tbuckley/cabot-search huggingface dataset:
S102 SOX2 initiates carcinogenesis in a novel organotypic model of bronchial dysplasia
Authors: LD Correia, H Farah, DM Rassl, RC Rintoul, T Sethi, TD Littlewood, GI Evan, F McCaughan
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown in a previous publication that amplification of SOX2 is an early and consistent event in the pathogenesis of this disease but its functional oncogenic potential remains uncertain. We aimed to test the impact of deregulated SOX2 expression in a novel organotypic system that recreates both the molecular and microenvironmental context in which squamous carcinogenesis occurs. Our objectives are: To develop a 3D <i>in vitro</i> model of bronchial dysplasia that recapitulates key molecular and phenotypic characteristics of the human disease. To test the hypothesis that SOX2 deregulation is a key initiating event in the pathogenesis of bronchial dysplasia. <h3>Methods</h3> We use lentiviral transduction to facilitate the inducible activation of SOX2 in immortalised bronchial epithelial cells iBECs. We use lentiviral shRNA and cutting edge CRISPR genome editing technology to introduce specific defects in key tumour suppressor pathways in order to recapitulate the molecular context seen <i>in vivo</i>. We incorporate the genetically manipulated iBECs at the air-liquid interface in a 3-dimensional tissue culture system that also comprises a stromal equivalent with embedded pulmonary fibroblasts and carefully defined media to build an organotypic model of bronchial dysplasia. <h3>Results</h3> We develop a model that recapitulates human bronchial dysplasia. SOX2 deregulation does not cause an obvious phenotype in standard tissue culture conditions, but can initiate the dysplastic phenotype in 3D culture systems. Loss of TP53 and PTEN are co-operating genetic events that potentiate the dysplastic phenotype. The alterations in cell signalling pathways recapitulate signatures seen in invasive squamous cell lung cancer. <h3>Conclusions</h3> In the appropriate molecular and microenvironmental context acute deregulation of SOX2 expression initiates and drives bronchial dysplasia. This confirms it’s oncogenic potential in human cells. This model can be used to test the impact of therapeutic agents aimed at chemoprevention and the potential for co-operating genetic lesions to drive disease progression.
A Randomized Trial of Chemotherapy and Hormonal Therapy in Advanced Breast Cancer
Authors: David T. Kiang, Juliette Gay, Anne Goldman, B.J. Kennedy
Journal: New England Journal of Medicine (1985)

We randomized 81 postmenopausal women with advanced breast cancer, whose tumors were rich in estrogen receptors or of unknown estrogen-receptor status, to receive either estrogen therapy alone or estrogen therapy combined with chemotherapy. An additional 31 patients, whose tumors were poor in estrogen receptors, were randomized to receive either chemotherapy alone or estrogen combined with chemotherapy. The median duration of follow-up was 87 months. In the receptor-rich group, the survival of the 21 patients receiving combined therapy was significantly longer than that of 19 patients receiving estrogen as initial therapy (followed by chemotherapy after failure or relapse). The median survivals were 72 and 29 months, respectively (P = 0.05 by the generalized Wilcoxon method). Among 41 patients with tumors of unknown receptor status, a survival advantage from combined therapy over chemotherapy was seen in the first two years and then disappeared. The survival in 31 patients with receptor-poor tumors was uniformly short regardless of the therapeutic method. We conclude that combined therapy offers a survival advantage in postmenopausal patients with receptor-rich tumors. (N Engl J Med 1985; 313:1241–6.)
RTRB-11MULTIPLE BRAIN METASTASES TREATED WITH SINGLE-ISOCENTER LINAC-BASED STEREOTACTIC RADIOSURGERY (SRS)
Authors: Benjamin W. Corn, Natan Shtraus, Yaron Meir, Nir Honig, Deborah T. Blumenthal, Felix Bokstein, Andrew A. Kanner
Journal: Neuro-Oncology (2015)

