tbuckley/cabot-search huggingface dataset:
Abstract 658: Phosphorylated HER3 levels associated with trastuzumab resistance inHER2gene amplified uterine serous carcinoma xenograft tumors
Authors: Silvia F. Hernandez, Celeste DiGloria, Jolijn Groeneweg, Darrell Borger, Rosemary Foster, Bo Rueda, Whitfield Growdon
Journal: Cancer Research (2015)

Abstract Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. Clinical trial has demonstrated that USC is impervious to trastuzumab therapy, though the mechanism is poorly understood. Since HER3 mediated signaling has been implicated in trastuzumab resistance in breast cancer, we sought to understand the relevance of HER3 activation in USC xenografts derived from the HER2 gene amplified (HER2:Chr 17 &amp;gt; 15) non-immortalized USC cell line ARK2. Cohorts of mice harboring xenografts derived from ARK2 were treated with either vehicle, trastuzumab (10 mg/kg IP BIW), lapatinib (150 mg/kg QD oral gavage) or the combination of trastuzumab and lapatinib for 21 days. Acute and chronic post treatment tumor samples were assessed for downstream signaling alterations. Single agent trastuzumab had no impact on xenograft growth compared to vehicle. Lapatinib alone resulted in significant tumorstatic effects (p &amp;lt; 0.01) and dual therapy with trastuzumab and lapatinib induced synergistic activity that significantly decreased tumor volume compared to all other arms (p &amp;lt; 0.01). Single agent trastuzumab was associated with rapid elevation in pHER3 levels with unchanged pAKT and pERK expression compared to vehicle. These elevated pHER3 levels were similarly elevated after the 21 day treatment. Anti-tumor activity observed in the lapatinib and dual lapatinib/trastuzumab arm was not associated with any alterations in pHER3 levels following 21 day treatment, though acute elevations in pHER3 were noted in the dual HER2 blockade arm at 24 hours after treatment. In conclusion, trastuzumab alone failed to impact USC xenograft growth and this innate resistance was associated with an elevation in pHER3 levels that was still evident in xenografts at the end of the treatment period. Unlike single agent trastuzumab, treatment arms that utilized lapatinib demonstrated significant anti-tumor activity with no increase in pHER3 above vehicle over the course of treatment. These data highlight HER3 activation as a possible trastuzumab resistance mechanism in USC that can be abrogated through the addition of lapatinib. Citation Format: Silvia F. Hernandez, Celeste DiGloria, Jolijn Groeneweg, Darrell Borger, Rosemary Foster, Bo Rueda, Whitfield Growdon. Phosphorylated HER3 levels associated with trastuzumab resistance in HER2 gene amplified uterine serous carcinoma xenograft tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 658. doi:10.1158/1538-7445.AM2015-658
The progressive elevation of alpha fetoprotein as diagnostic test of hepatocellular carcinoma
Authors: O. Arrieta, B. Cacho, D. Domville, A. Aguayo, E. Leon-Rodriguez
Journal: Journal of Clinical Oncology (2005)

4160 Background: Hepatocellular carcinoma (HCC) constitutes more than 90% of the primary liver tumors. It is associated with a poor prognostic and it depends on its early detection, as well as the patient’s liver reserve. The seric determination of alpha fetoprotein (αFP) has a sensibility for the diagnosis of HCC between 50–85% and a level greater than 400ng/mL, is highly specific for diagnosis. The objective of this study was to analyze the sensibility and specificity of the progressive increment of the αFP levels for the early detection of HCC in patients with liver cirrhosis (LC). Methods: For this study there were included one hundred patients with liver cirrhosis who were followed at the external consult of the Instituto Nacional de Ciencias Médicas y Nutrición (INCMNSZ), who had their αFP levels measured, without diagnostic of HCC by MRI with a follow-up period of three years, as well as fifty patients with with liver lesion by image studies and diagnosis of HCC by biopsy. Sensibility and specificity of the transversal measurement of αFP ≥ 400ng/mL and the progressive elevation of αFP with three determinations, were analyzed. The areas under the ROC curves of both diagnostic tests, were compared. Results: A sensibility and specificity of 17.5 and 100% respectively was found for the patients with αFP ≥ 400ng/mL, and for the elevation of ≥ 5ng/mL/month we found a sensibility of 76.2% and specificity of 98.3%. The area under the ROC curve was significantly greater for the progression of αFP (0.92) with three determinations than for the αFP levels (0.8) with p< 0.05. By comparing the area under the ROC curve of the transversal determination of αFP ≥ 400ng/mL with the progressive elevation ≥ 5ng/mL/month, we found a significant difference in favor of the progressive elevation of αFP ≥ 5ng/mL/month as a diagnostic test. Conclusions: The progressive elevation of 5ng/ml/month of αFP with three determinations in patients with liver cirrhosis is useful for the diagnosis of HCC and has a greater sensibility that its transversal measurement ≥ 400ng/mL. No significant financial relationships to disclose.
Radiation treatment of spinal tumors using Cyberknife radiosurgery
Authors: J. J. Liao, N. M. Nasr, G. J. Gagnon, F. C. Henderson, B. T. Collins, D. McRae, K. W. Harter
Journal: Journal of Clinical Oncology (2006)

