tbuckley/cabot-search huggingface dataset:
Myocyte cell damage after administration of doxorubicin or mitoxantrone in breast cancer patients assessed by indium 111 antimyosin monoclonal antibody studies.
Authors: M Estorch, I Carrió, D Martínez-Duncker, L Berná, G Torres, C Alonso, B Ojeda
Journal: Journal of Clinical Oncology (1993)

PURPOSE To compare myocyte cell damage induced by doxorubicin or mitoxantrone, we performed left ventricular ejection fraction (LVEF) measurements and indium 111 antimyosin antibody studies in a group of patients with advanced breast cancer who had been treated with these anthracycline derivatives. PATIENTS AND METHODS We studied 35 patients eligible to receive chemotherapy including the anthracyclines: doxorubicin or mitoxantrone (cumulative dose of doxorubicin, 500 mg/m2; or mitoxantrone, 120 mg/m2). LVEF was measured before and after 10 cycles of chemotherapy. Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). RESULTS Patients treated with doxorubicin presented with a significant decrease in LVEF after chemotherapy (before, 60.4% +/- 8.92%; after, 49.8% +/- 9.71%; P = .001). Antimyosin uptake was observed in all patients with a HLR of 2.03 +/- 0.25. Seven of eight patients with a HLR greater than 2.03 had a greater than 10% decrease in LVEF. Patients treated with mitoxantrone did not present with a decrease in LVEF after chemotherapy (before, 55.4% +/- 6.25%; after, 55.8% +/- 7.25%; not significant). Antimyosin uptake was observed in 14 of 17 patients with a HLR of 1.77 +/- 0.18 (P &lt; .05). CONCLUSION 111In antimyosin monoclonal antibodies defect myocardial cell damage produced by doxorubicin and mitoxantrone. In patients with advanced breast cancer, cumulative doses of 120 mg/m2 of mitoxantrone produce less myocardial cell damage than cumulative doses of 500 mg/m2 of doxorubicin. 111In antimyosin uptake without decrease in LVEF after treatment with mitoxantrone indicates the presence of myocyte cell damage, but not to the extent necessary to deteriorate function. These results indicate that 111In antimyosin antibody studies are useful in the noninvasive comparative assessment of cardiotoxicity produced by different anthracycline derivatives.
Use of sorafenib in recurrent hepatocellular carcinoma (HCC) after liver transplantation.
Authors: Joanne Wing-Yan Chiu, Thomas Cheung Yau, Tan To Cheung, Albert Chan, Siu-Ho Chok, Wing-Chiu Dai, Roland Ching-Yu Leung, See-Ching Chan, Chung-Mau Lo
Journal: Journal of Clinical Oncology (2015)

440 Background: Sorafenib (Sor) is the only approved systemic therapy for advanced HCC yet the safety and efficacy for its use in patients (pts) who developed recurrence after liver transplantation (LT) has not been established. There is an unmet need for treatment option in this group of pts. Methods: This is a retrospective analysis of pts treated with Sor for recurrent HCC post-LT in Queen Mary Hospital, Hong Kong. Results: During year Jan 2008 to Feb 2014, 25 post-LT pts with HCC recurrence were treated with Sor. Tacrolimus and sirolimus were the immunosuppressant of choice during the same treatment period in 76% (19/25) and 40% (10/25) pts respectively. All pts had Child-Pugh A liver function and ECOG performance status 0-1. Majority of pts were chronic hepatitis B carriers (88%) and male (88%). Median time to recurrence was 13.2 months (range 3.4-71.1). Intrahepatic recurrence and extrahepatic recurrence were found in 52% and 80% of pts respectively. Up to 68% of pts received the standard dose of 800 mg/day. The most common adverse events (AEs) were hand-foot syndrome (44%) and diarrhea (28%). G3 transaminase elevation was found in 4 pts (16%), in which 2 had histological evidence of acute graft rejection. Both cases were associated with tailing down of tacrolimus upon tumor progression, and the liver function recovered after adjustment of immunosuppressant. Nine pts (36%) required dose adjustment. The median maintenance dose was 400 mg/day. The median duration of treatment was 4.44 months (95% CI 2.53-6.44). Median time to progression was 6.21 months (95% CI 2.83-9.63). Median overall survival was 13.6 months (95% CI 7.69-19.61). Ten (40%) pts also received other subsequent systemic therapy. Conclusions: Sor given in combination with tacrolimus and sirolimus did not lead to unexpected graft rejection. The drug is in general tolerated in this population and toxicities appeared to be similar to non-transplant pts. Further study is required to evaluate for drug interaction and efficacy.
Ultrastructural, Cytochemical, and Biochemical Characterization of Alpha-Amylase Produced by Human Gastric Cancer Cells In Vitro
Authors: H Nomura, S I Tokumitsu, T Takeuchi
Journal: JNCI Journal of the National Cancer Institute (1980)

