tbuckley/cabot-search huggingface dataset:
RNA-Dependent DNA Polymerase in Preneoplastic Nodules and Tumors of the Mammary Gland of BALB/c Mice 2
Authors: A. S. Mukherjee, M. R. Banerjee
Journal: JNCI Journal of the National Cancer Institute (1974)

Normal mammary tissue, preneoplastic nodules 01 and 08 of mouse mammary tumor virus (muMTV)free BALB/c mice, an muMTV-positive D1 nodule, and the mammary neoplasms derived from each ef these-nodules were analyzed far RNA-dependent ONA polymerase (ROOP). In addition, 3-methylcholanthrene (MCA)-induced mammary tumors of BALB/c mice and muMTV-induced neoplasms of C3H mice were examined. The enzyme from the high-speed supernatant of tissue homogenate was purified by diethylaminoethyl-cellulose column chromatography by elution through a O.05-0.7M KCI gradient. ROOP was assayed in vitro at 37°C in a standard mixture containing Mg++ and dithiothreitol (OTT). The reaction was monitored by the rate of 3H-dTTP incorporation in an acid-insoluble fraction. Various synthetic polynucleotides and calf liver RNA were used as templates. ROOP was negligible in the mammary tissue of pregnant mice, modestly active in the 01 nodule, but highly active in the muMTV-free 08 and the muMTV-positive 01 nodules. In addition, it was extremely active in mammary neoplasms with or without muMTV, including the MCA-induced tumor. The enzyme from most tissues preferentially utilized polyrA dT10 and calf liver RNA as templates. However, the 01-muMTV nodule enzyme had a poor affinity for the biologic RNA template and the enzyme from the MCAinduced tumor failed to use the same template. Prior treatment of the template with pancreatic and T1 (Aspergillus oryzae) RNAse abolished the activity, and the reaction was sensitive to dimethylbenzyldemethyl rifampicin. The reaction product was sensitive to ONAse but resistant to RNAse and NaOH. These results indicate the presence of an ROOP in muMTV-free mammary nodules and tumors. Between the 2 virus-free nodules, the ROOP activity was more pronounced in the lesion with a greater tumor potential.
Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease.
Authors: F R Appelbaum, K M Sullivan, E D Thomas, C D Buckner, R A Clift, H J Deeg, P E Neiman, J E Sanders, P Stewart, R Storb
Journal: Journal of Clinical Oncology (1985)

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.
Impact of on-study corticosteroid use on efficacy and safety in the phase III AFFIRM study of enzalutamide (ENZA), an androgen receptor inhibitor.
Authors: Howard I. Scher, Karim Fizazi, Fred Saad, Kim N. Chi, Mary-Ellen Taplin, Cora N. Sternberg, Andrew J. Armstrong, Mohammad Hirmand, David Forer, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2013)

6 Background: ENZA increased median overall survival (OS) by 4.8 mo (P &lt;0.001, HR 0.63) vs placebo (PBO) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) post-docetaxel in AFFIRM (HI Scher et al, NEJM 2012). Corticosteroids (CS) can activate AR signaling in nonclinical models (J Richards, Can Res 2012). In a multivariate model of AFFIRM data baseline CS use was associated with reduced OS (HI Scher et al. ESMO 2012 abstract 899PD). The impact of CS use during study treatment in AFFIRM was evaluated to test if concomitant CS use is also associated with inferior outcomes. Methods: Pts were randomized 2:1 to ENZA 160 mg/d or PBO. Pts were allowed but not required to take CS. OS was the primary endpoint. In a post-hoc analysis On-study CS use was defined as oral CS user for ≥ 1 day on study. Results: On study CS use was 48% in ENZA and 45% in PBO pts. Prognostic factors were slightly better in the no CS group compared to the CS group. Use of CS regardless of treatment was associated median OS of 11.5 mo (95% CI: 10.5, 13.0) for CS pts vs median OS NM (NM, NM) for no CS pts (HR=0.40; 95% CI: 0.33, 0.48). ENZA was consistently superior to PBO for OS, radiographic progression free survival (rPFS) and time to PSA progression (TTPP), regardless of CS use (Table). Pts on CS had higher rates of grade 3 - 4 adverse events (AE) compared to no CS pts: 63.3% vs 34.4% respectively. Conclusions: In this post-hoc analysis, on study CS use was associated with reduced OS and higher rates of grade 3 -4 AEs in mCRPC pts post-docetaxel. While CS pts had worse outcomes, ENZA was consistently superior to PBO regardless of on study CS use. The inferior outcomes in CS pts may be due to unmeasured confounders or the biologic properties of CS use itself. Clinical trial information: NCT00974311. [Table: see text]
Genistein rescues pulmonary hypertension and attenuates abnormal vasoconstriction in rats lungs
Authors: Sachiko Kuriyama, Yoshiteru Morio, Tetsutaro Nagaoka, Kuniaki Seyama, Kazuhisa Takahashi
Journal: European Respiratory Journal (2012)

