tbuckley/cabot-search huggingface dataset:
Identification of Breast Cancer Patients With High Risk of Early Recurrence After Radical Mastectomy. I. Description of Study2
Authors: Gilbert H. Friedell, Ira S. Goldenberg, Ihor J. Masnyk, C. A. McMahan, Robert G. Ravdin, Jeremy B. Roberts, Albert Segaloff, Federico Welsch
Journal: JNCI Journal of the National Cancer Institute (1974)

A cooperative investigation was undertaken to assess the prognostic significance of combinations of various clinical, pathologic, and urinary steroid variables in patients with breast cancer treated by radical mastectomy. The protocol was detailed; data were collected for 19 selected variables from 98 patients in whom the 2-year recurrence or nonrecurrence status was known. Lymph node involvement and blood vessel invasion had prognostic significance when considered as single variables. Indices using multiple variables are under development.
Measurement of pharmacological antagonism produced by atropine in bronchi of normal and asthmatic subjects
Authors: M K Gillett, P D Snashall
Journal: European Respiratory Journal (1988)

The bronchial response of six normal and six asthmatic subjects to increasing concentrations of methacholine aerosol was measured by serial measurements of specific airways conductance (sGaw) in a body plethysmograph. On separate days, the subjects were premedicated with 0.9% NaCl, inhaled atropine at four different doses, or intravenous atropine at two different doses. Cumulative log dose-response curves were constructed. The provocative dose of methacholine needed to cause a 35% fall in sGaw was measured from each curve (PD35). The antagonism produced by a given atropine dose was quantified as the dose ratio, which was defined as the ratio of PD35 after atropine to PD35 after saline. In normal subjects, approximately equal amounts of atropine given by the inhaled or intravenous routes produced mean dose ratios of almost identical value. However, in asthmatic subjects inhaled atropine (1.28 mg, 4.4 mumol) produced a mean dose ratio 7.5 times greater than the mean value seen with intravenous atropine (1.0 mg, 3.46 mumol). Intravenous atropine (1.0 mg, 3.46 mumol) produced a mean dose ratio of 18.3 for all subjects, compared to a value of 26 predicted from in vitro experiments. The slope of the regression line for the relationship of log (dose ratio -1) vs -log atropine dose (Schild plot) for all subjects was -0.99. The actions we have observed are compatible with the main actions of atropine being that of a competitive antagonist at the muscarinic receptor. The greater blocking effect of inhaled atropine in some asthmatics suggests that a higher concentration of atropine is achieved at the muscarinic receptor by the inhaled route in these subjects.
EGFRmutations are associated with higher brain metastasis radio-sensitivity than KRAS mutations or wild type EGFR in non-small cell lung cancer patients (NSCLC)
Authors: Stéphane Renaud, Pierre-Emmanuel Falcoz, Georges Noël, Gilbert Massard, Michèle Beau-Faller
Journal: European Respiratory Journal (2014)

Introduction : Brain metastasis (BM) commonly occur in non-small cell lung cancer (NSCLC). Data on predictive value of radio-sensitivity of epidermal growth factor receptor (EGFR) mutation in BM are inconclusive. The aim of our study was to evaluate the radio-sensitivity of brain metastasis depending on the genomic status (EGFR, KRAS) of the primary NSCLC tumor. Material and Methods : Between January 2007 and December 2012, we retrospectively reviewed the data from 1971 patients who underwent a molecular testing for NSCLC and focused on 157 patients who underwent a radiation therapy (RT) for BM. Primary endpoint was radio-sensitivity assessed by RECIST criteria. Results : The median age was 58 years-old (28-90). Median follow-up time was 6.5 months (1-60). EGFR was mutated (mEGFR) in 16 patients (10.2%) whereas KRAS was mutated (mKRAS) in 45 patients (28.7%). Radio-sensitivity was significantly higher for mEGFR cases compared to wild type (WT) (OR: 4.96 (95% CI : 1.07 - 23.09, p=0.05)) or mKRAS patients (OR : 1.81 (95% CI : 1.21 – 3.95, p=0.03). Association of RT and treatment by EGFR-tyrosine kinase inhibitors (EGFR-TKI) showed a benefit on radio-sensitivity in mEGFR patients (OR : 5.32 (95% CI : 1.16 – 24.29, p=0.04), and on overall survival (OS) for mEGFR (22 months versus 8 months, p=0.06) as well as for EGFR/KRAS WT patients (17 months versus 8 months, p=0.04). Conclusion: mEGFR seems to be associated with higher radio-sensitivity than WT or mKRAS patients. The association of RT and EGFR-TKI seems to be beneficial on OS in mEGFR and EGFR/KRAS WT patients.
Immortal DNA Strand Cosegregation Requires p53/IMPDH–Dependent Asymmetric Self-renewal Associated with Adult Stem Cells
Authors: Lakshmi Rambhatla, Sumati Ram-Mohan, Jennifer J. Cheng, James L. Sherley
Journal: Cancer Research (2005)

