tbuckley/cabot-search huggingface dataset:
Folate-Targeted Gene Transfer in Vivo
Authors: Hans E.J. Hofland, Christophe Masson, Shaff Iginla, Irina Osetinsky, Joseph A. Reddy, Christopher P. Leamon, Daniel Scherman, Michel Bessodes, Pierre Wils
Journal: Molecular Therapy (2002)

Nonviral systemic delivery is one of the most attractive approaches for cancer gene therapy. To achieve this goal, various laboratories have developed cationic liposomes. However, when injected intravenously, cationic lipid–DNA complexes accumulate mostly into and transfect lung tissue. Here, we describe a method by which these complexes can be targeted to tumors using folic acid. Adding polyethylene glycol (PEG)–lipids to the complexes dramatically reduced both lung accumulation and gene transfer to lungs and tumors after intravenous administration. The presence of folic acid at the distal end of the PEG–lipid did not modify tumor accumulation of the complexes. However, with folate-targeted complexes, gene transfer activity was restored in tumors while the activity in lungs was reduced by 50- to 100-fold compared with nontargeted lipid–DNA complexes. This approach provides a first in vivo proof of concept to achieve targeted tumor gene delivery.
Abstract 2964: AZD7762-mediated gemcitabine sensitization does not require G2-M checkpoint abrogation in pancreatic cancer cells
Authors: Leslie A. Parsels, Daria M. Tanska, Joshua D. Parsels, Sonya D. Zabludoff, Jeffrey L. Brown, Meredith A. Morgan, Theodore S. Lawrence, Jonathan Maybaum
Journal: Cancer Research (2011)

Abstract Chk1 inhibition is a promising approach to sensitize pancreatic cancer to gemcitabine (Gem), the current standard therapy for both local control and metastatic disease. One hallmark and proposed biomarker of Chk1 inhibition is abrogation of the DNA damage-induced G2-M checkpoint and aberrant mitotic entry. It is unclear, however, whether this effect is necessary for chemosensitization. In this study, we tested the hypothesis that G2-M checkpoint abrogation is required for Gem sensitization in cells treated with the Chk inhibitor AZD7762. We first evaluated the ability of AZD7762 to abrogate the G2-M checkpoint in 6 pancreatic cancer cell lines. While AZD7762 sensitized each cell line to a moderately toxic concentration of Gem, G2-M checkpoint abrogation was only observed in 4 of the lines; AsPC1, MiaPaCa2, M-Panc96 and Panc1. Furthermore, only MiaPaCa2 and Panc1 cells underwent premature mitotic entry when treated with Gem + AZD7762. We next tested the hypothesis that G2-M checkpoint abrogation was responsible for AZD7762-mediated Gem sensitization by using the Cdk inhibitors roscovitine and purvalanol A to preserve the checkpoint in the presence of AZD7762 by directly inhibiting cyclinB-cdk1 and mitotic entry. While both Cdk inhibitors blocked mitosis in cells treated with Gem + AZD7762, the effects on chemosensitization varied. Only in AsPC1 and Panc1 cells did roscovitine prevent both G2-M checkpoint abrogation and Gem sensitization. Furthermore, cyclin B1 siRNA prevented AZD7762-mediated G2-M checkpoint abrogation in MiaPaCa2 and Panc1 cells, but did not prevent chemosensitization, suggesting AZD7762-mediated Gem sensitization does not require G2-M checkpoint abrogation. In addition to abrogating the Gem-induced G2-M checkpoint, AZD7762 promotes S-phase progression. Initial studies suggest AZD7762 may sensitize cells to Gem by abrogating the S-phase checkpoint and permitting S-phase progression in the presence of Gem-induced DNA damage. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2964. doi:10.1158/1538-7445.AM2011-2964
420O Erlotinib plus bevacizumab (EB) versus erlotinib alone (E) as first-line treatment for advanced non-squamous non–small-cell lung cancer (NSCLC) with activating EGFR mutation (mt): JO25567 exploratory subgroup analysis
Authors: Y. Hosomi, T. Seto, M. Nishio, K. Goto, N. Yamamoto, I. Okamoto, K. Tajima, N. Inagaki, N. Yamamoto
Journal: Annals of Oncology (2015)
Pregnancy Loss in the Antiphospholipid-Antibody Syndrome — A Possible Thrombogenic Mechanism
Authors: Jacob H. Rand, Xiao-Xuan Wu, Harry A.M. Andree, Charles J. Lockwood, Seth Guller, Jonathan Scher, Peter C. Harpel
Journal: New England Journal of Medicine (1997)