1545 Background: Morbidity associated with spinal tumors can leave patients with functional limitations, pain, and poor quality of life. Since the integrity of the spinal column and the spinal cord must be preserved, treatments are limited especially in the setting of previous radiotherapy. We describe our experience using Cyberknife fractionated stereotactic radiosurgery in the initial treatment and retreatment of spinal tumors and its impact on patient quality of life. Methods: 152 patients with primary or metastatic spinal tumors were treated to 228 spinal sites at Georgetown University Hospital from 2002 to 2005. Neurologic examination, pain assessment by visual analog scale (0–100), and quality of life evaluations by SF-12 survey (mental and physical health scores) were performed initially and at 1, 3, 6, 9, 12, 18, and 24 months following treatment. The primary endpoints were pain and quality of life. 44 patients (109 sites) received Cyberknife radiosurgery as a component of their initial management. The median dose delivered was 2400 cGy (range 1400–8000) in 1–5 fractions (median 3). Median tumor volume was 56 mm 3 (range 0.65–457.26). 108 patients (119 sites) with recurrent/persistent disease and a history of prior conventional radiation to the spine received Cyberknife radiosurgery as retreatment. Previous radiation doses ranged from 2000–5940 cGy. The median retreatment dose delivered was 2100 cGy (range 750–3500) in 1–5 fractions (median 3). Median tumor volume was 107.2 mm 3 (range 0.94–838.9). Results: Optimized treatment plans were designed with the goal of limiting spinal cord doses. Median follow up is 13 months. No complications have been observed, including treatment related myelitis. Across all patients, the mean initial pain score was 73. Mean pain scores decreased significantly after the first month to 49 and remained significantly lower (40–44) for over one year. SF-12 PCS (initial mean 33) and MCS scores (initial mean 47) remained stable during the duration of the study. Conclusions: Fractionated stereotactic radiosurgery using the CyberKnife is a safe and effective treatment capable of delivering high-dose radiation to primary and recurrent spinal tumors. Follow-up data demonstrates durable pain relief and stable quality of life. No significant financial relationships to disclose.
Coumarin Anticoagulant Therapy of Patients with T-Tube Drainage of the Common Bile Duct
Authors: Carlos E. Harrison, John A. Spittel, John M. Waugh
Journal: New England Journal of Medicine (1961)

THE value of coumarin anticoagulant therapy in both the prevention and the treatment of postoperative thromboembolic disease is well established.1 Patients who have external (T-tube) drainage of the common bile duct present a risk, theoretically at least, of bleeding associated with the use of coumarin anticoagulant therapy. The presence of a drainage tube sometimes aggravates bleeding, but perhaps even more important in these patients is the external drainage of bile. It has been amply demonstrated that the presence of bile salts in the gastrointestinal tract is necessary for the absorption of natural vitamin K, and it is also well recognized . . .
A Video Is Worth a Thousand Words
Authors: John C. Alverdy
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Neonatal Familial Primary Hyperparathyroidism
Authors: Donald A. Hillman, Charles R. Scriver, Sydney Pedvis, Israel Shragovitch
Journal: New England Journal of Medicine (1964)