Ectopic production of salivary-type amylase was demonstrated in a human gastric carcinoma cell line (KMK-2) maintained in vitro for more than 3 years. Electron-dense granules, which appeared as zymogens, were observed in the tumor tissue, in cancer cells in the peritoneal fluid (from which the present cell line had been derived), and in cultured cells in early passages. These granules, however, decreased and gradually disappeared during cultivation. Although such a morphologic alteration was recognized, the property of amylase synthesis has been maintained. The presence of alpha-amylase in the cultured cells was demonstrated cytochemically by the immunoperoxidase method. The enzyme secreted and accumulated in the culture medium was partially purified and characterized. Alpha-amylase of KMK-2 cells closely resembled salivary-type amylase in gel filtration profile and disk gel electrophoresis. Immunologic cross-reaction was observed between these enzymes. Secretion into the medium was constant, and the enzyme concentration in the cytoplasm was relatively high when the cells had reached confluence. Prednisolone increased the amylase production two-fold in the cells.
Stretch-induced Activation of Transforming Growth Factor-β<sub>1</sub> in Pulmonary Fibrosis
Authors: Aaron R. Froese, Chiko Shimbori, Pierre-Simon Bellaye, Mark Inman, Steffen Obex, Safoora Fatima, Gisli Jenkins, Jack Gauldie, Kjetil Ask, Martin Kolb
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Recent findings suggesting transforming growth factor (TGF)-β1 activation by mechanical stimuli in vitro raised the question of whether this phenomenon was relevant in vivo in the context of pulmonary fibrosis.Objectives: To explore the effect of mechanical stress on TGF-β1 activation and its signaling pathway in rat and human fibrotic lung tissue using a novel ex vivo model.Methods: Rat lung fibrosis was induced using transient gene expression of active TGF-β1. Lungs were harvested at Day 14 or 21 and submitted to various stimuli in a tissue bath equipped with a force transducer and servo-controlled arm.Measurements and Main Results: Fibrotic lung strips responded to tensile force by releasing active TGF-β1 from latent stores with subsequent increase in tissue phospho-Smad2/3. In contrast, measurable active TGF-β1 and phospho-Smad2/3 were not induced by mechanical stress in nonfibrotic lungs. Protease inhibition did not affect the release of active TGF-β1. A TGF-β1 receptor inhibitor, Rho-associated protein kinase inhibitor, and αv integrin inhibitor all attenuated mechanical stretch–induced phospho-Smad2/3 in fibrotic lung strips. Furthermore, the induction of phospho-Smad2/3 was enhanced in whole fibrotic rat lungs undergoing ventilation pressure challenge compared with control lungs. Last, tissue slices from human lung with usual interstitial pneumonia submitted to mechanical force showed an increase in TGF-β1 activation and induction of phospho-Smad2/3 in contrast with human nonfibrotic lungs.Conclusions: Mechanical tissue stretch contributes to the development of pulmonary fibrosis via mechanotransduced activation of TGF-β1 in rodent and human pulmonary fibrosis.
Population pharmacokinetic (PK) analysis of gefitinib in pediatric cancer patients
Authors: P. Schaiquevich, J. C. Panetta, S. Throm, N. C. Daw, J. R. Geyer, W. L. Furman, C. F. Stewart
Journal: Journal of Clinical Oncology (2008)