The mechanisms of vascular thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome are unknown. Levels of annexin V, a phospholipid-binding protein with potent anticoagulant activity, are markedly reduced on placental villi from women with this syndrome. Hypercoagulability in such women may therefore be due to the reduction of surface-bound annexin V by antiphospholipid antibodies. To test this idea, we studied how antiphospholipid antibodies affect levels of annexin V on cultured trophoblasts and human umbilical-vein endothelial cells and how they affect the procoagulant activity of these cells.
Drug resistance among tuberculosis cases in the European Union and European Economic Area, 2007 to 2012
Authors: M J van der Werf, C Ködmön, V Hollo, A Sandgren, P Zucs
Journal: Eurosurveillance (2014)

The European Union and European Economic Area (EU/EEA) tuberculosis (TB) surveillance system collects detailed information on resistance to TB drugs. Using this information, we provide an overview of the current TB drug resistance situation and trends in the EU/EEA by performing a descriptive analysis, including analysis of treatment outcomes, of the TB cases reported between January 2007 and December 2012. The percentages of TB cases with different drug resistance patterns have been stable with about 90% of the new laboratory-confirmed cases pan-susceptible, 6% monodrug-resistant, 2% polydrug-resistant, 2% multidrug drug-resistant (MDR) TB - excluding extensively drugresistant (XDR) TB -, and 0.2% XDR-TB. In previously treated laboratory-confirmed TB cases, the percentage with MDR-TB excluding XDR-TB declined until 2010 to 16% and remained stable thereafter. During the study period, the percentages of cases with monodrug- and polydrug-resistant TB remained constant at about 8% and 2% whereas the percentage of XDR-TB cases increased slightly to 2.6%. Treatment outcome results for all cases have been stable with overall 77.9% of the pan-susceptible cases, 69.6% of the monoresistant cases, 68.2% of the polyresistant cases, 32.2% of the MDR-TB cases (excluding XDR-TB), and 19.1% of the XDR-TB cases treated successfully. The treatment success rate target for new pulmonary culture-positive MDR-TB cases of 70% has not been reached. In addition, drug resistance surveillance can be improved by more complete reporting of drug susceptibility results and treatment outcome.
Aortic Stenosis in the Elderly
Authors: Robert E. Finegan, Ralph E. Gianelly, Donald C. Harrison
Journal: New England Journal of Medicine (1969)

In 78 patients over the age of 60 (average age of 64, the eldest being 80) who had severe aortic stenosis as an isolated valvular lesion, historical and physical findings proved to be similar to those in younger patients with severe aortic stenosis. In the older group the brachial arterial pulse pressure tended to be wide (60 to 65 mm of mercury), and the systolic arterial pressure exceeded 149 mm of mercury in 16 patients, including 13 of the 70 who were referred for surgery. The definitive diagnostic test was catheterization of the left side of the heart. Seventy patients underwent surgery, either valve debridement (nine), prosthetic valve replacement (52) or homograft replacement (nine). The operative mortality was 11.5 per cent, and the late mortality 20 per cent. Forty-four of the 48 survivors reported continued marked improvement (average survival of 25 months). These results justify an aggressive approach in the elderly patient with aortic stenosis.
Inadequate Parathyroid Response in Acute Pancreatitis
Authors: Giles M. Robertson, Edward W. Moore, Donald M. Switz, Glen W. Sizemore, Herschel L. Estep
Journal: New England Journal of Medicine (1976)

We studied nine consecutive hypocalcemic patients with acute pancreatitis to elucidate the mechanism of hypocalcemia. Mean serum ionized calcium, 0.97 mM, was below the normal mean of 1.16 mM (P less than 0.001). Seven of eight patients tested had normal parathyroid hormone levels. All responded to parenteral parathyroid extract by increasing serum ionized calcium and urinary cyclic AMP, indicating parathyroid-hormone-responsive target organs. Calcitonin and glucagon concentrations were increased above normal in some patients, but there was no relation with serum ionized calcium. Parenteral glucagon had no significant effect on serum ionized calcium or calcitonin concentrations. These findings suggest that neither glucagon nor calcitonin was primarily responsible for the hypocalcemia, which did not produce expected increases in serum parathyroid hormone concentrations. Relative parathyroid insufficiency may account for the persistent hypocalcemia frequently observed in patients with acute pancreatitis.
PT-10 * THE ROLE OF SURGERY IN PEDIATRIC BRAIN TUMORS IN POSTERIOR FOSSA
Authors: T. Miyagawa, M. Okada, H. Namba
Journal: Neuro-Oncology (2014)

