tbuckley/cabot-search huggingface dataset:
NEW GLIOMA-ASSOCIATED AUTO-ANTIBODIES
Authors: J. Fueyo, C. Conrad, C. Gomez-Manzano, W. A. Yung, F. Tufaro, F. Lang
Journal: Neuro-Oncology (2014)

BACKGROUND: Accumulating evidence has demonstrated that the immune system can recognize the antigenic changes in cancer cells, and further develop autoantibodies against these tumor-associated antigens (TAAs). Therefore, these cancer-associated autoantibodies might be used to identify the antigenic changes of cellular proteins involved in the transformation process. Antibodies to tumor antigens have advantages over other serum proteins as potential cancer biomarkers as they are highly specific and easily identified with high quality secondary reagents. Currently, there is a paucity of studies on autoantibodies against TAAs in gliomas. Here we examined the antibodies against TAAs in a Phase I clinical trial of patients with recurrent gliomas treated with the intratumoral injection of Delta-24-RGD oncolytic adenovirus (Fred Lang, Neurosurgery, MDACC, Director of the Trial). METHODS: Sera from 37 patients were analysed before the administration of Delta-24-RGD and then at several time points after the administration of the adenovirus. A solid phase-modified ELISA was used to assess antibodies against the following 31 antigens: BRAF, CABYR, CRISP3, CSAG2, DHFR, FHLT17, GAGE1, LDHC, MAGEA1, MAGEA3, MAGEA4, MAGEB6, MAPK1, MUC1, NLRP4, NYESO1, p53, PBK, PRAME, SOX2, SPANXA1,SSX2, TSGA10, TSSK6, TULP2, XAGE2, ZNF165. Expression of the proteins in tumors was confirmed using western blot and/or immunohistochemistry. Data were the result of at least two independent experiments. RESULTS: 1. The majority of the patients with recurrent gliomas harbor antibodies against TAAs. 2. The titer of antibodies against TAAs drastically decreased after total resection of the tumor. 3. After surgery the antibodies became again detectable predicting relapse. 4. 80% of patients' sera have antibodies against cancer testis antigens including NYESO1 and MAGE. 5. 60% of the patients showed antibodies against MAGEA1 o MAGEA3. 6. 40% of patients were positive for NYESO1 antibodies. 7. A small percentage of patients have antibodies against BRAF or SOX2. CONCLUSIONS: We report for the first time a systematic analysis of cancer-associated antibodies in patients with recurrent gliomas treated with oncolytic adenoviruses. As illustrated in this study, the serological screening of patients using solid phase ELISA for well characterized antigens offers new opportunities for analyzing the repertoire of the humoral immune response to human gliomas. Many of the listed antibodies were never analyzed before in gliomas. More intensive screening of patients after surgery may include frequent antibody screening (i.e. every 3–6 months) as an adjunct to serial MRIs. Of further clinical relevance several of the cancer/testis antigens identified are promising targets for cancer vaccines. SECONDARY CATEGORY: Tumor Biology.
Effect of Beta-Blockade on Mortality among High-Risk and Low-Risk Patients after Myocardial Infarction
Authors: Stephen S. Gottlieb, Robert J. McCarter, Robert A. Vogel
Journal: New England Journal of Medicine (1998)

Long-term administration of beta-adrenergic blockers to patients after myocardial infarction improves survival. However, physicians are reluctant to administer beta-blockers to many patients, such as older patients and those with chronic pulmonary disease, left ventricular dysfunction, or non–Q-wave myocardial infarction.
Analysis of Primary Breast Tumour Stromal Cells and Their Potential Role in Disease Progression.
Authors: M. Hartmann, R. Dwyer, M. Kerin
Journal: Cancer Research (2009)

