tbuckley/cabot-search huggingface dataset:
A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines.
Authors: Guro E Lind, Lin Thorstensen, Tone Løvig, Gunn I Meling, Richard Hamelin, Torleiv O Rognum, Manel Esteller, Ragnhild A Lothe
Journal: Molecular Cancer (2004)

Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS) and 9 microsatellite unstable (MSI) colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI) with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16 INK4a (CDKN2A α-transcript), p14 ARF (CDKN2A β-transcript), APC, and E-cadherin (CDH1). We compared the DNA methylation profiles of the cell lines with those of the primary tumors. Finally, we examined if the epigenetic changes were associated with known genetic markers and/or clinicopathological variables. The cell lines and primary tumors generally showed similar overall distribution and frequencies of gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed promoter methylation for hMLH1, MGMT, p16 INK4a , p14 ARF , APC, and E-cadherin, respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were methylated for the same genes. hMLH1 and p14 ARF were significantly more often methylated in MSI than in MSS primary tumors, whereas the remaining four genes showed similar methylation frequencies in the two groups. Methylation of p14 ARF , which indirectly inactivates TP53, was seen more frequently in tumors with normal TP53 than in mutated samples, but the difference was not statistically significant. Methylation of p14 ARF and p16 INK4a was often present in the same primary tumors, but association to diploidy, MSI, right-sided location and female gender was only significant for p14 ARF . E-cadherin was methylated in 14/34 tumors with altered APC further stimulating WNT signaling. The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same molecular alterations as do the primary carcinomas. The combined pattern of epigenetic and genetic aberrations in the primary carcinomas reveals associations between them as well as to clinicopathological variables, and may aid in the future molecular assisted classification of clinically distinct stages.
Cell lineage distribution atlas of the human stomach reveals heterogeneous gland populations in the gastric antrum
Authors: Eunyoung Choi, Joseph T Roland, Brittney J Barlow, Ryan O'Neal, Amy E Rich, Ki Taek Nam, Chanjuan Shi, James R Goldenring
Journal: Gut (2014)

Objective The glands of the stomach body and antral mucosa contain a complex compendium of cell lineages. In lower mammals, the distribution of oxyntic glands and antral glands define the anatomical regions within the stomach. We examined in detail the distribution of the full range of cell lineages within the human stomach. Design We determined the distribution of gastric gland cell lineages with specific immunocytochemical markers in entire stomach specimens from three non-obese organ donors. Results The anatomical body and antrum of the human stomach were defined by the presence of ghrelin and gastrin cells, respectively. Concentrations of somatostatin cells were observed in the proximal stomach. Parietal cells were seen in all glands of the body of the stomach as well as in over 50% of antral glands. MIST1 expressing chief cells were predominantly observed in the body although individual glands of the antrum also showed MIST1 expressing chief cells. While classically described antral glands were observed with gastrin cells and deep antral mucous cells without any parietal cells, we also observed a substantial population of mixed type glands containing both parietal cells and G cells throughout the antrum. Conclusions Enteroendocrine cells show distinct patterns of localisation in the human stomach. The existence of antral glands with mixed cell lineages indicates that human antral glands may be functionally chimeric with glands assembled from multiple distinct stem cell populations.
Celecoxib Decreases Ki-67 Proliferative Index in Active Smokers
Authors: Jenny T. Mao, Michael C. Fishbein, Bradley Adams, Michael D. Roth, Lee Goodglick, Longsheng Hong, Marie Burdick, E. Robert M. Strieter, Carmack Holmes, Donald P. Tashkin, Steven M. Dubinett
Journal: Clinical Cancer Research (2006)