SRS has been widely employed for treating multiple brain lesions using various techniques with multiple isocenters. A disadvantage of this approach is the prolonged treatment time, which is proportional to the number of lesions. Prolonged treatment time may lead to patient discomfort and movement with attendant risk of undertreating the lesion and increasing dose to normal brain tissue. To shorten treatment time, we and others have moved to a single iso-center approach, which enables parallel irradiation of multiple lesions instead of the conventional serial approach. The aim of this study is to evaluate the clinical results of this treatment approach. Between November-2010 and May-2014 we treated 162 patients with 2 or more lesions (2-5) with a single isocenter SRS approach. Pathologies treated included non-small cell lung cancer, breast cancer, colo-rectal cancer and melanoma, 46%, 22%, 10.7% and 8.7%, respectively. Patients were RPA class I (41.3%), II (26.7%), III (32.0%). Treatment plans were created using ERGO ++ (Elekta, Sweden) planning software or Eclipse™ (Varian, USA) planning software to create inverse intensity-modulated arc therapy (VMAT). Treatments were performed using Synergy-S micro-leaf beam modulator with 4mm leaves, or TruebeamSTx- Novalis with 2.5mm microleaf collimator in the center and 5mm in the periphery. Plans were created using single isocenter with fixed beams, static arcs and/or combination of the both with manual modification of the leave configuration to accommodate the shape and position of the lesions or VMAT plans consistent of 3-4 dynamic arcs. Median survival for RPA I, II, and III was 13.3 months (10.9-17.5), 6.48 months (4.9-8.7) and 4.6 months (3.9-5.5), respectively on Kaplan Meier Survival Analysis. Our initial results suggest that single-isocenter plans can be utilized to deliver conformity equivalent to that of multiple isocenter techniques and efficiently delivered requiring less than half the beam time required for multiple isocenter set ups.
Surgical Treatment of Diverticulitis of the Colon
Authors: Marshall K. Bartlett, William V. McDermott
Journal: New England Journal of Medicine (1953)

THE purpose of this paper is to advocate a more aggressive attitude toward the surgical treatment of diverticulitis of the colon, which in the past has usually been withheld until after complications of the disease have occurred. Certain features of this condition should be considered as indications for elective resection to forestall complications. The increased safety with which such procedures can now be accomplished, owing to improvements in preoperative preparation, technical advances and better understanding of postoperative care, have made this approach to the problem increasingly desirable.The ProblemIt is well recognized that diverticulosis of the colon is a . . .
The Diagnosis and Treatment of Infective Hepatitis
Authors: William C. Moloney
Journal: New England Journal of Medicine (1946)

INFECTIVE hepatitis has been known chiefly as a disease of war, but it has been described frequently during the past three decades as a sporadic, endemic and epidemic disease occurring in civilian populations all over the world.1 2 3 4 During World War II an unprecedented pandemic of infective hepatitis occurred, and the increasing prevalence of this serious disorder in civilian practice makes it imperative to utilize the newer concepts of the disease and to apply the knowledge and experience gained during the recent conflict to the best diagnostic and therapeutic advantage.It is impossible, in the present state of knowledge, to designate . . .
A Controlled Therapeutic Study of the Irritable-Bowel Syndrome
Authors: David S. Greenbaum, Roger K. Ferguson, Laurence A. Kater, Donald H. Kuiper, Lionel W. Rosen
Journal: New England Journal of Medicine (1973)

Treatment of the irritable-bowel syndrome has not been subjected to adequately controlled studies. Diphenylhydantoin has been reported to be effective. Twelve patients were treated for 20 weeks with 300 mg of diphenylhydantoin daily and with placebo in a randomized double-blind crossover study. Six manifestations scored daily were used as assessment criteria. Psychologic tests were performed. No significant differences (p less than 0.05) between diphenylhydantoin and placebo in any of these manifestations were found. There were positive correlations between frequency and severity of pain and disability but not between frequency, and consistence of stools and pain or disability. These manifestations were strikingly consistent for each patient between biweekly periods. Six of seven patients with the most pain had abnormal scores for neuroticism. There appears to be a rationale for dealing with psychologic factors as well as gut pain in the syndrome. This experimental design should be useful for evaluating other agents in this syndrome.
Childhood Social Environment and Hodgkin's Disease
Authors: Nancy Gutensohn, Philip Cole
Journal: New England Journal of Medicine (1981)

The epidemiologic similarities between Hodgkin's disease in the young and paralytic poliomyelitis suggest that Hodgkin's disease may be a rare consequence of a common infection, with the probability of oncogenesis increasing with age at the time of infection. In a study of 225 cases and 447 controls 15 to 39 years of age, we investigated the association of Hodgkin's disease with factors in childhood that influence age of exposure to infectious agents. Risk among persons with five or more siblings was nearly half that among those with one or none; risk was also reduced among persons of late birth order. Subjects who had lived in multiple-family homes had half the risk of those in single-family housing. Cases had fewer playmates and better-educated mothers than did controls, and cases had twice the rate of infectious mononucleosis. Risk is therefore associated with a set of factors that tend to decrease or delay early exposure to infections, and this association might be explained by a viral origin of the disease, with age at infection as a major modifier of risk. (N Engl J Med. 1981; 304:135–40.)
Prevention of Pulmonary Complications in Infants with Tracheotomy by Modification of the Tracheotomy Cannula
Authors: Arthur Winter, Edwin Gilmore
Journal: New England Journal of Medicine (1959)