Abstract It has emerged in recent years that interaction between breast cancer stromal and epithelial cells supports tumour progression through promotion of epithelial cell growth, migration and invasion. Although this is thought to be mediated through both secretion of paracrine factors and cell-cell contact, the precise mechanisms are poorly understood. The aim of this study was to further characterise stromal cells derived from primary breast tumours and potentially elucidate mechanisms through which they exert their action.Following written informed consent, specimens of human breast cancer were harvested from patients undergoing surgery. Cells were isolated from tumour (n=19) and tumour-associated normal (TAN, n=9) regions of breast tissue. Breast tissue obtained from reduction mammoplasty served as normal controls. Following tissue dissociation and digestion, stromal cells were isolated by differential centrifugation. Following culture of stromal cells, RNA was extracted, reverse transcribed and relative quantitative PCR performed using primers targeting Fibroblast Activation Protein (FAP), Transforming Growth Factor β (TGFβ), Transforming Growth Factor β Receptor II (TGFβRII), Matrix Metalloproteinase 3 (MMP3), and Vascular Endothelial Growth Factor A (VEGF A).There was a trend towards increased expression of VEGF A, TGFβRII and MMP3 in tumour compared to normal stromal cells, while the level of TGFβ expression was equivalent in all samples examined. There was a significant positive correlation between expression of the proangiogenic factor VEGF A and TGFβRII (Pearson correlation coefficient r=0.317, p&amp;lt;0.05). There was also a significant positive correlation between expression of FAP and TGFβRII (r=0.404, p&amp;lt;0.05).Tumour stromal cells have the potential to stimulate angiogenesis through secretion of paracrine factors such as VEGF. This proangiogenic factor is a known target of the TGFb signalling pathway. The elevated level of TGFβRII observed in this study may support TGFβ mediated upregulation of VEGF and thus promote tumour angiogenesis. Further characterisation of stromal cells and their impact on epithelial cell genotype and phenotype is critical to identify targets to inhibit initiation of the metastatic cascade. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4163.
Experts Call for Full Coordination of Cancer Effort, Increased Access to Care
Authors: Elaine Blume
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Experts Call for Full Coordination of Cancer Effort, Increased Access to Care Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 21, 2 November 1994, Pages 1578–1580, https://doi.org/10.1093/jnci/86.21.1578 Published: 02 November 1994
Sertraline and Hyponatremia
Authors: Joseph Kessler, Steven C. Samuels
Journal: New England Journal of Medicine (1996)

To the Editor: Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone have been reported in patients treated with sertraline (Zoloft).1–3 We describe the rapid onset of hyponatremia in an 82-year-old woman who was hospitalized for progressive alcohol dependence, delirium due to alcohol intoxication, and severe depressive symptoms that had begun after her husband's death three years earlier. Initially, she was treated with lorazepam, thiamine, folate, and ranitidine. On the third hospital day, she was given 25 mg of sertraline for her depression, and 50 mg daily thereafter. On the second day of sertraline therapy we began to . . .
Cerebral blood flow and metabolism in schizophrenia. The effects of barbiturate semi-narcosis, insulin coma and electroshock. 1948 [classical article]
Authors: S S KETY, R B WOODFORD
Journal: American Journal of Psychiatry (1994)

Studies by the use of the nitrous oxide technique on 22 schizophrenic patients show no deviation from values obtained in normal young males for cerebral blood flow and oxygen consumption. A clinically significant change in 8 patients given sodium pentothal or amytal intravenously is not associated with a measurable change in cerebral blood flow or cerebral oxygen consumption. Insulin hypoglycemia and coma is associated with a progressive decrease in cerebral utilization of oxygen and blood glucose, the cerebral circulation remaining unimpaired. The fall in blood glucose utilization is greater than that of oxygen. Electroshock is followed by a moderate decrease in metabolism and a marked decrease in cerebral blood flow in the face of a severe acidosis. Although there were no demonstrable deviations from the normal in this group of schizophrenic patients, our experience with this technique leads us to believe that it is worthy of extensive application in the study of the metabolic derangements in the brain ...
Effect of protein phosphatase 2A subunit gene haplotypes and proliferative breast disease on breast cancer risk.
Authors: WD Dupont, JP Breyer, KM Bradley, PA Schuyler, W Plummer, ME Sanders, DL Page, JR Smith
Journal: Cancer Research (2009)