Abstract Purpose: This study evaluated the feasibility of cyclooxygenase-2 (COX-2) inhibition for lung cancer chemoprevention. We hypothesized that treatment with oral Celecoxib, a selective COX-2 inhibitor, would favorably alter the biomarkers of lung cancer risk as measured by the Ki-67 proliferative labeling index (Ki-67 LI). Experimental Design: Twenty active heavy smokers were enrolled into a pilot study and treated with Celecoxib for 6 months. Bronchoscopies with bronchial biopsies were done before and after 6 months of Celecoxib treatment. H&amp;E stain for histologic grading and immunohistochemical examination for Ki-67 LI, COX-2, and survivin were carried out on serially matched biopsy samples to determine responses to treatment. Results: Treatment with Celecoxib significantly reduced Ki-67 LI in smokers by 35% (P = 0.016), and increased the expression of nuclear survivin by 23% (P = 0.036) without significantly changing that of cytoplasmic survivin. Conclusions: Our findings suggest that oral Celecoxib may be capable of modulating the proliferation indices and apoptotic balance in bronchial tissue of active smokers.
The Origins of Medulloblastoma Subtypes
Authors: Richard J. Gilbertson, David W. Ellison
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Childhood tumors containing cells that are morphologically and functionally similar to normal progenitor cells provide fertile ground for investigating the links between development and cancer. In this respect, integrated studies of normal cerebellar development and the medulloblastoma, a malignant embryonal tumor of the cerebellum, have proven especially fruitful. Emerging evidence indicates that the different precursor cell populations that form the cerebellum and the cell signaling pathways that regulate its development likely represent distinct compartments from which the various subtypes of medulloblastoma arise. Definitive characterization of each medulloblastoma subtype will undoubtedly improve treatment of this disease and provide important insights to the origins of cancer.
<i>Mycobacterium tuberculosis </i>Chaperonin 10 Stimulates Bone Resorption: A Potential Contributory Factor in Pott's Disease
Authors: Sajeda Meghji, Peter A. White, Sean P. Nair, Krisanavane Reddi, Kyle Heron, Brian Henderson, Andrea Zaliani, Gianluca Fossati, Paolo Mascagni, John F. Hunt, Michael M. Roberts, Anthony R.M. Coates
Journal: The Journal of Experimental Medicine (1997)

Pott's disease (spinal tuberculosis), a condition characterized by massive resorption of the spinal vertebrae, is one of the most striking pathologies resulting from local infection with Mycobacterium tuberculosis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. North Am. 27:95–103). The pathogenesis of Pott's disease is not established. Here we report for the first time that a protein, identified by a monoclonal antibody to be the Mt heat shock protein (Baird, P.N., L.M. Hall, and A.R.M. Coates. 1989. J. Gen. Microbiol. 135:931–939) chaperonin (cpn) 10, is responsible for the osteolytic activity of this bacterium. Recombinant Mt cpn10 is a potent stimulator of bone resorption in bone explant cultures and induces osteoclast recruitment, while inhibiting the proliferation of an osteoblast bone–forming cell line. Furthermore, we have found that synthetic peptides corresponding to sequences within the flexible loop and sequence 65–70 of Mt cpn10 may comprise a single conformational unit which encompasses its potent bone-resorbing activity. Our findings suggest that Mt cpn10 may be a valuable pharmacological target for the clinical therapy of vertebral tuberculosis and possibly other bone diseases.
A severe familial phenotype of Ichthyosis Curth-Macklin caused by a novel mutation in the<i>KRT1</i>gene
Authors: D.J. Fonseca, R.F. Rojas, J.I. Vergara, X. Ríos, C. Uribe, L. Chávez, F. Velandia, C.I. Vargas, C.M. Restrepo, P. Laissue
Journal: British Journal of Dermatology (2012)

Funding sources: This study was supported by the Universidad del Rosario, Grant CS/Genetics 2012. Conflicts of interest: none declared. Madam, Ichthyosis Curth–Macklin (ICM; Mendelian Inheritance in Man database #146590) is a rare genetic disorder that is clinically characterized by severe palmoplantar keratoderma. The skin of patients with ICM is characterized by extensive dark spiky or verrucous plaques that affect the large joints and the trunk. In some cases these lesions can cover the entire body. Differentiating keratinocytes of ICM tissues display ultrastructural anomalies such as keratin intermediate filaments (KIF), aggregation into peripheral shells, perinuclear vacuolization and binucleated cell formation.1 ICM, as well as other keratinopathic ichthyoses, is caused by mutations of the keratin 1 gene (KRT1) that lead to an impairment of the KIF network assembly in the cytoplasm of keratinocytes.2 At the protein level, these mutations are located in the variable (V2) domain of the protein.1, 3, 4 In this study, we report two related women of Colombian origin, affected by a severe ICM phenotype, who present a novel KRT1 mutation. These patients attended the Dermatology Unit of the Carlos Ardila Lulle Clinic of Bucaramanga (Colombia). This study has been approved by the Ethical Committee at Universidad del Rosario and was conducted according to the Declaration of Helsinki principles. The index case (IC) provided a consent form to participate in the study and signed it on behalf of her daughter.
Lidocaine in Cardiac Resuscitation from Ventricular Fibrillation
Authors: NORMAN L. CARDEN, JOHN E. STEINHAUS
Journal: Circulation Research (1956)

