tbuckley/cabot-search huggingface dataset:
Development of Skin Tumors in Mice Transgenic for Early Genes of Human Papillomavirus Type 8
Authors: Inke Diana Schaper, Gian Paolo Marcuzzi, Sönke Jan Weissenborn, Hans Udo Kasper, Volker Dries, Neil Smyth, Pawel Fuchs, Herbert Pfister
Journal: Cancer Research (2005)

Abstract The cutaneous human papillomavirus (HPV) 8 is clearly involved in skin cancer development in epidermodysplasia verruciformis patients and its early genes E2, E6, and E7 have been implicated in cell transformation in vitro. To examine the functions of these genes in vivo we integrated the complete early region of HPV8 into the genome of DBA/Bl6 mice. To target their expression to the basal layer of the squamous epithelia the transgenes were put under the control of the keratin-14 promoter. Transgenic mice were back-crossed for up to six generations into both FVB/N and Bl6 mouse strains. Whereas none of the HPV8 transgene–negative littermates developed lesions in the skin or any other organ, 91% of HPV8-transgenic mice developed single or multifocal benign tumors, characterized by papillomatosis, acanthosis, hyperkeratosis, and varying degrees of epidermal dysplasia. Squamous cell carcinomas developed in 6% of the transgenic FVB/N mice. Real-time reverse transcription-PCR showed highest expression levels for HPV8-E2, followed by E7 and E6. There was no consistent difference in relative viral RNA levels between healthy or dysplastic skin and malignant skin tumors. Whereas UV-induced mutations in the tumor suppressor gene p53 are frequently detected in human skin carcinomas, mutations in p53 were not observed either in the benign or malignant mouse tumors. Nonmelanoma skin cancer developed in HPV8-transgenic mice without any treatment with physical or chemical carcinogens. This is the first experimental proof of the carcinogenic potential of an epidermodysplasia verruciformis–associated HPV-type in vivo.
Prospective tracing of MLL-FRYL clone with low MEIS1 expression from emergence during neuroblastoma treatment to diagnosis of myelodysplastic syndrome
Authors: Blaine W. Robinson, Nai-Kong V. Cheung, Christos P. Kolaris, Suresh C. Jhanwar, John K. Choi, Neil Osheroff, Carolyn A. Felix
Journal: Blood (2008)
Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence
Authors: J. H. McDonald
Journal: Molecular Biology and Evolution (1998)

The neutral theory of molecular evolution predicts that the ratio of polymorphisms to fixed differences should be fairly uniform across a region of DNA sequence. Significant heterogeneity in this ratio can indicate the effects of balancing selection, selective sweeps, mildly deleterious mutations, or background selection. Comparing an observed heterogeneity statistic with simulations of the heterogeneity resulting from random phylogenetic and sampling variation provides a test of the statistical significance of the observed pattern. When simulated data sets containing heterogeneity in the polymorphism-to-divergence ratio are examined, different statistics are most powerful for detecting different patterns of heterogeneity. The number of runs is most powerful for detecting patterns containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic is most powerful for detecting patterns in which one end of the gene has high polymorphism and the other end has low polymorphism; and a newly developed statistic, the mean sliding G statistic, is most powerful for detecting patterns containing one or two peaks of polymorphism with reduced polymorphism on either side. Nine out of 27 genes from the Drosophila melanogaster subgroup exhibit heterogeneity that is significant under at least one of these three tests, with five of the nine remaining significant after a correction for multiple comparisons, suggesting that detectable evidence for the effects of some kind of selection is fairly common.
Amiloride delays the ischemia-induced rise in cytosolic free calcium.
Authors: E Murphy, M Perlman, R E London, C Steenbergen
Journal: Circulation Research (1991)

