tbuckley/cabot-search huggingface dataset:
Short Hairpin RNA–Mediated Inhibition of Matrix Metalloproteinase-1 in MDA-231 Cells: Effects on Matrix Destruction and Tumor Growth
Authors: Colby A. Wyatt, James C. Geoghegan, Constance E. Brinckerhoff
Journal: Cancer Research (2005)

Abstract Increased matrix metalloproteinase-1 (MMP-1) expression is associated with advanced stages of breast cancer and may be a predictive marker for the development of invasive disease. In this report, we used short hairpin RNA (shRNA) molecules to investigate whether MMP-1 production in MDA-231 breast cancer cells contributed to the degradation of a collagen matrix or tumor formation in nude mice. We created two groups of MDA-231 cell lines. MDA-231 cells containing a vector producing shRNA specific for MMP-1 had a &amp;gt;90% decrease in MMP-1 mRNA and protein compared with cells containing an empty vector, and blocking MMP-1 expression inhibited the in vitro collagenolytic activity of MDA-231 cells. When the cells were injected into the mammary fat pad, there was no difference in the frequency of tumor formation in mice. However, the average tumor size was larger in mice injected with cells containing the empty vector (1,216 ± 334 mm3) than in mice injected with cells expressing the MMP-1 shRNA (272 ± 117 mm3; P = 0.027). We conclude that MMP-1 expression is essential for the ability of MDA-231 cells to invade and destroy a collagen matrix and in vivo experiments suggest an important role for MMP-1 in breast tumor growth.
Population-Based Study of Changing Breast Cancer Risk in Icelandic BRCA2 Mutation Carriers, 1920–2000
Authors: Laufey Tryggvadottir, Helgi Sigvaldason, Gudridur H. Olafsdottir, Jon G. Jonasson, Thorvaldur Jonsson, Hrafn Tulinius, Jorunn E. Eyfjörd
Journal: JNCI Journal of the National Cancer Institute (2006)

Mutations in the BRCA genes increase the risk of breast cancer. Valid estimates of the magnitude of the lifetime risk of breast cancer in BRCA gene mutation carriers are needed for genetic counseling. Recent results suggest that penetrance has increased in recent birth cohorts. We examined the cumulative breast cancer incidence and mortality before age 70 over a diagnosis period of 80 years in Icelandic women who carried the BRCA2 founder mutation 999del5.Information on all breast cancers diagnosed in Iceland since 1911 was obtained from the Icelandic Cancer Registry. Mutation status was determined by molecular analysis of tissue samples for 847 breast cancer probands who were diagnosed from 1921 through 1985 and selected without knowledge of family history of breast cancer. We estimated the cumulative incidence and mortality from breast cancer before age 70 years in BRCA2 mutation carriers from the observed risks in first-degree relatives who were classified according to mutation status of probands and followed-up through 2002. Poisson modeling of these risks was also carried out. All statistical tests were two-sided.Of the 847 probands, 88 carried the BRCA2 999del5 mutation and 759 did not. According to Poisson modeling, the cumulative incidence of breast cancer before age 70 years in mutation carriers increased from 18.6% (95% CI = 11.0% to 29.5%) in calendar year 1920 to 71.9% (95% CI = 45.9% to 100%) in 2002 (P < .001); in relatives of probands who did not carry the BRCA2 mutation and in the general Icelandic population incidence increased over the same period from 2.6% to 10.7% and from 1.8% to 7.5%, respectively (all increases of approximately fourfold). During the same period, the cumulative risk of death from breast cancer before age 70 years for BRCA2 mutation carriers increased from 12.1% (95% CI = 5.3% to 23.9%) to 26.9% (95% CI = 10.9% to 55.5%) (P = .08). However, because the probands were breast cancer patients and not a random sample from the population, some bias in the estimation of time trends in penetrance cannot be ruled out.The results indicate that the penetrance of the Icelandic BRCA2 founder mutation increased nearly fourfold in 80 years, whereas the risk of death from breast cancer before age 70 years increased only approximately twofold. Changes in penetrance with time should be considered when penetrance is estimated.
Erythropoietin Stimulates Tumor Growth via EphB4
Authors: Sunila Pradeep, Jie Huang, Edna M. Mora, Alpa M. Nick, Min Soon Cho, Sherry Y. Wu, Kyunghee Noh, Chad V. Pecot, Rajesha Rupaimoole, Martin A. Stein, Stephan Brock, Yunfei Wen, Chiyi Xiong, Kshipra Gharpure, Jean M. Hansen, Archana S. Nagaraja, Rebecca A. Previs, Pablo Vivas-Mejia, Hee Dong Han, Wei Hu, Lingegowda S. Mangala, Behrouz Zand, Loren J. Stagg, John E. Ladbury, Bulent Ozpolat, S. Neslihan Alpay, Masato Nishimura, Rebecca L. Stone, Koji Matsuo, Guillermo N. Armaiz-Peña, Heather J. Dalton, Christopher Danes, Blake Goodman, Cristian Rodriguez-Aguayo, Carola Kruger, Armin Schneider, Shyon Haghpeykar, Padmavathi Jaladurgam, Mien-Chie Hung, Robert L. Coleman, Jinsong Liu, Chun Li, Diana Urbauer, Gabriel Lopez-Berestein, David B. Jackson, Anil K. Sood
Journal: Cancer Cell (2015)
Abstract P5-03-14: Low dose ionising radiation effects in normal breast progenitor sub-populations
Authors: JN Kavanagh, A Kissenpfennig, GW Irwin, KM Prise
Journal: Cancer Research (2013)