Background)  Recent studies suggest that the deregulation of endothelial nitric oxide synthase (eNOS) is accountable for in the development of pulmonary hypertension (PH). Genistein, a phytoestrogen derived from soybean, has been reported to improve endothelial function.  Objective)  We hypothesized that chronic treatment with genistein would prevent and reverse of hypoxic PH (HX) by improvement of eNOS function.  Method)  Daily treatment with either genistein (0.2mg/kg) or vehicle was started. After 3-wk hypoxic exposure, rats underwent cardiac catheterization, examination of right ventricular hypertrophy, morphological features, Western blot analysis, and immunoprecipitation were performed. For evaluation of the reversal effect, genistein treatment started after rats had been exposed to 3-wk hypoxia exposure, and were examined in the similar way as described above. Furthermore, we examined if genistein would attenuate abnormal vasoconstriction in HX by isolatetd perfused lung examination.  Result)  Genistein treatment prevented the progression of PH to right ventricular failure and restored vascular remodeling in HX. And also, genistein rescued preexisting PH. These effects were mediated by improvement of eNOS function and restoring the interaction of eNOS and eNOS-related proteins.Furthermore, exogenously administration of genistein rapidly attenuated abnormal vasoconstriction in HX by improvement of eNOS function.  Conclusion)  These results indicated that genistein not only had protective and reversal effects against the development of hypoxic PH, but also attenuated abnormal vasoconstriction of PH. The underlying mechanism might be related to the improvement of eNOS function.
Regression of Established Tumors and Induction of Tumor Immunity by Intratumor Chemotherapy
Authors: Robert C. Bast, Martin Segerling, Sarkis H. Ohanian, Steven L. Greene, Berton Zbar, Herbert J. Rapp, Tibor Borsos
Journal: JNCI Journal of the National Cancer Institute (1976)

The inoculation of a mixture of drugs and guinea pig hepatoma cells (line-10) induced tumor-specific immunity in about 20% of guinea pigs. When guinea pigs with established intradermal tumors were given various drugs ip, no cures were observed; in contrast, multiple intralesional injections of actinomycin D, 1,3-bis(2-chlorethyl)-1-nitrosourea, adriamycin, mitomycin C, and melphalan were effective in curing animals of their intradermal tumors at a time when there were tumor cells in the draining lymph nodes; dimethyl-triazenoimidazole carboxamide, methotrexate, 5-fluorouracil, and 6-mercaptopurine were not effective. More than 80% of the cured animals were immune to rechallenge with 10(6) line-10 tumor cells.
Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer.
Authors: J Herrstedt, T Sigsgaard, J Handberg, B M Schousboe, M Hansen, P Dombernowsky
Journal: Journal of Clinical Oncology (1997)