An increase in cytosolic free calcium (Cai) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Cai may occur as a result of exchange of Nai for Cao, which occurs as a result of an increase in Nai arising from exchange of Nao for H+i. The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Cai, Nai, ATP, and pHi during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Cai was measured using 19F nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Nai was measured using 23Na NMR, and the shift reagent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetramethylenephosph onate (Tm[DOTP]-5) was used to separate Nai and Nao. ATP and pH were determined from 31P NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Nai and Cai. After 20 minutes of ischemia, time-averaged Cai was 1.0 +/- 0.2 microM (mean +/- SEM) in amiloride-treated hearts compared with 2.3 +/- 0.9 microM in nontreated hearts. After 20 minutes of ischemia, Nai in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Nai was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Cai during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
The sonic hedgehog signaling pathway is reactivated in human renal cell carcinoma and plays orchestral role in tumor growth
Authors: Valérian Dormoy, Sabrina Danilin, Véronique Lindner, Lionel Thomas, Sylvie Rothhut, Catherine Coquard, Jean-Jacques Helwig, Didier Jacqmin, Hervé Lang, Thierry Massfelder
Journal: Molecular Cancer (2009)

Human clear cell renal cell carcinoma (CRCC) remains resistant to therapies. Recent advances in Hypoxia Inducible Factors (HIF) molecular network led to targeted therapies, but unfortunately with only limited clinical significance. Elucidating the molecular processes involved in kidney tumorigenesis and resistance is central to the development of improved therapies, not only for kidney cancer but for many, if not all, cancer types. The oncogenic PI3K/Akt, NF-kB and MAPK pathways are critical for tumorigenesis. The sonic hedgehog (SHH) signaling pathway is crucial to normal development.By quantitative RT-PCR and immunoblot, we report that the SHH signaling pathway is constitutively reactivated in tumors independently of the von Hippel-Lindau (VHL) tumor suppressor gene expression which is inactivated in the majority of CRCC. The inhibition of the SHH signaling pathway by the specific inhibitor cyclopamine abolished CRCC cell growth as assessed by cell counting, BrdU incorporation studies, fluorescence-activated cell sorting and beta-galactosidase staining. Importantly, inhibition of the SHH pathway induced tumor regression in nude mice through inhibition of cell proliferation and neo-vascularization, and induction of apoptosis but not senescence assessed by in vivo studies, immunoblot and immunohistochemistry. Gli1, cyclin D1, Pax2, Lim1, VEGF, and TGF-beta were exclusively expressed in tumors and were shown to be regulated by SHH, as evidenced by immunoblot after SHH inhibition. Using specific inhibitors and immunoblot, the activation of the oncogenic PI3K/Akt, NF-kB and MAPK pathways was decreased by SHH inhibition.These findings support targeting SHH for the treatment of CRCC and pave the way for innovative and additional investigations in a broad range of cancers.
Lymphocyte transformation in response to phytohaemagglutinin in primary biliary cirrhosis: The search for a plasma inhibitory factor
Authors: R. A. Fox, F. J. Dudley, M. Samuels, J. Milligan, S. Sherlock
Journal: Gut (1973)

The aim of this study was to determine the importance of plasma inhibitory factors in producing the impaired phytohaemagglutinin (PHA)-induced lymphocyte transformation that is seen in some patients with primary biliary cirrhosis. Twenty-six normal subjects and 12 patients with primary biliary cirrhosis were studied. The lymphocytes from each subject were cultured in the presence of autologous plasma and also in the presence of homologous plasma from a normal subject or from a patient with primary biliary cirrhosis. The results confirm that a proportion of patients with primary biliary cirrhosis are anergic and that the impaired lymphocyte transformation to PHA in vitro can be partially accounted for by the presence of inhibitory factors in the plasma. However, these factors are unlikely to account completely for the impaired transformation, it being probable that there are also abnormalities of the T lymphocytes themselves.
Smoking Bans Prevent Heart Attacks
Authors: Jonathan M. Samet
Journal: Circulation (2006)