The interruption of ventricular fibrillation following coronary occlusion in dogs was effected with the use of lidocaine. This technic caused no obvious sequelae and the recurrence of fibrillation was rare. It was used successfully in both normothermic and hypothermic animals although the proportion of successful resuscitations was less in the latter group.
Site, histological type, and thickness of primary cutaneous malignant melanoma in western Netherlands since 1980
Authors: L.M.T. VAN DER SPEK-KEIJSER, H.J. VAN DER RHEE, G. TÓTH, R. VAN WESTERING, J.A. BRUIJN, J.W.W. COEBERGH
Journal: British Journal of Dermatology (1997)

An increasing incidence of cutaneous malignant melanoma had been observed in the Netherlands. Therefore, between 1989 and 1992 a preventive skin cancer campaign was organized in part of western Netherlands. The effect of this screening campaign has yet to be evaluated by investigating the distribution of all in situ and invasive primary cutaneous melanoma according to anatomical subsite, tumour thickness, and histological type in a population-based study during 1980-92. A total number of 2236 (1361 female; 875 male) invasive and 580 (395 female; 185 male) in situ melanomas were diagnosed. The median age of patients with thin lesions was 46 years, intermediate lesions 54 years, and thick lesions 65 years, which may be indicative of slow tumour progression. The median thickness of the invasive lesions was 0.9 mm for women and 1.1 mm for men and the invasive to in situ ratio was 3.4 for female and 4.7 for male subjects, suggesting a reasonable awareness of melanoma in this population. The relative tumour density (RTD) was remarkably high for melanomas in the head/neck area for both sexes and invasive melanoma on the male trunk and the lower legs of females. The low RTD of invasive melanomas on the lower limbs of men and the high density in the head/neck area for both sexes are remarkable and support the aetiological role of ultraviolet exposure. It is concluded that our findings are in many ways similar to those of other descriptive studies.
Population-Based Study Evaluating and Predicting the Probability of Death Resulting From Thyroid Cancer and Other Causes Among Patients With Thyroid Cancer
Authors: Limin Yang, Weidong Shen, Naoko Sakamoto
Journal: Journal of Clinical Oncology (2012)

The purpose of this study was to evaluate the probability of death for patients with thyroid cancer and construct a comprehensive nomogram based on a competing risks model to predict cumulative incidence of death resulting from thyroid cancer, other cancers, and non-cancer-related causes.Patients diagnosed with thyroid cancer between 1988 and 2003 were selected for the study from the Surveillance, Epidemiology, and End Results program. We estimated probabilities of death resulting from thyroid cancer, other cancers, and noncancer causes and analyzed associations of patient and tumor characteristics with probability of death. A nomogram for predicting probability of death was built using a proportional subdistribution hazard competing risks model.The entire cohort comprised 29,225 patients with malignant thyroid cancer. Median duration of follow-up until censoring or death was 85 months (range, 0 to 239 months). Five-year probabilities of death resulting from thyroid cancer, other cancer, and noncancer causes were 1.9%, 0.8%, and 1.7%, respectively. Increasing age and tumor size, male sex, poorly differentiated carcinoma, lymph node involvement, and regional and metastatic disease were associated with increased cumulative incidence of death resulting from thyroid cancer.A nomogram based on a competing risks model was developed for predicting the probability of death for patients with thyroid cancer. Performance of the model was excellent. This nomogram may be useful for patients and clinicians when predictions are needed.
Adjuvant immunotherapy with BCG in squamous-cell bronchial carcinoma. Immune-reactivity in relation to immunostimulation (preliminary results in a controlled trial)
Authors: H M Jansen, T H The, G C De Gast, M T Esselink, A M Van Der Wal, N G M Orie
Journal: Thorax (1978)

