tbuckley/cabot-search huggingface dataset:
Inter-Religious Perspectives on Hope and Limits in Cancer Treatment
Authors: Alan B. Astrow, Ingrid Mattson, Rabbi James Ponet, Michelle White
Journal: Journal of Clinical Oncology (2005)

An 85-year-old woman, a retired nurse’s aide, has advanced metastatic breast cancer to the liver and bone. She recently transferred her care to a new hospital and physician, hoping for better results. Nevertheless, her disease has worsened despite maximal hormonal therapy and several chemotherapy regimens including cyclophosphamide, methotrexate, and fluorouracil, and doxorubicin, paclitaxel, navelbine, gemcitabine, and capecitabine. In addition, she has progressive kidney failure and heart disease. She is weak and nearly bedridden. She also finds it difficult to eat. Her oncologist has advised the patient that additional chemotherapy would not be helpful. He has attempted to shift the goal of treatment from life-prolonging interventions to comfort measures, and has consulted the palliative care team. The palliative care team has suggested referral to a home hospice program. The patient’s two sons, who, with her agreement, are directing her medical care, are unwilling to accept referral to a hospice program. They are upset that the oncologist is ‘‘giving up.’’ At a visit with the oncologist, the patient and her sons bring an Internet printout of the investigational agents angiostatin and endostatin. The oncologist suggests that the patient is too ill to be eligible for an experimental trial and that additional chemotherapy would not help. The patient’s sons express anger. ‘‘I’m very disappointed with oncology,’’ one son says. The patient belongs to a religious faith. She attends religious services, but not regularly. The patient’s sons appear to be very involved with their religion. They have been seen in the treatment area reading their religion’s holy book. Three scholars from the Muslim, Jewish, and Christian traditions were asked to respond to this clinical scenario by briefly introducing their faith’s tradition, and then addressing the case. The question posed to them was whether, and how, a religious perspective on these issues might have helped to illuminate the patient’s and the family members’ understanding of the issues at stake, and potentially have lessened the degree of conflict between family and professional staff.
Studies on a Transplantable Murine Rhabdomyosarcoma
Authors: K. Perk, A. F. Gazdar, E. R. Russell
Journal: JNCI Journal of the National Cancer Institute (1975)

Well-differentiated rhabdomyosarcomas developed in 8 of 10 BALB/c mice inoculated with cell-free extracts of two lesions arising in bats previously inoculated with the Moloney strain of murine sarcoma virus. The tumors could be transplanted in BALB/c mice and other strains of mice compatible at the H-2 locus. A tumorigenic clonal cell culture line (R2) was established from a transplanted tumor. Ultrastructural studies of the primary and transplanted tumors and R2 cells revealed thick and thin myofilaments characteristic of myoblasts. These cells contained numerous cisternal type-A virus-like particles, but no type-C particles were found. Attempts to recover, rescue, or chemically induce transforming or nontransforming viruses from transplantable tumors and the R2 cell line were unsuccessful. The tumor cells lacked the murine type-C virus gs antigen. Hybridization data confirmed the apparent lack of viral RNA in the tumor cells.
Vaccination against hepatitis C virus infection: Miles to go before we sleep
Authors: Jake T. Liang, Sawkat M. Anwer
Journal: Hepatology (1994)

A high incidence of community–acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees ( Pan troglodytes ) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccinees became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination.
Lymphotoxin Prevention of Diethylnitrosamine Carcinogenesis In Vivo&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J H Ransom, C H Evans, J A DiPaolo
Journal: JNCI Journal of the National Cancer Institute (1982)

Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo.
Heparanase: A New Metastasis-Associated Antigen Recognized in Breast Cancer Patients by Spontaneously Induced Memory T Lymphocytes
Authors: Nora Sommerfeldt, Philipp Beckhove, Yingzi Ge, Florian Schütz, Carmen Choi, Mariana Bucur, Christoph Domschke, Christof Sohn, Andreas Schneeweis, Joachim Rom, Dirk Pollmann, Dagmar Leucht, Israel Vlodavsky, Volker Schirrmacher
Journal: Cancer Research (2006)