n this issue of Circulation, Bartecchi and colleagues 1 describe a reduction in hospitalizations for acute myocardial infarction in Pueblo, Colo, after the implementation of a city-wide smoking ordinance.The ordinance, which was strictly enforced, prohibited smoking in all workplaces, including bars and restaurants, and in all buildings open to the public.The findings in Pueblo confirm a similar assessment of the consequences of a public smoking ban in Helena, Mont, which was the first such assessment reported. 2In the Montana study, the law was in force for 6 months before a challenge led to a court order suspending it.Admissions for acute myocardial infarction declined by 40% during the 6 months of the ban and then rose after it was lifted.
A Gonadotropin-Releasing Hormone-II Antagonist Induces Autophagy of Prostate Cancer Cells
Authors: Dong-Ki Kim, Ji Sook Yang, Kaushik Maiti, Jong-Ik Hwang, Kyungjin Kim, Dongseung Seen, Younghee Ahn, Cheolju Lee, Byeong-Cheol Kang, Hyuk Bang Kwon, Jun Cheon, Jae Young Seong
Journal: Cancer Research (2009)

Abstract Gonadotropin-releasing hormone-I (GnRH-I) is known to directly regulate prostate cancer cell proliferation. However, the role of GnRH-II in prostate cancer is unclear. Here, we investigated the effect of the GnRH-II antagonist trptorelix-1 (Trp-1) on growth of PC3 prostate cancer cells. Trp-1 induced growth inhibition of PC3 cells in vitro and inhibited growth of PC3 cells xenografted into nude mice. FITC-N3, an FITC-conjugated Trp-1 analogue, was largely present in the mitochondria of prostate cancer cells, but not in other cells that are not derived from the prostate. Trp-1–induced PC3 growth inhibition was associated with decreased mitochondrial membrane potential and increased levels of mitochondrial and cytosolic reactive oxygen species (ROS). Growth inhibition was partially prevented by cotreating cells with N-acetyl cysteine, an antioxidant. Cytochrome c release and caspase-3 activation were not detected in Trp-1–treated cells. However, Trp-1 induced autophagosome formation, as seen by increased LysoTracker staining and recruitment of microtubule-associated protein 1 light chain 3 to these new lysosomal compartments. Trp-1–induced autophagy was accompanied by decreased AKT phosphorylation and increased c-Jun NH2 terminal kinase phosphorylation, two events known to be linked to autophagy. Taken together, these data suggest that Trp-1 directly induces mitochondrial dysfunction and ROS increase, leading to autophagy of prostate cancer cells. GnRH-II antagonists may hold promise in the treatment of prostate cancer. [Cancer Res 2009;69(3):923–31]
Systematic Review: The Trousseau Syndrome Revisited: Should We Screen Extensively for Cancer in Patients with Venous Thromboembolism?
Authors: Marc Carrier, Grégoire Le Gal, Philip S. Wells, Dean Fergusson, Tim Ramsay, Marc A. Rodger
Journal: Annals of Internal Medicine (2008)

Background: Identifying previously undiagnosed cancer in patients with newly diagnosed venous thromboembolism (VTE) is important. Screening for malignant conditions can potentially diagnose more cases of cancer and at earlier stages, thereby preventing cancer-associated morbidity and perhaps mortality. Purpose: To summarize the period prevalence of previously undiagnosed cancer at baseline (within 1 month of VTE diagnosis), 6 months, and 12 months after VTE diagnosis and to quantify the additional value of an extensive cancer screening strategy (limited screening plus imaging techniques or tumor marker measurement) at baseline compared with more limited screening (history, physical examination, and simple widely available tests) at baseline. Data Sources: MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and Evidence-Based Medicine Reviews. Study Selection: A total of 36 studies that reported the prevalence of undiagnosed cancer at baseline, 6 months, and 12 months were selected. Fourteen articles and 1 abstract also met inclusion criteria for the assessment of extensive versus limited cancer screening. Data Extraction: Two reviewers independently extracted data onto standardized forms. Data Synthesis: The period prevalence of previously undiagnosed cancer in patients with unprovoked VTE was 6.1% (95% CI, 5.0% to 7.1%) at baseline and 10.0% (CI, 8.6% to 11.3%) from baseline to 12 months. An extensive screening strategy using computed tomography of the abdomen and pelvis statistically significantly increased the proportion of previously undiagnosed cancer detected from 49.4% (CI, 40.2% to 58.5%) (with limited screening alone) to 69.7% (CI, 61.1% to 77.8%) in patients with unprovoked VTE. Limitation: The investigators could not determine complication rates, cost-effectiveness, and difference in morbidity and mortality associated with extensive screening strategies. Conclusion: Previously undiagnosed cancer is frequent in patients with unprovoked VTE. Many cases of previously undiagnosed cancer are missed by screening. An extensive cancer screening strategy detects more malignant conditions than does a limited screening strategy.
Increased Risk of Locoregional Recurrence for Women With T1-2N0 Triple-Negative Breast Cancer Treated With Modified Radical Mastectomy Without Adjuvant Radiation Therapy Compared With Breast-Conserving Therapy
Authors: Bassam S. Abdulkarim, Julie Cuartero, John Hanson, Jean Deschênes, David Lesniak, Siham Sabri
Journal: Journal of Clinical Oncology (2011)

