tbuckley/cabot-search huggingface dataset:
Comparison of Two Standard Chemotherapy Regimens for Good-Prognosis Germ Cell Tumors: Updated Analysis of a Randomized Trial
Authors: Peter S. Grimison, Martin R. Stockler, Damien B. Thomson, Ian N. Olver, Vernon J. Harvey, Val J. Gebski, Craig R. Lewis, John A. Levi, Michael J. Boyer, Howard Gurney, Paul Craft, Amy L. Boland, R. John Simes, Guy C. Toner
Journal: JNCI Journal of the National Cancer Institute (2010)

The Australian and New Zealand Germ Cell Trials Group conducted a multicenter randomized phase III trial in men with good-prognosis germ cell tumors of two standard chemotherapy regimens that contained bleomycin, etoposide, and cisplatin but differed in the scheduling and total dose of cisplatin, the total dose of bleomycin, and the scheduling and dose intensity of etoposide. The trial was stopped early at a median follow-up of 33 months after a planned interim analysis found a survival benefit for the more dose-intense regimen. The aim of this analysis was to determine if this survival benefit was maintained with long-term follow-up. Between February 1994 and April 2000, 166 men with good-prognosis metastatic germ cell tumors defined by modified Memorial Sloan-Kettering criteria were randomly assigned to receive 3B 90 E 500 P (three cycles, repeated every 21 days, of 30 kU bleomycin on days 1, 8, and 15; 100 mg/m 2 etoposide on days 1–5; and 20 mg/m 2 cisplatin on days 1–5; n = 83) or 4B 30 E 360 P (four cycles, repeated every 21 days, of 30 kU bleomycin on day 1, 120 mg/m 2 etoposide on days 1–3, and 100 mg/m 2 cisplatin on day 1; n = 83). Endpoints included overall survival, progression-free survival, and quality of life and side effects, which were assessed using the Spitzer Quality of Life Index and the GLQ-8, respectively, before random assignment and during and after treatment. All analyses were by intention to treat. All P values are two-sided. The median follow-up was 8.5 years. All but five survivors (3%) were followed up for at least 5 years. Overall survival remained better in those assigned to 3B 90 E 500 P than in those assigned to 4B 30 E 360 P (8-year survival: 92% vs 83%; hazard ratio of death = 0.38, 95% confidence interval = 0.15 to 0.97, P = .037). Progression-free survival favored 3B 90 E 500 P but was not statistically significantly different between the treatment groups (8-year progression-free survival, 3B 90 E 500 P vs 4B 30 E 360 P: 86% vs 79%; hazard ratio of progression = 0.6, 95% confidence interval = 0.3 to 1.1, P = .15). At the end of treatment, average scores for most side effect scales favored 3B 90 E 500 P. After the completion of treatment, average GLQ-8 scores for numbness ( P = .003) and hair loss ( P = .04) and the Spitzer Quality of Life Index ( P = .05) favored 3B 90 E 500 P. The survival benefit of 3B 90 E 500 P over 4B 30 E 360 P was maintained with long-term follow-up.
High altitude pulmonary oedema: still a place for controversy?
Authors: J P Richalet
Journal: Thorax (1995)