<b>Jansen, H M, The, T H, de Gast, G C, Esselink, M T, van der Wal, A M, and Orie, N G M (1978).</b><i>Thorax</i>, <b>33</b>, 429-438. <b>Adjuvant immunotherapy with BCG in squamous-cell bronchial carcinoma. Immune-reactivity in relation to immunostimulation (preliminary results in a controlled trial).</b> Twenty-nine patients with, at operation, evidence of locally advanced primary squamous-cell bronchial carcinoma (stage II, UICC, Geneva, 1974) had lung resection to remove all the visible tumour. Postoperatively a randomly chosen group of 16 patients received adjuvant BCG immunostimulation by scarifications, while the control group received no adjuvant treatment. Follow-up studies were done from three to 23 months. Immune-reactivity in vivo with PPD and DNCB skin tests, and in vitro with E-rosetting tests and lymphocyte transformation tests with PHA, Con A, diphtheria toxoid, and PPD was monitored in 10 treated and in seven untreated patients. Recurrence rates decreased appreciably in the BCG-stimulated group after a six to 23 months9 follow-up (p&lt;0·005). A pronounced increase in both in-vivo and in-vitro immune-reactivity went in parallel with a more favourable clinical outcome in the BCG-treated group. In these cases there was a significant increase in skin reactivity to PPD three months after surgery (p&lt;0·025) and a statistically significant rise in lymphocyte reactivity to Con A (p&lt;0·05), diphtheria toxoid (p&lt;0·01), and PPD (p&lt;0·05) but not to PHA 12 months after surgery. DNCB skin reactivity increased as well in the BCG-treated group, but the number of individuals was too small for statistical evaluation. Increase in immune responsiveness did not occur in the control group and appeared to be independent of the initial immune state of the patients. No differences were found in the numbers of E-rosetting lymphocytes in relation to immunotherapy. It is concluded that adjuvant BCG immunotherapy used in patients with minimal residual bronchial carcinoma improves the prognosis and a favourable clinical outcome is mirrored by an increase in cellular immune reactivity.
Novel Interactions between TGF-β1 Actions and the 12/15-Lipoxygenase Pathway in Mesangial Cells
Authors: Young-Sook Kim, Zhong-Gao Xu, Marpadga A. Reddy, Shu-Lian Li, Linda Lanting, Kumar Sharma, Sharon G. Adler, Rama Natarajan
Journal: Journal of the American Society of Nephrology (2004)

Diabetic nephropathy (DN) is characterized by mesangial cell (MC) hypertrophy and progressive accumulation of glomerular extracellular matrix (ECM). It was reported recently that 12/15-lipoxygenase (12/15-LO) expression is increased in high-glucose (HG)-stimulated MC and in experimental DN. 12-LO products could also directly induce MC hypertrophy and ECM expression and mediate growth factor effects, thus implicating the 12/15-LO pathway in DN. Because TGF-beta is a major player in the pathogenesis of DN, whether there is an interplay between the TGF-beta and 12/15-LO pathways in MC was evaluated. Treatment of rat MC (RMC) with TGF-beta significantly increased levels of the 12/15-LO product 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and also 12/15-LO mRNA and protein expression. HG-induced TGF-beta mRNA expression in RMC was inhibited by a specific ribozyme and siRNA targeted to knockdown rat 12/15-LO. It is interesting that direct treatment of RMC with 12(S)-HETE increased TGF-beta mRNA and protein levels, as well as p-Smad2/3, which are TGF-beta-specific target transcription factors. 12(S)-HETE also increased transcription from a minimal TGF-beta promoter. Furthermore, TGF-beta expression and p-Smad2/3 levels were lower in MC from 12/15-LO knockout mice relative to control mice. Reciprocally, mouse MC stably overexpressing 12/15-LO had greater TGF-beta mRNA and also nuclear p-Smad2/3 relative to mock-transfected cells. 12/15-LO and TGF-beta could functionally signal and increase ECM expression via the p38 mitogen-activated protein kinase signaling pathway. These results indicate for the first time that the 12/15-LO and TGF-beta pathways can cross-talk and activate each other. These novel interactions may amplify the signal transduction cascades and molecular events that lead to DN.
Murine Lung Carcinogenesis Following Exposure to Ambient Ozone Concentrations&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: C Hassett, M G Mustafa, W F Coulson, R M Elashoff
Journal: JNCI Journal of the National Cancer Institute (1985)

Inbred strain A/J mice, responsive to the chemical induction of pulmonary adenomas, were used to assess any of several roles that the photochemical air pollutant ozone might play in lung carcinogenesis. In separate experiments, animals were exposed to two concentrations of ozone (0.31 +/- 0.01 and 0.50 +/- 0.02 ppm) intermittently for a 6-month period, to evaluate the potential of ozone to act as either a pulmonary carcinogen, a tumor promoter, or an inhalant capable of increasing lung tumor yield when exposure was in conjunction with a pulmonary carcinogen, urethane. Statistical analyses of results indicated that ozone exposure at both concentrations caused an increase in lung tumor number relative to clean air controls, but that ozone was not an effective tumor promoter under the conditions of our protocol. When ozone exposure immediately preceded treatment with urethane (CAS: 51-79-6), animals were at increased risk for the development of lung adenomas.
On Aortic Regurgitation and the Coronary Circulation
Authors: T. C. Allbutt
Journal: BMJ (1880)