Abstract The human breast is a radiosensitive tissue and radiation exposure is proposed to contribute to mammary gland carcinogenesis through changes to stem and progenitor cells that result in aberrant proliferation, differentiation and genome instability. However, little is known about the low dose radiation response (LD IR) under conditions of relevance to environmental and occupational and medical imaging exposures. This study utilises 2-D and 3-D breast models derived from two normal breast cell lines (MCF10A and HME1) and primary human mammary epithelial cells from reduction mammoplasty surgery, to investigate the mechanisms underpinning sensitivity of normal breast to LD IR and elucidate its role in breast cancer initiation and progression. We have shown that DNA damage can be detected in both cell lines after doses &amp;lt;50 mGy and that an increased level of DNA damage foci at 1 h post LD IR is observed in a subpopulation of cells. Using antibodies to cell surface markers suggested to be putative breast stem cell markers, we have performed Fluoresence Activated Cell Sorting (FACS) to isolate subpopulations from the MCF10A cell line. CD49fhi, EpCAM-, MUC1- cells thought to be progenitor like cells were found to be more resistant to LD IR than the EpCAM+, MUC1+ population. As the pathways that govern survival/proliferation of stem and progenitor cells versus differentiation are interconnected, we have investigated if radiation resistance is also correlated with changes to breast cell differentiation. It was observed that LD IR modulated breast cell lineage markers in 2D cultures of both cell lines. We subsequently found that radiation induces a decrease in MUC1 mRNA expression levels which coincides with increased Lef1 expression. Lef1 has been shown to promote Mre11 expression thereby conferring elevated DNA repair and radiation resistance in tumour cells. Based on our findings, we hypothesize that progenitor cell populations within normal breast cell lines may be more efficient at detecting DNA DSBs resulting from LD IR leading to a pro-survival response. We are currently investigating these effects in primary mammary epithelial cell samples, using FACS to isolate progenitor subpopulations. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-03-14.
A national confidential enquiry into community acquired pneumonia deaths in young adults in England and Wales
Authors: J C G Simpson
Journal: Thorax (2000)