High altitude pulmonary oedema: still a place for controversy?High altitude pulmonary oedema (HAPE) is defined as acute respiratory failure following exposure to high altitude hypoxia, developing in a normal subject with no pre- existing pulmonary or cardiac disease.It is one of the manifestations ofhigh altitude disease ofwhich the simplest form is acute mountain sickness (AMS), generally limited to headache, nausea and insomnia during the first few days spent above 2500 M.'2 In contrast to AMS, HAPE necessitates emergency management.It occurs 6-48 hours after rapid ascent to altitudes above 2500-4000 m.Severe exercise and cold exposure favour its occurrence.Subjects complain of shortness of breath disproportionate to the effort exerted, a dry followed by a productive cough, fatigue, and chest pain.Clinical examination reveals tachypnoea, tachycardia, mild fever, cyanosis, crepitant rales and rhonchi.3-5The heart rate is generally more than 120 beats/min and the respiratory rate more than 20 breaths/ min.There is no evidence of cardiac failure.When hospital facilities are available, radiographic examination shows diffuse infiltrates in two thirds of cases ("patchy distribution"), and prominence of pulmonary arteries.6Patchy distribution is seen on chest radiography early in the disease, becoming bilateral and diffuse in the more advanced state.7 Clearing of these exudates lags a day or two behind clinical improvement.58Electrocardiography shows tachycardia and signs of acute right ventricular overload.Doppler echocardiography may reveal tricuspid regurgitation or even tricuspid insufficiency.5 Haemo- dynamic parameters include a high pulmonary arterial pressure and low capillary wedge pressure.A mild leucocytosis may be found (rarely more than 14 000/mm3).8The arterial
Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism.
Authors: J R Martínez-Galán, P Pedraza, M Santacana, F Escobar del Ray, G Morreale de Escobar, A Ruiz-Marcos
Journal: Journal of Clinical Investigation (1997)

The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role.
Tetraspanin CD37 Directly Mediates Transduction of Survival and Apoptotic Signals
Authors: Rosa Lapalombella, Yuh-Ying Yeh, Liwen Wang, Asha Ramanunni, Sarwish Rafiq, Shruti Jha, Justin Staubli, David M. Lucas, Rajeswaran Mani, Sarah E.M. Herman, Amy J. Johnson, Arletta Lozanski, Leslie Andritsos, Jeffrey Jones, Joseph M. Flynn, Brian Lannutti, Peter Thompson, Paul Algate, Scott Stromatt, David Jarjoura, Xiaokui Mo, Dasheng Wang, Ching-Shih Chen, Gerard Lozanski, Nyla A. Heerema, Susheela Tridandapani, Michael A. Freitas, Natarajan Muthusamy, John C. Byrd
Journal: Cancer Cell (2012)

Tetraspanins are commonly believed to act only as "molecular facilitators," with no direct role in signal transduction. We herein demonstrate that upon ligation, CD37, a tetraspanin molecule expressed on mature normal and transformed B cells, becomes tyrosine phosphorylated, associates with proximal signaling molecules, and initiates a cascade of events leading to apoptosis. Moreover, we have identified two tyrosine residues with opposing regulatory functions: one lies in the N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, whereas the second lies in a predicted "ITAM motif" in the C-terminal domain of CD37 and counteracts death signals by mediating phosphatidylinositol 3-kinase-dependent survival.
Distinct Hypermethylation Profile of Primary Breast Cancer Is Associated with Sentinel Lymph Node Metastasis
Authors: Masaru Shinozaki, Dave S.B. Hoon, Armando E. Giuliano, Nora M. Hansen, He-Jing Wang, Roderick Turner, Bret Taback
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. Experimental Design: We conducted hypermethylation profiling of 151 primary breast tumors with association to known prognostic factors in breast cancer using methylation-specific PCR for six known tumor suppressor and related genes: RASSF1A, APC, TWIST, CDH1, GSTP1, and RAR-β2. Furthermore, correlation with sentinel lymph node (SLN) tumor status was assessed as it represents the earliest stage of metastasis that is readily detected. Hypermethylation for any one gene was identified in 147 (97%) of 151 primary breast tumors. The most frequently hypermethylated gene was RASSF1A (81%). Results: Hypermethylation of the CDH1 was significantly associated with primary breast tumors demonstrating lymphovascular invasion (P = 0.008), infiltrating ductal histology (P = 0.03), and negative for the estrogen receptor (P = 0.005), whereas RASSF1A and RAR-β2 gene hypermethylation were significantly more common in estrogen receptor–positive (P &amp;lt; 0.001) and human epidermal growth factor receptor 2–positive (P &amp;lt; 0.001) tumors, respectively. In multivariate analysis, hypermethylation of GSTP1 and/or RAR-β2 was significantly associated with patients having macroscopic SLN metastasis compared with those with microscopic or no sentinel node metastasis (odds ratio, 4.59; 95% confidence interval, 2.02-10.4; P &amp;lt; 0.001). In paired SLN metastasis, CDH1 was the most frequently methylated gene (90%) and provides evidence in patients corroborating its role in the clinical development of metastasis. Conclusion: Hypermethylation profiling of primary breast tumors is significantly associated with known pathologic prognostic factors and may have additional clinical and pathologic utility for assessing patient prognosis and predicting early regional metastasis.
Care of the elderly in general-practitioner hospitals
Authors: J R D Brown
Journal: BMJ (1981)