To evaluate the risk of locoregional recurrence (LRR) associated with locoregional treatment of women with primary breast cancer tumors negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (triple-negative breast cancer [TNBC]).
Role of Propionibacterium acnes in cancer risk
Authors: F.H.J. Rampen
Journal: British Journal of Dermatology (1989)

Journal Article Role of Propionibacterium acnes in cancer risk Get access F.H.J. Rampen F.H.J. Rampen Department of Dermatology, Sint Anna Hospital, J.Zwijsenlaan 121, 5342 BT Oss, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 2, 1 August 1989, Pages 279–280, https://doi.org/10.1111/j.1365-2133.1989.tb01813.x Published: 01 August 1989
Towards evidence-based classification in Paralympic athletics: evaluating the validity of activity limitation tests for use in classification of Paralympic running events
Authors: E M Beckman, S M Tweedy
Journal: British Journal of Sports Medicine (2009)

To classify Paralympic athletes, classifiers use test batteries to obtain an objective, pre-competition estimate of an athlete's training level. Five tests were evaluated to determine which combination explained the maximum variance in running performance in a non-disabled population. A non-disabled sample was required to permit psychometric evaluation of the tests without the confounding influence of impairment, and to provide an indication of normative performance.Sixty-seven non-disabled participants (male and female; mean (SD) age 24.78 (6.53) years) completed a six-test battery comprising a 30 m sprint (criterion activity limitation test) and five supplementary activity limitation tests: standing broad jump, four bounds, 10 m skip, running in place and split jumps.Test reliability was high for all tests (intraclass correlations = 0.80-0.99). Pearson correlations with the 30 m sprint were moderate to strong for standing broad jump (-0.82), four bounds (-0.80) and 10 m skip (0.67), but weaker for split jumps (0.35) and running in place (0.19). Multiple regression indicated that standing broad jump, four bounds and 10 m skip explained 75% of the variance in running performance.The test battery is reliable and valid in the non-disabled population and therefore has potential utility in Paralympic classification. Test results were normally distributed, a necessary prerequisite for meaningful interpretation of future studies in athletes with impairments. Further studies evaluating the battery in populations of athletes with impairments of coordination, strength and range of movement are now warranted.
Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents
Authors: Xu Wu, Baojun Chang, N. Scott Blair, Michelle Sargent, Allen J. York, Jeffrey Robbins, Gary E. Shull, Jeffery D. Molkentin
Journal: Journal of Clinical Investigation (2009)