A FTER tracheotomy in the infant, if the distance between the cricoid cartilage and the carina is too short, the end of the metal cannula can abut on the carina1 or pass into the right main-stem bronchus. This situation may cause partial bronchial obstruction, with all its attendant complications. Two cases are presented to demonstrate this occurrence, together with indications for revision of the tracheotomy cannula.Case ReportsCase l.§ A 16-month-old female infant (M.H. 94329) fell down a flight of stairs and struck her head, but was not unconscious. There was no consequent change in her state of consciousness, . . .
Proinsulin Secretion by a Pancreatic Beta-Cell Adenoma
Authors: Franco Melani, Will G. Ryan, Arthur H. Rubenstein, Donald F. Steiner
Journal: New England Journal of Medicine (1970)

In a patient with a pancreatic islet-cell adenoma, fasting serum immunoreactive insulin was 114 to 372 μU per milliliter, about five to 20 times the normal value, but 77 per cent of this "insulin" was found to be proinsulin. After intravenous administration of 1 g of tolbutamide an increase in absolute proinsulin concentration was observed. By means of a specific immunoassay, human C-peptide was detected in the expected elution position after gel filtration of serum extracts. After removal of the adenoma the serum levels of both proinsulin and insulin were very low, and proinsulin represented only 10 per cent of the total immunologic activity. In the tumor tissue, 52 per cent of the total immunologically reactive material was identified as proinsulin.
Case 9-1977
Authors: Raymond L.H. Murphy, Eugene J. Mark
Journal: New England Journal of Medicine (1977)

Presentation of CaseA 51-year-old man was admitted to the hospital because of dyspnea.He was in excellent health until 10 months previously, when a "pressing" pain developed in the anterior portion of the chest, with radiation to the left arm. He entered another hospital, where an x-ray film of the chest showed bilateral pleural thickening. Other studies were reported to be negative except for an elevated triglyceride level. An exercise test of cardiac function was said to show changes consistent with ischemic heart disease. Propranolol and isosorbide dinitrate were prescribed, and during the next 10 months he experienced only . . .
ATCT-15CB-018: A PHASE 2 TRIAL OF BEVACIZUMAB PLUS TPI 287, A NOVEL BRAIN PENETRABLE ANTI-MICROTUBULE AGENT, IN PATIENTS WITH RECURRENT GLIOBLASTOMA FOLLOWING PROGRESSION ON ANTI-ANGIOGENIC THERAPY
Authors: Samuel Goldlust, L. Burt Nabors, Solmaz Sahebjam, Sigmund Hsu, Nimish Mohile, Tara Benkers, Pierre Giglio, Jeffrey Raizer, Sandra Silberman, Priya Kumthekar, Samuel Singer, George Farmer
Journal: Neuro-Oncology (2015)

BACKGROUND: There is a significant unmet need for effective therapy for recurrent glioblastoma (GBM). TPI 287, a third-generation taxane that readily penetrates the blood brain barrier, is currently under investigation for the treatment of recurrent GBM in patients with and without prior exposure to bevacizumab (BEV). Here we report initial results from CB-018, a dose escalation multi-center trial designed to determine the maximum tolerated dose (MTD) and efficacy of TPI 287 in combination with BEV in patients that experienced disease progression on a prior BEV-containing regimen. METHODS: Patients with recurrent GBM following first relapse on a BEV-containing regimen are eligible for enrollment. BEV is administered at 10 mg/kg as an IV infusion once every 2 weeks. TPI 287 is administered as a 1-hour IV infusion every 3 weeks. Dose escalation of TPI 287 is planned until a dose-limiting toxicity (DLT) is observed, at which point additional patients will be enrolled to confirm the MTD. MRIs are obtained at the end of every six-week cycle with response assessment via RANO. RESULTS: As of June 2015, 13 patients have been enrolled in 3 dose-escalation cohorts (140, 160, and 170 mg/sq m of TPI 287). Among 8 patients evaluable for response, there has been one responder (CR) and 3 patients with stable disease. The combination regimen has been well-tolerated and no DLTs have been observed to date. Dose escalation continues. CONCLUSIONS: TPI 287 is safe and potentially efficacious in combination with bevacizumab for the treatment of BEV-refractory recurrent GBM. Updated safety and efficacy results will be presented.
A Cohort Study of Transcutaneous Oxygen Tension and the Incidence and Severity of Retinopathy of Prematurity
Authors: John T. Flynn, Eduardo Bancalari, Ellen Sim Snyder, Ronald N. Goldberg, William Feuer, Janet Cassady, Joyce Schiffman, Harold I. Feldman, Brian Baghynski, Edward Buckley, Jacqueline Roberts, Dennis Gillings
Journal: New England Journal of Medicine (1992)