INTRODUCTION: Intracranial tumors are the most common solid tumors in children. The infratentorial compartment will be the primary site for 60 - 70% of these tumors. Recent advances in the categorization of childhood brain tumors have improved risk-based treatment planning. The purpose of this study was to provide a review of the treatment of pediatric brain tumors in posterior fossa with emphasis on the role of surgery in the hierarchy of treatment option. MATERIALS AND METHODS: Twelve children ranging in the age from 7 months to 14 years were enrolled in this study. They were divided into 3 groups according to the following criteria; group I: tumors that currently have promising standard therapy; group II: tumors that currently have no or few promising standard therapy; group III: pathologically benign tumors. RESULTS: Four children with medulloblastoma were categorized into group I and all survived. Group II was constituted by many tumors, including AT/RT, GBM, anaplastic ependymoma, and ependymoma. The prognosis in group II was dismal. Two children with astrocytoma and oligodendroglial gliomatosis were categorized into group III and all survived. CONCLUSIONS: Adjuvant therapies, including radiotherapy and chemotherapy were effective in group I and III, therefore, tumor resection must be performed to avoid neurological sequelae and late effects. In group II, neurosurgery plays an important role for improving survival rate. Since each tumor has a different therapeutic schema and purpose of surgery, therefore, must be different, neurosurgeon should perform surgery with deep consideration in terms of the therapeutic history of each tumor.
Nasal Visualization on Radioiodine Whole-Body Scintigraphy Due to Benign Abnormality
Authors: Xue Jiang, Qiao Wang, Rui Huang
Journal: Clinical Nuclear Medicine (2015)

Nasal iodine activity can be observed on 123Iodine (123I) or 131I whole-body scintigraphy (WBS) commonly as a normal variant caused by nasal or salivary secretion of the tracer. We encountered 2 patients whose increased accumulation of 131I activity was associated with underlying abnormalities. One patient had a nasal polyp, whereas the other had an abscess.
Lack of Effectiveness of Bed Rest for Sciatica
Authors: Patrick C.A.J. Vroomen, Marc C.T.F.M. de Krom, Jan T. Wilmink, Arnold D.M. Kester, J. André Knottnerus
Journal: New England Journal of Medicine (1999)

Bed rest is widely advocated for sciatica, but its effectiveness has not been established. To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks, we randomly assigned 183 subjects to either bed rest or watchful waiting for this period. The primary outcome measures were the investigator's and patient's global assessments of improvement after 2 and 12 weeks, and the secondary outcome measures were changes in functional status and in pain scores (after 2, 3, and 12 weeks), absenteeism from work, and the need for surgical intervention. Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients' treatment assignments.After two weeks, 64 of the 92 patients in the bed-rest group (70 percent) reported improvement, as compared with 59 of the 91 patients in the control (watchful-waiting) group (65 percent) (adjusted odds ratio for improvement in the bed-rest group, 1.2; 95 percent confidence interval, 0.6 to 2.3). After 12 weeks, 87 percent of the patients in both groups reported improvement. The results of assessments of the intensity of pain, the bothersomeness of symptoms, and functional status revealed no significant differences between the two groups. The extent of absenteeism from work and rates of surgical intervention were similar in the two groups.Among patients with symptoms and signs of a lumbosacral radicular syndrome, bed rest is not a more effective therapy than watchful waiting.
A VERY LONG-TERM (18-MONTH) ARTERIAL PHARMACOKINETIC ASSESSMENT OF PACLITAXEL-COATED BALLOON TREATMENT IN PERIPHERAL ARTERIES OF SWINE
Authors: Carlos A. Gongora, Armando Tellez, Yanping Cheng, Krzysztof Milewski, masahiko shibuya, Gerard Conditt, jose narvaez, Juan Granada, Greg Kaluza
Journal: Journal of the American College of Cardiology (2014)
Four Types of Acute Post-Traumatic Intracranial Hemorrhage
Authors: J A Mattiello, M Munz
Journal: New England Journal of Medicine (2001)