2523 Background: Gefitinib is an orally active inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Neuroblastoma, rhabdomyosarcoma, osteosarcoma, and high-grade gliomas are known to express EGFR. Thus, three phase I studies evaluating gefitinib pharmacokinetics were conducted in children with recurrent/refractory solid tumors (COG ADVL0016 and SJZD1839) or brain tumors (PBTC007). Because of wide inter-individual variability in gefitinib disposition, the present study was conducted to describe the population PK of gefitinib and to assess the relationship between gefitinib disposition and patient covariates. Methods: Subjects received daily oral gefitinib ranging from 100 to 500 mg/m2 as single agent therapy for 8 to 10 days prior to PK evaluation. Multiple plasma samples were collected per subject and analyzed using a validated LC MS/MS assay. The data consisted of 73 subjects and 600 samples. Data were analyzed using NONMEM v5 to obtain gefitinib apparent oral clearance (CL/F), apparent volume of distribution (V/F), and the absorption rate constant (ka). Covariates investigated included demographic (age, body surface area [BSA]) and laboratory variables, concomitant drug therapy (dexamethasone, H2-receptor antagonist), and genetic polymorphisms in CYP3A4*1B, CYP3A5*3C, CYP3A5*6, ABCB1 (exon 21 and 26), and ABCG2 (exons 2 and 5). Results: Gefitinib pharmacokinetics were described by a one-compartment model with first-order absorption. BSA was a significant covariate (p<0.05). The mean population estimates were CL/F 17.8 L/h/m2, V/F 348 L/h/m2, ka 0.519 h-1. A significant relationship was found between CL/F and ABCB1 exon 21 (p<0.05) and ABCB1 exon 26 (p<0.05) polymorphisms. Specifically, CL/F was decreased in patients homozygous for exons 21 and 26 (36% and 20%, respectively) relative to wild-type and heterozygous. Conclusions: The results obtained are consistent with published data in adults. The relationship between gefitinib CL/F and ABCB1 genetic polymorphisms explained a significant amount of the interindividual variability in CL/F. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca
Post-radiation pulmonary epithelial regeneration from transplanted adult stem cells
Authors: R. Koratkar, U. Lakshmipathy, Y. Jiang, T. Kaur, B. Slater, C. M. Verfaillie, B. N. Jahagirdar
Journal: Journal of Clinical Oncology (2007)

7022 Background: Pneumonitis and pulmonary damage are common toxicities of chest radiation therapy (RT), which may be reduced by transplantation of stem cells that differentiate into pulmonary epithelium. Multipotent Adult Progenitor Cells (MAPC) are adult bone marrow (BM) derived cells, which after IV injection in NOD-SCID mice, differentiate into epithelial and hematopoietic tissues (Nature 418:41). Here we tested the ability of mouse (m) MAPC to regenerate epithelia after RT, in Fanconi Anemia C (FAC) mouse model, which inherently has DNA repair defects and is over sensitive to DNA-cross linking agents. Methods: One million, enhanced-green fluorescent protein (eGFP)- expressing, wild-type mMAPC were injected IV in FAC mice, 4–24 hours after 7.5 Gy (followed by mitomycin C {MMC} 0.1mg/kg/week X 4 in a subset) or 11 Gy RT. Non-eGFP expressing BM was co-transplanted after myeloablative (11 Gy) RT. BM, lungs, intestine and liver of the recipients were analyzed 3–10 months post-transplant for eGFP+ cells and epithelial (CK+) or hematopoietic (CD45+) differentiation using flowcytometry (BM) &amp; immunohistochemistry. Control FAC mice were identically treated but without MAPC. Results: MAPC engraftment (&gt;1% eGFP+ cells) was absent in all control mice. Following 7.5 Gy RT, autologous BM recovery occurred in all (N=10) mice and 1 mouse had 2.7% donor-derived hematopoietic (eGFP+/CD45+) cells after MMC. In both recipients of 11Gy RT, analyzed 9–10 months post-transplant, 5–7% of all CD45+ BM cells were donor MAPC-derived. No donor MAPC-derived epithelial cells were seen in the intestine or liver. However, lungs of most recipients had clusters of donor MAPC-derived epithelial cells, estimated to comprise 1–8% of all pulmonary epithelial cells, consistent with homing of MAPC in lungs following IV injection and their epithelial differentiation in the post-radiation, regenerative, pulmonary micro- environment. The highest degree of MAPC-derived pulmonary regeneration was seen following 11Gy RT that was persistent at 10 months post- transplant. Conclusions: Following radiation, IV injected mMAPC differentiate into hematopoietic and pulmonary epithelial cells that persist long-term. MAPC transplantation has the potential for reducing radiation-induced pulmonary toxicity. No significant financial relationships to disclose.
Formation of a Transplacental Mutagen, 1,3-Di(4-sulfamoylphenyl)triazene, From Sodium Nitrite and Sulfanilamide in Human Gastric Juice and in the Stomachs of Hamsters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H Endo, H Noda, N Kinoshita, N Inui, Y Nishi
Journal: JNCI Journal of the National Cancer Institute (1980)

