older from diverse educational and racial/ethnic backgrounds (blacks [1,938], whites [5,552], Hispanics [1,998] and other race/multi-racial [331]). Of the total sample, 1,305 participants have had cancer and 8,514 have not had cancer. More patients who have had cancer (14%) compared to those who have not had cancer (8%) reported memory problems. Having had cancer was independently associated with memory impairment (OR = 1.450 [95% CI = 1.121 to 1.875]). Other predictors of memory impairment included older age, sex, race/ethnicity, lower education, higher poverty, and poor general health (p < 0.01). Overall, people with cancer had a nearly 50% greater likelihood of memory problems than those without cancer. Conclusions: Cancer diagnosis was an independent predictor of memory impairment, which can exacerbate the disease burden and diminish quality of life. Strategies to reliably assess and control this problem for cancer patients and survivors are needed. No significant financial relationships to disclose.
Acute neurotoxicity in children with B-precursor acute lymphoid leukemia: an association with intermediate-dose intravenous methotrexate and intrathecal triple therapy--a Pediatric Oncology Group study.
Authors: D H Mahoney, J J Shuster, R Nitschke, S J Lauer, C P Steuber, N Winick, B Camitta
Journal: Journal of Clinical Oncology (1998)

PURPOSE To describe the incidence of acute neurotoxicity (NT) in children with lower risk B-precursor acute lymphoid leukemia (ALL) treated with intermediate-dose methotrexate (MTX) or divided dose oral MTX with or without intravenous (i.v.) mercaptopurine (MP) and extended intrathecal triple therapy. PATIENTS AND METHODS Thirteen hundred four patients were entered onto Pediatric Oncology Group (POG) 9005, a randomized phase III trial, between January 11, 1991 and September 1, 1994. After remission induction, patients were randomized to one of three 24-week intensification schedules: regimen A, MTX 1,000 mg/m2 i.v. infused over 24 hours and MP 1,000 mg/m2 i.v. infused over 6 hours; regimen B, low-dose repetitive MTX 30 mg/m2 orally every 6 hours for six doses and i.v. MP; or regimen C, i.v. MTX alone. Intensification was given every 2 weeks for 12 courses. CNS prophylaxis was age-adjusted intrathecal MTX (ITM). In August 1992, the CNS prophylaxis was changed to age-adjusted triple intrathecal therapy (TIT). Reports of grades 3 and 4 acute NT were reviewed. RESULTS Acute NT was reported in 95 of 1,218 (7.8%) eligible patients treated on POG 9005. The incidence by regimen was regimen A, 46 of 543 patients (8.3%); regimen B, 13 of 354 patients (3.7%); and regimen C, 36 of 321 patients (11.2%) (P &lt; .001). The majority of events were seizures and the median number of days to first occurrence of symptomatic NT after ITM or TIT was 10 to 11 days. Computed tomography (CT) or magnetic resonance imaging (MRI) evidence consistent with leukoencephalopathy (LE), with or without the presence of cerebral calcifications, was observed in 75% and 77.1 % of symptomatic patients treated on regimens A and C, respectively, but in only 15.4% of symptomatic patients treated on regimen B (P &lt; .001). Factors associated with an increased incidence of NT included increased cumulative exposure with repeated i.v. MTX (regimens A and C v B), increased MTX-leucovorin (LCV) ratio (regimens A and C v B), and choice and timing of TIT therapy. The use of i.v. MP during intensification did not appear to contribute to these complications. The switch to TIT CNS prophylaxis was associated with an inferior overall 4-year continuous complete remission (CCR) (P=.031) when compared with ITM. CONCLUSION Intensification with repeated i.v. MTX in the setting of low-dose LCV rescue was associated with a higher risk for acute NT and LE, especially in patients who received concomitant TIT. The long-term consequences for affected patients remain unknown.
The induction of MAGE-1 mRNA and protein expression in the 888-mel human melanoma cell line treated with 5-fluoro-2’-deoxycytidine
Authors: Jessie Hou, Edward Newman
Journal: Cancer Research (2008)