Figure 1. A 71-year-old man was pushed onto his back by a slow-moving vehicle. Initially, he was alert and fully oriented. In the emergency department, the patient was disoriented to place; the examination revealed no signs of injury, and coagulation studies were normal. Within 30 minutes after the initial evaluation, his neurologic status deteriorated. The axial section of a computed tomographic (CT) scan of the head, obtained without the addition of contrast medium, revealed four types of acute post-traumatic intracranial hemorrhage: an epidural hematoma (thick white arrow) and a squamous temporal fracture (which is not shown) on the left side, . . .
Clinical and Angiographic Features of Carotid Transient Ischemic Attacks
Authors: Michael S. Pessin, Gary W. Duncan, Jay P. Mohr, David C. Poskanzer
Journal: New England Journal of Medicine (1977)

To determine the prevalence of radiologically evident carotid stenosis in patients with transient cerebral ischemic attacks, we analyzed 95 consecutive hospitalized patients who during a two-year period had appropriate symptoms and also underwent angiography. Pure transient hemisphere symptoms affected 52 patients, pure monocular blindness occurred in 33, and 10 experienced each type of attack separately. Tight stenosis (less than or equal to 2 mm) or occlusion was present in 49 patients (52 per cent). Thirteen patients showed intracranial-branch occlusion, nine of whom had no notable stenosis. Only two clinical transient ischemic attack features correlated with angiographic findings: in transient hemisphere attacks lasting for one hour or longer, the carotid arteries revealed no notable stenosis (0.05 less than P less than 0.1); and separate hemisphere and ocular attacks in the same patient correlated with tight carotid stenosis. On the basis of the angiographic findings, the study indicates there are several distinct groups of patients with carotid transient ischemic attacks.
DSM-III: psychiatric diagnosis in a university population
Authors: R S Stangler, A M Printz
Journal: American Journal of Psychiatry (1980)

Using DSM-III the authors reviewed psychiatric diagnoses in a sample of 500 students at a university psychiatric clinic. They present prevalence data and associated age and sex characteristics of this population in relationship to their diagnostic findings and discuss these in the context of earlier epidemiologic studies and their impact on university mental health services.
US poised to outlaw late abortion technique
Authors: D. Bozalis
Journal: BMJ (1995)

The House of Representatives passed a bill, by a two-thirds majority (288-139), prohibiting late (at 19-20 weeks gestation) abortion using intrauterine cranial decompression. The bill now awaits judgment from the Senate Judiciary Committee for hearings. If the bill becomes law, physicians performing the procedure could face up to two years in prison. Chris Smith, Republican cochairman of the House Pro-Life Caucus, who introduced the bill in the House, described the vote as historic. During his emotional speech, the procedure was described in order to desanitize a form of abortion that he called barbaric torture. Patricia Schroeder, Colorado House Representative, argued that the wording of the bill allowed the procedure only when it was the only possible way of saving the mother's life; the woman's health and future fertility were, in effect, set aside. There is no exception clause for when the woman's life or health is endangered. Schroeder fears women will be forced to choose more dangerous methods of abortion and believes more discussion is required regarding health risks and a more precise definition of when the procedure may be used. She is joined by the California Medical Association, the American Medical Women's Association, the American College of Obstetricians and Gynaecologists, and the American Medical Association.
925 IL28B GENE VARIANTS AND METABOLIC PROFILE IN PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C
Authors: C. Rosso, M.L. Abate, R. Leung, D. Booth, L. Mezzabotta, S. Carenzi, G.P. Caviglia, F. Salamone, R. Gambino, M. Cassader, M. Rizzetto, A. Smedile, J. George, E. Bugianesi
Journal: Journal of Hepatology (2012)
Case 17-1997
Authors: Julian L. Seifter, Volker Nickeleit
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 67-year-old woman was admitted to the hospital because of azotemia with nausea, vomiting, and bloody diarrhea.The patient had been in excellent health until one week earlier, when she began to have nausea, vomiting, and diarrhea, with some stools appearing to consist entirely of blood. At the time, she was vacationing in Europe, where a physician gave her medications that she could not identify. Several days before admission, while still in Europe, the vomiting decreased, but the nausea persisted, with profound anorexia. Two days before admission, the diarrhea subsided, but she began to have progressive abdominal . . .
Abstract 5527: Overexpression of protein phosphatase 4 is associated with poor prognosis in patients with pancreatic ductal adenocarcinoma
Authors: Shaofan Weng, Weihong Chen, Hamilton R. Stanley, Deyali Chatterjee, Matthew H. Katz, Jeffrey E. Lee, Peter W. Pisters, Henry F. Gomez, James L. Abbruzzese, Jason B. Fleming, Huamin Wang, Hua Wang
Journal: Cancer Research (2012)