Abstract Abstract #3090 Background: A large number of genes encode components of complex growth factor signaling networks and may contribute to breast cancer risk. Prominent among these candidates are protein phosphatases that counter kinases of signaling cascades. We explored the role of a set of candidate genes encoding subunits of the major cellular protein phosphatase 2A (PP2A) in a cohort of women with a history benign breast disease. Women with a history of benign proliferative breast disease are at increased risk of subsequently developing breast cancer.&amp;#x2028; Materials and Methods: We evaluated genetic variation in a set of 49 candidate genes of signal transduction pathways for potential contributions to breast cancer risk. The study was conducted as a nested case-control investigation of a cohort of women with a history of benign breast disease. DNA prepared from the original archival benign breast biopsy was available for 301 women diagnosed with breast cancer on follow-up, and for 545 of their 602 matched controls. Controls were women who remained free of breast cancer, matched to cases in a 2:1 ratio by race, age, and year of entry biopsy.&amp;#x2028; Results: We observed that a PP2A structural subunit gene, PPP2R1A, and two regulatory subunit genes, PPP2R2A and PPP2R5E, each appeared to modify breast cancer risk with both risk-elevating and risk-reducing genetic variants. Only PPP2R2A was significantly associated with breast cancer after correction for multiple comparisons, with significant risk and protective haplotypes (OR = 1.79, study-wide P = 0.015, and OR = 0.62, study-wide P = 0.025, respectively). These variants interact with a history of proliferative breast disease to modify risk for breast cancer. In a dose model that included all three genes, breast cancer risk ranged from a 5.1-fold decrease to a 3.9-fold increase in risk, depending on the portfolio of variants inherited by a woman (study-wide P = 0.02).&amp;#x2028; Discussion: If confirmed by independent studies, PP2A may play a key role as a tumor suppressor in breast cancer that is able to augment as well as to nullify elevated risk associated with early benign proliferative breast disease. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3090.
Prevalence of Low Birth Weight and Preterm Delivery in Relation to the Interval between Pregnancies among White and Black Women
Authors: J S Rawlings, V B Rawlings, J A Read
Journal: New England Journal of Medicine (1995)

The higher mortality rate among black infants than among white infants in the United States results largely from the greater frequency of low birth weight and prematurity among black infants. Higher rates of low birth weight and preterm delivery have been associated with shorter intervals between pregnancies.
The Effect of Nisoldipine as Compared with Enalapril on Cardiovascular Outcomes in Patients with Non-Insulin-Dependent Diabetes and Hypertension
Authors: Raymond O. Estacio, Barrett W. Jeffers, William R. Hiatt, Stacy L. Biggerstaff, Nancy Gifford, Robert W. Schrier
Journal: New England Journal of Medicine (1998)

It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting–enzyme inhibitor enalapril as part of a larger study.
Case 19-1962
Authors: H. Richard Tyler
Journal: New England Journal of Medicine (1962)

Presentation of CaseA three-year-old female mongoloid child was referred to the hospital because of fever and nuchal rigidity.The patient had been in a state institution since three weeks of age because of mongolism. Cyanosis was present from birth, and she was believed to have congenital heart disease. She was otherwise well until five days before entry, when the temperature rose rapidly to 104.2°F. Physical examination revealed erythema of the tonsils and pharynx, and chloramphenicol therapy was begun. On the day of admission the temperature was 104.4°F., and the neck became stiff. The white-cell count was 15,600, with 63 . . .
The Interaction of High Mobility Group Proteins with the p160 Coactivator SRC-1; a Role in Endocrine Resistance.
Authors: A. Redmond, A. Stafford, M. McIlroy, A. Hill, L. Young
Journal: Cancer Research (2009)