THIS report concerns 2 male sibs with hypercalcemia caused by neonatal familial primary hyperparathyroidism. In the literature there are only a few reports of familial hyperparathyroidism.1 , 2 These patients were adults, and in each case, single or multiple parathyroid adenomas were found; the inheritance of the condition appears to be dominant. Primary hyperparathyroidism in childhood is uncommon. Seven examples of parathyroid adenomas in preadolescents have been reported,3 and none were familial. There have been three other reports in which there was diffuse parathyroid hyperplasia associated with hypercalcemia.4 5 6 In each case the condition was fatal in early infancy. The oldest sib in . . .
Leucine Aminopeptidase Activity
Authors: Alexander M. Rutenburg, Julius A. Goldbarg, Esteban P. Pineda
Journal: New England Journal of Medicine (1958)

LEUCINE aminopeptidase is a proteolytic enzyme that is capable of hydrolyzing L-leucyl peptides. It is widely distributed in bacteria, plants and animals and has been demonstrated in all human tissues assayed, with high activity in the duodenum, kidney and liver.1 2 3 The intracellular function of this enzyme is not known but probably involves hydrolysis of a peptide bond near an L-leucine residue or the transfer of L-leucine from one peptide molecule to another. In the small intestine this peptidase is active in the terminal phases of protein digestion. We have demonstrated it regularly in gastric juice, bile and duodenal secretion, in . . .
Cutaneous Anergy and Hodgkin's Disease
Authors: W. Wilson Schier
Journal: New England Journal of Medicine (1954)

THE association of the reticuloendothelial system with immunity is well known. It is not surprising, therefore, that disturbance of this system modifies the pattern of immunity. Blockage of the reticuloendothelial system by inert particulate matter has been shown to cause a temporary depression of antibody production.1 The association of Hodgkin's disease with a negative tuberculin reaction is familiar.2 Speculation concerning the significance of this phenomenon has been centered in large part on the relation of tuberculosis to Hodgkin's disease. Much attention has been given to establishing the tubercle bacillus in an etiologic role. Sternberg,3 as early as 1898, was convinced . . .
SP0213 Bone Directed Therapy in Osteoarthritis
Authors: G. Jones
Journal: Annals of the Rheumatic Diseases (2015)

It was hypothesized many years ago by Radin that osteoarthritis was a disease of subchondral bone. Advances in imaging notably MRI and DXA scanning have greatly enhanced our understanding of this process. There are a number of facets of bone involved in cartilage damage and/or loss in the knee. These include bone marrow lesions (BMLs), tibial plateau area, subchondral bone density (sBMD) and osteophytes. In addition, there is evidence that BMLs, bone attrition and osteophytes are also associated with symptoms although the latter is controversial. BMLs and tibial bone area also predict knee replacement independent of pain and radiographic changes suggesting they may be a marker of fast progression. Most of these changes tend to worsen over time. BMLs can worsen, stay static or improve over time and this fluctuation is associated with change in symptoms. There is also evidence that BMLs are linked to pain in the hip and tenderness in the hands. Taking these observations into account there are some key potential targets. We don9t know how to alter bone size or bone attrition. sBMD could be altered by antiresorptive agents but this would potentially be deleterious as it is higher sBMD that precedes cartilage damage and causing enhanced BMD loss would have the additional effect of increasing the risk of osteoporosis and fractures. Osteophyte progression in the spine can be slowed by alendronate based on a post hoc analysis of the original osteoporosis trial. Risedronate appeared to have no effect on the knee but this may reflect measurement issues. Observational data suggests BMLs are much less common in those taking bisphosphonates (but not other antiresorptives) while risedronate may slow progression of BMLs. Recently, a proof of principle trial of the potent IV agent zoledronic acid was performed where all subjects had BMLs. Chondroitin may also have an effect on BMLs. Strontium ranelate has also been shown to help pain and slow down radiographic change in knee osteoarthritis but it remains uncertain if this is mediated by its bone effects or a cartilage effect. Back pain is also less common with zoledronic acid. These data imply that we should be choosing lesion specific therapy for osteoarthritis especially bone targeted therapy for those with BMLs (and possibly osteophytes?). <h3>Disclosure of Interest</h3> None declared
A Knockout of a Transgenic Mouse — Animal Models of Sickle Cell Anemia
Authors: R L Nagel
Journal: New England Journal of Medicine (1998)