Abstract Increased expression and secretion of heparanase (Hpa) by tumor cells promotes tumor invasion through extracellular matrices, tissue destruction, angiogenesis, and metastasis. Here, we show the existence in breast cancer patients of Hpa-specific T lymphocytes by fluorescence-activated cell sorting flow cytometry using Hpa peptide-MHC class I tetramers. We furthermore show memory T-cell responses in a high proportion of breast cancer patients to Hpa-derived HLA-A2-restricted peptides, leading to production of IFN-γ and to generation of antitumor CTLs lysing breast cancer cells. Such CTLs recognized endogenously processed respective Hpa peptides on Hpa-transfected and Hpa-expressing untransfected breast carcinoma cells. According to these results and to the fact that such cells were not found in healthy people, Hpa seems to be an attractive new tumor-associated antigen and its HLA-A2-restricted peptides ought to be good candidates for peptide vaccination to reactivate memory immune responses to invasive and metastatic cancer cells. (Cancer Res 2006; 66(15): 7716-23)
The interleukin 23 receptor gene does not confer risk to systemic sclerosis and is not associated with systemic sclerosis disease phenotype
Authors: B Rueda, J Broen, O Torres, C Simeon, N Ortego-Centeno, M M V A P Schrijvenaars, M C Vonk, V Fonollosa, F H J van den Hoogen, M J H Coenen, J Sanchez-Román, M A Aguirre-Zamorano, R García-Portales, A Pros, M T Camps, M A Gonzalez-Gay, J Martin, T R D J Radstake
Journal: Annals of the Rheumatic Diseases (2008)

Multiple studies indicate the role of the interleukin (IL)-17/IL-23 axis in autoimmune diseases, including systemic sclerosis (SSc). The aim of the current study was to investigate the possible implication of the IL23R gene in SSc susceptibility and/or clinical phenotype.An initial case-control study in 143 Dutch patients with SSc and geographically matched healthy individuals (n = 246) was carried out and followed by a replication study in a cohort of 365 Spanish patients with SSc and 515 healthy individuals. Seven single nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected and genotyped using a Taqman assay.Using a Dutch cohort of patients with SSc and controls we observed an association between two (rs11209032, rs1495965) of the seven tested SNPs and disease susceptibility (allelic p values: p = 0.02 and p = 0.01 respectively). However, a replication study in an independent Spanish cohort did not confirm these findings and reveal no association of any of the IL23R-tested SNP with disease susceptibility or clinical phenotype. Similarly, a meta-analysis considering both populations did not reveal any significant association. In addition, no association was observed between IL23R genetic variants and SSc clinical phenotypes.Our results suggest that the IL23R gene is not associated with SSc susceptibility or clinical phenotype.
Hb Indianapolis [β112 (G14) Cys→Arg] as the probable cause of moderate hemolytic anemia and renal damage in a Brazilian patient
Authors: A. Fattori, E.M. Kimura, D.M. Albuquerque, D.M. Oliveira, F.F. Costa, M.F. Sonati
Journal: American Journal of Hematology (2007)

Abstract Hemoglobin (Hb) Indianapolis [β112 (G14) Cys→Arg] is a rare and slightly unstable β‐globin variant. All carriers described to date were clinically normal with only mild reticulocytosis. We report here a case of a Brazilian patient in whom hemolytic anemia and acute renal failure were probably caused by the presence of this variant. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Investigation of DNA damage response and apoptotic gene methylation pattern in sporadic breast tumors using high throughput quantitative DNA methylation analysis technology
Authors: Ranjana Pal, Niloo Srivastava, Rupali Chopra, Sailesh Gochhait, Pawan Gupta, Neeraj Prakash, Gaurav Agarwal, Rameshwar NK Bamezai
Journal: Molecular Cancer (2010)