elderly people (five men, 10 women; mean age 73 3 years; range 66-85 years) who had fallen at home but had not required hospital attendance.These were identified by a health visitor.Visual acuity was assessed in the subjects' living room with a Snellen chart modified for use at 3 m.Cullinan et all have emphasised that home lighting is often worse than that in a hospital clinic and thus visual acuity measured at home approximates more closely to reality.Comparing our group of fallers with a random sample of elderly people,2 we found our group to have significantly poorer visual acuity-at 65 years an average of 20`0 worse, at 70 years 531/ worse, at 75 years 590, worse, and at 80 years 61 I`) worse than that of an average person at that age.In fact, a typical 70-year-old in our group had the visual-acuity of an average 80-year-old.This may well contribute to Professor Isaacs's "errors in environmental perception.
Smoking ban in prisons would lead to more assaults on staff
Authors: Adrian O'Dowd
Journal: BMJ (2005)

Doctors and other staff working in prisons would face a greater risk of assault if smoking were to be banned in that environment, the head of the prison service has told MPs.

Phil Wheatley, director general of the Prison Service told the health select committee inquiry into smoking in public places last week that a complete ban would have serious repercussions and create control problems for staff.

The government's current proposals to introduce a partial smoking ban in enclosed public places by 2007 under its Health Bill introduced to parliament last month, could cause problems, he believed.

“I think …
Prevalence of anemia of chronic disease in patients with chronic obstructive pulmonary disease
Authors: Afroditi Boutou, Georgia Pitsiou, Ioannis Stanopoulos, Theodoros Kontakiotis, George Kyriazis, Panagiota Touplikioti, Nikolaos Chavouzis, Lazaros Sichletidis, Paraskevi Argyropoulou
Journal: European Respiratory Journal (2011)