Animal models of sickle cell anemia can be used to improve understanding of the pathophysiology of the disease, aid in the development of antisickling drugs, and test the feasibility of gene therapy. The basis of these interesting models is transgenic technology, in which foreign genes are introduced into the germ line of a mouse. With this method it is possible to create mice that carry the mutant sickle, or βS, gene and a normal human α-globin gene. In such animals, the human βS and α-globin genes code for sickle hemoglobin (α2βS 2), but . . .
Fluconazole and Enhanced Effect of Rifabutin Prophylaxis
Authors: Prem K. Narang, Carol Braun Trapnell, John R. Schoenfelder, James P. Lavelle, Joseph R. Bianchine
Journal: New England Journal of Medicine (1994)

To the Editor: The results of two double-blind, randomized, placebo-controlled trials published in the Journal (Sept. 16 issue)1 have shown that prophylactic treatment with rifabutin (300 mg per day) significantly reduces the incidence of Mycobacterium avium complex bacteremia. A Special Report in the same issue2 further recommends rifabutin prophylaxis in adults and adolescents with human immunodeficiency virus infection and CD4+ counts of 100 cells or less per cubic millimeter and suggests that effective primary prophylaxis could improve the patients' quality of life and survival. Fluconazole, a potent inhibitor of cytochrome P-450, significantly (P<0.01) increases both the maximal concentration and the . . .
Augmentation of Interleukin-2 Immunotherapeutic Effects by Lymphokine-Activated Killer Cells and Allogeneic Stimulation in Murine Tumor Cells
Authors: A M Eggermont, E P Steller, R T Ottow, W Matthews, P H Sugarbaker
Journal: JNCI Journal of the National Cancer Institute (1987)

Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were used in intraperitoneal and pulmonary tumor models in C57BL/6 mice. To maintain the immunotherapeutic effects of IL-2 plus LAK treatment but reduce its toxicity, ways were sought to augment IL-2 effects. The investigation showed that the adoptive transfer of LAK cells was a prerequisite for successful therapy of intraperitoneal cancer. When LAK cells were given on consecutive days within one course of immunotherapy, antitumor efficacy was augmented with additional doses of LAK cells. However, with the reduction of 1 complete cycle of IL-2 + LAK cells, no further reduction in intraperitoneal tumor was observed as compared to the reduction after 2 or 4 cycles. LAK cells generated from splenocytes of mice that had received an allogeneic tumor challenge 1 week earlier exerted a highly increased cytotoxicity as compared to normal LAK cells. Furthermore, the potentiation effect of an allogeneic response of the host at the tumor site was demonstrated by decreased numbers of lung implants and improved survival in mice given mixtures of syngeneic and allogeneic tumor cell suspensions. An alloimmune response within the microenvironment of tumor tissue markedly enhanced the antitumor effect of IL-2 against the syngeneic tumor. It was concluded that there is a fundamental need to improve the recruitment of adoptively transferred LAK cells or LAK precursors into tumor tissue. This may be the next step required in the further development of IL-2 and LAK immunotherapy.
Two-Year Costs and Quality in the Comprehensive Primary Care Initiative
Authors: Stacy B. Dale, Arkadipta Ghosh, Deborah N. Peikes, Timothy J. Day, Frank B. Yoon, Erin Fries Taylor, Kaylyn Swankoski, Ann S. O’Malley, Patrick H. Conway, Rahul Rajkumar, Matthew J. Press, Laura Sessums, Randall Brown
Journal: New England Journal of Medicine (2016)

The 4-year, multipayer Comprehensive Primary Care Initiative was started in October 2012 to determine whether several forms of support would produce changes in care delivery that would improve the quality and reduce the costs of care at 497 primary care practices in seven regions across the United States. Support included the provision of care-management fees, the opportunity to earn shared savings, and the provision of data feedback and learning support.
Conjunctival Biopsy in the Diagnosis of Sarcoidosis
Authors: Johann S. Bornstein, Michael I. Frank, David B. Radner
Journal: New England Journal of Medicine (1962)