1,3-Di(4-sulfamoylphenyl)triazene was abundantly produced by incubation of sulfanilamide (SA) and NaNO2 in human gastric juice. This reaction also occurred in acetate buffer (pH approximately 4) at 37 degrees C as well as in hydrochloric acid (pH < 1) under ice cooling, with the product forming in almost the same amount. This phenomenon indicated the broad range of conditions under which the reaction occurs. The intragastric formation of this triazene was also demonstrated in Syrian golden hamsters by the concurrent administration of SA and NaNO2. Mutants resistant to 8-azaguanine were induced in a dose-dependent manner in the culture of embryo cells that were derived from pregnant hamsters 24 hours after ip injection of this triazene.
GD2 expression in tumorspheres from neuroblastoma cell lines and in tumor-initiating cells derived from patient samples.
Authors: A. M. Hammill, P. Wang, L. M. Hansford, D. Kaplan, T. P. Cripe
Journal: Journal of Clinical Oncology (2010)

9568 Background: Neuroblastoma is the most common extracranial solid tumor of childhood. High-risk disease is associated with a poor prognosis, even with aggressive multimodal treatment. The COG has recently incorporated antibody therapy against the disialoganglioside GD2 into protocols for high-risk neuroblastoma. Methods: We cultured neuroblastoma cell lines so as to derive both a more adherent population of cells and tumorspheres, in addition to maintaining bulk cell lines. We then evaluated these subpopulations for expression of GD2 by flow cytometry. We similarly characterized GD2 expression in tumor initiating cells (TICs), cells derived from bone marrow of patients with neuroblastoma. We also tested sphere-forming ability, the ability to grow in serum-free sphere media, in sorted GD2 high versus low cells from cell line-derived subpopulations. Finally, we evaluated GD2 expression in both xenograft-derived tumors and in patient samples. Results: Tumorsphere cells derived from established neuroblastoma cell lines lack GD2 surface expression. Adherent cells have high levels of GD2 , while bulk cells show a mixed picture suggestive of both (sphere and adherent) subpopulations. Binding of the GD2 antibody to GD2+ cells results in a rapid change in their membrane permeability. Bulk cell lines sorted on the basis of their GD2 expression did not demonstrate any difference in their sphere-forming ability. Tumor initiating cells (TICs), like the cell line tumorspheres, showed very low to absent GD2 expression. Evaluation of tumors for GD2 expression patterns is ongoing. Conclusions: Tumorspheres, thought to be enriched for multipotent cancer stem cells, appear to have low to absent expression of the disialoganglioside GD2. Targeting of this molecule has become the standard of care in the treatment of neuroblastoma, with documented survival advantage at 2 years. Our data raise the possibility that while this treatment is useful for “debulking” much of the remaining disease, it may miss targeting stem cells in particular in some cases. In addition to GD2 targeting, strategies to specifically kill GD2-negative neuroblastoma cells may be needed to fully prevent late relapses. No significant financial relationships to disclose.
Abstract P084: Associations of Anger and Hostility with the Metabolic Syndrome: Cross-sectional Analyses from the Jackson Heart Study
Authors: Janice E Williams, Sharon B Wyatt, Mario Sims, Thomas H Mosley, Patricia M Dubbert, Thomas H Payne
Journal: Circulation (2012)

There is evidence that anger and hostility are positively associated with the metabolic syndrome. In turn, the metabolic syndrome mediates the association between anger and hostility and adverse cardiac events. Very little is known about these associations in African-American populations. We assessed the hypothesis that anger and hostility are positively associated with the metabolic syndrome in an African-American cohort. Participants were 2,732 African-American men and women, ages 45 – 95, who were enrolled in the Jackson Heart Study at baseline. Anger was measured using the Spielberger State-Trait Anger Inventory, and hostility was measured using the Cook-Medley Hostility Scale. The metabolic syndrome was defined by the National Cholesterol Education Program, Adult Treatment Panel III criteria. Overall anger, components anger-in and anger-out, and hostility scores were entered into separate logistic regression models as continuous variables. In models adjusted for age, sex, educational level, and physical activity, higher levels of overall anger (β = 0.024, p = 0.006), anger-in (β = 0.028, p = 0.04), anger-out (β = 0.037, p = 0.04), and hostility (β = 0.021, p = 0.04) were associated with an increased prevalence of the metabolic syndrome. The correlation between anger and hostility was statistically significant but not strong (r = 0.38, p &lt;0.0001). In men, 5 of the 16 individual anger items were significantly associated with the metabolic syndrome. The strongest was “I lose my temper” (β = 0.395, p = 0.003) and “I tend to harbor grudges” (β = 0.314, p = 0.008). In women, only 1 anger item, “I make sarcastic remarks” (β = 0.189, p = 0.04) was associated with the metabolic syndrome. In conclusion, higher levels of overall anger, anger-in, anger-out, and hostility were associated with an increased prevalence of the metabolic syndrome in middle- and older-aged African-American men and women. In men, an angry temperament and a tendency to hold grudges were particularly strong correlates of the metabolic syndrome. Increased understanding of the negative emotions anger and hostility among African-Americans may provide greater insights into cardiovascular disease risk in their population.
How much is too much high-dose cytosine arabinoside?
Authors: T P Duffy
Journal: Journal of Clinical Oncology (1985)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1985.3.5.601 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3998778 How much is too much high-dose cytosine arabinoside? T P DuffyxT P DuffySearch for articles by this author https://doi.org/10.1200/JCO.1985.3.5.601 First Page PDF © 1985 by American Society of Clinical Oncology
Imaging of angiogenesis in metastatic breast cancer by positron emission tomography (PET) using [18F]AH11585, an [18F]- labeled alphaVbeta3 (αvβ3) peptide
Authors: L. M. Kenny, E. Aboagye, P. S. Cohen, M. Miller, F. Turkheimer, A. Al-Nahhas, D. Blunt, R. C. Coombes
Journal: Journal of Clinical Oncology (2007)