Background:  Anemia of chronic disease (ACD) is a disorder occurring in subjects with chronic immune activation. Chronic Obstructive Pulmonary Disease is characterized by systemic inflammation, so it could be accompanied by ACD.   Aim:  To determine the prevalence of ACD among stable COPD patients.   Methods:  The initial study population consisted of consecutive clinically stable patients with COPD (post bronchodilation FEV 1 /FVC 30ng/ml, c) total binding iron capacity   Results:  The prevalence of ACD was 10.24% and it was mild (Hb level=12.1±0.7 g/dl)., The ACD patients, compared to the non-anemic ones, were more often males (93.1% vs 77.2%; p 1 % predicted.   Conclusions:  ACD could be another systemic manifestation of COPD, since its prevalence was approximately 10% among stable patients.
Effect of Connective Tissue Growth Factor on Hypoxia-Inducible Factor 1α Degradation and Tumor Angiogenesis
Authors: Cheng-Chi Chang, Ming-Tsai Lin, Been-Ren Lin, Yung-Ming Jeng, Szu-Ta Chen, Chia-Yu Chu, Robert J. Chen, King-Jen Chang, Pan-Chyr Yang, Min-Liang Kuo
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Connective tissue growth factor (CTGF) inhibits the metastatic activity of human lung cancer cells in a mouse model; however, the mechanism of this modulation is unclear. We investigated the role of angiogenesis in this process. Methods: CL1-5 and A549 human lung adenocarcinoma cells were stably transfected with vectors containing CTGF or hypoxia-inducible factor (HIF) 1α or with vector controls. Transfected cells were injected into nude mice (n = 10 per group), and tumor growth, metastasis, and mouse survival were measured. Excised xenograft tumors and primary human lung adenocarcinomas (n = 24) were subjected to immunohistochemistry with antibodies to the endothelial cell marker CD31 and to CTGF. Expression of HIF-1α and vascular endothelial growth factor (VEGF) A was assessed in vitro by using reporter gene assays. Cells were transiently transfected with HIF-1α mutant and antisense arrest-defective 1 protein (ARD-1), and HIF-1α acetylation was assayed by immunoprecipitation. All statistical tests were two-sided. Results: Xenograft tumors derived from CTGF transfectants grew more slowly than those from control-transfected cells and had reduced expression of HIF-1α and VEGF-A, vascularization (as assessed by CD31 expression), and metastasis (all P <.001). Xenograft tumors derived from CTGF-overexpressing cells that were transfected with HIF-1α had higher VEGF-A expression than CTGF-overexpressing xenografts. Mice with CTGF/HIF-1α xenografts had lower survival than mice carrying CTGF-overexpressing xenografts (CL1-5/Neo, mean = 69.6 days, 95% confidence interval [CI] = 53.9 to 85.3 days versus CL1-5/CTGF, mean = 102.1 days, 95% CI = 92.1 to 112.1 days; P = .001, CL1-5/CTGF, mean = 102.1 days, 95% CI = 92.1 to 112.1 days versus CL1-5/CTGF/HIF-1α, mean = 81.7 days, 95% CI = 66.5 to 96.9 days; P = .011, CL1-5/Neo, mean = 69.6 days, 95% CI = 53.9 to 85.3 days versus CL1-5/CTGF/HIF-1α, mean = 81.7 days, 95% CI = 66.5 to 96.9 days; P = .122). Tumors of patients with the same disease stage but with high CTGF protein expression had reduced microvessel density compared with tumors with low expression. Transfection with antisense-ARD1 decreased the level of acetylated HIF-1α and restored HIF-1α and VEGF-A expression in CTGF-overexpressing cells. Conclusion: CTGF inhibition of metastasis involves the inhibition of VEGF-A–dependent angiogenesis, possibly by promoting HIF-1α protein degradation.
Impact of the Obesity Epidemic on Cancer
Authors: Pamela J. Goodwin, Vuk Stambolic
Journal: Annual Review of Medicine (2014)

There is growing appreciation that the current obesity epidemic is associated with increases in cancer incidence at a population level and may lead to poor cancer outcomes; concurrent decreases in cancer mortality at a population level may represent a paradox, i.e., they may also reflect improvements in the diagnosis and treatment of cancer that mask obesity effects. An association of obesity with cancer is biologically plausible because adipose tissue is biologically active, secreting estrogens, adipokines, and cytokines. In obesity, adipose tissue reprogramming may lead to insulin resistance, with or without diabetes, and it may contribute to cancer growth and progression locally or through systemic effects. Obesity-associated changes impact cancer in a complex fashion, potentially acting directly on cells through pathways, such as the phosphoinositide 3-kinase (PI3K) and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways, or indirectly via changes in the tumor microenvironment. Approaches to obesity management are discussed, and the potential for pharmacologic interventions that target the obesity-cancer link is addressed.
eNOS gene transfer to vascular smooth muscle cells inhibits cell proliferation via upregulation of p27 and p21 and not apoptosis
Authors: J Sato
Journal: Cardiovascular Research (2000)