PURPOSE To investigate the antiemetic effect and tolerability of the 5-hydroxytryptamine3(5-HT3) antagonist ondansetron plus the dopamine D2 antagonist metopimazine versus ondansetron alone in patients receiving platinum-based chemotherapy. PATIENTS AND METHODS One hundred eleven chemotherapy-naive patients who were scheduled to receive two consecutive courses of platinum-based chemotherapy were randomized between ondansetron 8 mg intravenously (IV) followed by 8 mg orally twice a day plus metopimazine 35 mg/m2 as a 24-hour continuous infusion followed by 30 mg orally four times a day for 4 days, or ondansetron plus placebo. The study used a double-blind, crossover, placebo-controlled design. RESULTS Ninety-four patients completed the crossover. Complete response (CR; no emetic episodes) was obtained on day 1 in 77.7% of the patients who received the combination versus 50.0% of those who received ondansetron alone (P = .00002), and in 51.7% versus 31.0% on days 2 to 6 (P = .0009). The overall CR (days 1 to 6) was 48.9% versus 25.3% (P = .0002). Additionally, significantly less nausea was observed with the combination on day 1 (P = .0002), days 2 to 6 (P = .0001), and days 1 to 6 (P = .00004). Patient preference was 63.6% for the combination and 13.6% for ondansetron alone; 22.7% expressed no treatment preference (P &lt; .0001; therapeutic gain 50.0%; 95% confidence interval [CI], 31.6% to 68.4%). Adverse reactions were mild and without significant differences between the two treatments. CONCLUSION Metopimazine plus ondansetron was significantly superior to ondansetron alone, concerning all efficacy parameters assessed, in patients who received platinum-based chemotherapy.
The glomerulopathy of sickle cell disease
Authors: Kenneth I. Ataga, Vimal K. Derebail, David R. Archer
Journal: American Journal of Hematology (2014)

Sickle cell disease (SCD) produces many structural and functional abnormalities in the kidney, including glomerular abnormalities. Albuminuria is the most common manifestation of glomerular damage, with a prevalence between 26 and 68% in adult patients. The pathophysiology of albuminuria in SCD is likely multifactorial, with contributions from hyperfiltration, glomerular hypertension, ischemia-reperfusion injury, oxidative stress, decreased nitric oxide (NO) bioavailability, and endothelial dysfunction. Although its natural history in SCD remains inadequately defined, albuminuria is associated with increased echocardiography-derived tricuspid regurgitant jet velocity, systemic blood pressure, and hypertension, as well as history of stroke, suggesting a shared vasculopathic pathophysiology. While most patients with albuminuria are treated with angiotensin converting enzyme inhibitors/angiotensin receptor blockers, there are no published long-term data on the efficacy of these agents. With the improved patient survival following kidney transplantation, SCD patients with end-stage renal disease should be considered for this treatment modality. Given the high prevalence of albuminuria and its association with multiple SCD-related clinical complications, additional studies are needed to answer several clinically important questions in a bid to adequately elucidate its pathophysiology, natural history, and treatment.
Cotreatment of Hairy Cell Leukemia and Melanoma With the<i>BRAF</i>Inhibitor Dabrafenib
Authors: James S. Blachly, Gerard Lozanski, David M. Lucas, Michael R. Grever, Kari Kendra, Leslie A. Andritsos
Journal: Journal of the National Comprehensive Cancer Network (2015)

The activating BRAF mutation p.V600E has been identified in many cancers, including colon and lung adenocarcinomas, papillary thyroid cancer, malignant melanoma, and hairy cell leukemia (HCL). Malignant melanoma and HCL are of particular interest because of both the high proportion of cases harboring the mutation and the dramatic responses to BRAF inhibitor therapy reported in the literature. This report presents a patient with HCL and malignant melanoma with the BRAF p.V600E mutation, and discusses the successful treatment of both cancers with the BRAF inhibitor dabrafenib.
Efficacy of Contralateral Prophylactic Mastectomy in Women With a Personal and Family History of Breast Cancer
Authors: Shannon K. McDonnell, Daniel J. Schaid, Jeffrey L. Myers, Clive S. Grant, John H. Donohue, John E. Woods, Marlene H. Frost, Joanne L. Johnson, Diana L. Sitta, Jeffrey M. Slezak, Thomas B. Crotty, Robert B. Jenkins, Thomas A. Sellers, Lynn C. Hartmann
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age &lt; 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.
Functional classification of proteins for the prediction of cellular function from a protein-protein interaction network
Authors: Christine Brun, François Chevenet, David Martin, Jérôme Wojcik, Alain Guénoche, Bernard Jacq
Journal: Genome biology (2003)