Abstract Because they are long-lived and cycle continuously, adult stem cells (ASCs) are predicted as the most common precursor for cancers in adult mammalian tissues. Two unique attributes have been proposed to restrict the carcinogenic potential of ASCs. These are asymmetric self-renewal that limits their number and immortal DNA strand cosegregation that limits their accumulation of mutations due to DNA replication errors. Until recently, the molecular basis and regulation of these important ASC-specific functions were unknown. We developed engineered cultured cells that exhibit asymmetric self-renewal and immortal DNA strand cosegregation. These model cells were used to show that both ASC-specific functions are regulated by the p53 cancer gene. Previously, we proposed that IMP dehydrogenase (IMPDH) was an essential factor for p53-dependent asymmetric self-renewal. We now confirm this proposal and provide quantitative evidence that asymmetric self-renewal is acutely sensitive to even modest changes in IMPDH expression. These analyses reveal that immortal DNA strand cosegregation is also regulated by IMPDH and confirm the original implicit precept that immortal DNA strand cosegregation is specific to cells undergoing asymmetric self-renewal (i.e., ASCs). With IMPDH being the rate-determining enzyme for guanine ribonucleotide (rGNP) biosynthesis, its requirement implicates rGNPs as important regulators of ASC asymmetric self-renewal and immortal DNA strand cosegregation. An in silico analysis of global gene expression data from human cancer cell lines underscored the importance of p53-IMPDH-rGNP regulation for normal tissue cell kinetics, providing further support for the concept that ASCs are key targets for adult tissue carcinogenesis.
Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx.
Authors: D A Fein, W R Lee, A L Hanlon, J A Ridge, C J Langer, W J Curran, L R Coia
Journal: Journal of Clinical Oncology (1995)

PURPOSE A number of reports have documented the relationship between pretreatment hemoglobin level and local control and/or survival in the treatment of cervix, bladder, and advanced head and neck tumors. Consideration of correcting anemia before initiation of radiation therapy may prove increasingly important as clinical trials use intensive induction chemotherapy in the treatment of head and neck carcinomas. Neoadjuvant chemotherapy may produce anemia, which in turn may reduce the effectiveness of subsequent irradiation. MATERIALS AND METHODS One hundred nine patients with T1-2N0 squamous cell carcinoma of the glottic larynx were treated with definitive radiotherapy at the Fox Chase Cancer Center between June 1980 and November 1990. Follow-up times ranged from 26 to 165 months (median, 82). RESULTS The 2-year local control rate for patients who presented with a hemoglobin level &lt; or = 13 g/dL was 66%, compared with 95% for patients with a hemoglobin level more than 13 g/dL (P = .0018). The 2-year survival rate for patients with a hemoglobin level &lt; or = 13 g/dL was 46%, compared with 88% for patients with a hemoglobin level more than 13 g/dL (P &lt; .001). Cox proportional hazards regression analysis showed that hemoglobin level (P = .0016) was the only variable that significantly influenced local control (P = .0016) and survival (P &lt; .0001). CONCLUSION Patients who presented with hemoglobin levels more than 13 g/dL had significantly higher local control and survival rates. The strong apparent correlation between hemoglobin level, local control, and survival supports consideration of correcting anemia before initiation of radiation therapy.
Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer.
Authors: T Ahlert, W Sauerbrei, G Bastert, S Ruhland, B Bartik, N Simiantonaki, J Schumacher, B Häcker, M Schumacher, V Schirrmacher
Journal: Journal of Clinical Oncology (1997)

PURPOSE We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995. MATERIALS AND METHODS Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria. RESULTS Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A. CONCLUSION In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.
Multiple primary melanoma: the impact of atypical naevi and follow up
Authors: V. De Giorgi, S. Rossari, F. Papi, A. Gori, B. Alfaioli, M. Grazzini, E. Crocetti, A. Verdelli, C.W. Foo, T. Lotti
Journal: British Journal of Dermatology (2010)