The clinical implications of the diagnosis of sarcoidosis go well beyond the labeling of a syndrome. This is true not only because the etiology is yet to be determined but also because the clinical manifestations of sarcoidosis are simulated by numerous infectious and noninfectious agents.1 Exact diagnosis is of more than academic importance, particularly since the advent of corticosteroid therapy for sarcoidosis, for these drugs are capable of disseminating many of the granulomatous diseases of infectious origin.2 Sarcoidosis presents clinically as a systemic disease in which involvement of the mediastinal and peripheral lymph nodes, lungs, liver, spleen, skin, eyes, phalangeal . . .
The Nature of Benign Strictures in Ulcerative Colitis
Authors: S. J. M. Goulston, V. J. McGovern
Journal: New England Journal of Medicine (1969)

In a series of 19 examples of benign stricture of the colon in patients with chronic ulcerative colitis insufficient fibrosis was found in the resected specimens to account for the narrowing. Measurements of the various layers of the gut wall were made in both the portions involved and those not involved by stricture, and these were compared with similar measurements in resected specimens from patients with ulcerative colitis without stricture and in normal sigmoid colons. The most striking finding was that in ulcerative colitis the muscularis mucosae is hypertrophied and is in a state of contraction. In the zones of stricture the contraction appears to be so forceful that the inner circular coat of the muscularis mucosae pulls away from the outer longitudinal coat, thereby narrowing the lumen of the gut. The importance of this finding is that such strictures should be reversible.
Case 31-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, K.A. Eagle, J.T. Fallon
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 68-year-old man was transferred to this hospital because of an acute myocardial infarct with fever, pulmonary edema, and oliguria.The patient was in stable health until two weeks earlier, when he began to experience fatigue. One day before entry he played golf in the morning and then went to work. Substernal pain soon developed and increased rapidly, with the onset of dyspnea and sweating. He drove himself to another hospital, where an electrocardiogram showed evidence of an acute inferoposterior myocardial infarct. Streptokinase (1.5 million units) was injected by vein, with a continuous intravenous infusion of heparin. . . .
The Safety of Dipeptidyl Peptidase 4 Inhibitors and the Risk for Heart Failure
Authors: Benjamin M. Scirica
Journal: JAMA Cardiology (2016)

Darren K. McGuire, MD, MHSc; Frans Van de Werf, MD, PhD; Paul W. Armstrong, MD; Eberhard Standl, MD, PhD; Joerg Koglin, MD; Jennifer B. Green, MD; M. Angelyn Bethel, MD; Jan H. Cornel, MD; Renato D. Lopes, MD, MHS, PhD; Sigrun Halvorsen, MD; Giuseppe Ambrosio, MD; John B. Buse, MD; Robert G. Josse, MBBS; John M. Lachin, ScD; Michael J. Pencina, PhD; Jyotsna Garg, MS; Yuliya Lokhnygina, PhD; Rury R. Holman, MBChB; Eric D. Peterson, MD, MPH; for the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) Study Group
The Muscle Flap for Management of Osteomyelitis
Authors: Stephen J. Mathes
Journal: New England Journal of Medicine (1982)

Reconstructive surgeons now routinely use the muscle flap to cover a multitude of wounds complicated by bacterial infection and inadequate coverage. As early as 1946, Stark1 reported the successful use of a pedicled muscle flap to close the wound of chronic osteomyelitis after sequestrectomy. More recently, muscle flaps have been successfully transposed into infeeted median-sternotomy incisions after debridement of infected bone.2 With microsurgical techniques, muscle has been transplanted to distant sites, such as the cranium and distal tibia, to cover exposed, infected bone.3 4 5 In this issue, May and his associates report on a series of such cases in which they . . .
Syndrome of Anemia, Dysphagia and Glossitis (Plummer–Vinson Syndrome)
Authors: James T. Howell, Raymond W. Monto
Journal: New England Journal of Medicine (1953)

AN iron-deficiency anemia associated with chronic dysphagia and glossitis in women between forty and fifty years of age is now known as side-ropenic dysphagia. Historically, the entity has borne the name of the Plummer–Vinson syndrome,1 , 2 but the characteristics of the dysphagia and anemia had received attention in medical literature before Vinson's report in 1922.3 4 5 6 7 8 Classically, the patient complains of choking or fear of choking and delayed swallowing of food localized at the cricoid area of the neck. The onset of the dysphagia may be sudden but is often insidious and periodic. Frequent associated complaints are weakness, fatigue, nervousness and "dyspeptic" . . .