Abstract Background- Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR), apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, we performed DNA methylation study involving 17 gene promoter regions belonging to DNA damage response (DDR) and death receptor apoptotic pathway in 162 paired normal and cancerous breast tissues from 81 sporadic breast cancer patients, using a high throughput quantitative DNA methylation analysis technology. Results- The study identified five genes with statistically significant difference between normal and tumor tissues. Hypermethylation of DR5 (P = 0.001) , DCR1 (P = 0.00001) , DCR2 (P = 0.0000000005) and BRCA2 (P = 0.007) and hypomethylation of DR4 (P = 0.011) in sporadic breast tumor tissues suggested a weak/aberrant activation of the DDR/apoptotic pathway in breast tumorigenesis. Negative correlation was observed between methylation status and transcript expression levels for TRAIL , DR4 , CASP8 , ATM , CHEK2 , BRCA1 and BRCA2 CpG sites. Categorization of the gene methylation with respect to the clinicopathological parameters showed an increase in aberrant methylation pattern in advanced tumors. These uncharacteristic methylation patterns corresponded with decreased death receptor apoptosis (P = 0.047) and DNA damage repair potential (P = 0.004) in advanced tumors. The observation of BRCA2 -26 G/A 5'UTR polymorphism concomitant with the presence of methylation in the promoter region was novel and emerged as a strong candidate for susceptibility to sporadic breast tumors. Conclusion- Our study indicates that methylation of DDR-apoptotic gene promoters in sporadic breast cancer is not a random phenomenon. Progressive epigenetic alterations in advancing tumors result in aberrant DDR-apoptotic pathway thereby promoting tumor development. We propose, since pathological epigenetic changes of the DDR-apoptotic genes are reversible modifications, these could further be targeted for therapeutic interventions.
3-Phosphoinositide–Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma
Authors: Matthew Maurer, Tao Su, Lao H. Saal, Susan Koujak, Benjamin D. Hopkins, Christina R. Barkley, Jiaping Wu, Subhadra Nandula, Bhaskar Dutta, Yuli Xie, Y. Rebecca Chin, Da-In Kim, Jennifer S. Ferris, Sofia K. Gruvberger-Saal, Mervi Laakso, Xiaomei Wang, Lorenzo Memeo, Albert Rojtman, Tulio Matos, Jennifer S. Yu, Carlos Cordon-Cardo, Jorma Isola, Mary Beth Terry, Alex Toker, Gordon B. Mills, Jean J. Zhao, Vundavalli V.V.S. Murty, Hanina Hibshoosh, Ramon Parsons
Journal: Cancer Research (2009)

Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer.
Treatment of Latent Tuberculosis Infection
Authors: Helen R. Stagg, Dominik Zenner, Ross J. Harris, Laura Muñoz, Marc C. Lipman, Ibrahim Abubakar
Journal: Annals of Internal Medicine (2014)

Effective treatment of latent tuberculosis infection (LTBI) is an important component of TB elimination programs. Promising new regimens that may be more effective are being introduced. Because few regimens can be directly compared, network meta-analyses, which allow indirect comparisons to be made, strengthen conclusions.To determine the most efficacious regimen for preventing active TB with the lowest likelihood of adverse events to inform LTBI treatment policies.PubMed, EMBASE, and Web of Science up to 29 January 2014; clinical trial registries; and conference abstracts.Randomized, controlled trials that evaluated LTBI treatment in humans and recorded at least 1 of 2 prespecified end points (preventing active TB or hepatotoxicity), without language or date restrictions.Data from eligible studies were independently extracted by 2 investigators according to a standard protocol.Of the 1516 articles identified, 53 studies met the inclusion criteria. Data on 15 regimens were available; of 105 possible comparisons, 42 (40%) were compared directly. Compared with placebo, isoniazid for 6 months (odds ratio [OR], 0.64 [95% credible interval {CrI}, 0.48 to 0.83]) or 12 months or longer (OR, 0.52 [CrI, 0.41 to 0.66]), rifampicin for 3 to 4 months (OR, 0.41 [CrI, 0.18 to 0.86]), and rifampicin-isoniazid regimens for 3 to 4 months (OR, 0.52 [CrI, 0.34 to 0.79]) were efficacious within the network.The risk of bias was unclear for many studies across various domains. Evidence was sparse for some comparisons, particularly hepatotoxicity.Comparison of different LTBI treatment regimens showed that various therapies containing rifamycins for 3 months or more were efficacious at preventing active TB, potentially more so than isoniazid alone. Regimens containing rifamycins may be effective alternatives to isoniazid monotherapy.None.
DQw7 and the C4B null allele in rheumatoid arthritis and Felty's syndrome.
Authors: R Clarkson, A S Bate, D M Grennan, C Chattopadhyay, P Sanders, M Davis, C Kelly
Journal: Annals of the Rheumatic Diseases (1990)

