tbuckley/cabot-search huggingface dataset:
Late cardiac and pulmonary complications in breast cancer patients after adjuvant chemo-radiotherapy: 5-years follow-up
Authors: A. Niwinska, M. Tacikowska, Z. Miskiewicz, T. Pienkowski, J. Meder
Journal: Journal of Clinical Oncology (2004)

816 Background: The aim of the study was to evaluate late myocardial and pulmonary damage in breast cancer patients, after mastectomy and adjuvant sequential chemo-radiotherapy. Methods: Forty seven women with stage II and III breast cancer had mastectomy and sequential chemo-radiotherapy. In 40 patients (pts) chemotherapy with antracyclines and in 7- without antracyclines was administered. Radiotherapy included chest wall and regional lymph nodes, the specified dose was 45–50Gy /2 Gy. The high resolution computed tomography (HRCT) of the lungs, electrocardiography and echocardiography were performed after a mean time of 17 months, then, after a mean time of 33 months and finally, after a mean time of 65 months. Results: LUNGS-The first examination (after 17 monts) revealed no changes in 24 pts (51%). There were fibrotic changes in lung apex in 19 pts and 19 parietal fibrosis. In the second examination (after 33 months) a tendency to regression in parietal areas was observed (p=0.031). In third examination (after 65 months), the same percentage of pts −51% had no lung injury. The lung fibrosis was observed in 14 and parietal- in 13 pts.All these changes were discrete and asymptomatic and parietal fibrosis were invisible in chest X-ray. HEART- In first examination 7 of 47 pts had abnormal echocardiogram (ventricular dilatation, abnormal Left Ventricular Ejection Fraction). All of them received antracyclines. In 5 of them echocardiografic defect were asymptomatic and reversible at the time of second examination, in 2 -moderate toxicity was noted. The analysis of isodose distribution in all 7 cases excluded radiotherapy as a factor influencing toxicity. After 65 months, no new cardiac complications were observed and the improvement in echocardiography in 6 patients was observed (1 patient died because of disseminated disease). Conclusions: Modern postoperative radiotherapy caused no clinically significant lesions in lung and heart during 5 years of observation. Clinically important, reversible, myocardial changes, observed in 2 pts, seemed to be caused by antracyclines, but not by radiotherapy. No significant financial relationships to disclose.
Response to Open Peer Commentaries on “Fetal Risks, Relative Risks, and Relatives' Risks”
Authors: Howard Minkoff, Mary Faith Marshall
Journal: The American Journal of Bioethics (2016)

"Response to Open Peer Commentaries on “Fetal Risks, Relative Risks, and Relatives' Risks”." The American Journal of Bioethics, 16(2), p. W13
Expression of estrogen-responsive finger protein (Efp) is associated with advanced disease in human epithelial ovarian cancer
Authors: M. Sakuma, J. Akahira, T. Suzuki, S. Inoue, K. Ito, T. Moriya, H. Sasano, K. Okamura, N. Yaegashi
Journal: Journal of Clinical Oncology (2005)