Retinopathy of prematurity is a disease affecting the blood vessels of the retina in premature infants that may result in scarring, retinal detachment, and loss of vision. An association between this condition and the exposure of premature infants to supplemental oxygen has been postulated, but the relation between retinopathy of prematurity and blood oxygen levels has not been defined. The purpose of this study of a cohort of preterm infants was to correlate the incidence and severity of retinopathy of prematurity with the duration of exposure to different ranges of oxygen tension as measured by transcutaneous monitoring (tcPO2).
Pooled Human Plasma as a Volume Expander
Authors: Robert S. Hillman
Journal: New England Journal of Medicine (1964)

POOLED human plasma, stored for six months or longer at 30 to 32°C. to prevent the transmission of viral hepatitis,1 , 2 satisfies most criteria for a suitable plasma-volume expander in emergency situations. Until recently, its administration has been considered to be free from side reactions; Miller and Tisdall3 analyzed 10,000 pooled plasma transfusions and found allergic reactions in only 1 per cent. However, this reliability of plasma as a volume expander has now been questioned. Freedman and his associates4 and Hutchison et al.5 , 6 have demonstrated that the administration of fresh, nonautologous plasma usually results in a rapid loss of volumes greater . . .
Vulvar Herpes Simplex Infection
Authors: J Brennick, L Duncan
Journal: New England Journal of Medicine (1993)

Figure 1. Vulvar Herpes Simplex Infection. Characteristic histologic changes are seen in herpes simplex virus infection of the vulva. Panel A shows necrosis of the epidermis and dermis, with acute inflammation and nuclear debris on the left, viable mucosal keratinocytes on the right, and multinucleated giant cells in the center (arrow) (hematoxylin-eosin, x90). Panel B shows multinucleated cells with Cowdry type A intranuclear viral inclusions (arrow) (hematoxylin-eosin, x220). Panel C shows nuclear molding (the contours of adjacent nuclei conform to one another) with a ground-glass chromatin pattern (arrow) in an enlarged, multinucleated cell (hematoxylin-eosin, x480). In Panel D, a vaginal . . .
Normal Erythropoietic Helper T Cells in Congenital Hypoplastic (Diamond-Blackfan) Anemia
Authors: David G. Nathan, Diane G. Hillman, Leonard Chess, Blanche P. Alter, Bryan J. Clarke, Jacqueline Breard, David E. Housman
Journal: New England Journal of Medicine (1978)

To examine the erythropoietic function of T and null cells in congenital hypoplastic (Diamond-Blackfan) anemia, we fractionated the peripheral blood of three normal subjects and three affected patients into subclasses of null, T and B cells. Mixtures of these cells were co-cultured in plasma clots in the presence of erythropoietin. Erythroid colonies grew in cultures of normal null cells if either normal or patient T cells were co-cultured with them. Null cells of patients with hypoplastic anemia did not produce erythroid colonies under any culture conditions. We conclude that in this disorder, T cells function normally as helper cells in erythropoiesis and do not suppress colony formation, whereas the erythroid progenitor cells in the peripheral blood null-cell fractions are deficient in either number of function.
Post-chemoradiation surgical pathologic stage accurately predicts outcome of patients with esophageal or gastroesophageal junction carcinoma
Authors: T.-T. Wu, L. R. Chirieac, S. G. Swisher, R. U. Komaki, A. M. Correa, J. Roth, A. Rashid, S. R. Hamilton, J. A. Ajani
Journal: Journal of Clinical Oncology (2004)