Abstract Breast cancer affects one woman in ten in the western world and despite the phenomenal advances in recent years, the mortality rate still remains at around 35%. Resistance to current endocrine therapies, including tamoxifen and aromatase inhibitors, is common with recurrence of disease in 30-40% of patients. The estrogen receptor (ER) coactivator protein SRC-1 plays an important role in this resistance. We examined SRC-1 protein expression in a large cohort of breast cancer patients (n=560) and found expression to be a strong predictor of disease recurrence in patients treated with adjuvant tamoxifen (hazard ratio: 5.032, p&amp;lt;0.0001). Identification of SRC-1 interacting proteins will provide key insights into the role of SRC-1 in the development of tumour recurrence. We employed a mass spectrometry-based screen to identify proteins which could differentially interact with SRC-1 in endocrine resistant compared with endocrine sensitive breast cancer cells. Selected SRC-1 interacting proteins relevant to endocrine resistance include the high mobility proteins HMGB1 and HMGB2, which have previously been reported to enhance binding of the estrogen receptor to its response elements in target gene promoters. Immunoprecipitation assays confirmed increased interactions between HMGB2 and SRC-1 following treatment of the endocrine resistant cell line LY2 with tamoxifen and estrogen. Steroid treatment also increased trafficking of the coactivator and the SRC-1 interacting protein to the nucleus of tumour epithelial cells. Treatment enhanced recruitment of SRC-1 to the promoter of the oncogene c-Myc and enhanced target gene expression. HMGB2 expression in the breast cancer patient TMA correlated with SRC-1 and poor disease-free survival. These findings would indicate an important role for HMGB2 in the development of endocrine resistance in breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5138.
Clinical Observations before and after Mitral Valvuloplasty
Authors: John F. Otto, J. Morrison Hutcheson, Walter H. Abelmann, Dwight E. Harken, John E. Gary, Laurence B. Ellis
Journal: New England Journal of Medicine (1955)

OPERATIVE correction of the stenotic mitral valve has become an established surgical procedure during the past seven years, and is being performed with increasing frequency. Much has been learned about the indications for surgery, the surgical technics, the operative risks and complications, and the symptomatic improvement to be expected in properly selected patients. Much remains to be learned, and certain misunderstandings persist. It should be remembered that the scarred, deformed and often calcified mitral valve cannot be transformed into a normal structure even though its function may be improved. Furthermore, there are factors besides the anatomic deformity that contribute to . . .
F-18 FDG PET/CT in Evaluation of Pulmonary Sclerosing Hemangioma
Authors: Ko-Han Lin, Cheng-Pei Chang, Ren-Shyan Liu, Shyh-Jen Wang
Journal: Clinical Nuclear Medicine (2011)

Pulmonary sclerosing hemangioma (PSH), or the alternative name of "sclerosing pneumocytoma," is a rare benign neoplasm. PSH is often asymptomatic and presents as a solitary pulmonary nodule on radiologic imaging studies. Few articles have been reported to describe the FDG PET findings about PSH. We reported FDG PET findings of 6 cases of PSH and reviewed the literatures.FDG PET and PET/CT imaging studies of 6 patients with proven PSH were reviewed. The relation between the degree of FDG uptake and tumor size was analyzed.All 6 tumors were detected by FDG PET or PET/CT. Mean diameter of these tumors was 2.9 cm. Mean standard uptake value was 2.45 (range, 1.8-3.93). The maximal standard uptake value of FDG uptake was positively correlated with the tumor size (R = 0.9694, P < 0.05).PSH demonstrates low to moderate uptake on FDG PET imaging. The larger PSH has higher uptake and might be misrecognized as a malignancy. The possibility of false-positive result caused by PSH should be considered while interpreting FDG PET images of solitary pulmonary nodules.
Topical preparations for the treatment of psoriasis: a systematic review
Authors: J. Mason, A.R. Mason, M.J. Cork
Journal: British Journal of Dermatology (2000)