3143 Background: The estrogen-responsive ring finger protein (Efp) gene is one of the estrogen receptor (ER) target genes identified in the MCF-7 human breast cancer cell line using genomic binding-site cloning. Efp is considered to be essential for estrogen-dependent cell proliferation. In the present study, we studied correlations of Efp expression with clinicopathological parameters, Efp’s significance as a prognostic indicator, and relationships between Efp and ERs expressions in human epithelial ovarian cancer. Methods: A total of 100 epithelial ovarian cancer cases were examined immunohistochemically using antibodies for Efp, ERα, and ERβ. The correlation between Efp immunoreactivity and clinicopathological parameters was examined. The expression of Efp, ERα and ERβ and mRNA expressions of Efp, ERα, and ERβ were evaluated by immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively, in 12 ovarian cancer cell lines. Results: Efp immunoreactivity was detected in the cytoplasm of carcinoma cells in 63 out of 100 cases (63%). Efp expression was significantly higher in carcinomas with serous differentiation (P=0.0102) and advanced carcinomas (P=0.0259). No significant relationship was detected between Efp immunoreactivity and overall survival. There were high correlations between Efp and ERα and β immunoreactivity (Efp and ERα, P=0.022; Efp and ERβ, P=0.0323). In immunoblotting, Efp protein was detected in 8 out of 12 cell lines; furthermore, ERα and/or ERβ protein were detected in all 8 cell lines. Significantly higher mRNA levels were detected in the 8 cancer cell lines with Efp-immunoreactive bands than in the other 4 lines without Efp-immunoreactive bands (P=0.021). Conclusion: The expression of Efp is associated with advanced disease and serous histology, and is also correlated with ER status. Our results suggest that Efp could be a prognostic indicator in human epithelial ovarian cancer. No significant financial relationships to disclose.
Bromodomain-Containing Protein 4 (BRD4): A Novel Marker and Drug Target Expressed In Neoplastic Cells In Advanced Mast Cell Neoplasms
Authors: Ghaith Wedeh, Emir Hadzijusufovic, Sabine Cerny-Reiterer, Harald Herrmann, Katharina Blatt, Gregor Eisenwort, Gregor Hoermann, Wolfgang R Sperr, Leonhard Müllauer, Christopher R. Vakoc, James E Bradner, Hans-Peter Horny, Michael Willmann, Johannes Zuber, Michel Arock, Peter Valent
Journal: Blood (2013)
Abstract A2-21: Cancer malignancy induced by C-terminal truncated HBx in Huh-7 Hepatocellular carcinoma cells
Authors: Myeong-Eun Je Gal, Eui-Yeun Yi, Seung-Youn Jung, Yung-Jin Kim
Journal: Cancer Research (2015)

Abstract Hepatitis B virus-encoded HBx is well known causative factor for the Hepatocellular carcinoma (HCC). HBx interferes with several signaling pathways that are associated with cell proliferation and apoptosis. HBx c-terminal region has been known to play important roles in HBV associated HCC. HBx C-terminal mutant was known to show increased proliferation and invasiveness. In this study, we investigated a molecular mechanism of cancer malignancy induced by C-terminal truncated HBx. Huh-7 Hepatocellular carcinoma cells stably transfected with C-terminal truncated HBx showed higher migrative and invasive phenotype. In addition, the cells were more resistant to doxorubicin compared to cells transfected with full-length HBx. We also observed a higher efflux activity in the cells transfected with C-terminal truncated HBx due to the increased expression of ABCB1. These results suggest that C-terminal truncated HBx up-regulate ABCB1 expression which results in the enhanced efflux of drug. Therefore cancer cells containing C-terminal truncated HBx acquire drug resistancy, and show more malignant phenotypes. Citation Format: Myeong-Eun Je Gal, Eui-Yeun Yi, Seung-Youn Jung, Yung-Jin Kim. Cancer malignancy induced by C-terminal truncated HBx in Huh-7 Hepatocellular carcinoma cells. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-21.
A Phase I evaluation of IFN α-1b in solid tumors, lymphoma or myeloma
Authors: P. Masci, L. Rybicki, K. Tong, T. Olencki, B. Jacobs, L. Wood, E. Borden
Journal: Journal of Clinical Oncology (2004)

2550 Background: Interferon alpha 1 (IFN α-1) has been suggested from prior clinical data to be potentially better tolerated than IFN α-2. The objectives of this trial were to confirm the safety, tolerability and maximum dose of recombinant human IFN α-1b and to measure the effects of IFN α-1b on known IFN induced gene products. Methods: Recombinant human IFN α-1b purified to homogeneity (specific activity 1.0 * 108 units/mg on MDBK cells) was obtained from the Ministry of Public Health in Shanghai. Eligible patients had histologically confirmed metastatic malignancy refractory to standard treatments. Patients were sequentially enrolled to receive increasing doses of IFN α-1b administered by SQ injection daily. Patients were monitored weekly and side effects were graded by the NCI common toxicity criteria. Biologic effects of IFN α-1b were assessed by measuring products of the IFN stimulated genes β2-microglobulin, GTP-cyclohydrolase, ISG 15 and TRAIL at baseline and on days 2, 8 and 29. Seven patients enrolled to the first cohort received 15 μg/m2 of IFN α-1b daily. Six patients were enrolled to the second, third and fourth cohorts and received 45, 135 and 270 μg/m2 respectively. Results: Two grade III toxicities (fatigue and headache) occurred in the first cohort. No grade III toxicities were observed in the second and third cohorts. Grade III fever defined DLT in the fourth cohort. No patients experienced significant weight loss or decline in performance status. No grade IV toxicity related to IFN α-1b occurred in any of the cohorts. One patient with metastatic renal cell cancer treated in the highest dose cohort has had a confirmed partial response. Combined analysis demonstrated significant increases compared to baseline at days 2, 8 and 29 for β2-microglobulin and GTP-cyclohydrolase for all four cohorts (p<0.01). ISG 15 increased significantly over baseline in patients receiving the lowest dose while TRAIL showed significant sustained increases in the three higher dose cohorts (p<0.01). Conclusions: IFN α-1b appears well tolerated clinically and demonstrates differential biologic effects. No significant financial relationships to disclose.
Second line chemotherapy (CT) with gemcitabine (G) and vepesid (VP16) in platinum resistant (DDP-R) advanced ovarian cancer (AOC) patients
Authors: M. Bruzzone, M. Mencoboni, S. Mammoliti, F. Boccardo, L. Tacchini, C. Sonaglio, L. Miglietta
Journal: Journal of Clinical Oncology (2004)