Abstract Background: PP4 has been reported to be overexpressed in breast and lung cancers. While previous studies have identified the role of PP4 in activating NFκB and JNK signaling pathway, the expression and functions of PP4 in pancreatic cancer has not been studied in detail. Methods: We examined the expression of PP4 protein in 133 patient samples of stage II pancreatic ductal adenocarcinoma (PDA) samples by immunohistochemistry (IHC). To confirm our IHC results, we measured the expression levels of PP4 mRNA in 15 PDA samples and 15 benign pancreatic tissue sample by real time RT-PCR. We also measured PP4 protein levels in in 9 fresh frozen PDA samples and their paired benign pancreatic tissues by Western blot. Using univariate and multivariate analysis, we correlated PP4 expression with survival and other clinicopathologic features. Results: PP4 was overexpressed in 75 of 133 (56%) stage II PDA samples by immunohistochemistry. Compared to benign pancreatic tissue, PP4 protein levels were higher in 9 of 9 PDA samples by Western blot analysis. PP4 mRNA expression levels in PDA samples were significantly higher than benign pancreatic tissue, suggesting that overexpression of PP4 in PDA is due to increase mRNA expression. PP4 overexpression was associated with higher frequencies of distant metastasis (p=0.02) and poor overall and recurrence-free survivals (p = 0.002 and 0.005) independent of tumor size, margin status, and lymph node status (stage) in patients with stage II PDAs. Conclusions: Our study shows that PP4 is frequently overexpressed in PDA samples and is associated with poor prognosis in patients with stage II PDA. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDA. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5527. doi:1538-7445.AM2012-5527
Pulmonary Embolism Caused by Right Atrial Myxoma on FDG PET/CT
Authors: Qinghua Liu, Changjing Zuo, Taozhen Lv, Bin Cui
Journal: Clinical Nuclear Medicine (2013)

Pulmonary embolism derived from the right atrial myxoma is a rare event and can be difficult to recognize. A chest x-ray image from a 48-year-old woman with shortness of breath revealed multiple pulmonary nodules, which suggested lung metastases. An FDG PET/CT was performed for further evaluation. The images showed that the lung nodules had variable but mild FDG activity in general. There was 1 additional large FDG activity in the right atrium. The subsequent studies demonstrated that the patient experienced pulmonary embolism derived from the right atrial myxoma.
RT-26 * RE-RESECTION FOR RECURRENT HIGH GRADE GLIOMA IN THE SETTING OF RE-IRRADIATION: SURVIVAL OUTCOMES UPDATE
Authors: J. Palmer, J. Siglin, K. Yamoah, T. Dan, C. Champ, L. Kim, J. Glass, M. Werner-Wasik, C. Farrell, J. Evans, D. Andrews, W. Shi
Journal: Neuro-Oncology (2014)

BACKGROUND: While patients with high grade gliomas (HGG) experience a high rate of recurrence, current treatment at recurrence remains controversial. Historically, re-resection for recurrent GBM demonstrates a significant survival benefit following reoperation of 3-13 months compared to 1-2 months without treatment. Here we investigate whether re-resection will improve survival in patients receiving fractionated stereotactic radiotherapy (FSRT) for recurrence. METHODS: 231 patients with recurrent HGG treated with re-irradiation between 1994 and 2012 at our institution were analyzed. FSRT was delivered using daily fractions of 3.5 Gy, median total dose of 35 Gy. 105 patients also underwent re-resection. Survival was then analyzed comparing patients with and without re-resection. Median survival time (MST) was defined as survival from initial diagnosis. Survival time was analyzed using the Kaplan-Meier method. Univariate and multivariate analysis was performed. RESULTS: The MST for the entire group is 22.5 months. There is no significant difference in survival between patients who received re-resection vs no re-resection, the MST was 23 months, and 21.9 months respectively (HR 1.1, p = 0.6). Those undergoing re-resection, 30 received gross total resection and 75 subtotal resection, with a MST of 22.0 and 26 months, respectively (p = 0.24). On univariate analysis, age and histology were significant factors (P < 0.05). On multivariate analysis, age remained significant for survival but no other factor (chemotherapy, histology, extent of resection, eloquent location, KPS) was significant. CONCLUSIONS: Our data reveals there is no significant improvement in survival with the addition of re-resection to patients who received FSRT for recurrent HGG. To our knowledge, this data analyzes the largest cohort of HGG treated with FSRT with and without surgical resection after recurrence. We hypothesize that the favorable survival seen in our cohort is derived from local control benefit due to the addition of FSRT.