The aim of this study was to describe the frequency, causal pathogens, management, and outcome of a population of young adults who died from community acquired pneumonia (CAP).Pneumonia deaths in England and Wales in adults aged 15-44 were identified between September 1995 and August 1996. Patients with underlying chronic illness including HIV infection were excluded. Clinical details for each case were collected from the hospital and general practitioner records.Death from CAP was identified in 27 previously well young adults (1.2 per million population per year). Twenty were known to have consulted a GP for this illness. Nine received antibiotics before hospital admission. A causative pathogen was identified in 17 cases (Streptococcus pneumoniae in eight). Bacteraemia was present in seven. All patients who reached a hospital ward received antibiotics (69% within two hours of admission). The British Thoracic Society antibiotic guidelines for severe CAP were followed in only 10 cases. Cardiac arrest at home or on arrival at hospital occurred in six cases, one of whom was successfully resuscitated. Of the remaining 21 patients, 71% had two or more markers of severe CAP. All 22 who were admitted reached an intensive care unit, but 11 of these required transfer to another hospital for some aspect of intensive care. One third of patients died within 24 hours of presenting to the hospital.Death from CAP in previously fit young adults still occurs. While some deaths might be preventable by better patient management, most are unlikely to be preventable by current management practices.
Suicidal Behavior in Patients With Schizophrenia and Other Psychotic Disorders
Authors: Elizabeth D. Radomsky, Gretchen L. Haas, J. John Mann, John A. Sweeney
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Patients with schizophrenia are known to be at high risk for suicide attempts and dying by suicide. However, little research has been conducted to determine whether the risk for suicidal behavior is elevated among patients with psychosis in general. METHOD: This study evaluated 1-month and lifetime rates of suicidal behavior among 1,048 consecutively admitted psychiatric inpatients (ages 18 to 55 years) with DSM-III-R psychotic disorders. Demographic, clinical, and diagnostic correlates of suicidal behavior were examined. RESULTS: A high rate of suicidal behavior was found in the group: 30.2% reported a lifetime history of suicide attempts, and 7.2% reported a suicide attempt in the month before admission. The highest 1-month and lifetime rates were found in patients with schizoaffective disorder and major depression with psychotic features. Ratings of the medical dangerousness of the most recent suicide attempt on the basis of the extent of physical injury were higher in patients with schizophrenia spectrum psychoses. Agreement was high between emergency room assessments and semistructured interview assessments of suicidal behavior. CONCLUSIONS: Rates of suicidal behavior were high across a broad spectrum of patients with psychotic disorders; patients with a history of a current or past major depressive episode (as a part of major depressive disorder or schizoaffective disorder) were at a greater risk for suicide attempts, but patients with schizophrenia, on average, made more medically dangerous attempts. Risk factors for suicidal behavior in patients with psychosis appear to vary compared to those for the general population.
Annual report October 1998 to September 1999
Authors: J BRITTON
Journal: Thorax (2000)

1999 has been yet another successful year for Thorax with an improved impact factor (2.861, ISI Statistics, 1999) of which all who contribute to the journal can be proud.1 These new figures reflect the fact that we are now receiving work of the highest quality. Our initial policy aim of attracting high quality submissions is now taking effect, and we still believe that the journal can continue to improve and provide a competitive international forum for the best research in respiratory medicine.

Thorax has continued its development during the last year. The number of submissions remains high; out of 812 total submissions (including letters), 453 were original papers, the highest figure for five years (table 1), and in September we had the highest number submitted …
Verapamil for the Treatment of Acute Mania: A Double-Blind, Placebo-Controlled Trial
Authors: Philip G. Janicak, Rajiv P. Sharma, Ghanshyam Pandey, John M. Davis
Journal: American Journal of Psychiatry (1998)

This study investigated the efficacy of verapamil in acute mania.The study was a 3-week double-blind, random-assignment, parallel-group, placebo-controlled inpatient trial of verapamil for patients with acute mania. Of the 32 study patients, 15 were given placebo and 17 were given verapamil.Mean absolute change scores on the Mania Rating Scale at endpoint, with baseline scores as the covariates, did not differ between the verapamil and placebo groups. There were no significant differences between the two groups in age, sex, and presence of psychosis.The investigators found no benefit of verapamil over placebo in treating acute mania.
Distinct mechanisms of TGF- 1-mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis
Authors: G. Han
Journal: Journal of Clinical Investigation (2005)

In the present study, we demonstrated that human skin cancers frequently overexpress TGF-β1 but exhibit decreased expression of the TGF-β type II receptor (TGF-βRII). To understand how this combination affects cancer prognosis, we generated a transgenic mouse model that allowed inducible expression of TGF-β1 in keratinocytes expressing a dominant negative TGF-βRII (ΔβRII) in the epidermis. Without ΔβRII expression, TGF-β1 transgene induction in late-stage, chemically induced papillomas failed to inhibit tumor growth but increased metastasis and epithelial-to-mesenchymal transition (EMT), i.e., formation of spindle cell carcinomas. Interestingly, ΔβRII expression abrogated TGF-β1–mediated EMT and was accompanied by restoration of membrane-associated E-cadherin/catenin complex in TGF-β1/ΔβRII compound tumors. Furthermore, expression of molecules thought to mediate TGF-β1–induced EMT was attenuated in TGF-β1/ΔβRII–transgenic tumors. However, TGF-β1/ΔβRII–transgenic tumors progressed to metastasis without losing expression of the membrane-associated E-cadherin/catenin complex and at a rate higher than those observed in nontransgenic, TGF-β1–transgenic, or ΔβRII-transgenic mice. Abrogation of Smad activation by ΔβRII correlated with the blockade of EMT. However, ΔβRII did not alter TGF-β1–mediated expression of RhoA/Rac and MAPK, which contributed to increased metastasis. Our study provides evidence that TGF-β1 induces EMT and invasion via distinct mechanisms. TGF-β1–mediated EMT requires functional TGF-βRII, whereas TGF-β1–mediated tumor invasion cooperates with reduced TGF-βRII signaling in tumor epithelia.
Imaging in lung disease
Authors: M. Decramer, C. Roussos
Journal: European Respiratory Journal (2002)