Patients with melanoma are especially encouraged to have regular follow- up visits with their dermatologist and to perform total-body skin examination on a routine basis to identify new pigmented lesions or detect significant changes in existing naevi.To identify main risk factors (sex, age, number of common and atypical naevi, family history, phototype) associated with multiple primary melanomas (MPM) and to investigate the association between regular follow up and tumour thickness of a second primary melanoma.We performed a retrospective analysis of patients with MPM in order to evaluate risk factors for developing a second primary melanoma. Medical records of patients with melanoma who developed a second primary melanoma were selected from a database of all patients with histopathologically confirmed melanoma treated at the dermatology clinic of the University of Florence, Italy, from 2000 to 2004. Medical data culled from the patient records were as follows: medical history, number of typical naevi, presence of atypical naevi, Breslow thickness, Clark level and histotype of the melanomas, site of the melanomas and patient adherence to 6-month follow-up examinations.The presence of atypical naevi was associated with a higher risk of developing MPM (adjusted odds ratio 3·28, 95% confidence interval 1·35–7·44). Moreover, in the subjects who did not attend follow up, we noted that the thickness of the second melanoma was significantly higher, with a mean thickness of 1·22 mm, in comparison with patients with a careful adherence to follow up in whom the mean thickness was 0·36 mm (P = 0·0189).For the first time, the validity of this clinical approach has been supported by real comparison of thickness levels of second melanoma in patients with or without periodical follow up. Results obtained from this analysis show that follow up is an effective method for early detection of melanoma.
Evolution of transposable elements: an IS10 insertion increases fitness in Escherichia coli.
Authors: L Chao, S M McBroom
Journal: Molecular Biology and Evolution (1985)

Strains of Escherichia coli carrying Tn10, a transposon consisting of two IS10 insertion sequences flanking a segment encoding for a tetracycline-resistance determinant, gain a competitive advantage in chemostat cultures. All Tn10-bearing strains that increase in frequency during competition have a new IS10 insertion that is found in the same location in the genome of those strains. We mapped, by a gradient of transmission, the position of the new IS10 insertion. We examined 11 isolates whose IS10 insertion was deleted by recombinational crossing-over, and in all cases the competitive fitness of the isolates was decreased. These results show that the IS10-generated insertion increases fitness in chemostat cultures. We named the insertion fit::IS10 and suggest that transposable elements may speed the rate of evolution by promoting nonhomologous recombination between preexisting variations within a genome and thereby generating adaptive variation.
Prostate-specific antigen failure despite pathologically organ-confined and margin-negative prostate cancer: the basis for an adjuvant therapy trial.
Authors: A V D'Amico, R Whittington, S B Malkowicz, D Schultz, J E Tomaszewski, A Wein
Journal: Journal of Clinical Oncology (1997)

PURPOSE A multivariable analysis to evaluate the potential clinical and pathologic factors that predict for early biochemical failure in patients with pathologically organ-confined and margin-negative disease was performed to define patients who may benefit from adjuvant therapy. PATIENTS AND METHODS Three hundred forty-one prostate cancer patients treated with a radical retropubic prostatectomy between January 1989 and June 1995 and found to have pathologically organ-confined and margin-negative disease comprised the study population. A logistic regression multivariable analysis to evaluate the predictive value of the preoperative prostate-specific antigen (PSA) level, pathologic (prostatectomy) Gleason score, and pathologic stage on PSA failure occurring during the first postoperative year was performed. RESULTS Predictors of PSA failure during the first postoperative year in patients with pathologically organ-confined disease included pathologic Gleason score &gt; or = 7 (P = .0007) and preoperative PSA level greater than 10 (P &lt; .0001). Corresponding 3-year freedom-from-PSA-failure rates for these pathologic organ-confined patients with both, one, or neither of these factors were 60%, 75% to 84%, and 95%, respectively (P &lt; .0001). CONCLUSION Prostate cancer patients with pathologically organ-confined and margin-negative disease and a preoperative PSA level greater than 10 ng/mL or a pathologic Gleason score &gt; or = 7 have significant decrements in short-term PSA-failure-free survival. Therefore, these patients should be considered for adjuvant therapy in the setting of a phase III clinical trial.
Onychomycosis caused by Fusarium proliferatum
Authors: N. Hattori, A. Shirai, Y. Sugiura, W. Li, K. Yokoyama, Y. Misawa, K. Okuzumi, K. Tamaki
Journal: British Journal of Dermatology (2005)

Fusarium infections in humans are usually opportunistic, but the fungus sometimes infects healthy persons, causing keratomycosis or onychomycosis. Onychomycosis is usually caused by F. solani or F. oxysporum. We report the first two cases of onychomycosis caused by F. proliferatum, and discuss methods of diagnosis and effective treatment. Nail samples from the two patients were examined by direct microscopy, cultured, and identified morphologically and genetically as F. proliferatum. Both patients were treated successfully with oral itraconazole, even though the minimum inhibitory concentration of itraconazole was relatively high in Patient 1. This is the first report of F. proliferatum as an agent of onychomycosis. Itraconazole may be effective in the treatment of onychomycosis caused by F. proliferatum.
Community-acquired invasive aspergillosis and outdoor filamentous fungal spore load: a relationship?
Authors: M.-P. Brenier-Pinchart, B. Lebeau, J.-L. Borel, J.-L. Quesada, M.R. Mallaret, F. Garban, J.-P. Brion, L. Molina, J.-L. Bosson, A. Thiebaut-Bertrand, R. Grillot, H. Pelloux
Journal: Clinical Microbiology and Infection (2011)
THE EFFECTS OF ANAPHYLAXIS, AND OF HISTAMINE, UPON THE CORONARY ARTERIES IN THE ISOLATED HEART
Authors: E. Cowles Andrus, Herbert B. Wilcox
Journal: The Journal of Experimental Medicine (1939)