We here describe PRODISTIN, a new computational method allowing the functional clustering of proteins on the basis of protein-protein interaction data. This method, assessed biologically and statistically, enabled us to classify 11% of the Saccharomyces cerevisiae proteome into several groups, the majority of which contained proteins involved in the same biological process(es), and to predict a cellular function for many otherwise uncharacterized proteins.
Post-transplant obstructive lung disease ("bronchiolitis obliterans"): a clinical comparative study of bone marrow and lung transplant patients
Authors: F Philit, T Wiesendanger, E Archimbaud, JF Mornex, J Brune, JF Cordier
Journal: European Respiratory Journal (1995)

Patients at a single pulmonary centre who developed obstructive lung disease after bone marrow transplantation (BMT) and lung transplantation (LT) were studied, in order to compare the clinical expression of post-transplant obstructive lung disease (PTOLD) (bronchiolitis obliterans) in these two conditions, which have so far been studied separately. Nine out of 179 patients surviving more than 100 days after BMT (5%) and 9 out of 44 patients surviving more than 100 days after LT (20%) developed post-transplant obstructive lung disease. This was defined by an irreversible airflow obstruction, as characterized by a forced expiratory volume in one second divided by forced vital capacity (FEV1/FVC) of less than 70%, and a FEV1 of less than 70% of predicted value. The mean interval between transplantation and the diagnosis of post-transplant obstructive lung disease was 262 days and 217 days for BMT and LT patients, respectively. In all cases, pulmonary symptoms consisted of dyspnoea and progressively productive cough. Bronchial dilatation on high-resolution computed tomography scans was the main imaging feature present in both groups of patients at the onset of post-transplant obstructive lung disease. The mean FEV1/FVC ratio was 51 and 54% for BMT and LT patients, respectively. All BMT and LT patients had normal transfer coefficient. Clinical chronic graft-versus-host disease was present in all BMT patients before or concurrent with the onset of post-transplant obstructive lung disease, and all LT patients had presented at least one episode of acute lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
T cell exhaustion marker expression in the human lung in health and COPD in response to influenza infection
Authors: Richard McKendry, Cosma Spalluto, Ben Nicholas, Karl Staples, Tom Wilkinson
Journal: European Respiratory Journal (2013)

Chronic obstructive pulmonary disease (COPD) patients are susceptible to recurrent respiratory infections. This occurs despite increased numbers of CD8+ T cells in the COPD lung. We hypothesised that the inability of CD8+ T cells to successfully combat respiratory pathogens may be due to T cell “exhaustion”. Exhaustion is initiated by the binding of PD-1 on T cells to its ligand (PD-L1) expressed on epithelial cells and macrophages.  Lung tissue from patients undergoing airway re-sectioning was digested using collagenase to form single-cell suspensions before and after infection with A/H3N2/X31 influenza virus. Cells expressing PD-1, PD-L1 or viral NP-1 were quantified by multi-colour flow cytometry.  The proportion of CD8+ T cells in the lungs of COPD individuals (mean=39.1%, SD=13.6) was significantly higher (p=0.014, students t-test) than in controls (mean=25.5%, SD=11.3), reflecting previous findings with a corresponding decrease in the proportion of CD4+ T cells (p=0.03). PD-1 expressing CD4+ cells (mean=3.31%, SD=3.1) and CD8+ cells (mean=2.2%, SD=2.0) were detected in tissue, but not in the blood of these patients. PD-L1 could be detected on lung epithelial cells and macrophages. Upon influenza exposure, macrophages and epithelial cells were infected (mean=28.1%, SD=1.3 and mean=15.7%, SD=8.6 respectively) but there was only a significant increase in macrophage PD-L1 (p=0.012) expression in response to viral infection.  Elements of the exhaustion pathway are expressed in the human lung in stable COPD and are upregulated in response to viral infection.
In Vitro Antitumor Effect of Lymphoid Cells From Corynebacterium parvum-Treated Mice: Effect of Route of C. parvum Administration2
Authors: A. Ghaffar, R. T. Cullen
Journal: JNCI Journal of the National Cancer Institute (1977)