4028 Background: The prognosis of patients with localized esophageal and gastroesophageal junction (GEJ) carcinoma is best predicted by the surgical pathologic stage when surgery is the primary therapy. However, it is a dilemma in patients undergoing preoperative chemoradiotherapy (PreCTRT). We hypothesized that surgical pathologic stage altered by PreCTRT would predict patients outcome better than pretreatment clinical stage. Methods: Resected specimens of 235 (193 adenocarcinomas and 42 squamous cell carcinomas; median follow up = 31 months) patients with esophageal or GEJ carcinoma who underwent preCTRT were staged by AJCC (ypTNM stage) and by semi-quantitative assessment of residual cancer. Various clinicopathologic features, extent of residual cancer, and pre- and post- treatment stage were compared with disease-free survival (DFS) and overall survival (OS). Results: The post-treatment AJCC stage was 0 in 29% of patients, I in 11%, II in 34%, III in 20%, and IV in 6%. Pathologic complete response in the esophagus was observed in 33%. In univariate analyses, OS and DFS were predicted by the extent of residual cancer (p<0.0001 and p<0.0001, respectively), post-treatment AJCC stage (p<0.0001 and p<0.0001, respectively), and positive surgical resection margin status (p=0.01 and p=0.002, respectively), but not by age, gender, histologic type, clinical stage, or type of therapy used. In multivariate analyses, post-treatment AJCC stage (p=0.04) and extent of residual cancer (p=0.02) independently predicted OS, and only post-treatment AJCC stage predicted DFS (p=0.002). Conclusions: Our data indicate that post-treatment AJCC stage predicts OS and DFS for patients with esophageal and GEJ carcinoma undergoing preoperative therapy. These findings support the concept of benefit from preoperative therapy when downstaging is achieved. No significant financial relationships to disclose.
Lymphoma with Recurrent Cycles of Spontaneous Remission and Relapse — Possible Role of Apoptosis
Authors: Yael Kaufmann, Amira Many, Gideon Rechavi, Orna Mor, Miriam Biniaminov, Esther Rosenthal, Michal Levanon, Jacqueline Davidsohn, Irena Aizman, Ziva Mark, Frida Brok-Simoni, Bracha Ramot
Journal: New England Journal of Medicine (1995)

We describe a patient with a unique mantle-cell lymphoma, with cycles of acute illness alternating with spontaneous remissions. During the acute phase the patient had fever, generalized lymphadenopathy, hepatosplenomegaly, increased liver-enzyme concentrations, leukocytosis, and thrombocytopenia. These bouts remitted after two to three weeks without treatment. Fifteen such cycles were documented over a period of 50 months. During the acute phase blast-like B lymphocytes in the blood expressed surface IgM, IgD, and CD5, whereas during clinical remission a small population of IgM and CD5+ lymphocytes persisted. Two B-cell clones with differently rearranged heavy-chain genes consistently appeared in the blood during the . . .
The Association between Hospital Volume and Survival after Acute Myocardial Infarction in Elderly Patients
Authors: David R. Thiemann, Josef Coresh, William J. Oetgen, Neil R. Powe
Journal: New England Journal of Medicine (1999)

Patients with chest pain thought to be due to acute coronary ischemia are typically taken by ambulance to the nearest hospital. The potential benefit of field triage directly to a hospital that treats a large number of patients with myocardial infarction is unknown.
Which elderly patients with remitted depression remain well with continued interpersonal psychotherapy after discontinuation of antidepressant medication?
Authors: C F Reynolds, E Frank, P R Houck, S Mazumdar, M A Dew, C Cornes, D J Buysse, A Begley, D J Kupfer
Journal: American Journal of Psychiatry (1997)

This study was conducted to identify which elderly patients with remitted recurrent major depression remain well with maintenance interpersonal psychotherapy after discontinuation of active antidepressant medication (nortriptyline).The authors examined outcomes of maintenance therapy over 1 year for 47 elderly patients who were randomly assigned to monthly maintenance interpersonal psychotherapy with placebo (N = 19) or to placebo and a supportive medication clinic without interpersonal psychotherapy (N = 28). A Kaplan-Meier survival analysis was performed on the basis of treatment assignment and subjective sleep quality assessed by the Pittsburgh Sleep Quality Index, on which good subjective sleep quality is indicated by a score of 5 or lower.Nine (90%) of 10 patients reporting good subjective sleep quality (by 1 month into continuation treatment) remained well for at least 1 year when treated with monthly maintenance interpersonal psychotherapy, versus five (31%) of 16 patients with good sleep quality assigned to a medication clinic, three (33%) of nine patients with impaired sleep quality treated with maintenance interpersonal psychotherapy, and two (17%) of 12 patients with impaired sleep quality assigned to a medication clinic.Recovery of good subjective sleep quality by early continuation treatment is useful in identifying which remitted elderly depressed patients will remain well with monthly maintenance interpersonal psychotherapy, following discontinuation of antidepressant medication, and which patients may be more vulnerable to recurrence of major depressive episodes in the absence of antidepressant medication.