How Ca2+-dependent signaling effectors are regulated in cardiomyocytes, given the extreme cytoplasmic Ca2+ concentration changes that underlie contraction, remains unknown. Cardiomyocyte plasma membrane Ca2+-ATPase (PMCA) extrudes Ca2+ but has little effect on excitation-contraction coupling, suggesting its potential role in controlling Ca2+-dependent signaling effectors such as calcineurin. We generated cardiac-specific inducible PMCA4b transgenic mice that displayed normal global Ca2+ transient and cellular contraction levels and reduced cardiac hypertrophy following transverse aortic constriction (TAC) or phenylephrine/Ang II infusion, but showed no reduction in exercise-induced hypertrophy. Transgenic mice were protected from decompensation and fibrosis following long-term TAC. The PMCA4b transgene reduced the hypertrophic augmentation associated with transient receptor potential canonical 3 channel overexpression, but not that associated with activated calcineurin. Furthermore, Pmca4 gene–targeted mice showed increased cardiac hypertrophy and heart failure events after TAC. Physical associations between PMCA4b and calcineurin were enhanced by TAC and by agonist stimulation of cultured neonatal cardiomyocytes. PMCA4b reduced calcineurin nuclear factor of activated T cell–luciferase activity after TAC and in cultured neonatal cardiomyocytes after agonist stimulation. PMCA4b overexpression inhibited cultured cardiomyocyte hypertrophy following agonist stimulation, but much less so in a Ca2+ pumping–deficient PMCA4b mutant. Thus, Pmca4b likely reduces the local Ca2+ signals involved in reactive cardiomyocyte hypertrophy via calcineurin regulation.
Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B
Authors: Ramaswamy Govindan, Robert A. Kratzke, James E. Herndon, Gloria A. Niehans, Robin Vollmer, Dorothy Watson, Mark R. Green, Hedy L. Kindler
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma. Experimental Design: Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity. Results: The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression. Conclusions: Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.
Immunopathophysiological aspects of an emerging neonatal infectious disease induced by a bacterial superantigen
Authors: Naoto Takahashi, Hidehito Kato, Ken’ichi Imanishi, Keishi Miwa, Sadao Yamanami, Hiroshi Nishida, Takehiko Uchiyama
Journal: Journal of Clinical Investigation (2000)

We recently discovered an emerging neonatal infectious disease, neonatal toxic shock syndrome–like (TSS-like) exanthematous disease (NTED), which is induced by a superantigen, TSS toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). Here, we analyzed the activation and the response of TSST-1–reactive Vβ2+ T cells in NTED patients during the acute and recovery phases and in asymptomatic infants exposed to MRSA. In the acute phase, Vβ2+ T cells were anergic to stimulation with TSST-1 and underwent marked expansion, but by 2 months after disease onset, their numbers had declined to about 10% of the control level. Although the percentage of Vβ2+ T cells in the ten asymptomatic neonatal MRSA carriers was within the control range, these individuals could be divided into two groups on the basis of Vβ2+ T-cell activation. Vβ2+CD4+ T cells from three of these infants (Group 1) highly expressed CD45RO and were anergic to TSST-1, whereas in the other seven asymptomatic neonatal MRSA carriers (Group 2), these cells expressed CD45RO at the control level and were highly responsive to stimulation with TSST-1. The serum anti–TSST-1 IgG Ab titer was negligible in the four NTED patients in the acute phase and the three asymptomatic neonatal MRSA carriers in Group 1, but it was high in the seven asymptomatic carriers in Group 2. We suggest that maternally derived anti–TSST-1 IgGs helps to suppress T-cell activation by TSST-1 and protects infants from developing NTED.
Allergic contact dermatitis due to sesquiterpene lactones.
Authors: JEAN-LUC STAMPF, GILBERT SCHLEWER, GEORGES DUCOMBS, JEAN FOUSSEREAU, CLAUDE BENEZRA
Journal: British Journal of Dermatology (1978)

Several compounds containing the alpha-methylene-gamma-butyrolactone moiety have been tested on human volunteers and on guinea-pigs; the animals were experimentally sensitized by alantolactone, isoalantolactone and laurel oil. Of the two new lactones, spirolactone was the more reactive: this was confirmed by both animal and human testing. The synthetic lactones are less reactive than natural ones. alpha-Methylene-gamma-butyrolactone itself does not elicit cross-reactions in guinea pigs sensitive either to alantolactone or to isoalantolactone, or in patients sensitive to sesquiterpene lactones. The alpha-methylene-gamma-butyrolactone group is necessary for cross-reaction, but to be active, it has first to be substituted. It was also found that isoalantolactone, allegedly not allergenic, is in fact a sensitizer and cross-reacts with alantolactone. The cross-reaction between laurel and Frullania, found in man, also occurs in guinea-pigs. It is more evident when sesquiterpene lactone is the sensitizer and laurel used to elicit reaction.