14067 Background: In vivo imaging of avβ3 expression in tumors and tumor endothelial cells may be a useful biomarker of angiogenesis. [18F]AH11585 is a novel peptide containing an Arginine-Glycine-Aspartic Acid (RGD) motif that binds to avβ3 with high affinity designed for use in PET studies. Methods: 7 patients with metastatic breast cancer (aged 37–68 years) received intravenous injections of [18F]AH11585 and were scanned dynamically by PET over 61.5 mins. Radioactivity concentrations, derived from regions of interest placed on tumour and normal tissues, were analysed mathematically to determine the net irreversible uptake (Ki), fractional retention (FRT) and standardized uptake at 56.5min (SUV) of the radiotracer. Computed tomography (CT) was performed within 4 weeks of the scan. Results: Tumor lesions were clearly visible on PET images in 6/7 patients. In one patient with a palpable supraclavicular lymph node not visible on CT, we were unsure if a hyperintense region visible by PET was tumor. In total 18/19 tumor lesions were identified on both PET and corresponding CT images. Tumors in areas of low background were hyperintense (lung, bone, breast) whereas those in areas of high background were hypointense regions (liver). Tumors with central necrosis showed high uptake of [18F]AH11585 around the periphery only. Mathematical analysis demonstrated irreversible retention of [18F]AH11585 in tumors. [18F]AH11585-PET discriminated between non-liver lesions (n=10) and normal tissues: Ki (p=0.002), FRT (p=0.0039), SUV (p=0.002). Corresponding comparisons for liver lesions (n=8) were significant for FRT (p=0.0078) and SUV (p=0.0078) only. Conclusions: [18F]AH11585 PET is a promisng method for in vivo imaging of avβ3 integrin expression in metastatic breast cancer. No significant financial relationships to disclose.
Abstract 15089: Effect of Left Ventricular Diastolic Dysfunction on Outcomes of Atrial Fibrillation Ablation
Authors: Prabhat Kumar, Ankit Patel, J Paul Mounsey, Eugene H Chung, Jennifer D Schwartz, Irion W Pursell, Anil K Gehi
Journal: Circulation (2013)

Background: Left ventricular diastolic dysfunction (LVDD) is an important pathogenic factor for atrial fibrillation (AF). There is a little data on the effect of LVDD on recurrence of AF after cath...
Joint Action of Herpes Simplex Virus and 3-Methylcholanthrene in Production of Papillomas in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Satoshi Tanaka, Chester M. Southam
Journal: JNCI Journal of the National Cancer Institute (1965)

Intradermal inoculation of herpes simplex virus into mice during a 5-day period of 3-methylcholanthrene applications to the same skin area caused faster appearance and higher incidence of skin papillomas than the chemical alone. The magnitude of this difference varied directly with the amount of infective virus in the inoculum. Tests of skin for presence of infective virus at various intervals after inoculation indicated that the virus propagated in skin. Injection of non infective control preparations had little or no effect on papilloma development. Herpes virus alone never caused papillomas. When virus was inoculated 7 days before or 14 days after the first methylcholanthrene application, the incidence of papillomas did not increase significantly. Papillomas occurred only within the methylcholanthrene-treated area and were more frequent at the site of virus injection than at the periphery. These observations indicate that the increase in papilloma incidence occurred when herpes virus propagation coincided in time and place with the epidermal hyperplasia caused by the chemical, and that the virus by itself did not act as either an inducer or a promoter.