5082 Background: Recurrent AOC patients (pts) often receive several CT lines, some of which have detrimental impact on life quality and high cost. VP16 and G are well tolerated, active, relatively unexpensive drugs; VP16 can be given orally. We evaluated the activity and the toxicity of this combination in platinum resistant pts. Methods: 27 AOC pts received i.v.G 1000 mg/sqm d.1 and 8 and VP16 p.o. 100 mg/day for 5 days (d.8 – 12) every 21 days. All pts were pretreated with platinum/taxol (PT) regimens (5 pts did not receive Taxol due to allergic reaction) and were primary (disease progression (PD) during PT) (16 pts) or secondary (DDP sensible pts re-treated with more than 2 CT lines) (11 pts) DDP-R; 13 pts received G-VP16 as second line whereas this was a third or more advanced line treatment for 14 pts. Topotecan and/or Pegylated Doxorubicin were used before this treatment. Median age was 65 yrs (range 30 – 82) and median ECOG PS was 0 (range 0 – 1). Results: In 2 pts CT was stopped after 1 course due to intolerance to G (skin reaction) and in 5 pts is still ongoing. In 20 evaluable pts, 4 complete (20%) and 9 (45%) partial responses were observed (objective response rate = 65%); 5 pts had disease stabilization (25%) while 2 pts exhibited PD (10%).Median response duration was 6 months (range 1–14). Only WHO grade 3 leucopenia in 1 pt and thrombocytopenia in 2 pts were observed; no supportive G-CSF therapy or hospitalisation was required. Conclusions: G-VP16 seems to be a promising, well tolerated and low expensive second line CT for DDP-R AOC pts. No significant financial relationships to disclose.
Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution?
Authors: Jason E Lang, Jobayer Hossain, Janet T Holbrook, W Gerald Teague, Benjamin D Gold, Robert A Wise, John J Lima
Journal: Thorax (2016)

<h3>Background</h3> Obese children for unknown reasons report greater asthma symptoms. Asthma and obesity both independently associate with gastro-oesophageal reflux symptoms (GORS). Determining if obesity affects the link between GORS and asthma will help elucidate the obese-asthma phenotype. <h3>Objective</h3> Extend our previous work to determine the degree of associations between the GORS and asthma phenotype. <h3>Methods</h3> We conducted a cross-sectional study of lean (20%–65% body mass index, BMI) and obese (≥95% BMI) children aged 10–17 years old with persistent, early-onset asthma. Participants contributed demographics, GORS and asthma questionnaires and lung function data. We determined associations between weight status, GORS and asthma outcomes using multivariable linear and logistic regression. Findings were replicated in a second well-characterised cohort of asthmatic children. <h3>Results</h3> Obese children had seven times higher odds of reporting multiple GORS (OR=7.7, 95% CI 1.9 to 31.0, interaction p value=.004). Asthma symptoms were closely associated with GORS scores in obese patients (r=0.815, p&lt;0.0001) but not in leans (r=0.291, p=0.200; interaction p value=0.003). Higher GORS scores associated with higher FEV1-per cent predicted (p=0.003), lower airway resistance (R10, p=0.025), improved airway reactance (X10, p=0.005) but significantly worse asthma control (Asthma Control Questionnaire, p=0.007). A significant but weaker association between GORS and asthma symptoms was seen in leans compared with obese in the replicate cohort. <h3>Conclusion</h3> GORS are more likely to associate with asthma symptoms in obese children. Better lung function among children reporting gastro-oesophageal reflux and asthma symptoms suggests that misattribution of GORS to asthma may be a contributing mechanism to excess asthma symptoms in obese children.
Novel and potent telomerase antagonist (GRN163L) inhibits telomerase activity, resulting in telomere shortening and apoptosis of multiple myeloma cells
Authors: M. A. Shammas, H. Koley, P. Tassone, P. Neri, A. Protopopov, S. Gryaznov, A. Chin, K. C. Anderson, N. C. Munshi
Journal: Journal of Clinical Oncology (2005)