THE -:BRITISH MEVWA' JQRNAL- [JCne 1Q, iS8o.felt, sudden pain in the head, and noise in the ears.He was subject to Bush-ngs.He was not breathless on exertion.The pulse was abrupt and varying, in the sitting posPu e, fror 84 to I10, these, rates altern- ating within a-few seconds.The.sounds of the heart were sharp, and the first faintly double.He was advised to give. up tea, to take active exercise and cold showers, and to have tincture of nux vomica.andiron. in a biter infusion.CASE VIII.-Mrs.MI.B1, aged 38, a travelling re'ligieuse, had been in good health till she started on a long journey.a month previously, since when, having, been much worried in mind and body, and fre- quently deprived of her regular meals, she had taken very strong tea in large quantity, and often without much solid food.Latterly she had experienced fits of dyspnoea with palpitation, accompanied with a feeling as if she were "going to die"; these fits carre on in bed.She had-pain in the region of the heart; pulse snmall and rapid (120), but ;regukar; heart's action excited.; sounds sharp and clear.She had psoriasis guttata on the front of the chest; this had been always brought out by the free use of tea.She was ordered to have an Qpium.plaster applied to the frgjion of the heart, to take iron and nux vomica, and to give up thp-use of tea.CASE-Ix.-Mr.J. 0. 13., aged 35, a professional man of fine Jitysiqite amd-a-cive habits, temperate in regard to alcoholic stimulants, but fond of strong tea, which he had often taken three times, but invariably twice, in the day, and indulged in a cigarette occasionally; had had rheumatism, and w4s nervous in regard to his heart.Two years pre- viouslyhe experienced for the first time palpitation and want of breath -on exertion.Latterly, these attacks had becomiie miore frequent and severe.He was occasionally awakened by anomalous sensations in the
Comparison of Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting After Acute Myocardial Infarction Complicated by Cardiogenic Shock
Authors: Harvey D. White, Susan F. Assmann, Timothy A. Sanborn, Alice K. Jacobs, John G. Webb, Lynn A. Sleeper, Cheuk-Kit Wong, James T. Stewart, Philip E.G. Aylward, Shing-Chiu Wong, Judith S. Hochman
Journal: Circulation (2005)

The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial demonstrated the survival advantage of emergency revascularization versus initial medical stabilization in patients developing cardiogenic shock after acute myocardial infarction. The relative merits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with shock have not been defined. The objective of this analysis was to compare the effects of PCI and CABG on 30-day and 1-year survival in the SHOCK trial. Of the 302 trial patients, 128 with predominant left ventricular failure had emergency revascularization. The selection of revascularization procedures was individualized. Eighty-one patients (63.3%) had PCI, and 47 (36.7%) had CABG. The median time from randomization to intervention was 0.9 hours (interquartile range [IQR], 0.3 to 2.2 hours) for PCI and 2.7 hours (IQR, 1.3 to 5.5 hours) for CABG. Baseline demographics and hemodynamics were similar, except that there were more diabetics (48.9% versus 26.9%; P=0.02), 3-vessel disease (80.4% versus 60.3%; P=0.03), and left main coronary disease (41.3% versus 13.0%; P=0.001) in the CABG group. In the PCI group, 12.3% had 2-vessel and 2.5% had 3-vessel interventions. In the CABG group, 84.8% received > or =2 grafts, 52.2% received > or =3 grafts, and 87.2% were deemed completely revascularized. The survival rates were 55.6% in the PCI group compared with 57.4% in the CABG group at 30 days (P=0.86) and 51.9% compared with 46.8%, respectively, at 1 year (P=0.71). Among SHOCK trial patients randomized to emergency revascularization, those treated with CABG had a greater prevalence of diabetes and worse coronary disease than those treated with PCI. However, survival rates were similar. Emergency CABG is an important component of an optimal treatment strategy in patients with cardiogenic shock, and should be considered a complementary treatment option in patients with extensive coronary disease.