Abstract Summary Background There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. Objectives To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. Methods All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo-controlled trials of topical treatments for psoriasis; and (2) randomized head-to-head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to-head studies. Results There was a significant benefit in favour of active treatments against vehicle, SWMD: −1·06 (95% confidence interval [CI]: −1·26 to −0·86), approximately a 2-point improvement on a 12-point TSS after 6–8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: −1·51 (95% CI: −1·76 to −1·25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0·42 (95% CI: 0·12–0·72) approximately a 0·8-point improvement on a 12-point TSS. No important differences in withdrawal or reporting of adverse events were identified. Conclusions Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long-term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.
TWO-YEAR CLINICAL OUTCOMES OF THE NOBORI BIOLIMUS-ELUTING STENT AND XIENCE EVEROLIMUS-ELUTING STENT IN PATIENTS TREATED WITH IN-STENT RESTENOSIS
Authors: Takashi Hiromasa, Shoichi Kuramitsu, Takashi Morinaga, Yohei Kobayashi, Hiroyuki Jinnouchi, Takenori Domei, Makoto Hyodo, Shinichi Shirai, Kenji Ando, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2015)
Abstract 2851: Metronomic doxorubicin blocks hypoxia inducible factor-mediated responses to hypoxia in sarcomas and augments the effects of anti-VEGF therapy
Authors: Yeo-Jung Kim, Alexia Y. Zhang, Daniel Karl, Karin Eisenger, M. Celeste Simon, Sam S. Yoon
Journal: Cancer Research (2011)

Abstract Introduction: Levels of hypoxia and hypoxia inducible factors (HIFs) in human sarcomas correlate with tumor progression and metastasis. Prolonged anti-angiogenic therapy of sarcomas can inhibit tumor growth but may also increase hypoxia and HIF activation. The most commonly used chemotherapeutic drug for sarcomas, doxorubicin (dox), was recently found to block HIF binding to DNA at low metronomic doses. Methods: 20 patients with soft tissue sarcomas were treated with anti-VEGF antibody (bevacizumab). The tumors, before and after treatment, were examined for changes in microvessel density using CD31 immunohistochemical staining and global gene expression using microarrays. Patients’ tumors were then treated with a combination of bevacizumab and radiation followed by surgical resection. Expression of specific HIF-target genes in the response to hypoxia and/or dox was examined in vitro in 4 sarcoma cell lines by q-RT-PCR. HT1080 human sarcoma xenografts and sarcomas in genetically engineered LSL-KrasG12D/+Trp53fl/fl mice were treated with anti-VEGF receptor antibody (DC101) and/or metronomic dox and analyzed for levels of hypoxia, HIFs, and HIF-target genes. Results: Bevacizumab alone reduced microvessel density in sarcomas by a median of 53% (p&amp;lt;0.05). Gene set enrichment analysis of microarrays found the Gene Ontology category “Response to hypoxia” (which includes HIF-1a, HIF-2a, and ARNT) was upregulated in sarcomas with a poor response to combination therapy (bevacizumab plus radiation). Dox at 1-10 uM blocked HIF induction of VEGF and CA-9 in all 4 sarcoma cell lines by 83.7-97.0% and 88.6-97.6%, respectively, while inhibition of other HIF-target genes including c-MET and FOXM1 was variable. HT1080 sarcoma xenografts and LSL-KrasG12D/+Trp53fl/fl sarcomas demonstrated increasing hypoxia with larger tumor size and with treatment with an anti-VEGFR-2 antibody (DC101). Increasing hypoxia corresponded to greater nuclear expression of HIF-1α and HIF-2α, and metronomic Dox lowered expression of HIF-depended genes by up to 92.3%. Combining VEGFR-2 antibody and metronomic Dox therapies had a synergistic effect in suppressing tumor growth. Conclusion: Human sarcomas respond to increased hypoxia by expressing HIF-target genes which promote compensatory responses. This hypoxic response may be exacerbated by anti-VEGF therapies and promote resistance to such therapies. Low metronomic doses of dox can block activation of HIF-target genes and works synergistically with anti-VEGF therapies to inhibit tumor growth. 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 2851. doi:10.1158/1538-7445.AM2011-2851
Blindness after Fat Injections
Authors: Young-Hoon Park, Kyu Seop Kim
Journal: New England Journal of Medicine (2011)

A 32-year-old man presented with vision loss in the left eye. One week earlier, while under local anesthesia, he had had an autologous fat injection into his forehead to correct frown lines. During the injection, he felt a sudden, severe periocular pain and had complete vision loss in his left eye.