Corynebacterium parvum administration in CBA mice resulted in the stimulation in the peritoneal exudate and other lymphoid organs of cells which nonspecifically inhibited the tumor growth in vitro. The distribution of the antitumor activity in different organs was dependent on the route of C. parvum injection. Both ip and iv treatments stimulated antitumor activity in the peritoneal exudate, whereas the sc route was ineffective. Only iv treatment stimulated the antitumor activity in the blood, and only the sc route produced the antitumor activity in the lymph node. The antitumor activity following the sc treatment was confined mainly to nodes draining the site of C. parvum injection. All routes of treatment provoked some antitumor activity in the spleen, although the degree of the activity varied with the route in the order of ip, iv, and sc. The antitumor activity in all organs peaked between 4 and 14 days after C. parvum injection. This activity in all organs, except the spleen, disappeared by day 42 post treatment. The results are discussed in the light of the in vivo observations on the antitumor effects of C. parvum.
Epidermolysis bullosa simplex with<i>PLEC</i>mutations: new phenotypes and new mutations
Authors: A. Charlesworth, C. Chiaverini, J. Chevrant-Breton, M. DelRio, A. Diociaiuti, R.P. Dupuis, M. El Hachem, B. Le Fiblec, A.M. Sankari-Ho, A. Valhquist, E. Wierzbicka, J.P. Lacour, G. Meneguzzi
Journal: British Journal of Dermatology (2013)

Genetic mutations in the plectin gene (PLEC) cause autosomal recessive forms of epidermolysis bullosa simplex (EBS) associated with either muscular dystrophy (EBS-MD) or pyloric atresia (EBS-PA). Phenotype-genotype analysis has suggested that EBS-MD is due mostly to genetic mutations affecting the central rod domain of plectin, and EBS-PA to mutations outside this domain.This study aimed to describe new phenotypes of patients with EBS-MD and EBS-PA, to identify novel PLEC mutations and to establish genotype-phenotype correlations.Seven patients with a suspicion of EBS linked to PLEC mutations were included. A standardized clinical questionnaire was sent to the physicians in charge of each patient. Immunofluorescence studies of skin biopsies followed by molecular analysis of PLEC were performed in all patients.We report the first case of nonlethal EBS-PA improving with age, the first multisystemic involvement in a patient with lethal EBS-PA, and the first patients with EBS-MD with involvement of either the bladder or oesophagus. Eleven novel PLEC mutations are also reported.Our results confirm that EBS-PA is linked to mutations in the distal exons 1-30 and 32 of PLEC. Long-term survival is possible, with skin improvement, but a delayed onset of MD is probable. While EBS-MD is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the PLEC mutation(s), but no correlation with mucosal involvement has been found.
Metabolomic profiling of clinical sputum samples reveals novel biomarkers for the early identification of lung cancer patients
Authors: Simon Cameron, Keir Lewis, Manfred Beckmann, Gordon Allison, Robin Ghosal, Paul Lewis, Luis Mur
Journal: European Respiratory Journal (2014)

INTRODUCTION:  Developing novel screening and diagnosis methodologies will allow earlier diagnosis of lung cancer (LC), increasing the effectiveness of clinical interventions. We tested the potential of metabolomic profiling on sputum to differentiate between patients with and without LC.   METHODS:  Patients: We collected and processed the spontaneous sputum of 34 patients with suspected LC, alongside 33 healthy controls from staff at Swansea University, with no history of lung disease. Of the 34 patients, 23 were subsequently diagnosed with lung cancer (16 NSCLC, six SCLC, and one radiological diagnosis) at various stages of disease progression. Procedure: The 67 samples were profiled using linear quadrupole ion trap mass spectrometery (MS), with metabolite identifications confirmed using gas chromatography MS and fourier transform ion cyclotron resonance MS.   RESULTS:  Hierarchical cluster and principal component analyses clearly separated the clinically and non-clinically acquired samples. Analysis based on area under the receiver operating characteristic curve (AUC) revealed differential metabolites for patients with and without LC, with a maximum AUC value of 0.8 for a metabolite ratio that is able to differentiate between those clinical samples with LC from those without.   CONCLUSION  :  This preliminary analysis suggests sputum is a viable sample, and metabolomics has potential as a diagnostic and/or discriminator tool. Furthermore, it can identify specific key metabolites that could aid our understanding of the molecular pathogenesis of LC and possibly guide treatment targets.