Anaphylaxis in the isolated, perfused hearts of cats has been shown to be accompanied by a considerable, though transient, increase in coronary flow. This result is contrasted with that observed in the hearts of guinea pigs and rabbits in which the coronary arteries are constricted during anaphylaxis. Attention is directed to the fact that, in the hearts of these three species, the effects of anaphylaxis and of histamine are qualitatively parallel. The characteristic anaphylactic response in the isolated hearts of guinea pigs has been evoked: (a) in the organs removed from immune animals, (b) by each of two antigens (horse serum and egg albumen) under conditions of double sensitization, and (c) upon exposure of the hearts of passively sensitized animals to the type-specific polysaccharide of the pneumococcus. It is evident that, among the effects of anaphylaxis upon smooth muscle in various organs, there must be considered that upon the coronary arteries.
Biochemical Parameters of Resistance of an Adriamycin-Resistant Subline of P388 Leukemia to Emetine, an Inhibitor of Protein Synthesis
Authors: Manik P. Chitnis, Randall K. Johnson
Journal: JNCI Journal of the National Cancer Institute (1978)

The effects of emetine on protein and DNA synthesis in vitro and in vivo were compared in P388 leukemia cells (P388/S) and in an adriamycin-resistant subline of P388 leukemia (P388/ADR), which was completely cross-resistant in vivo to emetine. in P388/ADR cells in vitro no apparent resistance to emetine was found; no difference in cytotoxicity was evident in P388/S or P388/ADR cells exposed to emetine in vitro for 1 or 6 hours. Protein and DNA synthesis was inhibited to a similar extent in P388/S and P3881 ADR cells at equivalent concentrations of the drug. However, inhibition of protein synthesis by emetine In P3881 ADR cells was more reversible than in P388/S cells when the cells were exposed to emetine and subsequently incubated in drug-free medium for 1 hour prior to addition of labeled l-leucine. Differences between P388/S and P388/ADR cells were evident in vivo. The duration of inhibition (>90%) of protein and DNA synthesis in P388/ADR cells was about 8 hours compared to 24 hours in P388/S cells following administration of a therapeutic dose of 25 mg emetine/kg to tumor-bearlng mice. The level of radioactivity in the P388/ADR cells 24 hours after in vivo administration of the emetine analog, (±)-[3′-14C]2,3-dehydroemetine, was only 26% of that in P388/S cells. This evidence suggests that the resistance of P388/ADR to emetine is due to decreased retention of the drug.
The management of patients with acute destructive lung diseases in conditions of urgent thoracic surgery
Authors: Evgeny Korymasov, Armen Benyan, Sergey Pushkin, Anton Tepikin
Journal: European Respiratory Journal (2013)

Objective. Acute destructive lung diseases often require the treatment of thoracic surgeon. The results of surgical and therapeutic methods depend of type, sizes of destruction and complications. Important role have also the conditions of medical management.  Methods. For last 2-year period we have treated 303 patients with acute destructive lung diseases. They were 245 male, 58 female. The median age was 46 years. There were 118 patients with lung abscesses (38,9%), 151 patients with necrotizing pneumonia (49,9%), and 34 patients with lung gangrene (11,2%). We have registered such complications as pleurisy – at 12 patients, pleural empyema - at 58 patients, pulmonary hemorrhage – at 8 patients.  Results. If patient didn9t need the urgent surgical procedures we started with therapy and then estimate the efficacy of treatment. In all conservative treatment has been applicated at 207 patients (68,3%). 96 patients (31,7%) underwent surgical treatment. We have performed 16 lobectomies, 6 wedge resections, 5 pneumonectomies, 5 tracheostomies, 6 thoracoabscessostomies, 6 endovascular occlusions of bronchial arteries, 2 pleurectomies, 8 thoracoscopies, and 60 pleural drainages. From 114 operations 91 were urgent, 23 had been done later as acute process regressed. Clinical and roentgenologic recovery had been registered at 261 patient (86,1%). Chronization of disease developed at 18 patients (6,0%). General mortality was 24 patients (7,9%).  Conclusion. Despite of most of patients with acute destructive lung diseases had been treated conservatively, they had to be directed to thoracic divisions, because of frequent and sudden development of surgical situations.