Objective: Smooth muscle cell (SMC) proliferation is a critical component of vascular diseases such as atherosclerosis and restenosis. Nitric oxide (NO) donors and gene transfer of endothelial nitric oxide synthase (eNOS) have been shown to inhibit SMC proliferation. NO may cause this effect by delaying cell cycle progression and/or induction of apoptosis. The aim of the current study was to examine the mechanism of eNOS-mediated inhibition of SMC proliferation. In addition, the effect of eNOS expression in vascular SMCs on the expression of the cyclin dependent kinase inhibitors, p27 and p21 was examined. Methods: SMCs were transduced with an adenoviral vector encoding eNOS (AdeNOS) or β-galactosidase (AdβGal) at a multiplicity of infection of 100. Non-transduced cells served as additional controls. Transgene expression was sought by NADPH diaphorase staining, immunohistochemistry and Western Blotting. Functionality of the recombinant protein was assessed by measurement of cGMP. Cell cycle analysis was performed by flow cytometry and p27 and p21 expression were studied by western blot analysis. Apoptosis was sought by Annexin V staining and DNA laddering. Results: eNOS expression was detected in transduced SMCs. cGMP levels were increased in eNOS-transduced compared to control cells. Expression of eNOS in SMCs resulted in a delay in cell cycle progression and upregulation of p27 and p21. There was no increase in apoptosis detected in eNOS transduced cells after 24 or 72 h. Conclusion: eNOS gene transfer to vascular SMCs inhibits cell proliferation via upregulation of p27 and p21 resulting in a delay in cell cycle progression.
Hidradenitis suppurativa in Crohn's disease
Authors: L. S. OSTLERE, J.A.A. LANGTRY, P. S. MORTIMER, R.C.D. STAUGHTON
Journal: British Journal of Dermatology (1991)

Summary Three patients with Crohn's disease who developed the clinical features of hidradenitis suppurativa (HS) are reported. To our knowledge this association has not been previously described. These cases illustrate the similarity between cutaneous Crohn's and ano-genital HS once chronic and established.
Genetic Variations in the PI3K/PTEN/AKT/mTOR Pathway Are Associated With Clinical Outcomes in Esophageal Cancer Patients Treated With Chemoradiotherapy
Authors: Michelle A.T. Hildebrandt, Hushan Yang, Mien-Chie Hung, Julie G. Izzo, Maosheng Huang, Jie Lin, Jaffer A. Ajani, Xifeng Wu
Journal: Journal of Clinical Oncology (2009)

Purpose The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. Patients and Methods Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. Results We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes—AKT2 and FRAP1—were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). Conclusion These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen.
ICUD-EAU International Consultation on Bladder Cancer 2012: Chemotherapy for Urothelial Carcinoma—Neoadjuvant and Adjuvant Settings
Authors: Cora N. Sternberg, Joaquim Bellmunt, Guru Sonpavde, Arlene O. Siefker-Radtke, Walter M. Stadler, Dean F. Bajorin, Robert Dreicer, Daniel J. George, Matthew I. Milowsky, Dan Theodorescu, David J. Vaughn, Matthew D. Galsky, Mark S. Soloway, David I. Quinn
Journal: European Urology (2012)
Antitumoral Activity of Indomethacin on Experimental Esophageal Tumors
Authors: C A Rubio
Journal: JNCI Journal of the National Cancer Institute (1984)

The effect of treatment with indomethacin on diethylnitrosamine (DENA, CAS:55-18-5; N-nitrosodiethylamine)-induced esophageal tumors was investigated in 128 C57BL mice. The number of DENA-induced esophageal tumors was significantly reduced when indomethacin was given together with DENA from the outset, suggesting that indomethacin may prevent the induction of esophageal tumors in the C57BL mouse. Similarly, esophageal tumors were significantly reduced when indomethacin was given 4 months after DENA treatment, suggesting that the delayed indomethacin administration may inhibit the further appearance of additional esophageal tumors in the C57BL mouse.