The present supplement of the European Respiratory Journal comprises a number of reviews on Imaging in Lung Disease . It is the product of a symposium held in Barcelona, Spain, on June 23, 2001. The symposium was organized by the European Institute of Healthcare, set up by AstraZeneca. It represents the second symposium of this kind organized by the institute. The goals of the institute were extensively discussed in supplement 34 1. The potential role of pharmaceutical companies, together with other and perhaps more logical players in the field such as national and international professional societies, governmental bodies and bodies related to the European Commission, in the postgraduate education of chest physicians was also elaborated upon. The scientific programme of these meetings was designed by an independent programme committee. At the core of this programme committee are the two editors of the present supplement, who were united by nothing less than their commitment to excellence. Other members …
“Observation Status” for Hospitalized Patients
Authors: Ann M. Sheehy, Ben K. Graf, Sreedevi Gangireddy, Roger Formisano, Elizabeth A. Jacobs
Journal: JAMA Internal Medicine (2013)

Hospitalized patients in the United States are increasingly placed on "observation status." 1 The Centers for Medicare & Medicaid Services (CMS) state that observation should rarely exceed 48 hours. 2 At our hospital, however, observation stays frequently exceed 48 hours, particularly for adult general medicine patients, as our research group recently reported in this journal. 3 Reimbursement has not covered the costs, resulting in operating losses. 3 After our study was completed, CMS proposed a rules change, 4 assigning inpatient status and Medicare Part A coverage to all hospital stays of 2 midnights ("2 days") or longer, assuming medical necessity supported a 2 midnights-orlonger stay.With few exceptions, stays shorter than 2 midnights would be considered observation and therefore not be covered by Medicare Part A. The skilled nursing facility benefit under Medicare Part A would continue to require a 3-midnight ("3 day") stay.After payment of the specified deductible and applicable coinsurance, Medicare Part A covers hospital care and skilled nursing facility care, among other services.We used our data to assess the implications of the proposed rules change.
Impaired G1-Arrest, Autophagy, and Apoptosis in <i>Atg7</i> -Knockout Mice
Authors: Shun Kageyama, Masaaki Komatsu
Journal: Circulation Research (2012)

E xit from cell division cycle, induction of autophagy, and activation of apoptosis in response to metabolic stress occur simultaneously or sequentially.However, the molecular interrelation(s) between these intracellular events remains obscure.Recent work by Finkel et al 1 provides evidence that Atg7, an autophagy-related protein, regulates G1-arrest by interacting with p53 and that p53-mediated apoptosis is activated under autophagy-deficient conditions.
Mycobacterium bovis BCG promotes tumor cell survival from tumor necrosis factor-α-induced apoptosis
Authors: Sahana Holla, Devram Sampat Ghorpade, Vikas Singh, Kushagra Bansal, Kithiganahalli Narayanaswamy Balaji
Journal: Molecular Cancer (2014)

Increased incidence of lung cancer among pulmonary tuberculosis patients suggests mycobacteria-induced tumorigenic response in the host. The alveolar epithelial cells, candidate cells that form lung adenocarcinoma, constitute a niche for mycobacterial replication and infection. We thus explored the possible mechanism of M. bovis Bacillus Calmette-Guérin (BCG)-assisted tumorigenicity in type II epithelial cells, human lung adenocarcinoma A549 and other cancer cells. Cancer cell lines originating from lung, colon, bladder, liver, breast, skin and cervix were treated with tumor necrosis factor (TNF)-α in presence or absence of BCG infection. p53, COP1 and sonic hedgehog (SHH) signaling markers were determined by immunoblotting and luciferase assays, and quantitative real time PCR was done for p53-responsive pro-apoptotic genes and SHH signaling markers. MTT assays and Annexin V staining were utilized to study apoptosis. Gain- and loss-of-function approaches were used to investigate the role for SHH and COP1 signaling during apoptosis. A549 xenografted mice were used to validate the contribution of BCG during TNF-α treatment. Here, we show that BCG inhibits TNF-α-mediated apoptosis in A549 cells via downregulation of p53 expression. Substantiating this observation, BCG rescued A549 xenografts from TNF-α-mediated tumor clearance in nude mice. Furthermore, activation of SHH signaling by BCG induced the expression of an E3 ubiquitin ligase, COP1. SHH-driven COP1 targeted p53, thereby facilitating downregulation of p53-responsive pro-apoptotic genes and inhibition of apoptosis. Similar effects of BCG could be shown for HCT116, T24, MNT-1, HepG2 and HELA cells but not for HCT116 p53-/- and MDA-MB-231 cells. Our results not only highlight possible explanations for the coexistence of pulmonary tuberculosis and lung cancer but also address probable reasons for failure of BCG immunotherapy of cancers.
Distinct patterns of circulating endothelial cells in pulmonary hypertension
Authors: D. M. Smadja, L. Mauge, O. Sanchez, J.-S. Silvestre, C. Guerin, A. Godier, P. Henno, P. Gaussem, D. Israel-Biet
Journal: European Respiratory Journal (2010)