DQ beta and C4 null alleles have been defined in patients with rheumatoid arthritis, Felty's syndrome, and in control subjects. Comparison of DR4 positive subjects shows that rheumatoid disease without extra-articular features has no preferential associations with either DQ beta or C4 null variants. In Felty's syndrome there are significant associations with both the class II major histocompatibility complex (MHC) DQw7 allele (86% of DR4 positive patients with Felty's syndrome and 53% of DR4 positive controls) and the class III MHC C4B null allele (50% of patients with Felty's syndrome and 20% of DR4 positive controls). DQw7 and the C4B null allele are in linkage disequilibrium and the B44-Bf *S-C4A*3-C4B*Q0-DR4-DQw7 haplotype accounts for five of 24 DR4 positive haplotypes assigned in subjects with Felty's syndrome. The results were not accounted for by articular disease severity and suggest that articular and extra-articular forms of rheumatoid disease may be immunogenetically heterogeneous.
Cooperation between the transcription factors p63 and IRF6 is essential to prevent cleft palate in mice
Authors: Helen A. Thomason, Huiqing Zhou, Evelyn N. Kouwenhoven, Gian-Paolo Dotto, Gaia Restivo, Bach-Cuc Nguyen, Hayley Little, Michael J. Dixon, Hans van Bokhoven, Jill Dixon
Journal: Journal of Clinical Investigation (2010)

Cleft palate is a common congenital disorder that affects up to 1 in 2,500 live human births and results in considerable morbidity to affected individuals and their families. The etiology of cleft palate is complex, with both genetic and environmental factors implicated. Mutations in the transcription factor-encoding genes p63 and interferon regulatory factor 6 (IRF6) have individually been identified as causes of cleft palate; however, a relationship between the key transcription factors p63 and IRF6 has not been determined. Here, we used both mouse models and human primary keratinocytes from patients with cleft palate to demonstrate that IRF6 and p63 interact epistatically during development of the secondary palate. Mice simultaneously carrying a heterozygous deletion of p63 and the Irf6 knockin mutation R84C, which causes cleft palate in humans, displayed ectodermal abnormalities that led to cleft palate. Furthermore, we showed that p63 transactivated IRF6 by binding to an upstream enhancer element; genetic variation within this enhancer element is associated with increased susceptibility to cleft lip. Our findings therefore identify p63 as a key regulatory molecule during palate development and provide a mechanism for the cooperative role of p63 and IRF6 in orofacial development in mice and humans.
Metastases from Uveal Melanoma after Proton Beam Irradiation
Authors: Evangelos S. Gragoudas, Johanna M. Seddon, Kathleen M. Egan, Robert J. Glynn, Michael Goitein, John Munzenrider, Lynn Verhey, Marcia Urie, Andreas Koehler
Journal: Ophthalmology (1988)
Insulin Resistance–Related Factors, but not Glycemia, Predict Coronary Artery Disease in Type 1 Diabetes
Authors: Trevor J. Orchard, Jon C. Olson, John R. Erbey, Katherine Williams, Kimberly Y.-Z. Forrest, Leslie Smithline Kinder, Demetrius Ellis, Dorothy J. Becker
Journal: Diabetes Care (2003)

To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation.This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8-47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis > or =50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death.A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or > or =50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA(1) showed no association with subsequent CAD.These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.