6605 In cancer cells, telomerase activity helps maintain telomere length, provide enhanced replicative potential and avoid senescence. Chemical inhibitors of telomerase have been shown to reactivate telomere shortening and induce apoptotic cell death of tumor cells while having little or no effect on normal diploid cells. We evaluated the effects of a thio-phosphoramidate oligonucleotide specifically targeting the RNA component of telomerase (GRN163L). Confocal microscopy confirmed an efficient uptake of fluorescein isothiocyanate tagged GRN163L in >99% multiple myeloma (MM) cells. Complete loss of telomerase activity was observed in both INA6 and ARP myeloma cell lines as early as 6 hrs following exposure to 1 μM GRN163L, whereas a mismatch oligonucleotide control did not have significant effect. Telomerase inhibition was accompanied by a reduction in MM cell growth and survival. Treatment of INA6 cells with GRN163L for three weeks induced 96±4% and 100% cell death at 0.5 and 1 μM concentrations, respectively. The apoptotic cell death was confirmed by annexin V-labeling in 51% cells at two weeks after treatment. Apoptosis was associated with reduction in telomere length as determined using Telomere-FISH. The mean Telomere Fluorescence Intensity (TFI) on interphase chromosomes for control oligo treated INA6 cells was 87.1±6.2, while GRN163L treated cells showed a 2.4-fold reduction in telomere length with a mean TFI of 36.2±2.8To evaluate the effect of GRN163L in vivo, we used a SCID-hu murine model of multiple myeloma. In this murine model, human fetal bone chip is implanted in SCID mice and a human stromal cell-dependent GFP transduced cell line is injected inside human bone in mice. Tumor growth is then assessed by measuring levels of human MM-related protein released in mice blood. Following appearance of human-MM related protein in mice blood, GRN163L was injected at alternate days. In an ongoing experiment, a clear reduction in appearance of human myeloma related protein has been seen in mice blood, indicating tumor reduction following treatment. Evaluation of this agent in a large number of SCID-hu mice is underway prior to its clinical evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Geron Geron
Effects of zoledronic acid (ZOL) on proliferation of nasopharyngeal carcinoma (NPC) cell lines and synergistic effects of ZOL and cisplatin on NPC cell lines
Authors: B. R. Ghimire
Journal: Journal of Clinical Oncology (2009)

e13536 Background: Recent evidence suggests that zoledronic acid (ZOL) inhibits cancer cell proliferation and exerts synergistic antitumor activity at clinically achievable concentrations and have shown the potential to become attractive agents for cancer therapy. This study is the first to report the effects of ZOL on NPC cell lines. Methods: Cell proliferations were determined by MTT assay on four NPC cell lines CNE-1, CNE-2, SUNE-1 and 5–8F. NPC cell lines were seeded in a flat-bottomed 96well plate at 10 +4 in 200μl of medium per well and incubated with various concentrations of ZOL for 72 hours. IC 50 values for each cell lines were obtained using the non-linear regression program CalcuSyn. IC 10 values for ZOL and Cisplatin were calculated from the IC 50 curve of each four cell lines. For displaying the synergistic activity concentration equivalent to IC 10 of ZOL alone, Cisplatin alone and in combination were added. The entire specimen was incubated for a total of 72 hours and the absorbance was measured at a wavelength of 540nm in a multiwell spectrophotometer. Results: IC5O values (μM) of ZOL on NPC cell lines SUNE-1, CNE-1, CNE-2, 5–8F were 4.56±0.09, 11.96±0.50, 16.73±0.28, 11.01±0.64 respectively. Conclusions: The experiment establishes synergistic effects of ZOL and cisplatin in anti proliferation of NPC cell lines. Thus, ZOL in combination with other cytotoxic agents may be promising therapeutic strategies for NPC with bone metastasis. The efficacy and safety of ZOL for NPC should be verified in early phase clinical trials [Table: see text] No significant financial relationships to disclose.
Pharmacokinetic and pharmacodynamics (PK/PD) approach for myelosupressions of amrubicin (AMR) in patients with lung cancer
Authors: T. Kimura, S. Kudoh, S. Mitsuoka, N. Yoshimura, K. Hirata
Journal: Journal of Clinical Oncology (2008)