2612   5-Fluoro-2’-deoxycytidine (FdCyd) inhibits DNA methyltransferases which are responsible for methylation of the C-5 position of cytosine in CpG dinucleotides. FdCyd is able to induce expression of some genes silenced by DNA methylation through the reduction of methylation at their promoter region. The human  MAGE-1  gene is not expressed in any normal adult tissue except in testis and its CpG-rich 5’-region is methylated in normal cells. The MAGE-1 negative human melanoma cell line 888-mel was used as a model for studying the effects of FdCyd on the expression of  MAGE-1  mRNA and protein. Based on bisulfite sequencing methodology, we reported previously that the degree of methylation in a 5’-CpG island of untreated 888-mel cells varied substantially among the 17 individual CpGs. Overall, FdCyd decreased the methylation substantially at CpGs which were highly methylated to begin with. Because FdCyd caused demethylation of CpGs in  MAGE-1  gene 5’-region, we studied the expression of  MAGE-1  mRNA in 888-mel by real-time RT-PCR.  MAGE-1  mRNA was detected after 2 weeks of treatment with 10 and 100 μM FdCyd treatment. The expression increased gradually with longer exposure to 10 and 100 μM FdCyd. The level of  MAGE-1  expression with 100 μM treatment was higher than with 10 μM FdCyd treatment at each time point. The results from real-time RT-PCR indicated that expression of  MAGE-1  mRNA increased as function of both FdCyd concentration and time of exposure. Since  MAGE-1  mRNA in 888-mel cells was induced by FdCyd treatment, we investigated the MAGE-1 protein. MAGE-1 Ab-4 (Clone MA454, ThermoScientific) was used to detect the gene product. The immunoblot analysis was performed on extracts from 888-mel treated with 10 and 100 μM FdCyd for 8 and 10 weeks. MAGE-1 protein was detected in 888-mel treated with 10 μM FdCyd for 10 weeks or with 100 μM FdCyd for 8 and 10 weeks. In conclusion, FdCyd reduced the methylation of CpGs within  MAGE-1  5’-CpG island, induced the expression of MAGE-1 mRNA, and increased MAGE-1 protein. Our results indicated that FdCyd has similar effects on DNA methylation and gene expression as 5-aza-2’-deoxycytidine, although it is less potent. (Supported by DOD grant W81XWH-04-1-0538.)
A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study
Authors: Rafael Duran, Karun Sharma, Matthew R. Dreher, Koorosh Ashrafi, Sahar Mirpour, MingDe Lin, Ruediger E. Schernthaner, Todd R. Schlachter, Vania Tacher, Andrew L. Lewis, Sean Willis, Mark den Hartog, Alessandro Radaelli, Ayele H. Negussie, Bradford J. Wood, Jean-François H. Geschwind
Journal: Theranostics (2015)

Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent bead's location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model.RO Beads, which are based on LC Bead® platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT).Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the bead's interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads ≤300 µm were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy.RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.
A phase I trial of intravenous therapy with tumor suppressor FUS1-nanoparticles for recurrent/metastatic lung cancer
Authors: C. Lu, D. J. Stewart, L. Ji, R. Ramesh, G. Jayachandran, J. Erasmus, J. J. Lee, N. S. Templeton, J. D. McMannis, J. A. Roth
Journal: Journal of Clinical Oncology (2009)

e19065 Background: The tumor suppressor gene FUS1 is frequently inactivated early in lung cancer development. FUS1 mediates apoptosis in cancer cells but not normal cells through its interaction with Apaf1. DOTAP:cholesterol nanoparticles encapsulating a FUS1 expression plasmid showed selective uptake by cancer cells and activity in mouse xenograft metastatic lung cancer models. Methods: Patients with recurrent/metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous DOTAP:cholesterol FUS1 nanoparticles. Nanoparticle-DNA complexes were manufactured in GMP facilities to meet specifications of OD400, size, appearance, and transfection efficiency. Results: Patients have received doses ranging from 0.01–0.09 mg/kg at 3 week intervals. To date 23 patients have been entered on study at 6 dose levels, with 21 patients currently evaluable for the primary endpoint of cycle 1 toxicity. 70% of subjects had received 2 or more prior chemotherapy regimens. Among 4 patients treated without premedications, all 4 developed grade 2 or higher fevers within 24 hours of treatment. Among the 17 patients premedicated with dexamethasone and diphenhydramine, 4 developed grade 1 fever. There have been no other grade 2 or higher drug-related toxicities. Four patients received only one dose because of rapidly progressing disease at a site requiring local treatment. Fifteen patients received two or more doses and are evaluable for response, with 4 patients achieving stable disease and 11 patients progressing. Median survival time for all patients is 10.3 months. A maximum tolerated dose (MTD) has not been reached. Pre and 24 hour posttreatment tumor biopsies were obtained from 4 patients. A quantitative real time reverse transcriptase PCR (RT-PCR) analysis using a plasmid FUS1 sequence-specific probe have been performed on 3 paired-samples blinded to time of biopsy. A high level of plasmid FUS1 expression was detected in all 3 posttreatment samples but not in three pretreatment samples and negative controls by RT-PCR. Conclusions: DOTAP:cholesterol FUS1 nanoparticles can be safely administered intravenously in lung cancer patients with demonstrable gene expression in posttreatement tumor biopsies. [Table: see text]