The respective abundance of circulating endothelial cells and endothelial progenitor cells may reflect the balance between vascular injury and repair. As pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) can share features of pulmonary remodelling, we postulated that the two disorders might be associated with different types of pulmonary endothelial dysfunction. We studied 25 consecutive patients undergoing cardiac catheterisation for suspected pulmonary hypertension. Nine patients had PAH, nine had CTEPH, and seven had normal pulmonary arterial pressure and served as controls. Circulating endothelial cells were isolated with CD146-coated beads. CD34<sub>+</sub>CD133<sub>+</sub> cell and endothelial progenitor cell numbers were respectively determined by flow cytometry and cell culture, in peripheral vein and pulmonary artery blood. Plasma levels of soluble vascular endothelial growth factor (VEGF), soluble E-selectin and soluble vascular cell adhesion molecule (sVCAM) were measured by ELISA. No difference in progenitor counts or VEGF levels was found across the three groups. Compared to controls, circulating endothelial cell numbers were significantly increased in PAH but not in CTEPH, in keeping with the elevated soluble E-selectin and sVCAM levels found in PAH alone. In conclusion, PAH, in contrast to CTEPH, is associated with markers of vascular injury (circulating endothelial cells, soluble E-selectin and sVCAM) but not with markers of remodelling (endothelial progenitor cells, CD34<sub>+</sub>CD133<sub>+</sub> cells and VEGF).
Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells
Authors: Wei Wei, Mei-Sze Chua, Susan Grepper, Samuel K So
Journal: Molecular Cancer (2009)

Hepatocellular carcinoma (HCC) is an aggressive cancer, and is the third leading cause of cancer death worldwide. Standard therapy is ineffective partly because HCC is intrinsically resistant to conventional chemotherapy. Its poor prognosis and limited treatment options make it critical to develop novel and selective chemotherapeutic agents. Since the Wnt/beta-catenin pathway is essential in HCC carcinogenesis, we studied the inhibition of Wnt-1-mediated signaling as a potential molecular target in HCC.We demonstrated that Wnt-1 is highly expressed in human hepatoma cell lines and a subgroup of human HCC tissues compared to paired adjacent non-tumor tissues. An anti-Wnt-1 antibody dose-dependently decreased viability and proliferation of Huh7 and Hep40 cells over-expressing Wnt-1 and harboring wild type beta-catenin, but did not affect normal hepatocytes with undetectable Wnt-1 expression. Apoptosis was also observed in Huh7 and Hep40 cells after treatment with anti-Wnt-1 antibody. In these two cell lines, the anti-Wnt-1 antibody decreased beta-catenin/Tcf4 transcriptional activities, which were associated with down-regulation of the endogenous beta-catenin/Tcf4 target genes c-Myc, cyclin D1, and survivin. Intratumoral injection of anti-Wnt-1 antibody suppressed in vivo tumor growth in a Huh7 xenograft model, which was also associated with apoptosis and reduced c-Myc, cyclin D1, and survivin expressions.Our results suggest that Wnt-1 is a survival factor for HCC cells, and that the blockade of Wnt-1-mediated signaling may offer a potential pathway-specific therapeutic strategy for the treatment of a subgroup of HCC that over-expresses Wnt-1.
A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse
Authors: Anna Moles, Lindsay Murphy, Caroline L. Wilson, Jayashree Bagchi Chakraborty, Christopher Fox, Eek Joong Park, Jelena Mann, Fiona Oakley, Rachel Howarth, John Brain, Steven Masson, Michael Karin, Ekihiro Seki, Derek A. Mann
Journal: Journal of Hepatology (2013)