19054 Background: AMR is a novel synthetic 9-amino-anthracycline derivative, and a potent inhibitor of topoisomerase II with a broad spectrum of solid tumors. We previously reported the additive effects of AMR with cisplatin (CDDP) on human lung cancer cell lines. (Osaka City Med J. 2002) We conducted the PK/PD study of AMR in patients with lung cancer to examine the relation between drug concentrations (Cs) and treatment effects and toxicities. Methods: The patients, who were treated with AMR alone, combination of AMR+CDDP, or AMR+irinotecan (CPT-11), were enrolled. AMR were given at a dose of 30–40 mg/m2 on days 1–3. Plasma samples were collected at the point of pretreatment, 24-hour and 72-hour after the first drug administration. Drug Cs of AMR, amrubicinol (AMR-OH) (C- 13 hydroxy metabolite of AMR), CDDP and CPT-11 were determined by HPLC. Changes of drug Cs were tested by t-paired test, and correlations between toxicity grade (G) and drug Cs were tested by nonparametric Kruskal-Wallis test. Results: 38 patients (a median age of 65 years old (40–78),23 NSCLC, 14 SCLC, 1 thymic cancer) were enrolled. Total of 113 plasma samples were available. The averages of drug Cs of 24h-AMR, 72h-AMR, and 24h-AMR-OH, 72h-AMR-OH were 8.68 ng/ml ± 4.54 SD, 16.52 ng/ml ± 11.46 SD and 7.38 ng/ml ± 3.50 SD, 13.58 ng/ml ± 5.63 SD, with significant increasing from 24h- to 72h- samples (p<.0001, p<.0001), respectively. Toxicities include (N): G4 leukopenia (8), neutropenia (18), thrombocytopenia (2), anemia (1), and G3 nausea/vomiting (8), appetite loss (8), infection (5). The significant relationship were observed between the toxicity grade of leukopenia and the drug Cs of 24h-AMR-OH and 72h-AMR-OH (p=.009, p=.007); between neutropenia and 24h-AMR, 24h-AMR-OH and 72h-AMR-OH (p=.02, p=.01, and p=.007); between anemia and 72h-AMR, and 72h-AMR-OH (p=.02, and p=.04), respectively. The grade of nausea/vomiting tends to have a relation with 72h-AMR-OH (p=.0568). Two toxicity related deaths have been reported. 16 (42%) partial responses have been reported with no relations between drug Cs and responses. Conclusions: The plasma concentrations of AMR and AMR-OH are associated with the hematological and non-hematological toxicities treated with AMR in patients with lung cancer. No significant financial relationships to disclose.
Restriction-map variation with the yellow-achaete-scute region in five populations of Drosophila melanogaster.
Authors: W F Eanes, J Labate, J W Ajioka
Journal: Molecular Biology and Evolution (1989)

It has been proposed that the degree of recombination for a genomic region will affect the level of both nucleotide heterozygosity and the density of transposable elements. Both features of genomic diversity have been examined in a number of recent reports for regions undergoing relatively normal levels of recombination in Drosophila melanogaster. In this study the genomic variation associated with yellow-achaete-scute loci located at the tip of the X chromosome is examined by six-cutter restriction mapping. In this region, as usual for regions adjacent to telomeres, crossing-over is dramatically reduced, and published studies of visible mutants indicate extremely little restriction-map variation. Eight six-cutter restriction endonucleases were used to locate sequence variation in 14- and 16.5-kb regions in 109 lines sampled from North America, Africa, and Europe. The overall level of heterozygosity is estimated as 0.29%. Nine large insertions, all presumed to be transposable elements, were observed. Base-pair heterozygosity appears to be reduced compared with regions having normal levels of recombination. The estimated heterozygosity is much higher than reported in earlier studies of restriction-map variation among visible mutations in the complex. The incidence of large insertions is not elevated compared with that in other regions of the genome. This suggests that asymmetric synapsis and exchange is not an important mechanism for the elimination of transposable elements.